Q2 2024 Ionis Pharmaceuticals Inc Earnings Call

August 1, 2024

Operator: --this call is being recorded. At this time, I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.

D. Wade Walke: Thank you, Danielle. Before we begin, I encourage everyone to go to the Investors section of the analyst website to view the press release and related financial tables that we will be discussing today, including a reconciliation of GAAP to non-GAAP financials. We believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on this morning's call are Brett Monia, our Chief Executive Officer; Richard Geary, Chief Development Officer; Kyle Jenne, Chief Global Project Strategy Officer; and Beth Hougen, our Chief Financial Officer; Eric Swayze, Executive Vice President of Research; Eugene Schneider, Chief Clinical Development Officer; and Jonathan Birchall, Chief Commercial Officer, will also join us for the Q&A portion of our call. I'd like to draw your attention to Slide 3 in our presentation, which contains our forward-looking language statement. During this call, we will be making forward-looking language statements that are brd on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail. And with that, I'll turn the call over to Brett.

Speaker Change: Again, I encourage everyone to go to the investors section. Website to view the press release and related financial tables that we will be discussing today. A reconciliation of GAAP to non-GAAP financials. Believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on this morning's call are Brett ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, Halogenated, Chief Global Project strategy Officer, and Beth Hougen, Chief Financial Officer. Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: Website to view the press release and related financial tables that we will be discussing today. A reconciliation of GAAP to non-GAAP financials. Believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on this morning's call are Brett ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, Halogenated, Chief Global Project strategy Officer, and Beth Hougen, Chief Financial Officer. Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: A reconciliation of GAAP to non-GAAP financials. Believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on this morning's call are Brett ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, Halogenated, Chief Global Project strategy Officer, and Beth Hougen, Chief Financial Officer. Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: Believe non-GAAP financial results better represent the economics of our business and how we manage our business. We've also posted slides on our website that accompany today's call. With me on this morning's call are Brett ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, Halogenated, Chief Global Project strategy Officer, and Beth Hougen, Chief Financial Officer. Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: With me on this morning's call are Brett ammonia, our Chief Executive Officer, Richard Geary, Chief Development Officer, Halogenated, Chief Global Project strategy Officer, and Beth Hougen, Chief Financial Officer. Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: Eric Swayze Executive Vice President of Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of our call. I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: I would like to draw your attention to slide three in our presentation, which contains our forward looking language statements. During this call we will be making forward looking language statements that are based on our current expectations and beliefs. Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

D. Wade Walke: During this call, we will be making forward-looking language statements that are brd on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors contained in our SEC filings for additional detail. And with that, I'll turn the call over to Brett.

Speaker Change: Statements are subject to certain risks and uncertainties and our actual results may differ materially I encourage you to consult the risk factors contained in our SEC filings for additional detail. That I will turn the call over to Brett.

Speaker Change: That I will turn the call over to Brett.

Brett P. Monia: Thanks, Wade. Good morning, everyone, and thanks for joining us on today's call. We've achieved a great deal during the first half of this year, delivering many significant milestones as we continue to execute on our vision to bring better features to people with serious diseases. Today, Ionis discovered and developed medicines reaching more and more people, bolstered by two recent launches, WAINUA for people with hereditary ATTR polyneuropathy in the U.S., and QALSODY, the first approved treatment for a genetic cause of ALS currently available in the U.S. and now and available in Europe. And with the progress we're making across our pipeline, our medicines are well positioned to continue reaching more and more patients for years to come. The U.S. launch of our first Ionis co-branded medicine WAINUA is progressing well with AstraZeneca, and we expect to bring WAINUA to even more patients across the globe with the recent approval in Canada, and anticipated approval decision in Europe later this year, and with additional regulatory submissions completed in many other geographies with more coming.

Brett: We've achieved a great deal during the first half of this year delivering on many significant milestones as we continued to execute on our vision to bring better futures to people with serious diseases. Today, I honest discovered and developed medicines are reaching more and more people posted by two recent launches we knew for people with hereditary <unk> polyneuropathy in the U S. <unk>, Saudi the first approved treatment for a genetic corrective AOS currently available in the U S and now approved and available in Europe. And with the progress, we're making across our pipeline our medicines are well positioned to continue reaching more and more patients for years to come. The U S launch of our first <unk> co branded medicine, <unk> is progressing well with Astrazeneca and we expect to bring way noise, even more patients across the globe with the recent approval in Canada and. An anticipated approval decision in Europe later, this year and with the general regulatory. Submissions completed and many other geographies with more coming.

Brett: Today, I honest discovered and developed medicines are reaching more and more people posted by two recent launches we knew for people with hereditary <unk> polyneuropathy in the U S. <unk>, Saudi the first approved treatment for a genetic corrective AOS currently available in the U S and now approved and available in Europe. And with the progress, we're making across our pipeline our medicines are well positioned to continue reaching more and more patients for years to come. The U S launch of our first <unk> co branded medicine, <unk> is progressing well with Astrazeneca and we expect to bring way noise, even more patients across the globe with the recent approval in Canada and. An anticipated approval decision in Europe later, this year and with the general regulatory. Submissions completed and many other geographies with more coming.

Brett: And with the progress, we're making across our pipeline our medicines are well positioned to continue reaching more and more patients for years to come. The U S launch of our first <unk> co branded medicine, <unk> is progressing well with Astrazeneca and we expect to bring way noise, even more patients across the globe with the recent approval in Canada and. An anticipated approval decision in Europe later, this year and with the general regulatory. Submissions completed and many other geographies with more coming.

Brett: The U S launch of our first <unk> co branded medicine, <unk> is progressing well with Astrazeneca and we expect to bring way noise, even more patients across the globe with the recent approval in Canada and. An anticipated approval decision in Europe later, this year and with the general regulatory. Submissions completed and many other geographies with more coming.

Brett: An anticipated approval decision in Europe later, this year and with the general regulatory. Submissions completed and many other geographies with more coming.

Brett: Submissions completed and many other geographies with more coming.

Brett P. Monia: Today, we are even more confident in the potential of WAINUA to address the larger ATTR cardiomyopathy population. As the largest study ever conducted in this patient group, our ongoing landmark CARDIO-TTRansform trial is on track to deliver the most comprehensive and the most robust data set in this patient population. We believe WAINUA has the potential to be the treatment of choice for the global ATTR population. Our confidence is brd on WAINUA's strong efficacy profile as demonstrated in hereditary ATTR polyneuropathy and the freedom of simple at-home self-administration together with AstraZeneca's global cardiovascular commercialization leadership, along with our leadership and ATTR amyloidosis. As the renewal launch accelerates, we're also preparing for the launch of OLEZARSEN in FCS later this year, our first independent launch of a wholly owned medicine for Ionis.

with people with hereditary ATTR polyneuropathy in the U.S., and CALSATI, the first approved treatment for a genetic code of ALS currently available in the U.S. and now approved and available in Europe .

Brett Monia: and CalSati, the first approved treatment for genetic cause of ALS currently available in the U.S. and now approved and available in Europe. And with the progress we're making across our pipeline, our medicines are well-positioned to continue reaching more and more patients for years to come. The U.S. launch of our first Ionis co-branded medicine, Waynua, is progressing well with AstraZeneca. And we expect to bring Waynua to even more patients across the globe with the recent approval in Canada. An anticipated approval decision in Europe later this year and with additional regulatory submissions completed in many other geographies with more coming.

Brett: As the largest study ever conducted in this patient group are ongoing landmark cardio transform trial is on track to deliver the most comprehensive and the most robust data set in this patient population. We believe windows has the potential to be the treatment of choice for the global beauty care population. Our confidence is based on we knew a strong efficacy profile as demonstrated in hereditary <unk> polyneuropathy and a freedom of simple at home self administration together with Astrazeneca global cardiovascular commercialization leadership, along with our leadership and GTR amyloidosis. As we know our launch accelerates. We're also preparing for the launch of <unk> in FCS later this year, our first independent launch of a wholly owned medicine per eye on us.

And with the progress we're making across our pipeline, our medicines are well-positioned to continue reaching more and more patients for years to come.

Speaker Change: We believe windows has the potential to be the treatment of choice for the global beauty care population. Our confidence is based on we knew a strong efficacy profile as demonstrated in hereditary <unk> polyneuropathy and a freedom of simple at home self administration together with Astrazeneca global cardiovascular commercialization leadership, along with our leadership and GTR amyloidosis. As we know our launch accelerates. We're also preparing for the launch of <unk> in FCS later this year, our first independent launch of a wholly owned medicine per eye on us.

Speaker Change: Our confidence is based on we knew a strong efficacy profile as demonstrated in hereditary <unk> polyneuropathy and a freedom of simple at home self administration together with Astrazeneca global cardiovascular commercialization leadership, along with our leadership and GTR amyloidosis. As we know our launch accelerates. We're also preparing for the launch of <unk> in FCS later this year, our first independent launch of a wholly owned medicine per eye on us.

Brett Monia: Today, we are even more confident in the potential of Renewa to address the larger ATTR cardiomyopathy population. At the largest study ever conducted in this patient group, our ongoing landmark cardio transform trial is on track to deliver the most comprehensive and the most robust data set in this patient population. We believe WENDUA has the potential to be the treatment of choice for the global APTR population.

Today, we are even more confident in the potential of WENUA to address the larger ATTR cardiomyopathy population.

Speaker Change: As we know our launch accelerates. We're also preparing for the launch of <unk> in FCS later this year, our first independent launch of a wholly owned medicine per eye on us.

Brett P. Monia: OLEZARSEN represents one of the most meaning opportunities in our pipeline today as we prepare to first launch an FCS, a severe rare disease with no approved treatments in the U.S. and then to expand to the much larger sHTG patient population. Our NDA submission for OLEZARSEN was recently accepted with priority review. Our PDUFA date is set for December 19, and we're ready to bring this groundbreaking medicine to people with FCS. We also recently completed enrollment for our SHTG Phase III program, keeping us on track for data in the second half of next year. undefinedd on our significant first-mover advantage and our positive results demonstrated to date, if approved, we believe OLEZARSEN could be the standard of care for both FCS and sHTG. We're building on the capabilities we've established for WAINUA and OLEZARSEN in preparation for our anticipated launch of DONIDALORSEN for HAE prophyraxis next year. In our comprehensive clinical program, DONIDALORSEN has demonstrated strong evidence of meaningful benefit across multiple measures of disease with a favorable safety and tolerability profile. These data together with the potential for monthly or every two months self-administration using an auto-injector strengthen our belief that if approved, DONIDALORSEN has the potential to advance the treatment paradigm for people living with HAE. With positive Phase III data in hand, we expect to submit the NDA for DONIDALORSEN soon as we look to independently bring DONIDALORSEN to patients in the U.S.

Brett P. Monia: OLEZARSEN represents one of the most meaning opportunities in our pipeline today as we prepare to first launch an FCS, a severe rare disease with no approved treatments in the U.S. and then to expand to the much larger SHTG patient population. Our NDA submission for OLEZARSEN was recently accepted with priority review. Our PDUFA date is set for December 19, and we're ready to bring this groundbreaking medicine to people with FCS. We also recently completed enrollment for our SHTG Phase III program, keeping us on track for data in the second half of next year. undefinedd on our significant first-mover advantage and our positive results demonstrated to date, if approved, we believe OLEZARSEN could be the standard of care for both FCS and SHTG. We're building on the capabilities we've established for WAINUA and OLEZARSEN in preparation for our anticipated launch of DONIDALORSEN for HAE prophyraxis next year. In our comprehensive clinical program, DONIDALORSEN has demonstrated strong evidence of meaningful benefit across multiple measures of disease with a favorable safety and tolerability profile.

We believe WENUA has the potential to be the treatment of choice for the global APTR population.

Brett Monia: Our confidence is based on we knew a strong efficacy profile as demonstrated in hereditary ATTR polyneuropathy and the freedom of simple at-home self-administration, together with AstraZeneca's global cardiovascular commercialization leadership, along with our leadership in DTR amyloidosis. As the WENUA launch accelerates, we're also preparing for the launch of Olizarsin in FCS later this year, our first independent launch of a whole new medicine for Ionis. All this arson represents one of the most meaningful opportunities in our pipeline today as we prepare to first launch an FCS, a severe rare disease with no approved treatment in the U.S., and then to expand to the much larger SHTG patient population.

Our confidence is based on we knew a strong efficacy profile as demonstrated in hereditary ATTR polyneuropathy and the freedom of simple at-home self-administration.

Speaker Change: Our NDA submission for <unk> was recently accepted with priority review. <unk> date is set for December 19, and we're ready to bring this ground breaking medicine to people with Fcs. We also recently completed enrollment for our <unk> phase III program and keeping us on track for data in the second half of next year. Based on our significant first mover advantage in our positive results demonstrated to date. If approved we believe those are some could be the standard of care for both FCS and <unk>. We're building on the capabilities, we have established for renewal and <unk> in preparation for our anticipated launch of Domino version for HAE Prophylaxis next year. And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Speaker Change: <unk> date is set for December 19, and we're ready to bring this ground breaking medicine to people with Fcs. We also recently completed enrollment for our <unk> phase III program and keeping us on track for data in the second half of next year. Based on our significant first mover advantage in our positive results demonstrated to date. If approved we believe those are some could be the standard of care for both FCS and <unk>. We're building on the capabilities, we have established for renewal and <unk> in preparation for our anticipated launch of Domino version for HAE Prophylaxis next year. And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Together with AstraZeneca's global cardiovascular commercialization leadership, along with our leadership in DTR amyloidosis.

Speaker Change: We also recently completed enrollment for our <unk> phase III program and keeping us on track for data in the second half of next year. Based on our significant first mover advantage in our positive results demonstrated to date. If approved we believe those are some could be the standard of care for both FCS and <unk>. We're building on the capabilities, we have established for renewal and <unk> in preparation for our anticipated launch of Domino version for HAE Prophylaxis next year. And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Speaker Change: As the WENUA launch accelerates, we're also preparing for the launch of Olizarsin in FCS later this year, our first independent launch of a whole new medicine for Ionis.

Speaker Change: Based on our significant first mover advantage in our positive results demonstrated to date. If approved we believe those are some could be the standard of care for both FCS and <unk>. We're building on the capabilities, we have established for renewal and <unk> in preparation for our anticipated launch of Domino version for HAE Prophylaxis next year. And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

All this arson represents one of the most meaningful opportunities in our pipeline today as we prepare to first launch an FCS, a severe rare disease with no approved treatments in the U.S., and then to expand to the much larger SHTG patient population.

Speaker Change: We're building on the capabilities, we have established for renewal and <unk> in preparation for our anticipated launch of Domino version for HAE Prophylaxis next year. And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Brett Monia: Our NDA submission for Olazarsan was recently accepted with priority review. Our PDUPA date is set for December 19th, and we're ready to bring this groundbreaking medicine to people with FCS. We also recently completed enrollment for our SH2G Phase 3 program, keeping us on track for data in the second half of next year.

Our NDA submission for Olazarsan was recently accepted with priority review. Our PDUPA date is set for December 19th, and we're ready to bring this groundbreaking medicine to people with FCS.

Speaker Change: And our comprehensive clinical program <unk> has demonstrated strong evidence of meaningful benefit across multiple measures of disease. With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Speaker Change: With a favorable safety and Tolerability profile. These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Brett P. Monia: These data together with the potential for monthly or every two months self-administration using an auto-injector strengthen our belief that if approved, DONIDALORSEN has the potential to advance the treatment paradigm for people living with HAE. With positive Phase III data in hand, we expect to submit the NDA for DONIDALORSEN soon as we look to independently bring DONIDALORSEN to patients in the U.S. Outside the U S. Outside the U.S., our commercial partner Otsuka is preparing to file for marketing approval in Europe later this year. And with our recently expanded license agreement, Otsuka is also working to bring DONIDALORSEN to people with HAE in the Asia-Pacific region. Following WAINUA, OLEZARSEN and DONIDALORSEN, our next wave of wholly owned opportunities includes our program for Angelman Syndrome. undefinedd on the positive results from the HALOS Phase I/II study that we presented last week, we are advancing this potentially transformational medicine into a Phase III study, which we anticipate will begin in the first half of next year.

We also recently completed enrollment for our SH2G Phase 3 program, keeping us on track for data in the second half of next year.

Speaker Change: These data together with the potential for monthly or every two months up administration using an auto injector strengthen our belief that if approved <unk> has the potential to advance the treatment paradigm for people living with HIV. With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Brett Monia: Based on our significant first-mover advantage and our positive results demonstrated to date, if approved, we believe Olazarsin could be the standard of care for both FCS and SHTG. We're building on the capabilities we've established for Inua and Olazarsan in preparation for our anticipated launch of Dominoversion for HAE prophylaxis next year. In our comprehensive clinical program, Don Doloresan has demonstrated strong evidence of meaningful benefit across multiple measures of disease, with a favorable safety and tolerability profile.

Based on our significant first-mover advantage and our positive results demonstrated to date, if approved, we believe Olazarsin could be the standard of care for both FCS and SHTG.

Speaker Change: With positive phase III data in hand, we expect to submit the NDA for <unk> and as soon as we look to independently bring donegal worse into patients. In the U S.

Speaker Change: We're building on the capabilities we've established for renewa and olizarsin in preparation for our anticipated launch of domino lotion for HAE prophylaxis next year.

Speaker Change: In the U S.

Speaker Change: Outside the U S. Our commercial partner Otsuka is preparing to file for marketing approval in Europe later this year. And with our recently expanded license agreement on soup is also working to bring down for us into people with HIV in the Asia Pacific region. Following renewable resource endorsing our next wave of wholly owned opportunities includes our program for Angelman syndrome. Based on the positive results from the Halos phase one two study that we presented last week. We are advancing this potentially transformational medicine into a phase III study, which we anticipate will begin in the first half of next year.

Speaker Change: In our comprehensive clinical program, Don Doloresan has demonstrated strong evidence of meaningful benefit across multiple measures of disease with a favorable safety and tolerability profile.

Speaker Change: And with our recently expanded license agreement on soup is also working to bring down for us into people with HIV in the Asia Pacific region. Following renewable resource endorsing our next wave of wholly owned opportunities includes our program for Angelman syndrome. Based on the positive results from the Halos phase one two study that we presented last week. We are advancing this potentially transformational medicine into a phase III study, which we anticipate will begin in the first half of next year.

Brett Monia: These data, together with the potential for monthly or every two months self-administration using an auto-injector, strengthen our belief that, if approved, Donna Borson has the potential to advance the treatment paradigm for people living with HAE. With positive A3 data in hand, we expect to submit the NDA for Donald Morrison soon as we look to independently bring Donald Morrison to patients in the U.S. Outside the U.S., our commercial partner, Absuca, is preparing to file for marketing approval in Europe later this year. And with our recently expanded license agreement, HATSUKA is also working to bring down doors into people with HAE in the Asia Pacific region.

Speaker Change: Following renewable resource endorsing our next wave of wholly owned opportunities includes our program for Angelman syndrome. Based on the positive results from the Halos phase one two study that we presented last week. We are advancing this potentially transformational medicine into a phase III study, which we anticipate will begin in the first half of next year.

These data, together with the potential for monthly or every two months self-administration using an auto-injector, strengthen our belief that, if approved, Donna Borson has the potential to advance the treatment paradigm for people living with HAE.

Speaker Change: Based on the positive results from the Halos phase one two study that we presented last week. We are advancing this potentially transformational medicine into a phase III study, which we anticipate will begin in the first half of next year.

Speaker Change: With positive phase 3 data in hand, we expect to submit the NDA for Donald Wilson soon, as we look to independently bring Donald Wilson to patients in the U.S. Outside the U.S., our commercial partner, Absuca, is preparing to file for marketing approval in Europe later this year.

Brett P. Monia: ION582 is positioned to become the cornerstone of our wholly-owned neurology franchise, but today, which today includes five wholly-owned medicines in clinical development with more to come by the end of the year. Our accomplishments so far this year and the investments we're making move us closer to achieving our goal of bringing a steady cadence of new transformational medicine to patients for years to come, and generating next-level value for all Ionis stakeholders. With that, I'll turn the call over to Richard to discuss our recent pipeline progress and preview key upcoming events. Next, Kyle will review the WAINUA launch and our launch plans in progress for OLEZARSEN and DONIDALORSEN. And Beth will review our financial results. I'll then wrap up things before taking your questions. With that, over to Richard.

Speaker Change: And with our recently expanded license agreement, HATSUKA is also working to bring down aversion to people with HAE in the Asia-Pacific region.

Speaker Change: Our accomplishments so far this year and the investments, we're making and move us closer to achieving our goal of bringing a steady cadence of new transformational medicines to patients for years to come and generating next level value for all Iona stakeholders. With that I'll turn the call over to Richard to discuss our recent pipeline progress and premium key upcoming events next Kyle will review the way new launch and our launch plans and progress for <unk> and <unk> and. And that will review our financial results I will then wrap up things before taking your questions. With that over to Richard.

Brett Monia: Following Wynua, Olisarsson, and Donna Doloresan, our next wave of holeum opportunities includes our program for Angelman Syndrome. Based on the positive results from the HALOS Phase 1-2 study that we presented last week, we are advancing this potentially transformational medicine into a Phase 3 study, which we anticipate will begin in the first half of next year. Ion 582 is positioned to become the cornerstone of our wholly-owned neurology franchise, which today includes five wholly-owned medicines and clinical development, with more to come by the end of the year.

Speaker Change: Following Wynua, Olazarsan, and Donna Doloresan, our next wave of whole young opportunities includes our program for Angelman Syndrome.

Based on the positive results from the HALOS Phase 1-2 study that we presented last week, we are advancing this potentially transformational medicine into a Phase 3 study, which we anticipate will begin in the first half of next year.

Speaker Change: With that I'll turn the call over to Richard to discuss our recent pipeline progress and premium key upcoming events next Kyle will review the way new launch and our launch plans and progress for <unk> and <unk> and. And that will review our financial results I will then wrap up things before taking your questions. With that over to Richard.

Speaker Change: Ion 582 is positioned to become the cornerstone of our wholly-owned neurology franchise, which today includes five wholly-owned medicines and clinical development, with more to come by the end of the year.

Kyle: And that will review our financial results I will then wrap up things before taking your questions. With that over to Richard.

Kyle: With that over to Richard.

Richard Geary: Thank you, Brett. We are pleased that our pipeline delivered many important achievements to date this year. With WAINUA reaching more and more people with hereditary ATTR polyneuropathy. I am proud of all that Ionis team has accomplished to discover and develop this important new medicine and bring it to patients in need. Recent ATTR cardiomyopathy data further reinforces our confidence in the potential of WAINUA to improve cardiovascular outcomes in this estimated worldwide patient population of approximately 300,000 to 500,000. With over 1,400 patients enrolled, our ongoing CARDIO-T TRansform study is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy. And as a result, we expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we're conducting advanced cardiac imaging sub-studies, including an MRI sub-study and a [inaudible] sub-study, which will generate valuable data about the potential benefits of WAINUA in cardiomyopathy patients.

Brett Monia: Our accomplishments so far this year and the investments we're making move us closer to achieving our goal of bringing a steady cadence of new transformational medicines to patients for years to come and generating next level value for all Ionis stakeholders. With that, I'll turn the call over to Richard to discuss our recent pipeline progress and preview key upcoming events. Next, Kyle will review the Waynoa launch and our launch plans and progress for Olasarsson and Donoghue Wars, and that will review our financial results. I'll then wrap up things before I take you to your questions.

Richard: We are pleased with our pipeline delivered many important achievements to date this year. With <unk>, reaching more and more people with hereditary <unk> polyneuropathy. I am proud of all that our analyst team has accomplished to discover and develop this important new medicine and bring it to patients in need. Recent to ATT, our cardiomyopathy data further reinforces our confidence in the potential of <unk> to improve. Cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500000. With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Our accomplishments so far this year and the investments we're making move us closer to achieving our goal of bringing a steady cadence of new transformational medicines to patients for years to come and generating next level value for all Ionis stakeholders.

Richard: With <unk>, reaching more and more people with hereditary <unk> polyneuropathy. I am proud of all that our analyst team has accomplished to discover and develop this important new medicine and bring it to patients in need. Recent to ATT, our cardiomyopathy data further reinforces our confidence in the potential of <unk> to improve. Cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500000. With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Richard: I am proud of all that our analyst team has accomplished to discover and develop this important new medicine and bring it to patients in need. Recent to ATT, our cardiomyopathy data further reinforces our confidence in the potential of <unk> to improve. Cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500000. With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Speaker Change: With that, I'll turn the call over to Richard to discuss our recent pipeline progress and preview key upcoming events. Next, Kyle will review the Waynoa launch and our launch plans and progress for Olazarsan and Donadolorsan.

Richard: Recent to ATT, our cardiomyopathy data further reinforces our confidence in the potential of <unk> to improve. Cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500000. With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Richard: Cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500000. With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

and Beth will review our financial results. I'll then wrap up things before taking your questions.

Richard: With that, over to Richard. Thank you, Brett. We are pleased that our pipeline delivered many important achievements to date this year. With Wynua reaching more and more people with hereditary HTR polyneurophs. I am proud of all that our Ionis team has accomplished to discover and develop this important new medicine and bring it to patients in need. Recent ATTR cardiomyopathy data further reinforce our confidence in the potential of Wynua to improve cardiovascular outcomes in this estimated worldwide patient population of approximately 300 to 500,000. With over 1,400 patients enrolled, our ongoing Cardio T-Transform study is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy.

Richard: With over 1500 patients enrolled are ongoing cardio T. Transform study is the largest and most comprehensive study. Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

With that, over to Richard.

Richard: Thank you, Brett. We are pleased that our pipeline delivered many important achievements to date this year.

Richard: Ever conducted at ATT in ATR cardiomyopathy, and as a result, we expect the data we generate will enable physicians and payors to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Richard: With Wynua reaching more and more people with hereditary HTR polyneuropathy, I am proud of all that our Ionis team has accomplished to discover and develop this important new medicine and bring it to patients in need.

