Q1 2024 Ionis Pharmaceuticals Inc Earnings Call

May 7, 2024

Operator: At this time, I'd 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 Keith. Before we begin, I encourage everyone to go to the investors section of the Ionis website to view the press release and the related financial tables 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.

Before we begin I encourage everyone to go to the investors section of the youngest website to view the press release and the related financial tables, 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 with.

We've also posted slides on our website that accompany today's call.

With me this morning are Brett Monia, Chief Executive Officer, Kyle Jenne, Chief Global Product Strategy Officer, and Beth Hougen, Chief Financial Officer. Richard Geary, our Chief Development 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 the call.

Richard Geary, our Chief our Chief Development Officer, Eric Swayze Executive Vice President Research Eugene Schneider, Chief Clinical development Officer, and Jonathan Virtual Chief Commercial Officer will also join us for the Q&A portion of the call.

I would like to draw your attention to slide three which contains our forward-looking language statement. During this call we will be making forward-looking statements that are based 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.

And with that, I'll turn the call over.

Brett P. Monia: Thanks, Wade. Good morning everybody and thanks for joining us today.

2024 is off to a great start for Ionis as we continue to execute on our vision to bring better futures to people with serious diseases. With the recent U.S launch of our first Ionis co-branded medicine WAINUA, Ionis discovered medicines are now reaching even more people living with serious diseases. And we're on the cusp of independently delivering a steady stream of new transformational medicines to patients beginning with our planned launches of both OLEZARSEN and DONIDALORSEN. By uniting groundbreaking science and technology with a relentless passion to discover, develop, and deliver new transformational medicines to people in need, we believe Ionis is well positioned to unlock next level value.

With the recent U S launch of our first <unk> co branded medicine way Noah. I honest discovered medicines are now, reaching even more people living with serious diseases.

I honest discovered medicines are now, reaching even more people living with serious diseases.

And we're on the cusp of independently delivering a steady stream of new transformational medicines to patients beginning with our planned launches of both <unk> and <unk>. By uniting groundbreaking science and technology with a relentless passion to discover develop and deliver new transformational medicines to people in need we believe <unk> is well positioned to unlock next level value.

By uniting groundbreaking science and technology with a relentless passion to discover develop and deliver new transformational medicines to people in need we believe <unk> is well positioned to unlock next level value.

Operator: Recorded. At this time, I'd like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.

Unknown Executive: on our vision to bring better futures to people with serious diseases. With the recent U.S. launch of our first Ionis co-branded medicine, Wynua, Ionis has discovered medicines are now reaching even more people living with serious diseases. And we're on the cusp of independently delivering a steady stream of new transformational medicines to patients, beginning with our planned launches of Olazarsan and Donvillarsan. By uniting groundbreaking science and technology with a relentless passion to discover, develop, and deliver new transformational medicines to people in need, we believe Ionis is well-positioned to unlock next-level value for ATTR Polyneuropathy is on track in the U. Thank you very much.

Just two people with serious diseases.

WAINUA launch for ATTR polyneuropathy is on track in the U.S with our co commercialization partner AstraZeneca. While it's early days in the launch, we're pleased with the collective teams progress. The approval decisions in Europe and Canada expected later this year and additional regulatory submissions already completed, we expect to soon bring WAINUA to even more patients around the globe. And based on WAINUA's strong efficacy profile, together with the freedom of simple, [inaudible] self administration, we believe WAINUA is poised to become the therapy of choice for ATTR patients.

Unknown Executive: With the recent U S launch of our first <unk> co branded medicine, we Noah.

D. Wade Walke: Thank you, Keith. Before we begin, I encourage everyone to go to the investor section of the Ionis website to view the press release and the related financial tables we will be discussing today, including the 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 this morning are Brett Monia, Chief Executive Officer, Kyle Jenne, Chief Global Product Strategy Officer, and Beth Hougen, Chief Financial Officer. Richard Geary, our Chief Development Officer, Eric Swayze, Executive Vice President of Research, Eugene Schneider, Chief Clinical Development Officer, and Jonathan Birchler, Chief Commercial Officer, will also join us for the Q&A portion of the call. I would like to draw your attention to slide three, which contains our forward-looking language statement.