Richard: In addition, as part of our Phase III program, we are conducting advanced cardiac imaging sub studies, including an MRI sub study and our scintigraphy sub study. Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Richard: Recent ATTR cardiomyopathy data further reinforce our confidence in the potential of Wynua to improve cardiovascular outcomes in this estimated worldwide patient population of approximately 300,000 to 500,000.

Richard: Which will generate valuable data. That the potential benefits of <unk> in cardiomyopathy patients.

Richard: That the potential benefits of <unk> in cardiomyopathy patients.

Richard Geary: We were delighted that our recent OLEZARSEN NDA submission was accepted by the FDA for priority review, highlighting the potential of this medicine to make a profound difference in the lives of patients. Our submission was brd on the positive Phase III results in FCS that we presented and published earlier this year. In the Phase III BALANCE study in patients with FCS, OLEZARSEN showed substantial and durable triglyceride reductions. And importantly, for patients, physicians and payers alike, OLEZARSEN demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks, a remarkable 84% reduction in hospitalizations and a favorable safety and tolerability profile. We look forward to our upcoming December PDUFA date and assuming approval, bringing OLEZARSEN to people with FCS who currently have no approved treatments in the U.S. We are also developing OLEZARSEN for the much larger severe triglyceride patient population, and we recently completed enrollment in our extensive Phase III program for SHTG with more than 2,500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear, first-mover advantage for this wholly owned blockbuster opportunity.

Richard: With over 1,400 patients enrolled, our ongoing Cardiotransform study is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy.

Richard: Highlighting the potential of this medicine to make a profound difference in the lives of patients. Our submission was based on the positive phase III results in FCS that we presented and published earlier this year. And the phase III balanced study in patients with Fcs. <unk> showed a substantial and durable triglyceride reductions. And importantly for patients physicians and payers alike. <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: And as a result, we expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. In addition, as part of our Phase III program, we're conducting advanced cardiac imaging sub-studies, including an MRI sub-study and a scintigraphy sub-study, which will generate valuable data about the potential benefits of Waynua in cardiomyopathy. We were delighted that our recent Olusarsen NDA submission was accepted by the FDA for priority review, highlighting the potential of this medicine to make a profound difference in the lives of patients. Our submission was based on the positive phase 3 results in FCS that we presented and published earlier this year. Endophage Rebalance Study in Patients with FCS.

Richard: Our submission was based on the positive phase III results in FCS that we presented and published earlier this year. And the phase III balanced study in patients with Fcs. <unk> showed a substantial and durable triglyceride reductions. And importantly for patients physicians and payers alike. <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

And as a result, we expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape.

Richard: And the phase III balanced study in patients with Fcs. <unk> showed a substantial and durable triglyceride reductions. And importantly for patients physicians and payers alike. <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: <unk> showed a substantial and durable triglyceride reductions. And importantly for patients physicians and payers alike. <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: In addition, as part of our Phase III program, we're conducting advanced cardiac imaging sub-studies, including an MRI sub-study and a centigraphy sub-study, which will generate valuable data about the potential benefits of Waynua in cardiomyopathy patients.

Richard: And importantly for patients physicians and payers alike. <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: <unk> demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: Mark about 84% reduction in hospitalizations, and a favorable safety and Tolerability profile. We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: We were delighted that our recent Olusarsen NDA submission was accepted by the FDA for priority review, highlighting the potential of this medicine to make a profound difference in the lives of patients.

Speaker Change: We look forward to our upcoming December Paducah date and. Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Speaker Change: Assuming approval, bringing <unk> to people with FCS who currently have no approved treatments in the U S. We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Our submission was based on the positive phase 3 results in FCS that we presented and published earlier this year.

We are also developing <unk> for the much larger severe triglyceride patient population and we recently completed enrollment in our extensive phase III program for <unk> with more than 2500 patients enrolled across three studies. This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard: In the Phase 3 Balance Study in patients with FCS, folic acid showed substantial and durable triglyceride reductions.

Richard: All assortments showed substantial and durable triglyceride reduction, and importantly for patients, physicians and payers alike. Allison demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks. A remarkable 84% reduction in hospitalizations and a favorable safety and tolerability profile. We look forward to our upcoming December PDUCA day and, Assuming approval, bringing all of this arson to people with FCS who currently have no approved treatments in the U.S. We are also developing olisarcin for the much larger, severe, high triglyceride patient population, and we recently completed enrollment in our extensive Phase III program for SHTG with more than 2,500 patients enrolled across three studies.

Richard: and importantly for patients, physicians and payers alike.

Speaker Change: All SARs have demonstrated substantial and clinically meaningful reductions in acute pancreatitis attacks, a remarkable 84% reduction in hospitalizations, and a favorable safety and tolerability profile.

Speaker Change: This puts us on track for data in the second half of next year, maintaining our multiyear first mover advantage for this wholly owned blockbuster opportunity.

Richard Geary: Following closely behind Olezarsen is Donidalorsen for the prophylactic treatment of hereditary angioedema. We recently presented and published in the New England Journal of Medicine positive Phase III data from OASIS-HAE, our placebo-controlled trial. Additionally, we also presented positive data from OASIS plus. Our trial that includes an open-label cohort for patients rolling over from the Phase III study and a separate cohort that we refer to as the SWITCH study. DONIDALORSEN treatment significantly reduced HAE attacks. The reduction in HAE attacks translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control in a vast majority of patients. And with longer-term treatment, patients improve further on all these measures. Additionally, as of our most recent data cutoff in February, 98% of patients remain in the study. These positive data were further bolstered by the encouraging SWITCH results. The SWITCH study through week 17, patients showed a substantial reduction in their HAE attack rate with DONIDALORSEN treatment compared to baseline on their previous treatment. DONIDALORSEN treatment also resulted in improved quality of life measures and increased disease control.

We look forward to our upcoming December PDUCA date and, assuming approval, bringing all this arson to people with FCS who currently have no approved treatments in the U.S.

Speaker Change: Recently presented and published in the New England Journal of Medicine positive phase III data from <unk>, our placebo controlled trial. Additionally, we also presented positive data from Oasis plus our trial that includes an open label cohort for patients rolling over from the Phase III study. In a separate cohort and we referred to as the switch study. Contador some treatment significantly reduced HIV attacks the reduction in <unk> attacks. Translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control and a vast majority of patients. And with longer term treatment patients improve further on all of these measures. Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard: We are also developing olocarcin for the much larger, severe hydroglyceride patient population, and we recently completed enrollment in our extensive Phase III program for SHTG with more than 2,500 patients enrolled across three studies.

Speaker Change: In a separate cohort and we referred to as the switch study. Contador some treatment significantly reduced HIV attacks the reduction in <unk> attacks. Translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control and a vast majority of patients. And with longer term treatment patients improve further on all of these measures. Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard: This puts us on track for data in the second half of next year, maintaining our multi-year first mover advantage for this wholly owned blockbuster opportunity. Following closely behind, though, Sarson, is Donna DeLorsi, for the Prophylactic Treatment of Hereditary Androids.

Speaker Change: Contador some treatment significantly reduced HIV attacks the reduction in <unk> attacks. Translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control and a vast majority of patients. And with longer term treatment patients improve further on all of these measures. Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard: This puts us on track for data in the second half of next year, maintaining our multi-year first mover advantage for this wholly owned blockbuster opportunity.

Speaker Change: Translated into significant and clinically meaningful improvements in quality of life across multiple validated measures and high levels of disease control and a vast majority of patients. And with longer term treatment patients improve further on all of these measures. Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard: Following closely behind all Sarson is Donna DeLorsen.

Donna DeLorson: for the prophylaxis treatment of hereditary angioedema.

Richard: We recently presented and published in the New England Journal of Medicine positive phase 3 data from OASIS-HAE, our placebo-controlled trial. Additionally, we also presented positive data from OASIS-Plus, our trial that includes an open-label cohort for patients rolling over from the phase 3 study, and a separate cohort that we refer to as the switch study, out of the Orson treatment, significantly reduced HADT. The reduction in H.E.

Speaker Change: We recently presented and published in the New England Journal of Medicine positive phase III data from OASIS-HAE, our placebo-controlled trial.

Speaker Change: And with longer term treatment patients improve further on all of these measures. Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Speaker Change: Additionally, as of our most recent data cut off in February 98%. <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard Geary: Additionally, as of our most recent data cutoff in February, 98% of patients remain in the study. These positive data were further bolstered by the encouraging SWITCH results. The SWITCH study through week 17, patients showed a substantial reduction in their HAE attack rate with DONIDALORSEN treatment compared to baseline on their previous treatment. DONIDALORSEN treatment also resulted in improved quality of life measures and increased disease control.

Richard: Additionally, we also presented positive data from Oasis Plus, our trial that includes an open label cohort for patients rolling over from the Phase 3 study and a separate cohort that we refer to as the switch study.

Speaker Change: <unk> patients remain in the study. These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Speaker Change: These positive data were further bolstered by the encouraging switch results. The switch study through week 17 patients showed a substantial reduction in their HIV attack rate with Donna divorce and treatment compared to baseline on their previous treatment. Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard: out-of-doorsome treatment significantly reduced HAE attacks. The reduction in HAE attacks

Richard: attack. Translated into significant and clinically meaningful improvements in quality of life across multiple validated measures. High Levels of Disease Control in a Vast Majority of Patients. And with longer-term treatment, patients improve further on all these measures. Additionally, as of our most recent data cut off in February, 98% of OLE patients remain in the.

Richard: Translated into Significant and Clinically Meaningful Improvements in Quality of Life across Multiple Validated Measures and High Levels of Disease Control in a Vast Majority of Patients.

Speaker Change: Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Richard Geary: Importantly, more than 80% of patients surveyed reported a preference for DONIDALORSEN over their prior prophylactic treatment and nearly 90% of switch study patients remained in the study as of the data cutoff in February. In addition, to strong clinical results, DONIDALORSEN offers the potential for simple monthly or every two months self-administration via an autoinjector. Based on these data, we believe Donidalorsen could become a preferred prophylactic treatment for people with HAE. Our NDA, which we plan to submit soon will include data from OASIS, HAE, OASIS plus, OLE study switch and our Phase II study. Outside the U.S., Otsuka is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement, Otsuka also plans to bring DONIDALORSEN into patients in the Asia Pacific region. The rest of our rich Phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: And with longer-term treatment, patients improve further on all these measures.

Speaker Change: And nearly 90% of switch study patients remained in the study as of the data cutoff in February. In addition to strong clinical results Don at Dolores and offers the potential for simple monthly or every two months self administration via an auto injector. Based on these data, we believe <unk> could become a preferred prophylactic treatment for people with HIV. Our NDA, which we plan to submit soon. Will include data from Oasis Haa Oasis plus. OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: Additionally, as of our most recent data cutoff in February , 98% of OLE patients remain in the study.

Richard: These positive data were further bolstered by the encouraging switch research. Switch study through week 17, patients showed a substantial reduction in their HAD attack rate with Donna DeLorsen treatment compared to baseline on their previous treatment. Donna Dolores and treatment also resulted in improved quality of life measures and increased disease control.

Speaker Change: In addition to strong clinical results Don at Dolores and offers the potential for simple monthly or every two months self administration via an auto injector. Based on these data, we believe <unk> could become a preferred prophylactic treatment for people with HIV. Our NDA, which we plan to submit soon. Will include data from Oasis Haa Oasis plus. OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: These positive data were further bolstered by the encouraging switch results.

Richard: The switch study through week 17, patients showed a substantial reduction in their HAD attack rate with Donna DeWarsen treatment compared to baseline on their previous treatment.

Speaker Change: Based on these data, we believe <unk> could become a preferred prophylactic treatment for people with HIV. Our NDA, which we plan to submit soon. Will include data from Oasis Haa Oasis plus. OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: Importantly, more than 80% of patients surveyed, reporter of preference for Donna DeLorsen over their prior prophylactic treatment, and nearly 90% of switch study patients remain in the study as of the data cutoff. In addition to strong clinical results, Donna Dolorsan offers the potential for simple monthly or every two months self-administration via an audit. Based on these data, we believe Donor-Doloresan could become a preferred prophylactic treatment, for people with HAE.

Speaker Change: Our NDA, which we plan to submit soon. Will include data from Oasis Haa Oasis plus. OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: Donna Doloresan treatment also resulted in improved quality of life measures and increased disease control. Importantly, more than 80% of patients surveyed reported a preference for Donna Doloresan over their prior prophylactic treatment.

Speaker Change: Will include data from Oasis Haa Oasis plus. OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Speaker Change: OLED study switch and our phase II study. Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Speaker Change: Outside the U S. On Sucre is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: And nearly 90% of switch study patients remain in the study as of the data cutoff in February.

Speaker Change: And with the recent expansion of our license agreement. <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Speaker Change: <unk> also plans to bring Donegal worse into patients in the Asia Pacific Kris. The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: In addition to strong clinical results, Donna Dolorsan offers the potential for simple monthly or every two months self-administration via an autoinjector.

Speaker Change: The rest of our rich phase III pipeline is also advancing positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard: Based on these data, we believe Donor-Doloresan could become a preferred prophylactic treatment for people with HAE.

Richard: Our NDA, which we plan to submit soon, will include data from OASIS-HAE, OASIS Plus, OLE Study Switch and our Phase 2 study. Outside the U.S., Opsuka is preparing to submit for marketing approval in Europe later this year, and with the recent expansion of our license agreement, Otsuka also plans to bring Donna Dolores into patients in the Asia Pacific. The rest of our Rich Phase III pipeline is also advanced, positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Richard Geary: We recently completed enrollment in the pivotal arm zilganersen study for Alexander disease, keeping us on track for a Phase III readout next year. And GSK recently completed enrollment in the Phase III program for the parent person for chronic hepatitis B, which keeps the program on track for data in 2026. Coming right behind these programs, we have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases, five of which are wholly owned and we expect our wholly owned pipeline to expand later this year when two more medicines from our neuro disease franchise enter clinical development. ION582, our medicine for Angelman syndrome has transformational potential for the 100,000 of people living with this serious rare disorder who are in need of disease-modifying treatments. For this reason ION582 is poised to become the cornerstone of our wholly-owned neurology pipeline. We're encouraged by the recently presented positive early results from the HALOS study of ION582, and people with Angelman syndrome.

Richard: Our NDA, which we plan to submit soon, will include data from OASIS-HAE, OASIS Plus,

Richard: OLE Study Switch and our Phase 2 study.

Speaker Change: And GSK recently completed enrollment in the phase III program for the third person for chronic hepatitis B, which keeps the program on track for data in 2026. Coming right behind these programs, we have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases. Five of which are wholly owned and we expect that our wholly owned pipeline to expand later this year two more medicines from our neuro disease. Franchise enter clinical development. Ion find eight to our Madison for Angelman syndrome has transformational potential for the tens of thousands of people living with this serious rare disorder. Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: Outside the U.S., Otsuka is preparing to submit for marketing approval in Europe later this year. And with the recent expansion of our license agreement, Otsuka also plans to bring Donna DeWarsen to patients in the Asia-Pacific region.

Speaker Change: Coming right behind these programs, we have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases. Five of which are wholly owned and we expect that our wholly owned pipeline to expand later this year two more medicines from our neuro disease. Franchise enter clinical development. Ion find eight to our Madison for Angelman syndrome has transformational potential for the tens of thousands of people living with this serious rare disorder. Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: The rest of our rich Phase III pipeline is also advancing, positioning us to continue delivering a steady cadence of potentially transformational medicines to patients.

Speaker Change: Five of which are wholly owned and we expect that our wholly owned pipeline to expand later this year two more medicines from our neuro disease. Franchise enter clinical development. Ion find eight to our Madison for Angelman syndrome has transformational potential for the tens of thousands of people living with this serious rare disorder. Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Richard: We recently completed enrollment in the pivotal arm of our Zildjian-Nursen study for Alexander disease, keeping us on track for a phase three readout next year, and GSK recently completed enrollment in the Phase 3 program for Vipiravirsin for chronic hepatitis B, which keeps the program on track for data in 2026, coming right behind these folks. We have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases.

Speaker Change: Franchise enter clinical development. Ion find eight to our Madison for Angelman syndrome has transformational potential for the tens of thousands of people living with this serious rare disorder. Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: We recently completed enrollment in the pivotal arm of our Zilgin-Nursen study for Alexander disease, keeping us on track for a Phase III readout next year.

Speaker Change: Ion find eight to our Madison for Angelman syndrome has transformational potential for the tens of thousands of people living with this serious rare disorder. Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: and GSK recently completed enrollment in the Phase 3 program for Vipiravirsin for chronic hepatitis B, which keeps the program on track for data in 2026.

Speaker Change: Who are in need of disease modifying treatments for this reason I often find eight two. Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: Points to become the cornerstone of our wholly owned neurology pipeline. We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Speaker Change: Coming right behind these programs, we have our next wave of medicines, including a number of medicines to treat both rare and broad neurological diseases.

Speaker Change: We're encouraged by the recently presented positive early results from our Halo study of ion 582, and people with Angelman syndrome.

Richard: Five of which are wholly owned, and we expect our wholly owned pipeline to expand later this year when two more medicines from our neurodisease franchise enter clinical development. Ion 582, our medicine for Angelman syndrome, has transformational potential for the tens of thousands of people living with this serious rare disorder who are in need of disease-modifying treatments.

Richard: Five of which are wholly owned, and we expect our wholly owned pipeline to expand later this year when two more medicines from our NeuroDisease franchise enter clinical development.

Richard Geary: In this study, we demonstrated evidence of consistent and meaningful improvement on all key functional areas across multiple assessments. This included 97% of participants showing clinically meaningful improvement in overall Angelman syndrome symptoms on the SAS, CGI assessment. Improvements in measures of communication, cognition and motor function exceeded natural history on the Bayley-4, Vineland-3 and Orca assessments. Additionally, we observed consistent improvements across ages and genotypes. And we saw favorable safety and tolerability at all dose levels, including no discontinuations for adverse events that were considered related to study drug. Based on these positive data, we plan to advance ION582 and do a well-controlled Phase III study in the first half of next year. Alongside the positive Phase I/II data for Angelman syndrome several recent events have also occurred in our mid-stage pipeline. We were pleased to present positive Phase II data at EASL for ION224, our medicine targeting began to for the treatment of metabolic dysfunction associated steatohepatitis or MASH.

Speaker Change: This included 97% of participants showing clinically meaningful improvement in overall angelman syndrome symptoms on the SaaS CGI assessment. Improvements in measures of communication cognition and motor function exceeded natural history on the Bailey for Vineland three. And orca assessments. We observed consistent improvements across ages and genotype. And we saw favorable safety and Tolerability at all dose levels, including no discontinuation or adverse events that were considered related to study drug. Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Richard: ION582, our medicine for Angelman syndrome, has transformational potential for the tens of thousands of people living with this serious rare disorder.

Speaker Change: Improvements in measures of communication cognition and motor function exceeded natural history on the Bailey for Vineland three. And orca assessments. We observed consistent improvements across ages and genotype. And we saw favorable safety and Tolerability at all dose levels, including no discontinuation or adverse events that were considered related to study drug. Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Richard: For this reason, Ion 582 is poised to become the cornerstone of our wholly-owned neurology pipeline. We're encouraged by the recently presented positive early results from the HALO study of Ion 582 and people with Angelman syndrome. In the study, we demonstrated evidence of consistent and meaningful improvement on all key functional areas across multiple assessments. This includes 97% of participants showing clinically meaningful improvement in overall Angelman Syndrome symptoms on the SAS CGI assessment. Improvements in measures of communication, cognition, and motor function exceeded natural history on the Bayley-4 and Vineland-3, and Orca.

Richard: who are in need of disease modifying treatments. For this reason, ION582 is poised to become the cornerstone of our whole young neurology pipeline.

Richard Geary: Additionally, we observed consistent improvements across ages and genotypes. And we saw favorable safety and tolerability at all dose levels, including no discontinuations for adverse events that were considered related to study drug. Based on these positive data, we plan to advance ION582 and do a well-controlled Phase III study in the first half of next year. Alongside the positive Phase I/II data for Angelman syndrome several recent events have also occurred in our mid-stage pipeline. We were pleased to present positive Phase II data at EASL for ION224, our medicine targeting began to for the treatment of metabolic dysfunction associated steatohepatitis or MASH.

Richard: Additionally, we observed consistent improvements across ages and genotypes. And we saw favorable safety and tolerability at all dose levels, including no discontinuations or adverse events that were considered related to study drug. Based on these positive data. We plan to advance ION582 and do a well-controlled Phase III study in the first... Alongside the positive phase 1-2 data for Angelman syndrome, several recent events have also occurred in our mid-stage pipeline. We were pleased to present positive phase 2 data at ESL for ION224, our medicine targeting EGAD2 for the treatment of metabolic dysfunction associated steatohepatitis or MAD.

Speaker Change: And orca assessments. We observed consistent improvements across ages and genotype. And we saw favorable safety and Tolerability at all dose levels, including no discontinuation or adverse events that were considered related to study drug. Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Speaker Change: We observed consistent improvements across ages and genotype. And we saw favorable safety and Tolerability at all dose levels, including no discontinuation or adverse events that were considered related to study drug. Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Richard: We're encouraged by the recently presented positive early results from the HALO study of ION582 and people with Angelman syndrome.

And we saw favorable safety and Tolerability at all dose levels, including no discontinuation or adverse events that were considered related to study drug. Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Richard: In the study, we demonstrated evidence of consistent and meaningful improvement on all key functional areas across multiple assessments.

Speaker Change: Based on these positive data we. We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Speaker Change: We plan to advance <unk> into a well controlled phase III study in the first half of next year. Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Speaker Change: This includes 97% of participants showing clinically meaningful improvement in overall Angelman Syndrome symptoms on the SAS CGI assessment.

Speaker Change: Alongside the positive phase <unk> data for Angelman syndrome. Several recent events have also occurred in our mid stage pipeline. We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Speaker Change: Improvements in measures of communication, cognition, and motor function exceeded natural history on the Bayley-4, Mylan-3, and ORCA assessments.

Speaker Change: We were pleased to present positive phase II data at easel for ion two two for our medicines targeting <unk> two for the treatment of metabolic dysfunction associated Seattle hepatitis or Nash.

Speaker Change: Traditionally, we observed consistent improvements across ages and genotypes.

Richard Geary: Additionally, based on the encouraging Phase IB data, from ONIS-MAPTRX, also known as BIIB080, that were presented late last year by [inaudible] recently announced, they amended the ongoing Phase II Steleus study with the goal to accelerate a potential proof of concept outcome. As a result of this change, they are now projecting data in 2026. Also, we and our partners recently discontinued development for ION541 targeting Ataxin 2 for ALS and IONIS-FB-LRX for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet their primary efficacy endpoints. Importantly, [inaudible] continues to advance the IONIS-FB-LRX IgA nephropathy Phase III study that they initiated last year based on positive Phase II data. Looking ahead, we have several important milestones still to come this year. These include presenting new Phase II open-label extension data for DONIDALORSEN and data from the devote study, which is evaluating a higher dose of SPINRAZA as well as anticipated regulatory approvals and launches for WAINUA and OLEZARSEN and regulatory filings for DONIDALORSEN. With that, I'll turn the call over to Kyle.

Speaker Change: And we saw favorable safety and tolerability at all dose levels, including no discontinuations or adverse events that were considered related to study drug.

Speaker Change: We're presented late last year. <unk>. Recently announced amended the ongoing phase III <unk> study with the goal to accelerate our potential proof of concept the outcome as a result of this change they are now projecting data in 2026. Also we and our partners recently discontinued development for ion time for one targeting attacks into for AOS and <unk> X for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet the primary efficacy endpoints. Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Richard: Based on these positive data, we plan to advance ION582 into a well-controlled phase 3 study in the first half of next year.

Speaker Change: <unk>. Recently announced amended the ongoing phase III <unk> study with the goal to accelerate our potential proof of concept the outcome as a result of this change they are now projecting data in 2026. Also we and our partners recently discontinued development for ion time for one targeting attacks into for AOS and <unk> X for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet the primary efficacy endpoints. Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Speaker Change: Recently announced amended the ongoing phase III <unk> study with the goal to accelerate our potential proof of concept the outcome as a result of this change they are now projecting data in 2026. Also we and our partners recently discontinued development for ion time for one targeting attacks into for AOS and <unk> X for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet the primary efficacy endpoints. Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Richard: Alongside the positive phase 1-2 data for Angevin syndrome, several recent events have also occurred in our mid-stage pipeline.

Speaker Change: Also we and our partners recently discontinued development for ion time for one targeting attacks into for AOS and <unk> X for geographic atrophy. Both programs showed good target engagement and favorable safety, but did not meet the primary efficacy endpoints. Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Richard: We were pleased to present positive phase 2 data at ESL for ION224, our medicine targeting EGAD2, for the treatment of metabolic dysfunction associated steatohepatitis or MASH.

Speaker Change: Both programs showed good target engagement and favorable safety, but did not meet the primary efficacy endpoints. Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Richard: Additionally, based on the encouraging Phase 1B data from Ionis MAP-TRX, also known as BID-80, that were presented late last year by June, recently announced that they amended the ongoing Phase 2 CELIA study with the goal to accelerate a potential proof-of-concept outcome. As a result of this change, they are now projecting data in 2020. Also, we and our partners recently discontinued development for Ion 541, targeting a taxantu for ALS, and Ionis FB-LRX for geographic atrophy.

Richard: Additionally, based on the encouraging Phase 1b data from IonisMAP-T-Rx, also known as BID-80, that were presented late last year by...

Speaker Change: Importantly, Roche continues to advance the ion <unk> Iga nephropathy phase III study that they initiated last year. Just on positive phase II data.

Speaker Change: recently announced that they amended the ongoing Phase 2 Celia study with the goal to accelerate a potential proof-of-concept outcome. As a result of this change, they are now projecting data in 2026.

Speaker Change: Just on positive phase II data.

Richard Geary: Looking ahead, we have several important milestones still to come this year. These include presenting new Phase II open-label extension data for DONIDALORSEN and data from the devote study, which is evaluating a higher dose of SPINRAZA as well as anticipated regulatory approvals and launches for WAINUA and OLEZARSEN and regulatory filings for DONIDALORSEN. With that, I'll turn the call over to Kyle.

Speaker Change: Looking ahead, we have several important milestones still to come. This year. These include presenting new phase II open label extension data for Donna Dawson and data from the devote study, which is evaluating a higher dose of spin rahsaan. As well as anticipated regulatory approvals and launches for way, Noah and almost <unk> and regulatory filings for Dani tourism. With that I'll turn the call over to Pat.

Richard: Also, we and our partners recently discontinued development for ION 541, targeting a taxon 2 for ALS, and IONISF-B LRX for geographic atrophy.

Speaker Change: As well as anticipated regulatory approvals and launches for way, Noah and almost <unk> and regulatory filings for Dani tourism. With that I'll turn the call over to Pat.

Kyle: Both programs showed good target engagement and favorable safety, but did not meet their primary efficacy endpoints. Importantly, Roche continues to advance the Ionis FDL-Rx IgA property phase 3 study that they initiated last year based on positive phase 2 data. Looking ahead, we have several important milestones still to come this year. These include presenting new phase two open label extension data for Donna DeLorsen and data from the DEVOTE study, which is evaluating a higher dose of Spinrazide, as well as anticipated regulatory approvals and launches for Waynoa and Noah Sarsen and regulatory filings for Donnie DeWarsen. With that, I'll turn the call over to Kyle.

Richard: Both programs showed good target engagement and favorable safety, but did not meet their primary efficacy endpoints.

Speaker Change: With that I'll turn the call over to Pat.

Kyle Jenne: Thank you, Richard, we are pleased with the initial results of the WAINUA new launch with AstraZeneca following U.S. approval at the end of last year, including the significant growth quarter over quarter with an estimated 40,000 patients worldwide and fewer than 20% of patients on approved treatment, people with hereditary ATTR polyneuropathy remain underdiagnosed and largely underserved. As a result, a high unmet need remains that we and AstraZeneca are uniquely positioned to address. The combined team is working together seamlessly with shared goal to make WAINUA the preferred choice for patients with ATTR polyneuropathy. We continue to see good uptake among patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine, some switching from other treatments and some using WAINUA as an add-on treatment to their existing therapy. Prescribers and patients are recognizing WAINUA's strong clinical profile and patients value the ability to easily self-administer window up from their home. We expect to reach a growing number of patients as we continue to educate prescribers about the value that WAINUA brings.

Speaker Change: Importantly, Roche continues to advance the Ionis FDL-Rx IgA property phase 3 study that they initiated last year based on positive phase 2 data.

With an estimated 40000 patients worldwide and fewer than 20% of patients on an approved treatment. People with hereditary <unk> polyneuropathy remained under diagnose and largely underserved. As a result of high unmet need. James that we and Astrazeneca are uniquely positioned to address the. The combined team is working together seamlessly with a shared goal to make <unk> the preferred choice for patients with <unk> Polyneuropathy. We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Richard: Looking ahead, we have several important milestones still to come this year. These include presenting new Phase II open-label extension data for Donna Dolorsan and data from the DEVOTE study, which is evaluating a higher dose of Spinraza.

Speaker Change: People with hereditary <unk> polyneuropathy remained under diagnose and largely underserved. As a result of high unmet need. James that we and Astrazeneca are uniquely positioned to address the. The combined team is working together seamlessly with a shared goal to make <unk> the preferred choice for patients with <unk> Polyneuropathy. We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Speaker Change: As a result of high unmet need. James that we and Astrazeneca are uniquely positioned to address the. The combined team is working together seamlessly with a shared goal to make <unk> the preferred choice for patients with <unk> Polyneuropathy. We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Speaker Change: James that we and Astrazeneca are uniquely positioned to address the. The combined team is working together seamlessly with a shared goal to make <unk> the preferred choice for patients with <unk> Polyneuropathy. We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Richard: as well as anticipated regulatory approvals and launches for Waynoa and Noah Sarsen and regulatory filings for Donnie DeWarsen.

James: The combined team is working together seamlessly with a shared goal to make <unk> the preferred choice for patients with <unk> Polyneuropathy. We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Richard: And with that, I'll turn the call over to Kyle.

Kyle: Thank you, Richard. We are pleased with the initial results of the way NUA launched with AstraZeneca following U.S. approval at the end of last year, including the significant growth quarter over quarter. With an estimated 40,000 patients worldwide and fewer than 20% of patients on an approved treatment, people with hereditary ATTR polyneuropathy remain underdiagnosed and largely underserved. As a result, a high unmet need remains that we at AstraZeneca are uniquely positioned to address.

Speaker Change: We continued to see good uptake in patients in the second quarter with an encouraging mix of new patient starts, including some who are new to this class of medicine. Some switching from other treatments and some using <unk> as an add on treatment to their existing therapy. Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Kyle: Thank you, Richard. We are pleased with the initial results of the Waynua launch with AstraZeneca following the U.S. approval at the end of last year, including the significant growth quarter-over-quarter.

Speaker Change: With an estimated 40,000 patients worldwide and fewer than 20% of patients on an approved treatment, people with hereditary ATTR polyneuropathy remain underdiagnosed and largely underserved.

Speaker Change: Prescribers and patients are recognizing we noticed strong clinical profile and patients value the ability to easily self administer window up from their home.

Astrazeneca: As a result, a high unmet need remains that we at AstraZeneca are uniquely positioned to address.

Kyle Jenne: We expect to reach a growing number of patients as we continue to educate prescribers about the value that WAINUA brings. With our increased confidence in our ongoing cardio transform study for ATTR cardiomyopathy, we and AstraZeneca are progressing our pre-commercialization activities and investments to support the potential substantial opportunity WAINUA represents. We are leveraging and building upon our efforts for the WAINUA launch to prepare for our upcoming independent launches of OLEZARSEN and DONIDALORSEN. As Richard mentioned, we are developing OLEZARSEN for two indications, the rare FCS indication and the broader SHTG indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the Phase III FCS data that we presented at ACC. They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and in-patient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U.S. expanded access program for OLEZARSEN is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring OLEZARSEN to patients as soon as possible after anticipated approval.

Kyle Jenne: We expect to reach a growing number of patients as we continue to educate prescribers about the value that WAINUA brings.

Kyle: The combined team is working together seamlessly with a shared goal to make Wynua the preferred choice for patients with ATTR polyneuropathy. We continue to see good uptake among patients in the second quarter, with an encouraging mix of new patient starts, including some who were new to this class of medicine, some switching from other treatments, and some using Waynua as an add-on treatment to their existing therapy. Prescribers and patients are recognizing Waynua's strong clinical profile and patients value the ability to easily self-administer Waynua from their home.

Speaker Change: The combined team is working together seamlessly with a shared goal to make Wynua the preferred choice for patients with ATTR polyneuropathy

Speaker Change: With our increased confidence in our ongoing cardio transform study for <unk> cardiomyopathy, we and Astrazeneca are progressing our pre commercialization activities and investments to support the potential substantial opportunity window of represents. We are leveraging and building upon our efforts for the window of launch to prepare for our upcoming independent launches of all those arson and Donny to Larsen. As Richard mentioned, we are developing <unk> for two indications. Their Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the phase III FCS data that we presented at ACC. Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Kyle Jenne: With our increased confidence in our ongoing cardio transform study for ATTR cardiomyopathy, we and AstraZeneca are progressing our pre-commercialization activities and investments to support the potential substantial opportunity WAINUA represents. We are leveraging and building upon our efforts for the WAINUA launch to prepare for our upcoming independent launches of OLEZARSEN and DONIDALORSEN. As Richard mentioned, we are developing OLEZARSEN for two indications, the rare FCS indication and the broader SHTG indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the Phase III FCS data that we presented at ACC. They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and in-patient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U.S. expanded access program for OLEZARSEN is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring OLEZARSEN to patients as soon as possible after anticipated approval.

Speaker Change: We continued to see good uptake among patients in the second quarter with an encouraging mix of new patient starts, including some who were new to this class of medicine, some switching from other treatments, and some using Waynua as an add-on treatment to their existing therapy.

Speaker Change: We are leveraging and building upon our efforts for the window of launch to prepare for our upcoming independent launches of all those arson and Donny to Larsen. As Richard mentioned, we are developing <unk> for two indications. Their Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the phase III FCS data that we presented at ACC. Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Richard: Prescribers and patients are recognizing Waynua's strong clinical profile, and patients value the ability to easily self-administer Waynua from their home.

Kyle Jenne: As Richard mentioned, we are developing OLEZARSEN for two indications, the rare FCS indication and the broader SHTG indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the Phase III FCS data that we presented at ACC. They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and in-patient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U.S. expanded access program for OLEZARSEN is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring OLEZARSEN to patients as soon as possible after anticipated approval.

Speaker Change: As Richard mentioned, we are developing <unk> for two indications. Their Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the phase III FCS data that we presented at ACC. Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Richard: Their Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the phase III FCS data that we presented at ACC. Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Kyle: We expect to reach a growing number of patients as we continue to educate prescribers about the value that we know it brings. With our increased confidence in our ongoing CardioTransform study for ATTR cardiomyopathy, we at AstraZeneca are progressing our pre-commercialization activities and investments to support the potential, substantial opportunity we know it represents. We are leveraging and building upon our efforts for the WENUA launch to prepare for our upcoming independent launches of Ola Zarson and Donnie DeLors.

Richard: We expect to reach a growing number of patients as we continue to educate prescribers about the value that we know it brings.

Richard: We are pleased to receive positive feedback from key opinion leaders on the phase III FCS data that we presented at ACC. Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Astrazeneca: With our increased confidence in our ongoing cardio transform study for ATTR cardiomyopathy, we at AstraZeneca are progressing our pre-commercialization activities and investments to support the potential substantial opportunity when NOAA represents.

Speaker Change: Were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalization and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

We expect that these data will also be important in securing access from payers. In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Speaker Change: We are leveraging and building upon our efforts for the WENUA launch to prepare for our upcoming independent launches of Ola Zarson and Donny DeLorsen.

Speaker Change: In addition, the U S expanded access program for <unk> is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Kyle: As Richard mentioned, we are developing olizarsin for two indications. The rare FCS indication and the broader SHTG indication with anticipated first mover advantage in both settings. We are pleased to receive positive feedback from key opinion leaders on the Phase 3 FCS data that we presented at ACC. They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and inpatient hospital days. We expect that these data will also be important in securing access from payers. In addition, the U.S.

Richard: As Richard mentioned, we are developing olizarsin for two indications.

Richard: the rare FCS indication, and the broader SHTG indication with anticipated first mover advantage in both settings.

Speaker Change: We are putting the final touches on our independent launch plans to bring <unk> to patients as soon as possible after anticipated approval.

Kyle Jenne: Our medical affairs team has been meeting with physicians and working to improve disease awareness through disease education. Earlier this year, we hired our first Ionis National Sales Director, and now with the December 19 PDUFA date set, we have recently hired and are now training our customer-facing team with extensive rare disease experience in preparation for the FCS launch. To bolster our field teams efforts, we are deploying a tailored omnichannel strategy to further enhance our relationships with patients and health care professionals. Finally, we are building a world-class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale our commercial capabilities as we prepare for the SHTG indication to realize the full blockbuster potential of OLEZARSEN. DONIDALORSEN for the prophylactic treatment of HAE is our next planned launch after OLEZARSEN. And based on the positive results we have seen in the comprehensive development program, we are excited with what DONIDALORSEN could mean for people with HAE. HAE is a well-defined patient population with an estimated 20,000 people affected in the U.S. and Europe, while prophylactic treatment in the U.S. is well accepted by patients and physicians, there continues to be a need in the market continues to grow.

Speaker Change: We are pleased to receive positive feedback from key opinion leaders on the Phase 3 FCS data that we presented at ACC.

Speaker Change: Earlier this year, we hired our first I honest national sales director and now with the December 19th <unk> date set we have recently hired and are now training our customer facing team with extensive rare disease experience in preparation for the FCS launch. To bolster our field team's efforts we are deploying a tailored omnichannel strategy to further enhance our relationships with patients and healthcare professionals. Finally, we are building a world class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale, our commercial capabilities as we prepare for the <unk> indication to realize the full blockbuster potential of <unk>. So under the Larson for the prophylactic treatment of HCA is our next planned launch after all as <unk> and. And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: They were particularly impressed with the reduction in acute pancreatitis attacks and the substantial reductions in hospitalizations and inpatient hospital days.

Speaker Change: We expect that these data will also be important in securing access from payers.

Kyle: Expanded Access Program for Alzheimer's is in place, enabling patients to have access to treatment ahead of potential approval. We are putting the final touches on our independent launch plans to bring Olazarsyn to patients as soon as possible after anticipated approval. Our medical affairs team has been meeting with physicians and working to improve disease awareness through disease education. Earlier this year, we hired our first Ionis National Sales Director.

Speaker Change: In addition, the U.S. Expanded Access Program for Alzheimer's is in place, enabling patients to have access to treatment ahead of potential approval.

Speaker Change: To bolster our field team's efforts we are deploying a tailored omnichannel strategy to further enhance our relationships with patients and healthcare professionals. Finally, we are building a world class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale, our commercial capabilities as we prepare for the <unk> indication to realize the full blockbuster potential of <unk>. So under the Larson for the prophylactic treatment of HCA is our next planned launch after all as <unk> and. And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: We are putting the final touches on our independent launch plans to bring Olazarsyn to patients as soon as possible after anticipated approval. Our medical affairs team has been meeting with physicians and working to improve disease awareness through disease education.

Kyle Jenne: Finally, we are building a world-class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale our commercial capabilities as we prepare for the SHTG indication to realize the full blockbuster potential of OLEZARSEN. DONIDALORSEN for the prophylactic treatment of HAE is our next planned launch after OLEZARSEN. And based on the positive results we have seen in the comprehensive development program, we are excited with what DONIDALORSEN could mean for people with HAE. HAE is a well-defined patient population with an estimated 20,000 people affected in the U.S. and Europe, while prophylactic treatment in the U.S. is well accepted by patients and physicians, there continues to be a need in the market continues to grow.

Speaker Change: Finally, we are building a world class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term. We plan to further scale, our commercial capabilities as we prepare for the <unk> indication to realize the full blockbuster potential of <unk>. So under the Larson for the prophylactic treatment of HCA is our next planned launch after all as <unk> and. And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: We plan to further scale, our commercial capabilities as we prepare for the <unk> indication to realize the full blockbuster potential of <unk>. So under the Larson for the prophylactic treatment of HCA is our next planned launch after all as <unk> and. And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: Earlier this year we hired our first Ionis National Sales Director and now with the December 19th biducadate set we have recently hired and are now training our customer facing team with extensive rare disease experience in preparation for the FCS launch.

Kyle: And now, with the December 19th PDUCA date set, we have recently hired and are now training our customer-facing team with extensive rare disease experience in preparation for the FCS launch. To bolster our field team's efforts, we are deploying a tailored omni-channel strategy to further enhance our relationships with patients and healthcare professionals. Finally, we are building a world-class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term.

Speaker Change: So under the Larson for the prophylactic treatment of HCA is our next planned launch after all as <unk> and. And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: And based on the positive results, we have seen in the comprehensive development program. We are excited with what <unk> could mean for people with HCA. HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Speaker Change: To bolster our field team's efforts, we are deploying a tailored omni-channel strategy to further enhance our relationships with patients and health care professionals.

Speaker Change: HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians there continues to be a need in the market continues to grow.

HCA has a well defined patient population with an estimated 20000 people affected in the U S and Europe, while prophylactic treatment in the U S is well accepted by patients and physicians

Richard: Finally, we are building a world-class patient and caregiver support team to provide a seamless customer experience to help patients initiate treatment and remain on therapy long term.

there continues to be a need in the market continues to grow.

Kyle: We plan to further scale our commercial capabilities as we prepare for the SHTG indication to realize the full blockbuster potential of a Lazarus. Donnie Doloresan for the prophylactic treatment of HAE is our next plan launch after Olazarsan. And based on the positive results we have seen in the Comprehensive Development Program, we are excited with what Donnie Mellorson could mean for people with HAE. HEE is a well-defined patient population with an estimated 20,000 people affected in the U.S. and Europe.

Kyle Jenne: Outside the U.S., acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe. Many people in HAE are unsatisfied with current treatments and are looking for the option that reduces frequency and severity of attacks that also offers good tolerability and convenience. This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life. As a result, patients have a history of switching treatments seeking to find the best therapy for them. We believe DONIDALORSEN could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapies. With strong clinical data, including switch data and the simplicity of monthly or every two months self-administration be an autoinjector, we believe DONIDALORSEN combines the attributes that people with HAE are looking for in a single attractive treatment, assuming approval. Today, I'm pleased to share that we are right where we should be in preparing for upcoming launches. Our infrastructure to support commercialization is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market. Now, I'll turn it over to Beth.

Richard: We plan to further scale our commercial capabilities as we prepare for the SHTG indication to realize the full blockbuster potential of Olizarsin.

Speaker Change: Many people at HCA are unsatisfied with current treatments and are looking for the option that reduces frequency and severity of attacks that also offers good tolerability and convenience. This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life as. As a result patients have a history of switching treatments seeking to find the best therapy for them. We believe done into Lorson could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy. With strong clinical data, including switch data and the simplicity of monthly or every two months self administration via an auto injector. We believed <unk> combines the attributes that people with <unk> youre looking for in a single attractive treatment assuming approval. Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Richard: Donnie Doloresan for the prophylactic treatment of HAE is our next planned launch after Olazarsan

Richard: And based on the positive results we have seen in the Comprehensive Development Program, we are excited with what Donny Doloresan could mean for people with HAE.

Speaker Change: This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life as. As a result patients have a history of switching treatments seeking to find the best therapy for them. We believe done into Lorson could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy. With strong clinical data, including switch data and the simplicity of monthly or every two months self administration via an auto injector. We believed <unk> combines the attributes that people with <unk> youre looking for in a single attractive treatment assuming approval. Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Speaker Change: HEE is a well-defined patient population with an estimated 20,000 people affected in the U.S. and Europe. While prophylactic treatment in the U.S. is well accepted by patients and physicians, there continues to be a need and the market continues to grow.

Speaker Change: As a result patients have a history of switching treatments seeking to find the best therapy for them. We believe done into Lorson could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy. With strong clinical data, including switch data and the simplicity of monthly or every two months self administration via an auto injector. We believed <unk> combines the attributes that people with <unk> youre looking for in a single attractive treatment assuming approval. Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Kyle: While prophylactic treatment in the U.S. is well accepted by patients and physicians, there continues to be a need, and the market continues to grow. Outside the U.S., acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe. Many people with HAE are unsatisfied with current treatments and are looking for the option that reduces frequency and severity of attacks, that also offers good tolerability and convenience.

We believe done into Lorson could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy. With strong clinical data, including switch data and the simplicity of monthly or every two months self administration via an auto injector. We believed <unk> combines the attributes that people with <unk> youre looking for in a single attractive treatment assuming approval. Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Speaker Change: Outside the U.S. acute therapies have historically been the standard of care. However, prophylactic treatments are gaining ground, especially in Europe.

Speaker Change: With strong clinical data, including switch data and the simplicity of monthly or every two months self administration via an auto injector. We believed <unk> combines the attributes that people with <unk> youre looking for in a single attractive treatment assuming approval. Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Richard: Many people with HAE are unsatisfied with current treatments and are looking for the option that reduces frequency and severity of attacks that also offers good tolerability and convenience.

Kyle Jenne: Today, I'm pleased to share that we are right where we should be in preparing for upcoming launches. Our infrastructure to support commercialization is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market. Now, I'll turn it over to Beth.

Kyle: This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life. As a result, patients have a history of switching treatments, seeking to find the best therapy for them. We believe donudolorsan could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy.

Speaker Change: Today I am pleased to share that we are right, where we should be in preparing for our upcoming launches our infrastructure to support commercialization is in place and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market now. Now I'll turn it over to Beth.

Richard: This is a disease that typically appears in childhood, so patients have to manage their disease throughout most of their life. As a result, patients have a history of switching treatments, seeking to find the best therapy for them.

Speaker Change: We believe Donnie Doloresan could be a preferred prophylactic treatment for both patients new to therapy and patients currently on available therapy.

Speaker Change: Now I'll turn it over to Beth.

Elizabeth L. Hougen: Thanks Kyle. Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicine to the market. We continue to generate meaningful revenue, while investing our capital to independently launch several new medicine over the next few years that have a combined multibillion dollar peak sales potential. We are also investing in advancing our next wave of Holly unmatched. Let's continue to make great progress in the first half of this year. Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Elizabeth L. Hougen: Thanks, Kyle. Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicines to the market. We continue to generate meaningful revenue while investing our capital to independently launch several new medicines over the next few years, that have a combined multi-billion dollar peak sales potential. We are also investing into advancing our next wave of wholly owned medicines, which continued to make great progress in the first half of this year. In addition to our recent pipeline achievements, we've delivered strong financial results, keeping us on track to achieve our financial guidance. We earned revenues of $225 million, $345 million for the second quarter and first half of this year, respectively. As we remain the primary source of our commercial revenue was $57 million and $95 million of royalties in the second quarter and year to date. Notably, SPINRAZA product sales increased 25% from the first quarter to the second quarter due to growth from both the U.S. and ex-U.S. markets. Additionally, in the second quarter of the WAINUA launch products sales were $16 million, bringing year-to-date sales to $21 million. As a result, our WAINUA royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period.

Beth: Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicine to the market. We continue to generate meaningful revenue, while investing our capital to independently launch several new medicine over the next few years that have a combined multibillion dollar peak sales potential. We are also investing in advancing our next wave of Holly unmatched. Let's continue to make great progress in the first half of this year. Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Kyle: With strong clinical data, including switch data, and the simplicity of monthly or every two-month self-administration via an auto-injector, we believe Dianodilorsin combines the attributes that people with HAE are looking for in a single, attractive treatment, assuming approval. Today, I'm pleased to share that we are right where we should be in preparing for our upcoming launches. Our infrastructure to support commercialization is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market. Now, I'll turn it over to Beth. Thanks, Kyle.

Speaker Change: With strong clinical data, including SWITCH data, and the simplicity of monthly or every two-month self-administration via an auto-injector, we believe Diodaloracin combines the attributes that people with HEA are looking for in a single, attractive treatment, assuming approval.

Beth: We continue to generate meaningful revenue, while investing our capital to independently launch several new medicine over the next few years that have a combined multibillion dollar peak sales potential. We are also investing in advancing our next wave of Holly unmatched. Let's continue to make great progress in the first half of this year. Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Beth: We are also investing in advancing our next wave of Holly unmatched. Let's continue to make great progress in the first half of this year. Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Richard: Today I am pleased to share that we are right where we should be in preparing for our upcoming launches, our infrastructure to support commercialization is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to the market.

Beth: Let's continue to make great progress in the first half of this year. Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Beth: Addition to our recent pipeline achievements, we delivered strong financial results keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Elizabeth L. Hougen: In addition to our recent pipeline achievements, we've delivered strong financial results, keeping us on track to achieve our financial guidance. We earned revenues of $225 million, $345 million for the second quarter and first half of this year, respectively. As we remain the primary source of our commercial revenue was $57 million and $95 million of royalties in the second quarter and year to date. Notably, SPINRAZA product sales increased 25% from the first quarter to the second quarter due to growth from both the U.S. and ex-U.S. markets. Additionally, in the second quarter of the WAINUA launch products sales were $16 million, bringing year-to-date sales to $21 million. As a result, our WAINUA royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period.

Speaker Change: Now, I'll turn it over to Beth. Thanks, Kyle.

Beth: Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicines to the market. We continue to generate meaningful revenue while investing our capital to independently launch several new medicines over the next few years that have a combined multi-billion dollar peak sales potential. We are also investing in advancing our next wave of wholly owned medicines, which continue to make great progress in the first half of this year.

Beth: We earned revenues of $225 million and $345 million. <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Beth: Our results in the second quarter and first half of this year reflect the excellent progress we've made toward our goal to bring a steady cadence of medicines to the market.

Beth: <unk> quarter and first half of this year respectively. <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Beth: <unk> remain the primary thrust of our commercial revenue with $57 million and $95 million of royalties in the second quarter and year to date. Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Beth: We continue to generate meaningful revenue while investing our capital to independently launch several new medicines over the next few years that have a combined multi-billion dollar peak sales potential.

Beth: Notably <unk> product sales increased 25% from the first quarter to the second quarter due to growth from both the U S and ex U S market. Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Speaker Change: We are also investing in advancing our next wave of wholly owned medicines, which continue to make great progress in the first half of this year.

Beth: In addition to our recent pipeline achievements, we delivered strong financial results, keeping us on track to achieve our financial guidance. We earned revenues of $225 million and $345 million for the second quarter and first half of this year respectively.

Beth: Additionally, in the second quarter of the way, new and launch product sales were $16 million, bringing year to date sales to $21 million as a result, our newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year to date period. R&D revenue also increased in the second partner in year to date,

Speaker Change: In addition to our recent pipeline achievements, we delivered strong financial results, keeping us on track to achieve our financial guidance.

Richard: We earned revenues of $225 million and $345 million for the second quarter and first half of this year, respectively.

Beth: Finraza remained the primary source of our commercial revenue, with $57 million and $95 million of royalties in the second quarter and year to date. Notably, Spinraza product sales increased 25% from the first quarter to the second quarter due to growth from both the U.S. and ex-U.S. markets. Additionally, in the second quarter of the Waynua launch, product sales were $16 million, bringing year-to-date sales to $21 million. As a result, our Waynua royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year-to-date period.

Elizabeth L. Hougen: R&D revenue also increased in the second quarter and year to date, reflecting the value that our pipeline and technology continue to generate. As planned, our non-GAAP operating expenses for the second quarter and year to date increased over the same periods last year, driven by higher SG&A expenses. Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year, respectively, as we continued to make investments to prepare for our upcoming independent launches of OLEZARSEN and DONIDALORSEN. Notably, we built out our commercial team, including our field organization, and they are enthusiastically preparing for FCS launch. Our SG&A expenses also included our minority portion of WAINUA U.S. launch expenses. And as planned, our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same periods last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million, of which approximately $175 million will come from non-cash amortization of partner payments we received in prior years. Looking to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

R&D revenue also increased in the second partner in year to date, reflecting the value that our pipeline and technology continue to generate.

R&D revenue also increased in the second partner in year to date,

Richard: Finraza remained the primary source of our commercial revenue, with $57 million and $95 million of royalties in the second quarter and year to date.

reflecting the value that our pipeline and technology continue to generate. As planned our non-GAAP operating expenses for the second quarter and year to date increased over the same period last year driven by higher SG&A expenses. Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year, respectively. As we continue to make investments to prepare for upcoming independent launches of <unk> and <unk>. Notably, we built out our commercial team, including our sales organization. They are enthusiastically preparing for Fcs launch. Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Beth: As planned our non-GAAP operating expenses for the second quarter and year to date increased over the same period last year driven by higher SG&A expenses. Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year, respectively. As we continue to make investments to prepare for upcoming independent launches of <unk> and <unk>. Notably, we built out our commercial team, including our sales organization. They are enthusiastically preparing for Fcs launch. Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Richard: Notably, Spinraza product sales increased 25% from the first quarter to the second quarter due to growth from both the U.S. and ex-U.S. markets.

Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year, respectively. As we continue to make investments to prepare for upcoming independent launches of <unk> and <unk>. Notably, we built out our commercial team, including our sales organization. They are enthusiastically preparing for Fcs launch. Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Richard: Additionally, in the second quarter of the Waymoon launch...

Richard: Product sales were $16 million, bringing year-to-date sales to $21 million.

Richard: As a result, our way newer royalty revenue increased quarter over quarter to $4 million for the second quarter and $5 million for the year-to-date period.

Beth: Notably, we built out our commercial team, including our sales organization. They are enthusiastically preparing for Fcs launch. Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Beth: R&D revenue also increased in the second quarter in year-to-date, reflecting the value that our pipeline and technology continue to generate. As planned, our non-GAAP operating expenses for the second quarter and year to date increased over the same periods last year, driven by higher SG&A expenses.

Richard: R&D revenue also increased in the second quarter in year-to-date, reflecting the value that our pipeline and technology continue to generate.

Beth: They are enthusiastically preparing for Fcs launch. Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Beth: Our SG&A expenses also included our minority portion of Wayne New <unk> U S launch expenses. And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Speaker Change: As planned, our non-GAAP operating expenses for the second quarter and year to date increased over the same periods last year, driven by higher SG&A expenses.

Beth: And as planned our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year. Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Beth: Our ST&A expenses increased 46% and 31% for the second quarter and first half of this year respectively, as we continue to make investments to prepare for our upcoming independent launches of Olufsarsson and Daniel DeLarsen. Notably, we built out our commercial team, including our field organization, and they're enthusiastically preparing for FCS launch. Our ex-GNA expenses also included our minority portion of WANUA U.S. launch expenses. And as planned, our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year.

Speaker Change: Our SG&A expenses increased 46% and 31% for the second quarter and first half of this year respectively.

Beth: Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million. Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Speaker Change: as we continue to make investments to prepare for our upcoming independent launches of Olufarsin and Dania Doloresan.

Beth: Of which approximately $175 million will come from non cash amortization of partner payments, we received in prior years. Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Richard: Notably, we built out our commercial team, including our field organization, and they are enthusiastically preparing for our FCS launch.

Beth: Listening to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Speaker Change: Our ex-GNA expenses also included our minority portion of WANUA U.S. launch expenses.

Elizabeth L. Hougen: We expect commercial revenue to increase as the launch of the ramp for renewal and counterparty and from higher anticipated SPINRAZA royalties as our tiered royalty rate increases. Additionally, we expect our R&D revenue, which often fluctuates from quarter to quarter due to the timing of achieving various collaboration milestones to be lower in the second half of the year. Importantly, however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from AstraZeneca, if we knew is approved in the EU. We continue to project our full year 2024 operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of onetime costs last year. And similar to the first half of this year, the increase will be driven primarily from sales and marketing expenses as we prepare for our back-to-back independent launches of OLEZARSEN and DONIDALORSEN. We are on track to end the year with $1.7 billion in cash as we continue to make strategic investments in the substantial opportunities before us today, including our late-stage program and our next wave of innovative medicine. So as you can see, we delivered a strong second quarter and first half.

Speaker Change: And as planned, our R&D expenses decreased slightly for the second quarter and were flat for the first half of this year compared to the same period last year.

Beth: Our results for the first half of the year keep us on track to meet our 2024 financial guidance, including revenue of more than $575 million, of which approximately $175 million will come from non-cash amortization of partner payments we received in prior years. Looking to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4. We expect commercial revenue to increase as the launches ramp for Waynua and Calfati and from higher anticipated spinrods of royalties as our tiered royalty rate increases. Additionally, we expect our R&D revenue, which often fluctuates from quarter to quarter due to the timing of achieving various collaboration milestones, to be lower in the second half of the year.

Beth: Additionally, we expect our R&D revenue, which often fluctuate from quarter to quarter due to the timing of achieving various collaboration milestone. To be lower in the second half of the year. Currently however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from Astrazeneca. If we knew is approved in the EU. We continue to project our full year 2020 for operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of one time costs last year. And similar to the first half of this year the increase will be driven primarily from sales and marketing expenses as we prepare for our back to back independent launches of <unk> and <unk>. We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Richard: Our results for the first half of the year keep us on track to meet our 2024 financial guidance.

Richard: including revenue of more than $575 million, of which approximately $175 million will come from non-cash amortization of partner payments we received in prior years.

Beth: To be lower in the second half of the year. Currently however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from Astrazeneca. If we knew is approved in the EU. We continue to project our full year 2020 for operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of one time costs last year. And similar to the first half of this year the increase will be driven primarily from sales and marketing expenses as we prepare for our back to back independent launches of <unk> and <unk>. We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Currently however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from Astrazeneca. If we knew is approved in the EU. We continue to project our full year 2020 for operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of one time costs last year. And similar to the first half of this year the increase will be driven primarily from sales and marketing expenses as we prepare for our back to back independent launches of <unk> and <unk>. We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Richard: Looking to the second half of this year, we expect our total revenue to be slightly lower compared to the first half and weighted more to Q4.

Beth: We continue to project our full year 2020 for operating expenses to increase by a mid to high single digit percentage compared to 2023, excluding the impact of one time costs last year. And similar to the first half of this year the increase will be driven primarily from sales and marketing expenses as we prepare for our back to back independent launches of <unk> and <unk>. We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Richard: We expect commercial revenue to increase as the launches ramp for Waynua and Calfati, and from higher anticipated spin-rods of royalties as our tiered royalty rate increases.

Beth: And similar to the first half of this year the increase will be driven primarily from sales and marketing expenses as we prepare for our back to back independent launches of <unk> and <unk>. We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Richard: Additionally, we expect our R&D revenue, which often fluctuates from quarter to quarter, due to the timing of achieving various collaboration milestones.

Beth: We are on track to end here with one $7 billion in cash as we continue to make strategic investments in the substantial opportunity before us today. Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Beth: Importantly, however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from AstraZeneca, if we knew it was approved in the EU. We continue to project our full-year 2024 operating expenses to increase by a mid-to-high single-digit percentage compared to 2023, excluding the impact of one-time costs last year. And similar to the first half of this year, the increase will be driven primarily from sales and marketing expenses as we prepare for our back-to-back independent launches of Ola Zarson and Donny DeLore.

Richard: to be lower in the second half of the year. Importantly, however, we still have the opportunity to earn sizable payments, including a $30 million milestone payment from AstraZeneca, if we knew it was approved in the EU.

Beth: Including our late stage program and our next wave of innovative medicine. So as you can see we delivered a strong second quarter and first half.

Richard: We continue to project our full-year 2024 operating expenses to increase by a mid-to-high single-digit percentage compared to 2023, excluding the impact of one-time costs last year.

Beth: So as you can see we delivered a strong second quarter and first half.

Elizabeth L. Hougen: Before I turn it back to Brett, I'd like to provide you with a look beyond this year to our path to revenue growth and increasing value as we deliver on our goal to bring more medicines to more people. With our strong development and regulatory progress, Ionis is at a critical inflection point. We have several near-term commercial opportunities with significant potential to help patients in need. In parallel, we are advancing our next wave of potentially transformational medicines and our technology. As a result, we plan to continue to strategically invest our capital resources to ensure we unlock the full potential of our promising near and longer-term portfolio. Our investments are focused in four key areas. First, in our go-to-market activities, enabling us to realize the full value of our medicines, which includes investing in our upcoming independent launches for OLEZARSEN and DONIDALORSEN. Our expenses in this area also include our newer cost share with AstraZeneca for the hereditary ATTR polyneuropathy launch in the U.S. As we approach the anticipated OLEZARSEN launch for the broader severe high triglyceride population. We will scale our capabilities and increase our go-to-market expenses to support the larger opportunity. And as we and AstraZeneca approach a potential ATTR cardiomyopathy launch for WAINUA, our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multi-billion dollar revenue potential that these important medicines represent.

Richard: And similar to the first half of this year, the increase will be driven primarily from sales and marketing expenses as we prepare for our back-to-back independent launches of Ola Zarson and Donny Doloresit.

Brad: With our strong development and regulatory progress. <unk> is at a critical inflection point, we have several near term commercial opportunities with significant potential to help patients in need. Parallel. <unk>, our next wave of potentially transformational medicines and our technology as a result. <unk> continued to strategically invest our capital resources. To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Speaker Change: <unk> is at a critical inflection point, we have several near term commercial opportunities with significant potential to help patients in need. Parallel. <unk>, our next wave of potentially transformational medicines and our technology as a result. <unk> continued to strategically invest our capital resources. To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Beth: We are on track to end the year with $1.7 billion in cash as we continue to make strategic investments in the substantial opportunities before us today, including our late stage program and our next wave of innovative medicine. So as you can see, we delivered a strong second quarter and first half. Before I turn it back to Brett, though, I'd like to provide you with a look beyond this year to our Path to Revenue.., and increasing value as we deliver on our goal to bring more medicine to more people.

Richard: We are on track to end the year with $1.7 billion in cash as we continue to make strategic investments in the substantial opportunities before us today, including our late-stage program and our next wave of innovative medicine.

Brad: Parallel. <unk>, our next wave of potentially transformational medicines and our technology as a result. <unk> continued to strategically invest our capital resources. To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Brad: <unk>, our next wave of potentially transformational medicines and our technology as a result. <unk> continued to strategically invest our capital resources. To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Elizabeth L. Hougen: In parallel, we are advancing our next wave of potentially transformational medicines and our technology. As a result, we plan to continue to strategically invest our capital resources to ensure we unlock the full potential of our promising near and longer-term portfolio. Our investments are focused in four key areas. First, in our go-to-market activities, enabling us to realize the full value of our medicines, which includes investing in our upcoming independent launches for OLEZARSEN and DONIDALORSEN. Our expenses in this area also include our newer cost share with AstraZeneca for the hereditary ATTR polyneuropathy launch in the U.S. As we approach the anticipated OLEZARSEN launch for the broader severe high triglyceride population. We will scale our capabilities and increase our go-to-market expenses to support the larger opportunity.

Brad: <unk> continued to strategically invest our capital resources. To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Richard: So as you can see, we delivered a strong second quarter and first half.

Brad: To ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Speaker Change: Before I turn it back to Brett though, I'd like to provide you with a look beyond this year to our path to revenue growth and increasing value as we deliver on our goal to bring more medicine to more people.

Brad: Our investments are focused in four key areas. First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Brad: First in our go to market activity activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for <unk> and <unk>. Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Beth: With our strong development and regulatory progress, Ionis is at a critical inflection point. We have several near-term commercial opportunities with significant potential to help patients in need. In parallel, we are advancing our next wave of potentially transformational medicines and our technology. As a result, we plan to continue to strategically invest our capital resources, to ensure we unlock the full potential of our promising near and longer term portfolio. Our investments are focused in four key areas, in our go-to-market activities, enabling us to realize the full value of our medicine, which includes investing in our upcoming independent launches for Ola Sarsen and Donna DeLore.

Richard: with our strong development and regulatory progress.

Richard: Ionis is at a critical inflection point.

Richard: We have several near-term commercial opportunities with significant potential to help patients in need.

Brad: Our expenses in this area also included <unk> cost sharing with Astrazeneca for the hereditary <unk> Polyneuropathy launch. As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Richard: In parallel, we are advancing our next wave of potentially transformational medicine and our technology. As a result, we plan to continue to strategically invest our capital resources.

As we approach the anticipated <unk> launch for the broader severe high triglyceride population, we will scale, our capabilities and increase our go to market expenses to support the larger opportunity. And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Richard: to ensure we unlock the full potential of our promising near and longer term portfolio.

Brad: And as we and Astrazeneca approach potential atti cardiomyopathy launch for <unk> New App. Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Richard: Our investments are focused in four key areas.

Elizabeth L. Hougen: And as we and AstraZeneca approach a potential ATTR cardiomyopathy launch for WAINUA, our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multi-billion dollar revenue potential that these important medicines represent. Second, we continue to advance our late-stage pipeline. All of our ongoing large Phase III studies are fully enrolled with more than 4,000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data readouts, and we bring new medicines to patients over the next couple of years. Third, we are increasing our investments and our next wave of medicines, including development and pre-commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicines, such as ION582 for Angelman syndrome. And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles well into the future. As you can see, we are strategically investing our capital towards growth opportunities. Importantly, we expect our investments to power strong revenue growth and positive cash flow as our medicines reach more and more patients in need, positioning us to deliver next-level value for all Ionis stakeholders for years to come. And with that, I'll turn the call back over to Brett.

Richard: First, in our go-to-market activities, enabling us to realize the full value of our medicines.

Brad: Our expenses will increase consistent with the much larger cardiomyopathy opportunity. Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Brad: Importantly, our planned investments are right sized for the combined multibillion dollar revenue potential. These important medicines represent.

Richard: which includes investing in our upcoming independent launches for Ola Zarsen and Donna DeLorsen.

Beth: Our expenses in this area also include our way newer cost share with AstraZeneca for the hereditary ATTR polyneuropathy launch in the U.S. As we approach the anticipated Olazarsan launch for the broader severe high-triglyceride population. We will scale our capabilities and increase our go-to-market expenses to support the larger opportunities. And as we in AstraZeneca approach a potential ATTR cardiomyopathy launch for Wynua. Our expenses will increase consistent with the much larger cardiomyopathy effort.

Richard: Our expenses in this area also include our way newer cost share with AstraZeneca for the hereditary ATTR polyneuropathy launch in the U.S.

Brad: These important medicines represent.

Elizabeth L. Hougen: Second, we continue to advance our late-stage pipeline. All of our ongoing large Phase III studies are fully enrolled with more than 4,000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data readouts, and we bring new medicines to patients over the next couple of years. Third, we are increasing our investments and our next wave of medicines, including development and pre-commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicines, such as ION582 for Angelman syndrome. And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles well into the future.

Brad: Second we continued to advance our late stage pipeline. All of our ongoing large phase III studies are fully enrolled with more than 4000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data readout and we bring new medicines to patients over the next couple of years. Third we are increasing our investments in our next wave of medicine, including development and pre commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicine. Such as ion fighting too for Angelman syndrome. And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile well into the future. So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Brad: All of our ongoing large phase III studies are fully enrolled with more than 4000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data readout and we bring new medicines to patients over the next couple of years. Third we are increasing our investments in our next wave of medicine, including development and pre commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicine. Such as ion fighting too for Angelman syndrome. And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile well into the future. So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Richard: As we approach the anticipated olazarsan launch for the broader severe high triglyceride population.

Richard: We will scale our capabilities and increase our go-to-market expenses to support the larger opportunity.

Richard: And as we in AstraZeneca approach a potential ATTR cardiomyopathy launch for Wynua, our expenses will increase consistent with the much larger cardiomyopathy opportunity.

Brad: Third we are increasing our investments in our next wave of medicine, including development and pre commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicine. Such as ion fighting too for Angelman syndrome. And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile well into the future. So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Elizabeth L. Hougen: Third, we are increasing our investments and our next wave of medicines, including development and pre-commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology medicines, such as ION582 for Angelman syndrome. And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles well into the future.

Beth: Importantly, our planned investments are right-sized for the combined multibillion-dollar revenue potential that these important medicines represent. Second, we continue to advance our late-stage pipeline. All of our ongoing large Phase III studies are fully enrolled with more than 4,000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth as the data read out and we bring new medicines to patients over the next couple of years.

Richard: Importantly, our planned investments are right-sized for the combined multi-billion dollar revenue potential that these important medicines represent.

Brad: Such as ion fighting too for Angelman syndrome. And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile well into the future. So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Richard: Second, we continue to advance our late-stage pipeline.

Brad: And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile well into the future. So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Richard: All of our ongoing large Phase III studies are fully enrolled with more than 4,000 patients in all and are currently in the heaviest period of investment. We expect these investments to fuel our continued value generation and revenue growth.

Elizabeth L. Hougen: As you can see, we are strategically investing our capital towards growth opportunities. Importantly, we expect our investments to power strong revenue growth and positive cash flow as our medicines reach more and more patients in need, positioning us to deliver next-level value for all Ionis stakeholders for years to come. And with that, I'll turn the call back over to Brett.

Brad: So as you can see we are strategically investing our capital toward growth opportunity in <unk>. Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Brad: Shortly we expect our investments to power, our strong revenue growth and positive cash flow as our medicines reach more and more patients in need. Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Richard: It's a data readout and we bring new medicines to patients over the next couple of years.

Beth: Third, we are increasing our investments and our next wave of benefits. Including development and pre-commercialization expenses for our growing wholly owned pipeline of potentially groundbreaking neurology, such as ION582 for Angelman Syndrome. And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicine. Competitive Profiles well into the future.

Richard: Third, we are increasing our investments on our next wave of medicines.

Brad: Positioning us to delivering next level of value for all stakeholders for years to come. That I will turn the call back over to Brad.

Richard: including development and pre-commercialization expenses for our growing wholly-owned pipeline of potentially groundbreaking neurology medicines.

Brad: That I will turn the call back over to Brad.

Brett P. Monia: Thank you, Beth. As just summarized, we have made great progress in the first half of this year. And in the second quarter alone, we've achieved a great deal with many important successes, which include continued strong start to the renewal launch for hereditary ATTR polyneuropathy in the United States, approval in Canada and submissions under review in many additional territories. Positive FCS data for OLEZARSEN which we presented at ACC, which were the basis for our NDA submission, which was recently accepted by the FDA with priority review. Positive HAE data for DONIDALORSEN presented at Yaki. It will be the basis of our upcoming regulatory submissions, and we completed enrollment for the Phase III OLEZARSEN and SHTG program this past quarter. Keeping us on track for data next year. We also presented positive data from the HALOS Phase I/II study in people with Angelman syndrome, and we are well along in preparing for our end-of-Phase II meeting with the FDA scheduled for this fall with plans to advance this important medicine for Phase III development next year. And we delivered solid second quarter and first half financial results, keeping us on track to achieve our 2024 financial guidance.

Brad: As just summarized we have made great progress in the first half of this year and in the second quarter alone. We've achieved a great deal with many important successes which include. Our continued strong start to the way new launch for hereditary <unk> polyneuropathy in the United States approval in Canada, and submissions under review and many traditional territories. Positive FCS data for <unk> in which we presented at ACC, which were the basis for our NDA submission submission, which was recently accepted by the FDA with priority review. Positive Hai data for dialing the worst presented at Yaqui. That will be the basis of our upcoming regulatory submissions. And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Richard: such as ION582 for Angelman syndrome.

Richard: And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles well into the future.

Brad: Our continued strong start to the way new launch for hereditary <unk> polyneuropathy in the United States approval in Canada, and submissions under review and many traditional territories. Positive FCS data for <unk> in which we presented at ACC, which were the basis for our NDA submission submission, which was recently accepted by the FDA with priority review. Positive Hai data for dialing the worst presented at Yaqui. That will be the basis of our upcoming regulatory submissions. And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Beth: So as you can see, we are strategically investing our capital toward growth opportunities. Importantly, we expect our investments to power strong revenue growth and positive cash flow as our medicines reach more and more patients in need, positioning us to deliver next-level value for all Iona stakeholders for years to come. And with that, I'll turn the call back over to Brett.

Richard: So as you can see, we are strategically investing our capital toward growth opportunities.

Richard: Importantly, we expect our investments to power strong revenue growth and positive cash flow as our medicines reach more and more patients in need, positioning us to deliver next-level value for all Iona stakeholders for years to come. And with that, I'll turn the call back over to Brett.

Brad: Positive FCS data for <unk> in which we presented at ACC, which were the basis for our NDA submission submission, which was recently accepted by the FDA with priority review. Positive Hai data for dialing the worst presented at Yaqui. That will be the basis of our upcoming regulatory submissions. And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brad: Positive Hai data for dialing the worst presented at Yaqui. That will be the basis of our upcoming regulatory submissions. And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brett Monia: Thank you, Beth. As just summarized, we have made great progress in the first half of this year, and in the second quarter alone, we've achieved a great deal with many important successes, which include, Our continued strong start to the renewal launch for hereditary ATTR polyneuropathy in the United States, approval in Canada, and submissions under review in many additional territories. Positive FCS data for olizarsin, which we presented at ACC, which were the basis for our MDA submission, which was recently accepted by the FDA with priority review. Positive HAE data for Donna Doloresan presented at IACHI.

Brett: Thank you, Beth. As just summarized, we have made great progress in the first half of this year. In the second quarter alone, we've achieved a great deal with many important successes, which include

Brad: That will be the basis of our upcoming regulatory submissions. And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brad: And we completed enrollment for the phase III <unk> program this past quarter, keeping us on track for data next year. We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brett: A continued strong start to the renewal launch for hereditary ATTR polyneuropathy in the United States, approval in Canada, and submissions under review in many additional territories.

Brad: We also presented positive data from the Halo phase one two study in people with Angelman syndrome. And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brad: And we are well along in preparing for our end of phase two meeting with the FDA scheduled for this fall with plans to advance this important medicine phase III development next year. And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Richard: Positive FCS data for olizarsin, which we presented at ACC, which were the basis for our MDA submission, which was recently accepted by the FDA with priority review.

Brad: And we delivered solid second quarter, and first half financial results keeping us on track to achieve our 2024 financial guidance.

Brett P. Monia: Based on the strong progress we've made across our business this year, we are well positioned to continue building on our positive momentum as we execute towards achieving all of our strategic priorities. We've aligned where we are today by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients. Our pipeline is delivering, we achieved multiple marketing approvals and positive key data readouts over the past year, and we are poised to build on the strong momentum in the near term. We have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market. In parallel, our partnered programs are progressing on track with important Phase III readouts next year and beyond. We are also focused on extending our leadership position in [inaudible] type therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas and opening of new areas for drug discovery.

Richard: Positive HAE data, for Donna DeLorsen, presented at IACHI.

Brett Monia: That will be the basis of our upcoming regulatory submission. And we completed enrollment for the Phase 3 Olazarsan SHQG program this past quarter, keeping us on track for data next year. We also presented positive data from the HALOS Phase 1-2 study in people with Angelman syndrome.

Brett: That will be the basis of our upcoming regulatory submissions.

Brett: And we completed enrollment for the Phase 3 old-exhaustion SHQT program this past quarter, keeping us on track for data next year.

Brad: We've arrived where we are today by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients. Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and we are poised to build on the strong momentum in the near term we have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market. In parallel our partnered programs are progressing on track with important phase III Readouts next year and beyond. We are also focused on extending our leadership position in <unk> therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.

Brett: We also presented positive data from the HALOS Phase 1-2 study in people with Angelman syndrome.

Brett Monia: And we are well along in preparing for our end of Phase 2 meeting with the FDA scheduled for this fall, with plans to advance this important medicine into Phase 3 development next year. And we delivered solid second quarter and first half financial results, keeping us on track to achieve our 2024 financial guide. Based on the strong progress we've made across our business this year, we are well positioned to continue building on our positive momentum as we execute towards achieving all of our strategic priorities.

Brett: And we are well along in preparing for our end of Phase 2 meeting with the FDA scheduled for this fall, with plans to advance this important medicine into Phase 3 development next year.

Brad: Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and we are poised to build on the strong momentum in the near term we have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market. In parallel our partnered programs are progressing on track with important phase III Readouts next year and beyond. We are also focused on extending our leadership position in <unk> therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.

Brett: And we delivered solid second quarter and first half financial results, keeping us on track to achieve our 2024 financial guidance.

Brett P. Monia: We have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market. In parallel, our partnered programs are progressing on track with important Phase III readouts next year and beyond. We are also focused on extending our leadership position in [inaudible] type therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas and opening of new areas for drug discovery.

Brett: Based on the strong progress we've made across our business this year, we are well positioned to continue building on our positive momentum as we execute towards achieving all of our strategic priorities.

Brad: In parallel our partnered programs are progressing on track with important phase III Readouts next year and beyond. We are also focused on extending our leadership position in <unk> therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.

Brett Monia: We've arrived where we are today by being focused on a clear vision and a clear set of strategic objectives, which include building and advancing our pipeline and delivering medicine that we conceive, discover, and develop directly to patients. Our pipeline is delivering.

Brad: We are also focused on extending our leadership position in <unk> therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.

Brett: We've arrived where we are today by being focused on a clear vision and a clear set of strategic objectives which include building and advancing our pipeline and delivering medicine that we conceive, discover, and develop directly to patients.

Brett Monia: We achieved multiple marketing approvals and positive key data readouts over the past year, and we are poised to build on the strong momentum in the near term. We have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market. In parallel, our partner programs are progressing on track with important phase readouts next year and beyond. We are also focused on extending our leadership position in organ and glute type therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas, and opening up new areas for drug discovery.

Brett P. Monia: All of this sets us up to continue bringing a steady cadence of new medicines to patients for years to come. And we're looking forward to sharing our progress as we build on our recent achievements and accomplish our strategic objectives. And with that, I'll now open the call up for questions before moving into the Q&A portion of our meeting, I just ask that our analysts please limit yourselves to a single question as we have quite a long, long queue, and we'd like to get as many people in into the queue and ask their questions as much as possible. So with that, Danielle, we can open it up for questions.

Brett: Our pipeline is delivering. We achieved multiple marketing approvals and positive key data readouts over the past year, and we are poised to build on the strong momentum in the near term. We have prioritized building our wholly owned pipeline and are now advancing several of these medicines towards the market.

Brad: We're looking forward to sharing our progress as we build on our recent achievements and accomplish our strategic objectives. And with that I'll now open the call up for questions before moving into Q&A portion of our of our meeting. I just asked that our analysts please limit yourselves to a single question is we have quite a long while in Q1, we'd like to get as many people into the queue and ask their questions as much as possible so with that Danielle. We can open up for questions.

Speaker Change: And with that I'll now open the call up for questions before moving into Q&A portion of our of our meeting. I just asked that our analysts please limit yourselves to a single question is we have quite a long while in Q1, we'd like to get as many people into the queue and ask their questions as much as possible so with that Danielle. We can open up for questions.

Brett: In parallel, our partner programs are progressing on track, with important phase readouts next year and beyond.

Danielle: I just asked that our analysts please limit yourselves to a single question is we have quite a long while in Q1, we'd like to get as many people into the queue and ask their questions as much as possible so with that Danielle. We can open up for questions.

Brett: We are also focused on extending our leadership position in OBGYN-type therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas, and opening up new areas for drug discovery.

Speaker Change: We can open up for questions.

Brett Monia: All of this sets us up to continue bringing a steady cadence of new medicines to patients for years to come. We're looking forward to sharing our progress as we build on our recent achievements and accomplish our strategic objectives. And with that, I'll now open the call up for questions before moving into the Q&A portion of our meeting. I just ask that our analysts, please limit yourselves to a single question as we have quite a long, long queue.

Operator: Thank you. We will now begin the question and answer session. To ask a question you may press star then one on your touchtone phone. If you are using a speakerphone, please pick up the handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. Again, it's star one to ask a question. The first question comes from Akash Tewari from Jefferies. Please go ahead.

Brett: All this sets us up to continue bringing a steady cadence of new medicines to patients for years to come.

Speaker Change: Touchtone phone you are using a speakerphone. Please pick up this handset before pressing the keys. At any time. Your question has been addressed and you would like to withdraw. Your question. Please press Star then two again its star one to ask a question. The first question comes from cash to worry from Jefferies. Please go ahead.

Brett: We're looking forward to sharing our progress as we build on our recent achievements and accomplish our strategic objectives.

Speaker Change: At any time. Your question has been addressed and you would like to withdraw. Your question. Please press Star then two again its star one to ask a question. The first question comes from cash to worry from Jefferies. Please go ahead.

Speaker Change: And with that, I'll now open the call up.

Speaker Change: for questions before moving into the Q&A portion of our meeting. I just ask that our analysts please limit yourselves to a single question as we have quite a long, long queue, and we'd like to get as many people into the queue and ask their questions as much as possible. So with that, Danielle, you can open it up for questions.

Akash Tewari: Hey, this is Amy on for Akash. Thanks so much for taking your questions. So one on ATTR-CM, there's been some debate on if you need a certain level of TTR to have a cardioprotective effect. Have you seen anything in your own data around this theory? And do you expect any differences with the silencer approach using an all-cause mortality versus the CBD mortality composite primary endpoint. Finally, do you have the flexibility to change your primary endpoint if needed? Thanks so much.

Brett Monia: And we'd like to get as many people in, into the queue and ask their questions as much as possible. So with that, Danielle, you can open up for questions. Thank you. We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys.

Operator: If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. Again, it's star 1 to ask a question. The first question comes from Akash Tiwari from Jefferies. Please go ahead. Hey, this is Aimee Ansarakash.

Danielle: Thank you. We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone.

Speaker Change: Mortality versus the CBD mortality composite primary endpoint finally, do you have the flexibility to change your primary endpoint if needed. Thanks, so much.

Speaker Change: If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. Again, it's star 1 to ask a question. The first question comes from Akash Tiwari from Jeffries. Please go ahead.

Brett P. Monia: Thank you, Amy. So we have seen that--we don't believe that there's any evidence of a threshold effect for TTR lowering to achieve benefit in either polyneuropathy, or in cardiomyopathy endpoints. We're very pleased with the magnitude of TTR reductions that we have seen in our in all of our studies for WAINUA for polyneuropathy, I'm very pleased with the level of magnitude of TTR lowering we're getting. But I don't believe that there's any believable evidence out there that suggest a specific threshold effect for our TTR lowering to produce benefit either in polyneuropathy or in cardiomyopathy, we believe--our primary endpoint isn't all in cardiovascular mortality and hospitalizations, and that's what we're laser focused on. We also have as secondary endpoints specifically CV mortality as well as all-cause mortality. And we think they're both very important. Next question.

Speaker Change: We have seen that we don't believe that there's any evidence of a threshold effect for GTR lowering too. To achieve benefit in either a polyneuropathy or. In. In cardiomyopathy. Endpoints. Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Operator: Thanks so much for taking our questions. So one on ATTR-CM, there's been some debate on if you need a certain level of TTR to have a cardioprotective effect. Have you seen anything in your own data around this theory?

Speaker Change: To achieve benefit in either a polyneuropathy or. In. In cardiomyopathy. Endpoints. Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: Hey, this is Amy on 3rd Class. Thanks so much for taking our questions.

Speaker Change: In. In cardiomyopathy. Endpoints. Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: In cardiomyopathy. Endpoints. Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: Endpoints. Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: So one on ATTR-CM, there's been some debate on if you need a certain level of TTR to have a cardioprotective effect.

Speaker Change: Very pleased with the magnitude of GTR reductions that we have seen in our in all of our studies for <unk>. For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Amy: Have you seen anything in your own data around this theory, and do you expect any differences with a silencer approach using an all-cause mortality versus a C-B-D mortality composite primary endpoint? Finally, do you have the flexibility to change your primary endpoint if needed? Thanks so much.

Speaker Change: For Polyneuropathy very pleased with the level of magnitude detail, though and we are getting but I don't believe that theres any believable evidence out there that suggests a specific threshold effect. For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: For GTR lowering to produce benefit either in polyneuropathy. Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Operator: And do you expect any differences with a silencer approach using an all-cause mortality versus a C-B mortality composite primary endpoint? Finally, do you have the flexibility to change your primary endpoint if needed? Thanks so much.

Amy: Thank you, Amy.

Speaker Change: Sure. Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Cardio. <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: <unk>. We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: We don't believe that there's any evidence of a threshold effect for TTR lowering to achieve benefit in either polyneuropathy or in cardiomyopathy endpoints.

Speaker Change: We believe our primary endpoint is in cardio vascular mortality and hospitalization and that's what we're laser focused on we also have as secondary endpoints. Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Operator: Thank you, Amy. So, we have seen, we don't believe that there's any evidence of a threshold effect for TTR lowering to achieve benefit in either polyneuropathy or in cardiomyopathy endpoints. We're very pleased with the magnitude of TTR reductions that we have seen in all of our studies for RUANUA, for polyneuropathy. I'm very pleased with the magnitude of TTR lowering we're getting, but I don't believe that there's any believable evidence out there that suggests a specific threshold effect for TTR lowering to produce benefit either in polyneuropathy or in cardiomyopathy.

Speaker Change: We're very pleased with the magnitude of TTR reductions that we have seen in all of our studies for RUANUA for polyneuropathy. I'm very pleased with the magnitude of TTR lowering we're getting.

Speaker Change: Specifically CV mortality as well as all cause mortality and we think they are both both very important. Next next study our next question.

Speaker Change: Next next study our next question.

Operator: The next question comes from Myles Minter from William Blair. Please go ahead.

Amy: I don't believe that there's any believable evidence out there that suggests a specific threshold effect.

Myles Minter: Hi, just on the timing of the cardio TTR transform readout, I mean, is it fair to say that you're at least waiting for data at ASA in London that might have read through to your trial? And if that is the case, what exactly would you be looking for out of that dataset to stick with the decision that you write that out early or just wait until the full 140 weeks are up in that study? Thanks very much.

Brett: for TTR lowering to produce benefit either in polyneuropathy or in cardiomyopathy.

Operator: We believe our primary endpoint is in cardiovascular mortality and hospitalizations, and that's what we're laser-focused on. We also have, as secondary endpoints, specifically CV mortality as well as all-cause mortality, and we think they're both very important, next next study our next question, The next question comes from Miles Minter from William Blair, please go ahead. Oh hey, just on the timing of the Cardio TTR Transform readout, I mean, is it fair to say that you're at least waiting for data at ESC in London that might have read through to your trial, and if that is the case, you know, what exactly, Thanks, Miles.

Brett: We believe our primary endpoint is in cardiovascular mortality and hospitalizations and that's what we're laser focused on. We also have secondary endpoints, specifically CV mortality as well as all-cause mortality. We think they're both...

Speaker Change: Stick with the decision that you generate that out early or just a widening. For 140 weights are up in that study thanks very much.

Speaker Change: For 140 weights are up in that study thanks very much.

Brett P. Monia: Thanks, Miles. And so we're very pleased with the way the cardio transform study is advancing. We are particularly pleased with the blinded events that we're continuing to evaluate, both CV hospitalizations as well as mortality. It's going very well, right on track. As the first silencer readout in this indication, we're very much looking forward to any and all additional data that we can see, which we think will be very nice read-through to our cardio transform study. As you know, we have the largest by far study ever conducted in this patient population. And we think that anything we see from other molecules in the silencer trials are going to be very, very good read-throughs to what we expect to see in our study. So we're very much looking forward to any and all data that comes from future presentations on the silencer class. Next question, please.

Brett: Both very important.

Speaker Change: Next question.

Speaker Change: Advancing. We're particularly pleased with the. The blinded events that were continuing to. Right. Both ardent CV hospitalizations as well as mortality. It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: We're particularly pleased with the. The blinded events that were continuing to. Right. Both ardent CV hospitalizations as well as mortality. It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Brett: The next question comes from Myles Minter from William Blair. Please go ahead.

Speaker Change: The blinded events that were continuing to. Right. Both ardent CV hospitalizations as well as mortality. It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: Right. Both ardent CV hospitalizations as well as mortality. It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: Both ardent CV hospitalizations as well as mortality. It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Myles Minter: I just on the timing of the cardio TTR transform readout I mean is it fair to say that you're

Speaker Change: It's going very well right on track. As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Myles Minter: at least waiting for data at ESC in London that might have read through to your trial and if that is the case, you know, what exactly would you be looking for out of that data set to stick with the decision that you're going to read that out early or just wait until the full 140 weeks are up in that study. Thanks very much.

Speaker Change: As the first silencer to read out in this indication were very much looking forward to any and all additional data that we can. C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: C, which we think. It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: It would be a very nice return to our cardio transform study. As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Operator: So we're very pleased with the way the CardioTransform study is advancing. We are particularly pleased with the blinded events that we're continuing to evaluate, both CV hospitalizations, as well as mortality. It's going very well, right on track.

Speaker Change: As you know. B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: B, we have the largest by far. Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: Thanks, Myles. So, we're very pleased with the way the CardioTransform study is advancing. We are particularly pleased with the blinded events that we're continuing to evaluate, both CV hospitalizations as well as mortality.

Speaker Change: Study ever conducted in this patient population. <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: <unk>. Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: Anything we see from. Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: Other molecules in the silence requests are going to be very very good returns to what we expect to see in our study. So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Speaker Change: So we're very much looking forward to any and all data that comes from from future presentations on site on a silencer class. Next question please.

Operator: As the first silencer to read out in this indication, we're very much looking forward to any and all additional data that we can see, which we think will be a very nice read-through to our CardioTransform study. As you know, you know, we have the largest by far study ever conducted in the patient population and we think that anything we see from other molecules in the silencer class are going to be very, very good read-throughs to what we expect to see in our study.

Myles Minter: It's going very well, right on track.

Brett: As the first silencer to read out in this indication, we're very much looking forward to any and all additional data that we can see, which we think will be a very nice read-through to our CardioTransform study.

Speaker Change: Next question please.

Operator: The next question comes from Mani Foroohar from Leerink Partners. Please go ahead.

<unk>: <unk> from Leerink partners. Please go ahead.

Mani Foroohar: Hey, guys, you have Ryan on for Mani. Thanks for taking our question. Can you just talk a little bit about any early insights from the when you will launch and how you see that in forming a potential launch strategy in cardiomyopathy, and kind of alongside that, maybe what pre-commercialization activities you guys are undertaking in cardiomyopathy? Thanks.

Brett: As you know, we have the largest by far study ever conducted in the patient population.

Operator: So we're very much looking forward to any and all data that comes from future presentations on the silencer class. Next question, please. The next question comes from Manny Fuhar from Lear, Inc. Partners. Please go ahead. Hey guys, you have Ryan on for money.

Brett P. Monia: --well, I'm sorry, Jonathan.

Speaker Change: Im sorry, Jonathan Yes.

Jonathan Birchall: Yes, we're thanks for your question. We're very pleased with the early insights regarding with the PN launch and, as Kyle referenced, we're seeing patients are new to treatment. We're seeing patients or restrict switching from existing treatments, and we're seeing patients having we know are added on to their current treatment. And so we receive--are pleased with what we're seeing. It's very early days. This is a foundation year for the launch of WAINUA, but we think there's certainly significant opportunity here when you think through the potential patient population of both PN and CM and the number of patients who are potentially underdiagnosed, and fundamentally, the relatively small numbers today who were actually treated. And what we're pleased with is that we seeing prescribing from both neurology and cardiology, and both centers of excellence as well as in the community. And that I think bodes well, not just for the PM launch, a nice progression, but also the transition obviously into future indications. Obviously, when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We will have to wait for future data readouts of our own pretty comprehensive programs.

Speaker Change: Very pleased with the early insights, we're getting with <unk>. The pm launch. As Carl referenced. We are seeing patients are new to treatment, we're seeing patients. Switching from existing treatments. Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Speaker Change: The pm launch. As Carl referenced. We are seeing patients are new to treatment, we're seeing patients. Switching from existing treatments. Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: As Carl referenced. We are seeing patients are new to treatment, we're seeing patients. Switching from existing treatments. Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: We are seeing patients are new to treatment, we're seeing patients. Switching from existing treatments. Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: Switching from existing treatments. Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Operator: Thanks for taking our question. Can you just talk a little bit about any early insights from the way new a launch and how you see that informing a potential launch strategy in cardiomyopathy and kind of alongside that, you know, maybe what pre commercialization activities you guys are undertaking in cardiomyopathy? Thanks.

Carl: Seeing patients having. Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Ryan: Hey guys, you have Ryan on for Monty. Thanks for taking our question. Can you just talk a little bit about any early insights from the way Newell launched and how you see that informing a potential launch strategy in cardiomyopathy? And kind of alongside that, you know, maybe what pre-commercialization activities you guys are undertaking in cardiomyopathy? Thanks.

Carl: Having way newer added onto their current treatment. So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

So we're super pleased with what we're seeing it's very early days. This is a foundation year of a launch of way Noah, but we think. Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: Certainly significant opportunity here when you think through the potential patient population. Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Operator: Thanks for your question. We're very pleased with the early insights we're getting with the PN launch. As Kyle referenced, we're seeing patients who are new to treatment, we're seeing patients who are switching from existing treatments, and we're seeing patients having way newer added on to their current treatment. So we're super pleased with what we're seeing. It's very early days.

Carl: Panna and CFM. The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: The number of patients who are potentially under diagnosed. And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: And fundamentally the relatively small numbers today, who are actually. Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Carl: Treated. What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Randy: What we please randy but we've seen priest. Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Speaker Change: We're seeing patients who are new to treatment, we're seeing patients who are switching from existing treatments, and we're seeing patients having Wayneua added on to their current treatment.

Speaker Change: Prescribing from both neurology and cardiology, both centers of excellence as well as in the community and that I think bodes well not just for the launch. Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Operator: This is a foundation year for the launch of Wayneua. But we think there's certainly significant opportunity here when you think through the potential patient population of both PN and CN, and the number of patients who are potentially underdiagnosed. And fundamentally, the relatively small numbers today who are actually treated.

Speaker Change: Progression, but also the transmission obviously into future indications, obviously when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Speaker Change: We'll have to wait for. For future data readouts of our own pretty comprehensive programs.

Speaker Change: For future data readouts of our own pretty comprehensive programs.

Kyle Jenne: Yeah, two quick things to add. First on the payer access side of things, we're seeing payers cover window up very quickly. So, that the prescription process, the patients actually starting on drug is going very, very well. That tells us that the right types of patients are being identified. And it's also telling us that physicians are justifying the prior authorization process with the sense of urgency, which tells you that these patients need treatment and they see the value in WAINUA. The second thing I'll just mention is around our patient engagement team. Our PEM team is directly interacting with these patients and getting feedback on a real-time basis, patients are extremely pleased at when they start WAINUA at the ability to self-inject with the autoinjector. Very well-tolerated, very easy to use, a very convenient for those patients and the profile of WAINUA is really playing out the way that we expected it to in the market.

Operator: And what we're pleased with is that we're seeing prescribing from both urology and cardiology and both centers of excellence as well as in the community. And that, I think, bodes well not just for the PM launch and that progression, but also the transition, obviously, into future indications. Obviously, when it comes to some of those future indications, it's very premature to speculate as to what might happen there. We'll have to wait for future data readouts of our own pretty comprehensive program. Yeah, two quick things to add.

Speaker Change: Here's cover window up very quickly so from the prescription process of patients actually starting on drug is going very very well that tells us that the right types of patients are being identified and it's also telling us that physicians are justifying the prior authorization process with the sense of urgency, which tells us that these patients need treatment and they see the valley. <unk> and <unk>. The second thing I'll, just mention is around our patient engagement team. Our <unk> team is directly interacting with these patients and getting feedback on a real time basis Ah patients are extremely pleased when they start way NOLA at the ability to self inject with the auto injector very well tolerated very easy to use a very. For those patients and the profile of <unk> is really playing out the way we expected it to in the market.

Speaker Change: And that, I think, bodes well not just for the PM launch and that progression, but also the transition, obviously, into future indications.

Speaker Change: <unk> and <unk>. The second thing I'll, just mention is around our patient engagement team. Our <unk> team is directly interacting with these patients and getting feedback on a real time basis Ah patients are extremely pleased when they start way NOLA at the ability to self inject with the auto injector very well tolerated very easy to use a very. For those patients and the profile of <unk> is really playing out the way we expected it to in the market.

Operator: First, on the payer access side of things, we're seeing payers cover Waynua very quickly. So, from the prescription process, the patient's actually starting on drug is going very, very well. That tells us that the right types of patients are being identified, and it's also telling us that physicians are justifying the prior authorization process with a sense of urgency, which tells you that these patients need treatment and they see the value in Waynua.

Speaker Change: Yeah, two quick things to add. First, on the payer access side of things,

Brett: We're seeing payers cover Waynua very quickly. So from the prescription process, the patient's actually starting on drug.

Speaker Change: For those patients and the profile of <unk> is really playing out the way we expected it to in the market.

Speaker Change: is going very, very well. That tells us that the right types of patients are being identified. And it's also telling us that physicians are justifying the prior authorization process with a sense of urgency, which tells you that these patients need treatment and they see the value in Waynua.

Brett P. Monia: Next question, please.

Operator: The next question comes from Yanan Zhu from Wells Fargo Securities. Please go ahead.

Yanan Zhu: Great. Thanks for taking our questions. Wondering about what's your takeaway from Roche's recent presentation there? Angelman syndrome Phase II data at the ASF meeting? And also separately, given the similar development time line of your Angelman syndrome program, and Ultragenyx program, do you think FDA will want to apply the same pivotal endpoint to both programs? Or is there a possibility that the agency could allow different primary endpoints based on strength of data? Thank you.

Operator: The second thing I'll just mention is around our patient engagement team. Our PIM team is directly interacting with these patients and getting feedback on a real-time basis. Patients are extremely pleased when they start Waynua at the ability to self-inject with the auto-injector.

Wondering about what sort of takeaway from Roche's recent presentation. Single. Phase two data at the ASF meeting. And also separately. Given the similar. Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Brett: The second thing I'll just mention is around our patient engagement team. Our PIMM team is directly interacting with these patients and getting feedback on a real-time basis.

Single. Phase two data at the ASF meeting. And also separately. Given the similar. Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Speaker Change: Phase two data at the ASF meeting. And also separately. Given the similar. Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Brett: Patients are extremely pleased when they start Waynua at the ability to self-inject with the auto-injector. Very well tolerated, very easy to use, very convenient for those patients, and the profile of Waynua is really playing out the way that we expected it to in the market.

And also separately. Given the similar. Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Speaker Change: Given the similar. Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Speaker Change: Development timeline of your implements single program and <unk> program do you think the FDA will want to apply the same pivotal endpoint. Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Speaker Change: Both programs or is there a possibility that the agency could allow different primary endpoints based on the strength of data. Thank you.

Operator: Very well-tolerated, very easy to use, very convenient for those patients, and the profile of Waynua is really playing out the way that we expected it to in the market. Next question, please. The next question comes from Yanan Zhu from Roth Fargo Securities. Please go ahead.

Brett: Next question, please.

Speaker Change: The next question comes from Yanan Zhu from Roth Fargo Securities. Please go ahead.

Brett P. Monia: Thanks Yanan, and I'll take the first question, then I'll ask Eugene to comment on the primary endpoint in any harm and harmonization in primary endpoints arrangements. So, we are very pleased to see the data that Roche presented on their Angelman's program. And particularly, we were pleased with the fact that the data are further supported our confidence in our Phase I/II data that we presented at ASF, specifically that the rank order of improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was an expressive communication, followed by expressive, receptive communication, followed by cognition, followed by motor function and so on. And that's exactly what we reported, which get bolsters it further confidence in our results to date. We are also pleased with the magnitude of benefit we're seeing compared to their program, which really looks like when you really compare apples to apples, and you convert fairly treated daily for outcomes both very well. We will likely have even better efficacy at lower doses compared to what was presented, but we were pleased to see what they showed because of the consistency in sub domain benefit between the two programs. Eugene?

Operator: Great, thanks for taking our questions. Wondering about what's your takeaway from Roshi's recent presentation of their Andromeda Syndrome Phase II data at the ASF meeting? And also separately, given the similar development timeline of your Andromeda Syndrome Program and Ultragenics Program, do you think FDA will want to apply the same pivotal endpoint to both programs, or is there a possibility that the agency could allow different primary endpoints based on strength of data? Thank you. Thanks, Shannon. I'll take the first question, then I'll ask Eugene to comment on the primary endpoint and any harmonization, in primary endpoints for Angelman.

Eugene: The primary endpoint in any organization. And primary endpoints for Angelman so. We're very pleased to see the data that Roche presented on the Angelman program and particularly we are pleased with the fact that. The data are further supported. Our confidence and our phase <unk> data that we presented at ASN specifically. That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: And primary endpoints for Angelman so. We're very pleased to see the data that Roche presented on the Angelman program and particularly we are pleased with the fact that. The data are further supported. Our confidence and our phase <unk> data that we presented at ASN specifically. That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: We're very pleased to see the data that Roche presented on the Angelman program and particularly we are pleased with the fact that. The data are further supported. Our confidence and our phase <unk> data that we presented at ASN specifically. That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: and also separately...

Eugene: The data are further supported. Our confidence and our phase <unk> data that we presented at ASN specifically. That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: Our confidence and our phase <unk> data that we presented at ASN specifically. That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: That the rank order. Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: Improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Eugene: The biggest magnitude that they reported was intercept was an expressive communication followed by expressive. Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: Thanks, Yanan. I'll take the first question and then I'll ask Eugene to comment on the primary end point and any harmonization.

Operator: So we were very pleased to see the data that Roche presented on their Angelman's program and particularly we were pleased with the fact that the data further supported our confidence in our phase 1-2 data that we presented at ASF, specifically that the rank order of improvements that they reported with respect to the magnitude of improvement was exactly what we reported. The biggest magnitude that they reported was in receptive, was in expressive communication followed by expressive receptive communication, followed by cognition, followed by motor function and so on and that's exactly what we reported which bolsters it further confidence that you know in our in our results to date.

Eugene: Receptive communication, followed by cognition followed by. Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: in Primary Endpoints for Angel Women.

Eugene: Motor function and so on and Thats exactly what we reported which bolsters and further confidence. In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: We are very pleased to see the data that Roche presented on their Angel Wings program, and particularly we are pleased with the fact that

Eugene: In our in our results to date. We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: The data further supported our confidence in our Phase I-II data that we presented at ASF.

Speaker Change: We were. Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: Also pleased with the magnitude of benefit we're seeing compared to their program, which really. It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: Specifically, that the rank order of improvements that they reported with respect to the magnitude of improvement was exactly what we reported.

Speaker Change: It looks like when you really compare apples to apples and you convert daily to daily for outcomes. Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Speaker Change: Bodes very well, we would likely have even better efficacy at lower doses compared to where Roche presented but we were pleased to see what these but they showed because of the consistency in sub domain benefit. The two programs.

Brett: The biggest magnitude that they reported was in expressive communication followed by receptive communication.

Speaker Change: The two programs.

Brett: followed by Cognition, followed by...

Eugene Schneider: Yeah well, regarding our primary endpoint and conversations to be had with the agency, of course, we're looking forward to updating you after we've had our discussions. There's--from our standpoint, this will be data driven. We certainly do believe that the data and consistency of what we see in our Phase I/II study gives us pretty good idea what we would like to see in a pivotal study, but it's still to be seen what the specific primary endpoint will end up being. We'll certainly give you an update. Is there a precedence to have a slightly different primary endpoint? Of course, there's plenty of precedent in neurology space as well as [inaudible] I mean, if you look at ATTR-CM that's another example where primary endpoint is not identical for two very similar programs. Stay tuned, we will certainly--we'll be happy to provide you an update.

Speaker Change: Yes. Regarding the primary endpoint the conversation to be had. With the agency of course, we're looking forward to updating you after. We've had our discussions. From our standpoint, there is this will be data driven we certainly do believe that with. Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Brett: [inaudible]

Jim: Regarding the primary endpoint the conversation to be had. With the agency of course, we're looking forward to updating you after. We've had our discussions. From our standpoint, there is this will be data driven we certainly do believe that with. Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Jim: With the agency of course, we're looking forward to updating you after. We've had our discussions. From our standpoint, there is this will be data driven we certainly do believe that with. Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Operator: We were also pleased with the magnitude of benefit we're seeing compared to their program, which really looks like when you really compare apples to apples, and you convert daily three to daily four outcomes, it bodes very well. We look like we have even better efficacy at lower doses compared to what we're always presented. But we were pleased to see what they showed because of the consistency in subdomain benefit between the two programs. Eugene?

Brett: We're also pleased with the magnitude of benefit we're seeing compared to their program, which really looks like...

Speaker Change: We've had our discussions. From our standpoint, there is this will be data driven we certainly do believe that with. Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: From our standpoint, there is this will be data driven we certainly do believe that with. Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Brett: When you really compare apples to apples and you convert daily 3 to daily 4 outcomes, it bodes very well. We look like we have even better efficacy at lower doses compared to what LaRoche presents. But we're pleased to see what they...

Speaker Change: Data and consistency of what we see in our phase one two. Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: Sorry. Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: Gives us pretty good. Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: Idea of what we would like to see the pivotal study. Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Eugene: But they showed because of the consistency in subdomain benefit between the two programs. Eugene?

Speaker Change: Still to be seen what the specific primary endpoint will end up being. Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Operator: Yeah, well, regarding those primary endpoints and conversations to be had, at the agency, of course, we're looking forward to updating you after we've had our discussion. From our standpoint, this will be data-driven. We certainly do believe that the data and consistency of what we see in our Phase I-II, The study gives us a pretty good idea of what we would like to see. Unfortunately, I cannot speak to this study, but it is still to be seen what the specific primary endpoint will end up being, certainly give you an update. Is there a precedence?

Speaker Change: Certainly give you give you an update is there a precedence. To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Eugene: Yeah well regarding those primary endpoints and conversations to be had with the agency of course we're looking forward to updating you after we've had our discussions.

Speaker Change: To have a slightly different a different primary endpoint of course, there is plenty of precedent. Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: Neurology space as well as outside I mean, if you look at. EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

EBIT RCM. Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Eugene: But there is, from our standpoint, this will be data-driven. We certainly do believe that the data and consistency of what we see in our Phase I-II

Speaker Change: Other example, where primary endpoint is not identical very similar programs. Stay tuned we will certainly we'll be happy to provide you an update.

Speaker Change: Stay tuned we will certainly we'll be happy to provide you an update.

Eugene: The study gives us pretty good...

Brett P. Monia: Thanks, [inaudible].

Operator: The next question comes from Jessica Fye from JP Morgan. Please go ahead.

Speaker Change: And then, of course, we have the idea of what we would like to see in the final study, but it's still to be seen what the specific primary endpoint will end up being. We'll certainly give you an update. Is there a precedence?

Jessica Fye: Hey there, thanks for taking my question. On the back of the top line HELIOS-B data, what's your latest expectation for whether silencers and TTR cardiomyopathy will mainly be used in combination with stabilizers versus as monotherapy? Thank you.

Speaker Change: On the back of the topline Helios B data. What's your latest expectation for whether silencers and TCR cardiomyopathy will mainly is in combination with stabilizers versus as monotherapy.

Operator: to have a slightly different or different primary endpoint. Of course, there's plenty of precedence in neurology space as well as outside. I mean, if you look, ADTRCM, that's another example where primary employment is not identical to very similar programs.

Jessica Fye: What's your latest expectation for whether silencers and TCR cardiomyopathy will mainly is in combination with stabilizers versus as monotherapy.

Eugene: to have a slightly different or different primary endpoint. Of course, there's plenty of precedence in neurology space as well as outside. I mean, if you look at.

Eugene: ADTRCM. That's another example where primary employment is not identical for two very similar programs.

Kyle Jenne: Yes, I'd be happy to talk to that. This is Kyle. Thanks, Jessica. The data that ultimately is going to drive this, we believe that as a starting point, I think ultimately it will come down to physicians and patients making a decision around the profile of treatment that they want in that decision. But we see it right now, we are seeing WAINUA used in combination, obviously, as HATTR polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now. We think that will continue to progress over time, and we also believe that based on the data, and the way that data plays out, will be justification for physicians to be able to justify that to the payers whenever they submit these requests and trying to get the drugs approved. So I think it's ultimately data in driven by physicians and patients.

Operator: Stay tuned, we will certainly be happy to provide you with more information. Thanks, Yannick. Next question. Very helpful.

Thanks Jessica. The data ultimately is going to drive this we believe. That is a starting point I think ultimately it will come down to physicians and patients, making a decision around the profile of treatment that they want and that decision. But when we see it right now we are seeing we knew are used in combination obviously is. H <unk> polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Speaker Change: The data ultimately is going to drive this we believe. That is a starting point I think ultimately it will come down to physicians and patients, making a decision around the profile of treatment that they want and that decision. But when we see it right now we are seeing we knew are used in combination obviously is. H <unk> polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Eugene: Stay tuned, we will certainly be happy to provide you an update.

Speaker Change: That is a starting point I think ultimately it will come down to physicians and patients, making a decision around the profile of treatment that they want and that decision. But when we see it right now we are seeing we knew are used in combination obviously is. H <unk> polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Speaker Change: Thanks Yanan, next question. That was very helpful.

Operator: The next question comes from Jessica Fye from J.P. Morgan. Please go ahead. Hey there, thanks for taking my question. On the back of the top line Helios V data. What's your latest? for Weather Silence.

Speaker Change: The next question comes from Jessica Fye from J.P. Morgan. Please go ahead.

Speaker Change: But when we see it right now we are seeing we knew are used in combination obviously is. H <unk> polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Jessica Fye: Hey there, thanks for taking my question.

Speaker Change: H <unk> polyneuropathy indication combined with cardiomyopathy indication for the stabilizers currently. So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Jessica Fye: On the back of the top line Helios V data, what's your latest expectation for whether silencers in TTR cardiomyopathy will mainly be used in combination with stabilizers versus as monotherapy? Thank you.

Operator: Cardiomyopathy will mainly be used in combination with stabilizers, versus Esmona Therapeutics. Yeah, I'd be happy to talk to that. This is Kyle.

Speaker Change: So we're seeing it happen now we think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Speaker Change: And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients and just to add to that.

And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved so I think it's ultimately data and driven by physicians and the patients

Operator: Thanks, Jessica. The data ultimately is going to drive this, we believe. That is a starting point. I think ultimately it will come down to physicians and patients making a decision around the profile of treatment that they want in that decision. We have several imaging studies in process, and we think that if anyone is going to be able to show really meaningful improvements in combination versus monotherapy across the board, whether it be imaging or clinical endpoints, we're going to be in the best position to do so.

Brett P. Monia: And just add to that, as you know, Jeff, we have--we're positioned to have the richest data set across the board on a primary or secondary and some endpoints and subgroups. And we're going to have a great deal of data in combination usage as well as a monotherapy, second to none. And that includes data on key endpoints, clinical endpoints such as hospitalizations, mortality, six-minute walk test, biomarkers and so on. But also in the imaging studies, we have several imaging studies in process. And we think that if anyone's been able to show meaningful improvements in combination versus monotherapy across the board, whether the imaging, or clinical endpoints, we're going to be in the best position to do so. And we think that will, as Kyle said, because this is a data driven environment, we're going to invest position to actually have data to support combination usage. Next question, please.

Jess: Jess we have. We're positioned to have the richest data set across the board on primaries, both secondary endpoints. The end points and sub groups and we're going to have a. Great deal of data and combination usage as well as a monotherapy second to none. And that includes data on. Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: We're positioned to have the richest data set across the board on primaries, both secondary endpoints. The end points and sub groups and we're going to have a. Great deal of data and combination usage as well as a monotherapy second to none. And that includes data on. Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: The end points and sub groups and we're going to have a. Great deal of data and combination usage as well as a monotherapy second to none. And that includes data on. Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: Great deal of data and combination usage as well as a monotherapy second to none. And that includes data on. Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Speaker Change: cardiomyopathy indication for the stabilizers currently.

Jess: And that includes data on. Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Speaker Change: So we're seeing it happen now. We think that that will continue to progress over time. And we also believe that based on the data and the way that that data plays out will be justification for physicians to be able to justify that to the payers whenever they submit these requests and try to get the drugs approved. So I think it's ultimately data and driven by physicians and patients.

Jess: Key endpoints clinical endpoints, such as hospitalizations mortality six minute walk test biomarkers and so on but also in the imaging studies, we have several imaging studies in process and we think that is. Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: Anyone has been able to show meaningful improvements in combination versus the monotherapy. Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Speaker Change: And just to add to that, as you know, Jess, we have, you know, we're positioned to have the richest data set across the board on primary as well as secondary and sub-endpoints and subgroups, and we're going to have

Jess: Across the board, but at the imaging or clinical endpoints, where we're going to be divested in the best position to do so and we think that that will as Kyle said because this is a data driven. Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: a great deal of data in combination usage as well as in monotherapy, second to none.

Jess: Environment. We're going to invest position to actually have the data to support combination usage. Next question please.

Kyle: We're going to invest position to actually have the data to support combination usage. Next question please.

Jess: And that includes data on, you know, key endpoints, clinical endpoints, such as hospitalizations, mortality, six-minute walk tests, biomarkers, and so on, but also in the imaging studies.

Speaker Change: Next question please.

Operator: The next question comes from Allison Bratzel from Piper Sandler. Please go ahead.

Speaker Change: That's all from Piper Sandler. Please go ahead.

Allison Bratzel: Hey, good morning, guys, and thanks for taking my question. Maybe one on PELACARSEN, since that Phase III data and regulatory filing are coming up next year. Could you just talk to or frame like what you'd like to see in that readout? And maybe in broad strokes, what gives you confidence in the differentiation of this asset in what could be a competitive space. Color on that or the next-gen program would be helpful. Thank you.

Allison: Maybe one on on pellet Carson. That phase III data and regulatory filings coming up next year. Could you just talk to her airframe like what you'd like to see and that read out. Maybe in broad strokes, what gives you confidence in differentiation of this asset. And what could be a competitive space color on that or the next Gen program would. What would be helpful. Thank you.

Speaker Change: We have several imaging studies in process, and we think that...

Speaker Change: That phase III data and regulatory filings coming up next year. Could you just talk to her airframe like what you'd like to see and that read out. Maybe in broad strokes, what gives you confidence in differentiation of this asset. And what could be a competitive space color on that or the next Gen program would. What would be helpful. Thank you.

Speaker Change: If anyone has been able to show really meaningful improvements in combination versus monotherapy,

Speaker Change: Could you just talk to her airframe like what you'd like to see and that read out. Maybe in broad strokes, what gives you confidence in differentiation of this asset. And what could be a competitive space color on that or the next Gen program would. What would be helpful. Thank you.

Kyle: across the board, whether it be imaging or clinical endpoints, we're going to be in the best position to do so. And we think that that will, as Kyle said, because this is a data-driven, you know, environment, we're going to be in the best position to actually have the data to support combination usage.

Operator: And we think that that will, as Kyle said, because this is a data-driven environment, we're going to be in the best position to actually have the data to support combination. Next question. The next question comes from Allison Bratzel from Pepper Fandler. Please go ahead. Hey, good morning, guys.

Maybe in broad strokes, what gives you confidence in differentiation of this asset. And what could be a competitive space color on that or the next Gen program would. What would be helpful. Thank you.

Speaker Change: And what could be a competitive space color on that or the next Gen program would. What would be helpful. Thank you.

Speaker Change: What would be helpful. Thank you.

Speaker Change: Next question, please.

Brett P. Monia: Yeah, Allison so, there's not the only the only news on PELACARSEN is really that the study is on track to read out on has scheduled next year. Everything is going very well. And our partner Novartis is well positioned with first mover advantage in this first-to-market patient population--this enormous patient population. Everything we're seeing in the Phase III study is very supportive of this being set up for a successful outcome. First mover advantage is really important, and we know Novartis has substantial lead to the market. Yeah, the program--our follow-on program with Novartis on the follow-on program is advancing well, maybe I'll ask Eric Swayze to comment on how things are going.

Speaker Change: The next question comes from Allison Bratzel from Pepper Sandler. Please go ahead.

Speaker Change: No there's not. The only the only moves on pellet Carson is really that the study is on track to read out. Next year. Everything is going very well. <unk>. Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Operator: And thanks for taking my question. Maybe one on Pella Carson, since that phase three data and regulatory filing are coming up next year. Could you just talk to or frame what you'd like to see in that readout? And maybe in broad strokes, you know, what gives you confidence in differentiation of this asset? You know, and what could be a competitive space? You know, color in that, or the next gen program? Would that be helpful?

Speaker Change: The only the only moves on pellet Carson is really that the study is on track to read out. Next year. Everything is going very well. <unk>. Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Allison Bratzel: Hey, good morning guys, and thanks for taking my question.

Allison Bratzel: Maybe one on Pellicarson, since that phase 3 data and regulatory filing are coming up next year.

Speaker Change: Next year. Everything is going very well. <unk>. Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: Everything is going very well. <unk>. Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

<unk>. Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: Our partner Novartis. Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Allison Bratzel: Could you just talk to or frame what you'd like to see in that readout, and maybe in broad strokes, you know, what gives you confidence in differentiation of this asset?

Speaker Change: Is well positioned with first mover advantage in this in this first to market. Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: Patient population was enormous patient population everything we're seeing in the phase III study is very supportive of this being set up for a successful outcome. Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: and what could be a competitive space.

Speaker Change: You know, color on that, or the NextGen program would be helpful. Thank you.

Operator: Thank you. Yeah, Allison, so, you know, there's not the only the only news on telecarson is really that the study is on track to read out as scheduled next year. Everything is going very well and, you know, our partner Novartis is well positioned with first mover advantage in this first to market patient population, this enormous patient population. Everything we're seeing in the phase 3 study is very supportive of this being set up for a success.

Speaker Change: Outcome first mover advantage is really important and we would novartis are have substantial lead to. To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Brett: Yeah, Allison, so, you know, there's not, the only news on Pella-Carson is really that the study is on track to read out as scheduled next year.

Speaker Change: To the market. Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: Yes the program there. A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Speaker Change: A follow on program to Novartis with Novartis on a follow on program is advancing well. Maybe I'll ask Eric Swayze to comment on how the how things are going.

Brett: Everything is going very well and you know our partner Novartis is well positioned with first-mover advantage in this in this first-to-market patient population, this enormous patient population.

Eric Swayze: Maybe I'll ask Eric Swayze to comment on how the how things are going.

Eric Swayze: Things are going great. We've been working closely with Novartis, looking at a variety of ways to extend the dosing interval and make a great [inaudible] drug. And I'm sure we'll discuss it in some time as the program advances further. But I can't say more than that at this time, but very pleased with the progress we've been making on new technologies, SIRNAs in particular, and a broad range of other things beyond what would be minimal for the LPA permanent group.

Eric Swayze: <unk> to extend the dosing interval. And making great helping oriented growth. I'm sure, we will discuss it and sometimes as the program advances further, but I can't really say more than that at this time, but very pleased with the progress we've been making. On new technologies, <unk> and <unk> in particular, and a broad range of other things beyond what would be medical for the okay.

Brett: Everything we're seeing in the phase 3 study is very supportive of this being set up for a successful trial.

Speaker Change: And making great helping oriented growth. I'm sure, we will discuss it and sometimes as the program advances further, but I can't really say more than that at this time, but very pleased with the progress we've been making. On new technologies, <unk> and <unk> in particular, and a broad range of other things beyond what would be medical for the okay.

I'm sure, we will discuss it and sometimes as the program advances further, but I can't really say more than that at this time, but very pleased with the progress we've been making. On new technologies, <unk> and <unk> in particular, and a broad range of other things beyond what would be medical for the okay.

Operator: First mover advantage is really important and we with Novartis have a substantial lead to the market. Um, uh, yeah, the program that, um, uh, our follow-on program to Novartis, uh, with Novartis on the follow-on program is advancing well. Um, maybe I'll ask Eric Swayze to, uh, comment on how the, how things are going.

Brett: outcome. First-mover advantage is really important and we with Novartis all have substantial lead to the market.

Speaker Change: On new technologies, <unk> and <unk> in particular, and a broad range of other things beyond what would be medical for the okay.

Speaker Change: Yeah, the program that, our follow-on program to Novartis, with Novartis on the follow-on program is advancing well, maybe I'll ask Eric Swayze to comment on how things are going.

Brett P. Monia: We feel very comfortable that we're going to achieve our objectives with Novartis on a follow-on molecule, things are going very well. There's obviously a lot of benchmarks out there today, there's a lot to compare to. Next question, please.

Speaker Change: <unk>. Our objectives with Novartis on our pharma molecule things are going very well. A lot of benchmarks out there today. Theres, a lot lots of compared to where please. Next question please.

Speaker Change: Our objectives with Novartis on our pharma molecule things are going very well. A lot of benchmarks out there today. Theres, a lot lots of compared to where please. Next question please.

Operator: Things are going great. We've been working closely with Novartis, looking at a variety of ways to extend the dosing interval and make a great LP lowering drug. And I'm sure we'll discuss it in some time as the program advances further, but I can't really say more than that at this time. But very pleased with the progress we've been making on new technologies, siRNAs in particular, and a broad range of other things beyond what would be medical for the LPA program.

Speaker Change: A lot of benchmarks out there today. Theres, a lot lots of compared to where please. Next question please.

Eric Swayze: These are going great. We've been working closely with Novartis.

Speaker Change: Theres, a lot lots of compared to where please. Next question please.

Eric Swayze: looking at a variety of ways to extend the dosing interval.

Speaker Change: Next question please.

Speaker Change: and make a great help in lowering your drug.

Operator: The next question comes from Yaron Werber from TD Cowen. Please go ahead.

Speaker Change: I'm sure we'll discuss it.

Speaker Change: Please go ahead.

Eric Swayze: And sometimes the program advances further, but I can't really say more than that at this time. But I'm very pleased with the progress we've been making on new technologies, siRNAs in particular, and a broad range of other things beyond what would be meant for the LPA program.

Yaron Werber: Great, also thanks for taking my question. I also have just a quick follow up on WAINUA. And as you look at the HELIOS-B data and I'm totally obviously you're aware that you're probably going to be waiting for the full HELIOS-B results. But as you think about with a much powered trial design, where could you potentially differentiate? And how important will that combo data be, just given that overall and butcher will get a broad label for TTR? Thank you.

Speaker Change: And as you look at the Helios B data and I'm totally obviously aware that publicly. Probably going to be waiting for the full Helios b results, but as you think about with a much powered. Trial design, what could potentially differentiate. And how important will dot combo data be just given that. Overall in virtual we will get a broad label for <unk>. Thank you.

Speaker Change: Probably going to be waiting for the full Helios b results, but as you think about with a much powered. Trial design, what could potentially differentiate. And how important will dot combo data be just given that. Overall in virtual we will get a broad label for <unk>. Thank you.

Operator: We feel very comfortable that we're going to achieve our objectives with Novartis on a Pharma molecule. Things are going very well. There's obviously a lot of benchmarks out there today, so there's a lot to compare to.

Eric Swayze: We feel very comfortable that we're going to achieve our objectives with Novartis on a follow-on molecule. Things are going very well. There's obviously a lot of benchmarks out there today, so there's a lot to compare to. We're pleased.

Trial design, what could potentially differentiate. And how important will dot combo data be just given that. Overall in virtual we will get a broad label for <unk>. Thank you.

Speaker Change: And how important will dot combo data be just given that. Overall in virtual we will get a broad label for <unk>. Thank you.

Operator: We're pleased. Next question. The next question comes from Yaron Werber from T.D. Cohen.

Speaker Change: Overall in virtual we will get a broad label for <unk>. Thank you.

Brett P. Monia: Well, thank you Yaron. As the largest study ever conducted in this patient population, by far, we think we have the opportunity to differentiate in several different areas, but it will be very interesting to see the onset of action for silencers and whether or not our onset of action is going to be similar or faster. It could be very interesting to see the combination data, as you alluded to just now, as we touched on earlier, combination data, it can be very important, patient population. And despite having a broad label, which we expect to have as well, cardiologists are data-driven, and they're going to need to see data before advocating for combination usage. I think we're well positioned to have that data. As [inaudible] health class categories are gonna be very important to see how mild patients are doing, moderately ill patients and severely ill patients are doing. All of this, when you have a well-powered study, rich data--and provide--set up have the rich dataset, you have the potential ability to differentiate across the board. Anything to add to that Eugene?

Eric Swayze: Next question, please.

Aaron: Thank you Aaron. As the largest study ever conducted in this patient population by far we think we have the opportunity to differentiate in several different areas. It'll be very interesting to see. The. The onset of action. For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Eric Swayze: The next question comes from Yaron Werber from TB Cohen. Please go ahead.

Speaker Change: As the largest study ever conducted in this patient population by far we think we have the opportunity to differentiate in several different areas. It'll be very interesting to see. The. The onset of action. For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Operator: Please go ahead. Right. I also, thanks for taking my question. I also have just a quick follow up on Waynua. And if you look at the Helios B data, and I'm totally obviously aware that the you're probably going to be waiting for the full Helios B results. But if you think about with a much powered trial design, where can you potentially differentiate, and how important will that combo data be just given that overall Lumbutra will get a broad label for TTR?

Yaron Werber: Thanks for taking my question. I also have just a quick follow-up on Waynua and you look at the Helios B data and I'm totally obviously aware that the you're probably going to be waiting for the full Helios B results but as you think about with a much-powered

Aaron: It'll be very interesting to see. The. The onset of action. For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: The. The onset of action. For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: The onset of action. For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: For silences, and whether or not our onset of action is going to be. Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Jessica Fye: trial design, where can you potentially differentiate and how important will that combo data be just given that overall Lumbutra will get a broad label for TTR? Thank you.

Aaron: Similar or faster its going be very interesting. The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: The combination data as you alluded to just now and it will be touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: Combination data is going to be very important in this patient population and despite having a broad label, which. We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Operator: Thank you. Well, thanks, Ion. As the largest study ever conducted in this patient population, by far, we think we have the opportunity to differentiate in several different areas. It'll be very interesting to see, you know, the onset of action for silencers and whether or not our onset of action is going to be similar or faster. It's going to be very interesting to see the combination data, as you alluded to just now, as we touched on earlier.

Yaron: Well, thank you, Yaron.

Aaron: We expect to have as well. Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: Cardiologists are data driven and. And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Speaker Change: As the largest study ever conducted in this patient population, by far, we think we have the opportunity to differentiate in several different areas. It will be very interesting to see, you know, the onset of action.

Aaron: And they're going to need to see data. Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: Before advocating for combination usage I think we're well positioned. To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: To have that data. New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

New York Health class. The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Aaron: The categories are going to be very important to see how mild patients are doing moderately ill patients and severely ill patients who are doing all of this when you have when you have a well powered study of rich and providing setup have the rich dataset you have the potential ability to differentiate across the board. And to add to that you can.

Yaron: for our silencers and whether or not our onset of action is going to be similar or faster. It's going to be very interesting.

Yaron: to see the combination data as you alluded to just now and as we touched on earlier. Combination data is going to be very important in this patient population and despite having a broad label, which

Operator: Combination data is going to be very important in this patient population. And despite having a broad label, which we expect to have as well, cardiologists are data-driven and they're going to need to see data before advocating for combination usage. I think we're well positioned to have that. You know, New York health class categories are going to be very important to see how mild patients are doing, moderately ill patients, and severely ill patients.

Aaron: And to add to that you can.

Eugene Schneider: No, not really, Brett. I think you characterized it. I think the power really comes from the size of the study and also an ability to look at subpopulations, which were really well positioned to do.

Speaker Change: We characterize it I think the power really comes from the size of the study and also an ability to look at subpopulations, which we're really. Well positioned to do.

Yaron: we expect to have as well. Cardiologists are data-driven, and they're gonna need to see data before advocating for combination usage. I think we're well-positioned to have that data.

Speaker Change: Well positioned to do.

Brett P. Monia: Thank you, Yaron. Next question.

Speaker Change: Next question.

Operator: The next question comes from Jason Gerberry from Bank of America. Please go ahead.

Jessica Fye: You know, New York health class categories are going to be very important to see how mild patients are doing, moderately ill patients, and severely ill patients.

Jason Gerberry: Hey, guys. Thanks for taking my question. I wanted to come back to the cardio transform timing question. So it sounds like we're going to get pretty deep, detailed and granular data from our Alnylam. How do you see, in terms of multiple curves on overall mono? Subgroups with famous background, including mortality. So it seems like you'll have everything you need to know post ESC on whether or not the 2025 interim is in the cards. So, is it fair for investors to get or expect maybe a clear message as of the third quarter update on which way you're going to go as the base case 2026 or whether or not you're look to 2025 interim? Thanks.

Operator: All of this, when you have a well-powered study and set up to have the rich data set, you have the potential ability to differentiate across the board. Anything to add to that, Eugene? No, not really, Brett.

I wanted to come back to the cardio transform timing question. So it sounds like. We're going to get pretty deep detailed and granular data from our dialogue at ESC in terms of multiple curves that overall mono. Subgroups with famous background, including mortality. So it seems like you'll have everything you need to know post ESC on whether or not. 225 interim is in the cards. So is it fair for investors to get their expect maybe a clear message as of the third quarter update on which way Youre going to go is the base case, 'twenty, 'twenty, six or whether or not youll. We look to 'twenty five interim thanks.

Jessica Fye: All of this, when you have a well-powered study and set up to have the rich data set, you have the potential ability to differentiate across the board.

Speaker Change: We're going to get pretty deep detailed and granular data from our dialogue at ESC in terms of multiple curves that overall mono. Subgroups with famous background, including mortality. So it seems like you'll have everything you need to know post ESC on whether or not. 225 interim is in the cards. So is it fair for investors to get their expect maybe a clear message as of the third quarter update on which way Youre going to go is the base case, 'twenty, 'twenty, six or whether or not youll. We look to 'twenty five interim thanks.

Subgroups with famous background, including mortality. So it seems like you'll have everything you need to know post ESC on whether or not. 225 interim is in the cards. So is it fair for investors to get their expect maybe a clear message as of the third quarter update on which way Youre going to go is the base case, 'twenty, 'twenty, six or whether or not youll. We look to 'twenty five interim thanks.

Eugene: Anything to add to that, Eugene? No, not really, Brett. You characterized it. I think the power really comes from the size of the study and also an ability to look at subpopulations, which we're really well positioned to do.

Speaker Change: 225 interim is in the cards. So is it fair for investors to get their expect maybe a clear message as of the third quarter update on which way Youre going to go is the base case, 'twenty, 'twenty, six or whether or not youll. We look to 'twenty five interim thanks.

Jessica Fye: Thank you, Yaron. Next question.

Operator: You characterized it. I think the power really comes from the size of the study and also an ability to look at subpopulations, which were really well-presented. Thank you, Aaron. Next question. The next question comes from Jason Gerberry from Bank of America, please go ahead. Hey guys, thanks for taking my question. I wanted to come back to the cardio transform timing question, so it sounds like we're gonna get. Coding granular data for malonylam at ESC in terms of multiple curves on overall mono, Subgroups with feminist background, including mortality, so it seems like you'll have everything you need to know post-AESC on whether or not The 2025 interim is in the cards.

Speaker Change: The next question comes from Jason Gerberry from Bank of America. Please go ahead.

Speaker Change: We look to 'twenty five interim thanks.

Jason Gerberry: Hey guys, thanks for taking my question. I wanted to come back to the cardio transform timing question. So it sounds like we're going to get pretty deep detailed and granular data from Mount Nile at ESC in terms of multiple curves on overall mono and

Brett P. Monia: Yeah, thanks, Jason. So, Ionis and our partner, AstraZeneca had been thinking about this quite a bit on our base case remains sound or 40 weeks of treatment, which brings it to mid-2026. The study were to go to completion. But we are committed to bringing WAINUA to patients as fast as possible, if it makes sense to do so. And certainly, as I mentioned earlier, following up on our blinded events and following up on the studies that we're running is most important for any new information that we get from other treatments in this in the same class, the silencer class is going to be informative on what we do. With that said, we can't get ahead of regulators, we're going to want to get on buy-in on anything. We do, with respect to an earlier readout with the FDA, EMA, before I make any proclamations out there publicly. So timing is a bit uncertain right now, but rest assured that we and AstraZeneca are working on this on very thoughtfully.

Speaker Change #101: <unk> and our partner Astrazeneca. I have been thinking about. It's quite a bit. Our base case remains under 40 weeks of treatment, which brings us to mid 2026. The current study were to go to completion. We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: I have been thinking about. It's quite a bit. Our base case remains under 40 weeks of treatment, which brings us to mid 2026. The current study were to go to completion. We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: It's quite a bit. Our base case remains under 40 weeks of treatment, which brings us to mid 2026. The current study were to go to completion. We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Our base case remains under 40 weeks of treatment, which brings us to mid 2026. The current study were to go to completion. We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change: Subgroups with famous background, including mortality, so it seems like you'll have everything you need to know post-AESC on whether or not...

Speaker Change #101: The current study were to go to completion. We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

We are committed to bringing it to patients as fast as possible. If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Operator: So is it fair for investors to get or expect maybe a clear message as of the third quarter update on which way you're going to go as the base case 2026 or whether or not you'll, Thanks, Jason. So Ionis and our partner AstraZeneca, you know, have been thinking about this quite a bit. Our base case remains down to 40 weeks of treatment, which brings us to mid-2026. If the study were to go to completion.

Speaker Change #101: If it makes sense. To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: To do so. And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: And certainly as I mentioned earlier. Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Following upon our blinded events and following up on the studies that we're running is most important but any new information that we get from. Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Other treatments in this and are in the same class as islands of class are going to be informative. Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Sure. What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: What we do. With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: With that said, we can't get ahead of regulators, we're going to want to get. Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Operator: But you know, we are committed to bringing WENUA to patients as fast as possible, if it makes sense to do so. And certainly, as I mentioned earlier, you know, following up on our blinded events and following up on the studies that we're running is most important. But any new information that we get from other treatments in the same class, the silencer class, are going to be informative on what we do. With that said, we can't get ahead of regulators.

Buying on anything we do with respect to an earlier readout. With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: With the FDA EMA. Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Before before making any. Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change #101: Proclamations out there publicly so timing is a bit uncertain right now. But rest assured that we and Astrazeneca are working on this very thoughtfully.

Speaker Change: And certainly, as I mentioned earlier, you know, following up on our blinded events and following up on the studies that we're running is most important, but any new information that we get from other treatments in the same class, the silencer class, are going to be informative.

Speaker Change #101: But rest assured that we and Astrazeneca are working on this very thoughtfully.

Jason Gerberry: Okay. Thanks, so much.

Operator: The next question comes from Jay Olson from Oppenheimer. Please go ahead.

Brett: on what we do.

Jay Olson: Hey, congrats on all the progress and thanks for taking the question. Can you talk about your launch preparation for OLEZARSEN in FCS.? And how should we expect the launch uptake and eventual opportunity in FCS and also the early access program, how many patients you have? And will those patients switch over to commercial product soon after approval? Thank you.

Operator: We're going to want to get a buy-in on anything we do with respect to an earlier readout with the FDA, the EMA, before making any proclamations out there publicly. So timing is a bit uncertain right now, but rest assured that we in AstraZeneca are working on this very thoughtfully. Thanks so much.

Speaker Change #102: Launched uptake and eventual opportunity in Fcs. Also the early access program, how many patients you have and where those patients switch over to. Commercial product soon after approval. Thank you.

Speaker Change #103: Also the early access program, how many patients you have and where those patients switch over to. Commercial product soon after approval. Thank you.

Commercial product soon after approval. Thank you.

Richard Geary: Yes, thanks for your question. We're really pleased with the progress we're making and have continued to make, obviously a preparation started a couple of years ago with the medical affairs team. And subsequent to that, we built out all the commercial functions that you would expect, whether that's in our mark to market access, patient support that Kyle referenced with return of build-out and in our industry leading support effort for our patients. And to bring you right up to date, we've now started hiring and training our field teams ready to engage with customers. So the [inaudible] has gone very well and is certainly on track aligned with our regulatory progress, which with breakthrough designation has been, at this point, very timely. And that, we think, sets us up for a positive launch. And obviously to your question, specifically about the expanded access program, with all patients, let's be honest before that, who've been in our pivotal registration studies that are obviously patients that at launch. We hope to provide the opportunity to move on to commercial drug. And the EAP is now in the hands of our medical team and they're talking to customers today and patients are progressing through the administration, or the administrative side of getting access to OLEZARSEN through that program. So all in all, we are doing a lot of work, as you can imagine, but very much on track to be ready to launch just as soon as the FDA provides approval. Fingers crossed.

Speaker Change #105: We're really pleased with the progress we're making. <unk> continued to make. Obviously preparation started couple of years ago with our medical affairs team and subsequent to that we built out. All the commercial functions that you would expect whether that's marketing market access patient support. Carl referenced we're trying to build out. Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Operator: The next question comes from Jay Olsen from Oppenheimer. Please go ahead. Oh, hey, congrats on all the progress. And thanks for taking the question. Can you talk about your launch preparation for Olazarsan and FCS?

Brett: Thanks so much.

Brett: The next question comes from Jay Olsen from Oppenheimer. Please go ahead.

Speaker Change #104: <unk> continued to make. Obviously preparation started couple of years ago with our medical affairs team and subsequent to that we built out. All the commercial functions that you would expect whether that's marketing market access patient support. Carl referenced we're trying to build out. Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #104: Obviously preparation started couple of years ago with our medical affairs team and subsequent to that we built out. All the commercial functions that you would expect whether that's marketing market access patient support. Carl referenced we're trying to build out. Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Operator: And how should we expect the, launch uptake and eventual opportunity in the FCS. Also, the Early Access Program, how many patients you have, and will those patients switch over to commercial product soon after approval? Thank you. Yeah, thanks for your question.

Speaker Change #104: All the commercial functions that you would expect whether that's marketing market access patient support. Carl referenced we're trying to build out. Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #104: Carl referenced we're trying to build out. Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #104: Industry, leading support. For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Jay Olsen: Also, the Early Access Program, how many patients you have, and will those patients switch over to commercial product soon after approval? Thank you.

Speaker Change #104: For our patients and to bring you right up to date, we've managed started hiring and training. Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Operator: We're, we're really pleased with the progress we're making, and have continued to make. Obviously, our preparation started a couple of years ago with the medical affairs team. And subsequent to that, we built our, All the commercial functions that you would expect, whether that's, you know, marketing, market access, patient support, that Kyle referenced, we're trying to build out, you know, industry-leading support there for our patients. And that, we think, sets us up for a positive launch. Obviously, to your question specifically about the Expanded Access Program, we've got patients, let's be honest, before that, who've been in our pivotal registration studies that are obviously patients that launch.

Speaker Change #104: Our field teams. Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #104: Ready to engage. With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change: Yeah, thanks for your question. We're really pleased with the progress we're making and have continued to make. Obviously, our preparation started a couple of years ago with the medical affairs team, and subsequent to that, we've built out...

Speaker Change #104: With customers so. The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #106: The bill. It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #106: It's gone very well and is certainly on track aligns with our regulatory progress, which with breakthrough designation has been. But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #106: But at this point. Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change: All the commercial functions that you would expect, whether that's marketing, market access, patient support that Kyle referenced, we're trying to build out.

Speaker Change #106: Timely. Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Matt We think sets us up for a positive launch. Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #107: Obviously to your to your question specifically about the expanded access program, we got patients, let's be honest before that and we've been in. Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Brett: And to bring you right up to date, we've now started hiring and training our field teams.

Speaker Change #107: Pivotal registration studies. Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #107: Obviously patients at launch. We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Brett: [inaudible]

Speaker Change #107: We hope to provide the opportunity to move on to commercial drug. AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: AAP is. Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Now in the hands of our medical team and they're talking to customers today. <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: <unk>. Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Regressing through. The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: The administration. On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: On the administrative side of getting access to <unk> through that program. So all in all we are doing a lot of work as you can imagine. But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change: Obviously, to your question specifically about the Expanded Access Program, we've got patients, let's be honest, before that, who've been in our pivotal registration studies that are obviously patients that launch

Speaker Change #108: But very much on track to be ready to launch. Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: Just as soon as. The FDA. It provides approval fingers crossed.

Speaker Change #108: The FDA. It provides approval fingers crossed.

Speaker Change #108: It provides approval fingers crossed.

Operator: We hope to provide the opportunity to move on to commercial drug and the EAP is now in the hands of our medical team and they're talking to customers today and patients are progressing through the administration or the administrative side of getting access to OLSRs and through that program. So all in all, we are doing a lot of work as you can imagine. We're very much on track to be ready to launch just as soon as the FDA provides us with the vaccine. Okay, next question. The next question comes from Mike Holtz from Morgan Stanley. Please go ahead.

Brett P. Monia: Thanks, Jay. Next question, please.

Brett: We hope to provide the opportunity to move on to commercial drug, and the EAP is now

Jay: Jay next question please.

Operator: Next question comes from Mike Ulz from Morgan Stanley. Please go ahead.

Mike Ulz: Hey, guys, thanks for taking the question. Maybe just one on the neurology pipeline with Angelman sort of emerging as your lead programs. Can you maybe highlight what do you view as the next key opportunity there? And if there's any potential read-through from what you learned in Angelmans? Thanks.

Brett: in the hands of our medical team, and they're talking to customers today, and patients are progressing through.

Mike <unk>: Maybe just one on the neurology pipeline with Angelman is sort of emerging as your lead program can you maybe highlight what you view as the next key opportunity there and if theres any potential read through from what you've learned in England's thanks.

Eugene Schneider: Yes, sure. Happy to. Thanks for your questions. Certainly, we are delighted to have Angelman's service kind of the linchpin of the neuroscience portfolio, but it is a very rich portfolio following the Angelman Phase III program. Just to name a few paramount that balance currently, certainly the zilganersen, which is now fully enrolled and its pivotal study. As we recently announced, this is the next molecule that we're super excited about. It's an ultra-rare disease. It fits very well with our neurology portfolio. Those studies progressing wwll, there's great feedback from sites and investigators on kind of the quality of the study conduct. And behind zilganersen, of course, we are delighted to have our [inaudible] program progressing well. Our pre-owned program really kind of making great strides in first in human experiments that are now conducting. So we're looking forward to sharing lots of data with you over the coming months, and certainly years in that rich area of research and development for us. our wholly-owned neurology pipeline.

Brett: But very much on track to be ready to launch just as soon as the FDA provides approval. Fingers crossed.

Speaker Change #111: We are delighted to have Andrew minutes service kind of the linchpin of the neuroscience portfolio. A very rich portfolio following. So the interim phase III program. Just to name a few that are most of the bounce currently certainly the nursing, which is now fully enrolled in a pivotal study. Sure. As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

A very rich portfolio following. So the interim phase III program. Just to name a few that are most of the bounce currently certainly the nursing, which is now fully enrolled in a pivotal study. Sure. As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Jay: Jay, next question please.

Speaker Change #111: So the interim phase III program. Just to name a few that are most of the bounce currently certainly the nursing, which is now fully enrolled in a pivotal study. Sure. As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Jay: The next question comes from Mike Holtz from Morgan Family. Please go ahead.

Operator: Hey guys, thanks for taking the question. Maybe just one on the neurology pipeline, you know, with Angelman sort of emerging as your lead program. Can you maybe highlight, you know, what you view as the next key opportunity there? And if there's any potential read through from what you learned, Thanks for your questions.

Speaker Change #111: Just to name a few that are most of the bounce currently certainly the nursing, which is now fully enrolled in a pivotal study. Sure. As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Mike Holtz: Hey guys, thanks for taking the question. Maybe just one on the neurology pipeline, you know, with Angelman sort of emerging as your lead program. Can you maybe highlight, you know, what you view as the next key opportunity there, and if there's any potential read-through from what you learned in Angelman's? Thanks.

Speaker Change #111: Sure. As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: As we recently announced. This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: This molecule that we're super excited about it. In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: In ultra rare diseases fits very well with our. Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Operator: Certainly we are delighted to have Angelman as service, kind of the linchpin of the neuroscience portfolio, but it is a very rich portfolio following [inaudible] Just to name a few that are most advanced currently, certainly the Zilver Nursen, which is now fully enrolled in its pivotal study. As we recently announced, this is the next molecule that we're super excited about. It's an ultra-rare disease.

Speaker Change #111: Urology portfolio. The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change: Yeah, sure, happy to. Thanks for your question. Certainly, we are delighted to have Angelman as service, kind of the linchpin of the neuroscience portfolio. But it is a very rich portfolio following

Speaker Change #111: The study is progressing well. Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: Great feedback from sites and investigators. The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: The quality of the study conduct. And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

And behind so the nurse and of course, we are delighted to have. Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Thoughts AOS program progressing well, our pre owned program really making great strides in first in human experiments that we're now conducting so. So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Jay: of the Angel Montage III program.

Speaker Change: Just to name a few that are most advanced currently, certainly the Zilver Nursen, which is now fully enrolled in its pivotal study.

Speaker Change #111: So we're looking forward to sharing. Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: Lots of data with you over the coming months. And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change: As we recently announced, this is the next molecule that we're super excited about. It's an ultra-rare disease. It fits very well with our neurology portfolio.

Speaker Change #111: And certainly years in that. Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Speaker Change #111: Rich. Area of research and development for Us. Our wholly owned neurology pipeline

Operator: It fits very well with our neurology portfolio. The study's progressing well. There's great feedback from sites and investigators on kind of the quality of the study conduct, and behind Logan Narsin, of course, we are delighted to have. Our FOSS ALS program progressing well, our PRE-ON program really making great strides in first-in-human experiments that we're now conducting.

Speaker Change #111: Area of research and development for Us. Our wholly owned neurology pipeline

Eugene: Our wholly owned neurology pipeline thanks Eugene.

Our wholly owned neurology pipeline

Brett P. Monia: Our wholly-owned neurology pipeline--thanks, Eugene--is positioned to grow and expand in addition to the programs that are in the clinic today, we expect to start two additional wholly-owned neurology programs by end of this year, and more next year, for both rare as well as larger indications, more highly prevalent indications. I also want to highlight the great progress we're making to extend our leadership technologically in neurology. Our most advanced backbone chemistry MSPA will enter--is expected to clinical development for a CNS indication later this year, which is focused on reducing dose frequency very meaningfully. We're also making great progress in traversing the blood-brain barrier using subcutaneous or intravenous administration--in frequent administration. And we're looking forward to maybe our first candidate overcome the BBB early 2025, and we're looking forward to talking about that as well. So CNS is here now and we're leading this space, and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike. Next question please.

thanks Eugene. <unk> to grow and expand in addition to the programs that are in the clinic today, we expect to start two additional <unk>. Wholly owned neurology programs by the end of this year. And more next year. For both. Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: <unk> to grow and expand in addition to the programs that are in the clinic today, we expect to start two additional <unk>. Wholly owned neurology programs by the end of this year. And more next year. For both. Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Speaker Change: The study is progressing well. There's great feedback from sites and investigators on kind of the quality of the study conduct.

Eugene: Wholly owned neurology programs by the end of this year. And more next year. For both. Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Speaker Change: And behind Logan Nurson, of course, we are delighted to have...

And more next year. For both. Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: For both. Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: Rare as well as larger indications. So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Speaker Change: Our FOSS ALS program progressing well, our PREON program really making great strides in first-in-human experiments that we're now conducting.

Eugene: So highly prevalent indications I also want to highlight the great progress, we're making to extend our leadership technologically and neurology. R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Operator: We're looking forward to sharing. Lots of data with you over the coming months. Unknown Executive, Huidong Wang, Jason Gerberry, Eugene Schneider, Elizabeth Hougen, Brett Monia, Kyle Jenne, Elizabeth Hougen, Brendan Smith, Onaiza Cadoret, Eugene Schneider, Jason Gerberry, Eugene Schneider, area of research and development.

Jay: So, we're looking forward to sharing lots of data with you over the coming months and certainly years in that rich area of research and development for us.

Eugene: R. Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: Our most advanced backbone chemistry MSP. Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Enter is expect to enter clinical development and see for a CNS indication later this year, which is which is focused on reducing dose frequency. Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Operator: Our wholly-owned neurology pipeline, thanks Eugene, is positioned to grow and expand. In addition to the programs that are in the clinic today, we expect to start two additional wholly-owned neurology programs by the end of this year and more next year for both rare as well as larger indications, more highly prevalent indications. I also want to highlight the great progress we're making to extend our leadership technologically in neurology. Our most advanced backbone chemistry, MSPA, is expected to enter clinical development and seek for a CNS indication later this year, which is focused on reducing dose frequency very meaningfully.

Eugene: Our whole young neurology pipeline, thanks Eugene, is positioned to grow and expand in addition to the programs that are in the clinic today. We expect to start two additional whole young neurology programs by the end of this year and more next year.

Eugene: Very meaningfully we're also making great progress and traversing the blood brain barrier, using subcutaneous or intravenous administration infrequent and administration. And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: for both rare as well as larger indications, more highly prevalent indications.

Eugene: And we're looking forward to maybe our first candidates overcoming the BBB. Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: Early 2025, and we're looking forward to talking about that as well. So CNS is here and now and we are. We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: I also want to highlight the great progress we're making to extend our leadership technologically in neurology.

Eugene: Our most advanced backbone chemistry, MSPA, is expected to enter clinical development and seek for a CNS indication later this year, which is focused on reducing dose frequency very meaningfully.

Eugene: We're leading in this space and we continue to expect to extend our leadership position in CNS going forward. Thanks, Mike next question please.

Eugene: Thanks, Mike next question please.

Operator: The next question comes from Larry--I'm Sorry, excuse me, Gary Nachman from Raymond James. Please go ahead.

Operator: We're also making great progress in traversing the blood-brain barrier using subcutaneous or intravenous administration, infrequent administration, and we're looking forward to maybe our first candidate overcoming the BBB early 2025, and we're looking forward to talking about that as well. She are now and we're.

Eugene: We're also making great progress in traversing the blood-brain barrier using subcutaneous or intravenous administration, infrequent administration.

Gary Nachman: Great, thanks, guys. For Donnie, when you submit the NDA, what indication will you be looking for in the label and are you optimistic the switch data will actually be included on the label, which will be so important for these HAE patients. Any chance you could get a priority review? Or is that likely a standard review? And when will you start building out that commercial team? How much could you fully leverage what you're doing currently with OLEZARSEN? Thanks.

Speaker Change #112: Dani. When you submit the NDA what indications you would be looking for in the label and are you optimistic the switch data will actually be included on the label, which will be so important for these patients. Any chance you could get a priority review or is it likely a standard review. When will you start building out that commercial team. How much could you fully leverage what youre doing currently with <unk>. Thanks.

Gary Nachman: When you submit the NDA what indications you would be looking for in the label and are you optimistic the switch data will actually be included on the label, which will be so important for these patients. Any chance you could get a priority review or is it likely a standard review. When will you start building out that commercial team. How much could you fully leverage what youre doing currently with <unk>. Thanks.

Eugene: And we're looking forward to maybe our first candidate overcoming the BBB early 2025. And we're looking forward to talking about that as well. So CNS is here now, and we're...

Speaker Change #114: Any chance you could get a priority review or is it likely a standard review. When will you start building out that commercial team. How much could you fully leverage what youre doing currently with <unk>. Thanks.

Operator: Thank you for reading this space and we continue to expect to extend our leadership. Thanks, Mike. Next question, please. The next question comes from Gary Nachman from Raymond James. Please go ahead.

Speaker Change #114: When will you start building out that commercial team. How much could you fully leverage what youre doing currently with <unk>. Thanks.

Eugene: We're leading in this space and we continue to expect to extend our leadership position.

Speaker Change #115: How much could you fully leverage what youre doing currently with <unk>. Thanks.

and CNN's Colin Pollard.

Colin Pollard: Thanks, Mike. Next question, please.

Speaker Change #116: Thanks, Gary I'll take the first couple of questions and then Jonathan could touch on the build out of the commercial team with regard to the indication of course.

Brett P. Monia: Thanks, Gary. Eugene will take the first couple of questions and then Jonathan could touch on the build-out of the commercial team.

Brett: The next question comes from Gary Nachman from Raymond James. Please go ahead.

Operator: Great. Thanks, guys. For Donny, when you submit the NDA, what indication will you be looking for on the label? And are you optimistic the switch data will actually be included on the label, which will be so important for these HAU patients? Any chance you could get a priority review, or is it likely a standard review?

Eugene Schneider: With regard to the indication, of course, we're seeking a broad indication for prophylaxis of attacks in hereditary angioedema, and we're pretty comfortable with how things are progressing. Obviously, it is pretty determined what the final label looks like and the indications. We are some--sorry, what was the second part of the sub-question--switch data, sorry--yes, along the same line, again, it's really early to speculate on what the final label is, we will do our best to. We believe our program--our pivotal program is very comprehensive and we also believe that the data that we collected and the switch populations is important for physicians to be aware of. So we'll make sure that this data is shared broadly, whether it's publication or it ends up in the label, we can't really speculate today.

Gary Nachman: Great. Thanks, guys. For Donny, when you submit the NDA, what indication will you be looking for on the label? And are you optimistic the switch data will actually be included on the label, which will be so important for these HAE patients?

Jonathan: We're seeking a broad indication for prophylaxis of attacks and renter angioedema. We're pretty comfortable with. Things are progressing obviously. To be determined what the final label looks like indications paper. We are. Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Jonathan: We're pretty comfortable with. Things are progressing obviously. To be determined what the final label looks like indications paper. We are. Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Jonathan: Things are progressing obviously. To be determined what the final label looks like indications paper. We are. Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Jonathan: To be determined what the final label looks like indications paper. We are. Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change: Any chance you could get a priority review, or is it likely a standard review? And when will you start building out that commercial team? How much could you fully leverage what you're doing currently with Ola Darson? Thanks.

Operator: And when will you start building out that commercial team? And how much could you fully leverage what you're doing currently with Ola Darson? Thanks, Gary. Eugene will take the first couple of questions, and then Jonathan can touch on the build-out of the commercial. Yeah, with regard to the indication, of course, we're seeking a broad indication for prophylaxis of attack. Director Andrea Dima and we're pretty comfortable with how things are progressing obviously it is, to be determined what the final label was, we are, Sorry, what was the second part of the subquestion? We expect to have switch data. The switch data, that's right.

Jonathan: We are. Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change #118: Sorry, what was the second part of the sub question, we expect to add switch data the switch data and we'll try it. Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change #118: Along the same line again, it's really early to speculate on what the final label as we will do our best to. We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change: Thanks Gary. Eugene will take the first couple of questions and then Jonathan can touch on the build out of the commercial team.

Speaker Change #118: We believe our program. Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change #118: Our pivotal program is very comprehensive them. We also believe that the data that we collected and switch. <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Eugene: With regard to the indication, of course, we're seeking a broad indication for prophylaxis of attacks in hereditary angioedema, and we're pretty comfortable with how things are progressing. Obviously, it is to be determined what the final label looks like in the indication space.

Speaker Change #118: <unk>, which populations important for physicians to be aware of so we will make sure that this. Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change #118: Data is shared broadly whether its publication or it ends up in the label. Can't really speculate today.

Speaker Change #119: Can't really speculate today.

Brett P. Monia: Yeah, and I'll just touch on that a little bit more, Gary, on the switch data is very important we believe from a safety standpoint, which we think bodes very well for, including in the label. I mean, these patients switch all the time, right? And actually having data that informs physicians on how to safely switch patients, such that they avoid getting our GAAP and our protection against HAE attacks is going to be very important. And we think that will--and of course, the FDA is focused on safety and protection against disease progression. So we think that bodes very well for us to get in the label. But as Eugene said, it's some risky to get ahead of the regulators on what the label will look like. But we think that we have a pretty good shot at that. Jonathan, how's the launch prep going?

Speaker Change: We are, sorry, what was the second part of the subquestion? We expect to have switched data. Switched data, that's right. And yeah, along the same line, again, it's really early to speculate on what the final label is. We will do our best to, we believe our program...

Speaker Change #119: Touch on that. A little bit more Gary. The switch data. Is very important and we believe from a safety standpoint, which we think bodes very well for including it in the label I mean, these patients switch all the time right and and. Actually having data. That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Speaker Change #120: A little bit more Gary. The switch data. Is very important and we believe from a safety standpoint, which we think bodes very well for including it in the label I mean, these patients switch all the time right and and. Actually having data. That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Operator: And yeah, along the same line, again, it's really early to speculate on what the final label is. We will do our best to. We believe our program. Our pillow program is very comprehensive, and we also believe that the data that we collected in the switch populations is important for physicians to be aware of, so we'll make sure that, Data is shared broadly, whether it's publication or it ends up in the label. I can't really speculate.

Gary Nachman: The switch data. Is very important and we believe from a safety standpoint, which we think bodes very well for including it in the label I mean, these patients switch all the time right and and. Actually having data. That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Gary Nachman: Is very important and we believe from a safety standpoint, which we think bodes very well for including it in the label I mean, these patients switch all the time right and and. Actually having data. That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Speaker Change: Our pillow program is very comprehensive, and we also believe that the data that we collected in the switch populations is important for physicians to be aware of, so we'll make sure that this...

Gary Nachman: Actually having data. That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Gary Nachman: That informs physicians on how to safely switch patients. It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Speaker Change #121: It's that the avoided. GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Speaker Change #121: GAAP in their protection against GE taxes going to be very important and we think that will and of course. The FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label, but as Eugene said. We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Eugene: Data is shared broadly, whether it's publication or it ends up in the label, we can't really speculate today.

Operator: Yeah, I'll just touch on that a little bit more, Gary. You know, the switch data is very important, we believe, from a safety standpoint, which we think bodes very well for including it in the label. I mean, these patients switch all the time, right?

Speaker Change: Yeah, and I'll just touch on that.

Speaker Change: A little bit more, Gary. You know, the switch data...

Speaker Change #122: We don't. It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Gary Nachman: is very important, we believe, from a safety standpoint, which we think bodes very well for including it in the label. I mean, these patients switch all the time, right? And actually having data that informs physicians on how to safely switch patients.

Speaker Change #122: It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom bodes prep is going well.

It's risky to get ahead of regulators on what the label looks like but we think that we have a pretty good shot at that Jonathan has much prepcom

Operator: And actually having data that informs physicians on how to safely switch patients such that they avoid getting a gap in their protection against HAE attacks is gonna be very important. And we think that will, and of course, the FDA is focused on safety and protection against disease progression. So we think that that bodes very well for us to get in the label. But as Eugene said, it's risky to get ahead of regulators on what a label will look like.

Jonathan Birchall: Launch prep is going well. And as you could imagine, this is coming so hot on the heels of the potential as the launch that we talked about it. But the launch prep on the commercial side for Doni is well advanced, there are a lot of capabilities that we built and for OLEZARSEN, we can leverage for Doni, whether that's the medical affairs function, first and foremost, that's been done established product trials, and that's now leading in the HAE space, we've got brand teams, access teams, building out the value dossiers and patient services is also well advanced to ready to support patients in HAE space, and omnichannel as well, a capability that we feel very confident that we built well at Ionis now, and is a capability that's very applicable close to the FCS launch, but also the HAE launch service. So, there's a lot of synergy going on the commercial side, albeit a lot of that is being appropriately built and to best serve each of those launches in the markets and the challenges that they present.

Speaker Change #123: As you can imagine this is coming. On the heels of the potential that's awesome launch that we talked about it but the launch prep on the commercial side for <unk> is well advanced but a lot of capabilities that we built. For all of US are awesome that we can. Leverage for Dani, whether that's the medical affairs function first and foremost that's been well established protocols on what's now leaning in. In the HIV space, we've got brand themes access teams building out the value dossiers. Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Speaker Change #124: On the heels of the potential that's awesome launch that we talked about it but the launch prep on the commercial side for <unk> is well advanced but a lot of capabilities that we built. For all of US are awesome that we can. Leverage for Dani, whether that's the medical affairs function first and foremost that's been well established protocols on what's now leaning in. In the HIV space, we've got brand themes access teams building out the value dossiers. Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Eugene: such that they avoid getting a gap in their protection against HAE attacks is going to be very important and we think that will and of course the FDA is focused on safety.

Speaker Change #124: For all of US are awesome that we can. Leverage for Dani, whether that's the medical affairs function first and foremost that's been well established protocols on what's now leaning in. In the HIV space, we've got brand themes access teams building out the value dossiers. Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Leverage for Dani, whether that's the medical affairs function first and foremost that's been well established protocols on what's now leaning in. In the HIV space, we've got brand themes access teams building out the value dossiers. Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Speaker Change: and protection against disease progression. So we think that that bodes very well for us to get in the label. But as Eugene said,

Eugene: It's risky to get ahead of regulators on what a label will look like, but we think that we have a pretty good shot at that.

Speaker Change #124: In the HIV space, we've got brand themes access teams building out the value dossiers. Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Operator: But we think that we have a pretty good shot at that. Jonathan, how's the launch prep going? Launch prep is going well. As you can imagine, this is coming hot on the heels of the potential Olusarsan launch that we've talked about. But the launch prep on the commercial side for Donny is well advanced.

Jay: Jonathan, how's the water prep going?

Speaker Change #124: Patient services is also. While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Jonathan: Launch prep is going well. As you can imagine, this is coming hot on the heels of the potential Olisarson launch that we talked about. The launch prep on the commercial side for Donny is well advanced. There are a lot of capabilities that we've built.

Speaker Change #124: While advanced are ready to support patients and. Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Speaker Change #124: Space and. Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Speaker Change #124: Omnichannel as well. Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Operator: There are a lot of capabilities that we've built for Olusarsan that we can leverage for Donny, whether that's the medical affairs function, first and foremost, that's been well established for Olusarsan that's now leading in the HAE space. We've got brand teams, access teams building out the value dossiers. Patient services is also well advanced and ready to support patients in the HAE space. And Omnichannel as well is a capability that we feel very confident that we've built well with Ionis now and is a capability that's very applicable both to the FCS launch, but also the HAE launch.

Speaker Change #124: Capability, but we feel very confident that we have been well at <unk> now is a capability that's very applicable both to the FCS launch, but also the entry. So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Jonathan: for all his awesome work that we can...

Jonathan: leverage for Donnie whether that's the medical affairs function first and foremost that's been well established for all of us and that's now leaning in

Speaker Change #124: So there's that. A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Speaker Change #124: A lot of synergy going on on the commercial side, albeit a lot of that is being appropriately built. To best serve each of each of those launches in the market some of the challenges that they present.

Jonathan: in the HAE space. We've got brand teams, access teams building out the value dossiers.

Speaker Change #124: To best serve each of each of those launches in the market some of the challenges that they present.

Jay: Patient Services is also well-advanced and ready to support patients in the HAE space. And Omni-Channel as well is a capability that we feel

Brett P. Monia: We're also very pleased with the progress [inaudible] making for submission and preparing for launch in Europe. So stay tuned for that as well. Next question, please.

Speaker Change #124: With the progress <unk> is making. Pretty submission and preparing for launch in Europe, So stay tuned for that as well. Next question please.

Speaker Change #124: Pretty submission and preparing for launch in Europe, So stay tuned for that as well. Next question please.

Speaker Change #125: Next question please.

Operator: The next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Jay: very confident that we've been built well at IONIS now and is a capability that's very applicable both to the FCS launch but also the HAE launch.

Salveen Richter: Good morning. Thanks for taking--or good afternoon, thanks for taking my question. Could you just speak to the work you're doing here on oligos with next-generation backbones and the other modalities you're looking at, and when these programs might enter the clinic? Thank you.

Jay: There's a lot of synergy there on the commercial side, albeit a lot of that is being appropriately built to best serve each of those launches and the markets and the challenges that they present.

Speaker Change #128: These programs might enter the clinic. Thank you.

Eric Swayze: Sure. So, as Brett mentioned earlier, the first compound that incorporates our MSPA backbone will enter the clinic for a neurology indication later this year. And the objectives there are to trying to extend the dosing interval with the enhanced stability of that backbone, which it provides, and we'll see how it performs. We all we also have a compound in development with a partner, AstraZeneca that uses our buy cycle program to deliver our drug to the cardiac muscle in this case. That program is moving forward and we look to start [inaudible] this year, and that's progressing nicely. And that's an SIRNa coupled to the bi-cycle program. And we also have it in internal SIRNa program for a follow-on indication for liver targets that we anticipate getting headed towards development this year. And then beyond that, we've been making some really nice progress in our blood-brain worth, both with our bi-cycle collaboration, and also the [inaudible] collaboration, which we announced earlier this year or very late last year. And we had some scientists from the team present some of that data at a recent tides meeting, with early mouse data in Vectura's collaboration, it looks fantastic. And we'll continue to provide some more data updates. And hopefully, if everything goes according to plan, we can get some molecules that cross the blood-brain barrier program for our new wholly-owned neurology pipeline into development early next year.

Jay: We're also very pleased with the progress ATSUKA is making for submission and preparing for launch in Europe, so stay tuned for that as well.

Speaker Change #130: Compounded incorporates our MSP a backbone. Enter the clinic for neurology indications later this year and. The objectives, there are to try and extend the dosing interval with the enhanced stability of that backbone, which which it provides and we'll see how it performs. We also have a compound in development with our partner Astrazeneca that uses our lifecycle program to deliver. Drug to the cardiac muscle in this case. That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #131: Enter the clinic for neurology indications later this year and. The objectives, there are to try and extend the dosing interval with the enhanced stability of that backbone, which which it provides and we'll see how it performs. We also have a compound in development with our partner Astrazeneca that uses our lifecycle program to deliver. Drug to the cardiac muscle in this case. That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Operator: So there's a lot of synergy there on the commercial side, albeit a lot of that is being appropriately built to best serve each of those launches and the markets and the challenges that they present. We're also very pleased with the progress ATSUCA is making for submission and preparing for launch in Europe. So stay tuned for that. Next question, please. The next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Good morning, thanks for taking, or good afternoon, thanks for taking my question.

Speaker Change: Next question, please.

Speaker Change #132: The objectives, there are to try and extend the dosing interval with the enhanced stability of that backbone, which which it provides and we'll see how it performs. We also have a compound in development with our partner Astrazeneca that uses our lifecycle program to deliver. Drug to the cardiac muscle in this case. That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change: The next question comes from Salveen Richter from Goldman Sachs. Please go ahead.

Salveen Richter: Good afternoon. Thanks for taking my question. Could you just speak to the work you're doing here on oligos with next generation backbones and the other modalities you're looking at and when these programs might enter the clinic? Thank you.

Operator: Could you just speak to the work you're doing here on oligos with next-generation backbones and the other modalities you're looking at and when these programs might enter the clinic? Thank you. Sure, so as Brett mentioned earlier, the first compound that incorporates our MSPA backbone will enter the clinic for a neurology indication later this year and, The objectives there are to try and extend the dosing interval with the enhanced stability of that backbone, which it provides, and we'll see how it performs. We also have a compound in development with a partner, AstraZeneca, that uses our Bi-Cycle program to deliver a drug to the cardiac muscle in this case.

Speaker Change #132: We also have a compound in development with our partner Astrazeneca that uses our lifecycle program to deliver. Drug to the cardiac muscle in this case. That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: Drug to the cardiac muscle in this case. That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: That program. As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: As moving forward and we look to start RMB talks this year and. That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change: Sure, so as Brett mentioned earlier, the first compound that incorporates our MSPA backbone will enter the clinic for a neurology indication later this year and

Speaker Change #132: That's progressing nicely and Thats, an SRO coupled. Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: Coupled to the buy cycle program. And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: And we also have. And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: And internal <unk> program. For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Salveen Richter: The objectives there are to try and extend the dosing interval with the enhanced stability of that backbone, which it provides, and we'll see how it performs. We also have a compound in development with a partner, AstraZeneca, that uses our Bi-Cycle program to deliver

Speaker Change #132: For a follow on indication for a liver target, we anticipate getting headed towards development. This year. And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

And then beyond that we've been making some really nice progress in our blood brain worth. Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: Both with our bicyclic collaboration. And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: And also the victorious collaboration which we. Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Salveen Richter: drug to the cardiac muscle in this case.

Operator: That program.., is moving forward, and we look to start IND talks this year, and that's progressing nicely, and that's an siRNA coupled to the bi-cycle program. And we also have an internal siRNA program for a follow-on indication for liver target that we anticipate getting headed towards development this year. And then beyond that, we've been making some really nice progress in our blood-brain work, folks with our bicycle collaboration, and also the Vectoris collaboration, which we announced earlier this year, very late last year. And we had some scientists from the team present some of that data at a recent TIDES meeting with early mouse data in Vectoris collaboration. It looks fantastic.

Speaker Change #132: Announced. Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: Earlier, this year and very late last year, and we had some scientists from the team presents some of that data at a recent <unk> meeting with early loss data in Victoria collaborations looks fantastic and we will continue to provide some more data updates and hopefully. If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Salveen Richter: is moving forward and we look to start IND Talks this year.

Salveen Richter: That's progressing nicely, and that's an siRNA coupled to the bi-cycle program. And we also have an internal siRNA program for a follow-on indication for liver target that we anticipate getting headed towards development this year.

If everything goes according to plan, we can get some molecules that cross the blood brain barrier program for our wholly owned neurology pipeline into development. Early early next year,

Speaker Change #132: Early early next year, Thanks, Eric and I will just add to that.

Early early next year,

Salveen Richter: And then beyond that, we've been making some really nice progress in our blood-brain work.

Brett P. Monia: Thank Eric, and I'll just add to that. So I mean, you can expect to see in the not-too-distant future, new programs advancing towards development, focused on neuromuscular diseases, skeletal muscle, specifically to further extend our leadership in neurology. And also, we're pleased with the progress we're making with Meta genomics on gene editing. We have several programs there that are advancing very nicely preclinically, and I think next year could be a very informative year, very interesting year in our gene editing program with respect to new information coming out, as to what our strategy is, and what our first molecules will be. So stay tuned for that. We're making great progress across the board in diversifying and expanding our technological capabilities. And with that, I think we have time for one more question.

Speaker Change #133: I mean, you can expect to see in the not too distant future. New programs advancing towards development focused on neuromuscular diseases in skeletal muscle specific cleantech further extend our leadership in neurology. And also we are pleased with the progress, we're making with meta genomics. On gene editing, we have several programs there that are advancing very nicely pre clinically and I think next year could be a very informative year very interesting year. And our gene editing program with respect to new information coming out on as to what our strategy is and what our first molecules will be so stay tuned for that we're making great progress across the board in diversifying and expanding our technological capabilities. And with that I think we have time for one more question.

Salveen Richter: both with our bicycle collaboration.

Speaker Change #134: New programs advancing towards development focused on neuromuscular diseases in skeletal muscle specific cleantech further extend our leadership in neurology. And also we are pleased with the progress, we're making with meta genomics. On gene editing, we have several programs there that are advancing very nicely pre clinically and I think next year could be a very informative year very interesting year. And our gene editing program with respect to new information coming out on as to what our strategy is and what our first molecules will be so stay tuned for that we're making great progress across the board in diversifying and expanding our technological capabilities. And with that I think we have time for one more question.

Salveen Richter: and also the Vectoris collaboration, which we...

Salveen Richter: Announced earlier this year, very late last year, and we had some scientists from the team present some of that data at a recent TIDES meeting with early mouse data in the Vectoris collaboration, it looks fantastic, and we'll continue to provide some more data updates and hopefully

Speaker Change #135: And also we are pleased with the progress, we're making with meta genomics. On gene editing, we have several programs there that are advancing very nicely pre clinically and I think next year could be a very informative year very interesting year. And our gene editing program with respect to new information coming out on as to what our strategy is and what our first molecules will be so stay tuned for that we're making great progress across the board in diversifying and expanding our technological capabilities. And with that I think we have time for one more question.

Operator: And we'll continue to provide some more data updates. And hopefully, if everything goes according to plan, we can get some molecules that cross the blood-brain barrier program for our whole neurology pipeline into development early next year. Thanks, Eric.

On gene editing, we have several programs there that are advancing very nicely pre clinically and I think next year could be a very informative year very interesting year. And our gene editing program with respect to new information coming out on as to what our strategy is and what our first molecules will be so stay tuned for that we're making great progress across the board in diversifying and expanding our technological capabilities. And with that I think we have time for one more question.

Salveen Richter: If everything goes according to plan, we can get some molecules that cross the blood-brain barrier program for our whole neurology pipeline into development early next year.

Speaker Change #135: And our gene editing program with respect to new information coming out on as to what our strategy is and what our first molecules will be so stay tuned for that we're making great progress across the board in diversifying and expanding our technological capabilities. And with that I think we have time for one more question.

Operator: And I'll just add to that, Salveen, you can expect to see, in the not-too-distant future, new programs advancing towards development focused on neuromuscular diseases, skeletal muscles specifically, to further extend our leadership in neurology. And also, we're pleased with the progress we're making with metagenomy on gene editing. We have several programs there that are advancing very nicely preclinically. And I think next year could be a very informative year, a very interesting year in our gene editing program with respect to new information coming out as to what our strategy is and what our first molecule is. Stay tuned for that.

Eric Swayze: Thanks, Eric, and I'll just add to that, Salveen, you can expect to see in the not-too-distant future new programs advancing towards development focused on neuromuscular diseases, skeletal muscles specifically, to experiment.

And with that I think we have time for one more question.

Operator: The next question comes from Konstant Biliouris from BMO Capital Markets. Please go ahead.

Salveen Richter: to extend our readership in neurology.

Speaker Change: And also, we're pleased with the progress we're making with metagenome.

Konstant Biliouris: Hello. Thanks for taking our question and congrats on the progress. Can you talk a little bit about the cardio transform enrolled population, and specifically the differences between the geographies and the follow up from the originally enrolled population, and the population who were enrolled after the changes you made to the statistical design. And if you expect any impact from the differences between these two populations? Thank you.

Speaker Change: on gene editing. We have several programs there that are advancing very nicely preclinically.

Speaker Change #136: Right. How do we attack enrolled population and specifically the differences between the geographies and the follow up from the original enrolled population and the population who. Well overall after the changes you made to the statistical design. And if you expect any impact from the differences between these two populations.

Speaker Change: And I think next year could be a very informative year, a very interesting year in our gene editing program with respect to new information coming out as to what our strategy is and what our first molecules will be.

Speaker Change #138: How do we attack enrolled population and specifically the differences between the geographies and the follow up from the original enrolled population and the population who. Well overall after the changes you made to the statistical design. And if you expect any impact from the differences between these two populations.

Operator: We're making great progress across the board in diversifying and expanding our technological. And with that, I think we have time for one more question. The next question comes from Kostas Biliouris from BMO Capital Markets. Please go ahead.

Speaker Change: So stay tuned for that. We're making great progress across the board in diversifying and expanding our technological capabilities.

Speaker Change #139: Well overall after the changes you made to the statistical design. And if you expect any impact from the differences between these two populations.

Speaker Change: And with that, I think we have time for one more question.

Speaker Change #140: And if you expect any impact from the differences between these two populations.

Operator: Hello, thanks for taking our question and congrats on the progress. Can you talk a little bit about the cardio-transformed enrolled population and specifically the differences between the geographies and the follow-up from the originally enrolled population and the population who.., were enrolled after the changes you made to the statistical design, and if you expect any impact from the differences between these two populations. Thank you. Thanks, Kostas. So we, of course, haven't shared the demographics for our CardioTransform study yet.

Speaker Change: The next question comes from Kostas Biliouris from BMO Capital Markets. Please go ahead.

Brett P. Monia: Thanks, Konstant. So we, of course, haven't shared the demographics for our cardio transform study yet. We look forward to doing that in the future. We really are pleased with the enrollment in this study. And as we've said, we have a nice balance in this big study, the largest study ever conducted in TTR cardiomyopathy, nice balance between monotherapy patients as well as patients on combination treatment. We're also very pleased with very small percentages are dropping in families and study. It's going exactly as planned. We're pleased with the [inaudible] percentages of patients we have with [inaudible] Health Class one, two and three in the study. And everything we have seen that has come out in this space with respect to other people's patient demographics supports our decision to expand our study to take to account for a patient population that's been diagnosed much earlier in their disease. So, we couldn't be more pleased with the way the study is going, including our patient demographics. So, thanks for the question, Konstant. And I think we have--it's time to wrap things up. I'm really, really want to thank everybody who joined us today for your participation and your questions. We're very proud of everything we've accomplished this past quarter, first half of this year, and we plan to build on this momentum to achieve even greater successes in the second half of this year. And we're very much looking forward to providing updates on the progress we continue to make this year as well as into next year. So thank you very much, everybody, and have a great day.

Speaker Change #142: Of course, I haven't shared the demographics for our cardio transform study we look forward to doing that in the future. We really are pleased with the enrollment. In this study. And. And as we've said we have a nice balance in this in this big study the largest study ever conducted in <unk> cardiomyopathy nice bounce between monotherapy patients as growers. Patients on combination treatment. We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Kostas Biliouris: Hello, thanks for taking our question and congrats on the progress. Can you talk a little bit about the cardio-transformed enrolled population and specifically the differences between the geographies and the follow-up from the originally enrolled population and the population who...

Speaker Change #142: In this study. And. And as we've said we have a nice balance in this in this big study the largest study ever conducted in <unk> cardiomyopathy nice bounce between monotherapy patients as growers. Patients on combination treatment. We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: And. And as we've said we have a nice balance in this in this big study the largest study ever conducted in <unk> cardiomyopathy nice bounce between monotherapy patients as growers. Patients on combination treatment. We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: And as we've said we have a nice balance in this in this big study the largest study ever conducted in <unk> cardiomyopathy nice bounce between monotherapy patients as growers. Patients on combination treatment. We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change: were enrolled after the changes you made to the statistical design.

Speaker Change #142: Patients on combination treatment. We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: We're also very pleased with. Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change: and if you expect any impact from the differences between these two populations. Thank you.

Very small percentages or drop ins into parameters in the study it's going exactly as planned we are pleased with the Mac with the percentages of patients we have with New York Health class, one two and three in the study. And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Operator: We look forward to doing that in the future. We really are pleased with the enrollment in this study. And as we've said, we have a nice balance in this big study, the largest study ever conducted in PTR cardiomyopathy, nice balance between monotherapy patients as well as, Patients on Combination Treatment. We're also very pleased with very small percentages of drop-ins and families in the study. It's going exactly as planned. We're pleased with the percentages of patients we have with New York Health Class 1, 2, and 3 in the study.

Speaker Change: Thanks, Kostas. So, we, of course, haven't shared the demographics for our Cardiac Transform study yet. We look forward to doing that in the future. We really are pleased with the enrollment in the study, and as we've said, we have a nice balance.

Speaker Change #142: And. We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: We everything we've seen. That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: That has come out in this space with respect to other People's patient demographics supports our decision tree. Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change #142: Expand our study to take into account for a patient population that's been diagnosed. Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change: in this big study, the largest study ever conducted in UDT care cardiomyopathy, nice balance between monotherapy patients as well as...

Speaker Change #142: Much earlier in their disease so. <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change: and patients on combination treatment.

Speaker Change #142: <unk>. We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Brett P. Monia: So, thanks for the question, Konstant. And I think we have--it's time to wrap things up. I'm really, really want to thank everybody who joined us today for your participation and your questions. We're very proud of everything we've accomplished this past quarter, first half of this year, and we plan to build on this momentum to achieve even greater successes in the second half of this year. And we're very much looking forward to providing updates on the progress we continue to make this year as well as into next year. So thank you very much, everybody, and have a great day.

Speaker Change #142: We couldn't be more pleased with the with the way the study is going including our our patient demographics. Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Speaker Change: We're also very pleased with, you know, very small percentages of drop-ins and families in the study. It's going exactly as planned. We're pleased with the percentages of patients we have with New York Health Class 1, 2, and 3 in the study.

Cosmos: Thanks for the question Cosmos. It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Cosmos: It's time to wrap things up Im really really want to thank everybody who joined US today for your participation and your questions. We're very proud of everything we've accomplished this past quarter and first half of this year. And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Operator: Everything we've seen that has come out in this space with respect to other people's, We couldn't be more pleased with the way the study is going, including our patient demographics. Thanks for the question, Kostas, and I think it's time to wrap things up. I really, really want to thank everybody who joined us today for your participation and your questions. We're very proud of everything we've accomplished this past quarter, first half of this year.

Speaker Change: and you know we everything we've seen that has come out in this space with respect to other people's patient demographics supports our decision to expand our study to take into account for a patient population that's being diagnosed

Cosmos: And we plan. Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Cosmos: Plan to build on this momentum. To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

Cosmos: To achieve even greater successes in the second second half of this year and we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So thank you very much everybody and have a great day.

much earlier in their disease. So, we couldn't be more pleased with the way the study is going, including our patient demographics.

Operator: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Speaker Change: Thanks for the question, Kostas. I think it's time to wrap things up. I really want to thank everybody who joined us today for your participation and your questions. We're very proud of everything we've accomplished this past quarter, the first half of this year.

Operator: And we're planning to build on this momentum to achieve even greater successes in the second half of this year. And we're very much looking forward to providing you.., on the progress we continue to make this year as well as into next year. So, thank you very much everybody and have a great. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect. Goodbye.

Speaker Change: And we're planning to build on this momentum to achieve even greater successes in the second half of this year. And we're very much looking forward to providing you updates on the progress we continue to make this year as well as into next year. So, thank you very much everybody and have a great day.

Speaker Change: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

Speaker Change: Goodbye.

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