Wade Walke: Thank you, Keith. Before we begin, I encourage everyone to go to the investor section of the Ionis website to view the press release and the related financial tables we will be discussing today, including the 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 this morning are Brett Monia, Chief Executive Officer, Kyle Jenne, Chief Global Product Strategy Officer, and Beth Hougen, Chief Financial Officer. Richard Geary, our Chief Development Officer, Eric Swayze, Executive Vice President of Research, Eugene Schneider, Chief Clinical Development Officer, and Jonathan Birchler, Chief Commercial Officer, will also join us for the Q&A portion of the call. I would like to draw your attention to slide three, which contains our forward-looking language statement.

Unknown Executive: I honest discovered medicines are now, reaching even more people living with serious diseases.

While it's early days in the launch we're pleased with the collective teams progress. The approval decisions in Europe, and Canada expected later this year and additional regulatory submissions already completed we. We expect to soon bring we knew it to even more patients around the globe and based on what we knew is strong efficacy profile together with the freedom of simple. Monthly self administration, we believe window is poised to become the therapy of choice for <unk> patients.

The approval decisions in Europe, and Canada expected later this year and additional regulatory submissions already completed we. We expect to soon bring we knew it to even more patients around the globe and based on what we knew is strong efficacy profile together with the freedom of simple. Monthly self administration, we believe window is poised to become the therapy of choice for <unk> patients.

Unknown Executive: And we are on the cusp of independently delivering a steady stream of new transformational medicines to patients beginning with our planned launches of <unk> and <unk>.

We expect to soon bring we knew it to even more patients around the globe and based on what we knew is strong efficacy profile together with the freedom of simple. Monthly self administration, we believe window is poised to become the therapy of choice for <unk> patients.

Unknown Executive: By uniting groundbreaking science and technology with a relentless passion to discover develop and deliver new transformational medicines to people in need we believe ion is well positioned to unlock next level value.

Monthly self administration, we believe window is poised to become the therapy of choice for <unk> patients.

We continue to advance our cardio transform study of WAINUA for the larger ATTR cardiomyopathy indication with the potential for data as early as 2025. As the largest study ever conducted in this patient population, the landmark cardio transform trial is on track to deliver the most comprehensive and robust dataset. We expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with AstraZeneca's global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we are well positioned to bring WAINUA to patients in the U.S and around the globe.

Unknown Executive: When you launch for <unk> Polyneuropathy is on track in the U S with our co commercialization partner Astrazeneca.

Unknown Executive: While it's early days in the launch we're pleased with the collective teams progress.

As the largest study ever conducted in this patient population. The landmark cardio transform trial is on track to deliver the most comprehensive and robust dataset. We expect the data, we generate will enable physicians and payers to make informed treatment decisions and this dynamic treatment landscape. And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in <unk> amyloidosis. We believe we are well positioned to bring we know what the patients in the U S and around the globe.

Unknown Executive: The approval decisions in Europe, and Canada expected later this year and additional regulatory submissions already completed we expect to soon bring it to even more patients around the globe and based on we knew as strong efficacy profile together with the freedom of simple at home monthly self administration, we believe window is poised to become the third.

We expect the data, we generate will enable physicians and payers to make informed treatment decisions and this dynamic treatment landscape. And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in <unk> amyloidosis. We believe we are well positioned to bring we know what the patients in the U S and around the globe.

D. Wade Walke: During this call, we will be making forward-looking statements that are based 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.

Wade Walke: During this call, we will be making forward-looking statements that are based 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.

And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in <unk> amyloidosis. We believe we are well positioned to bring we know what the patients in the U S and around the globe.

Unknown Executive: <unk> of choice for <unk> patients.

Unknown Executive: We continue to advance our CardioTransform study of Waynua for the larger ATTR cardiomyopathy indication, with the potential for data as early as 2025. As the largest study ever conducted in this patient population, the landmark CardioTransform trial is on track to deliver the most comprehensive and robust data set. We expect the data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with AstraZeneca's global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we are well positioned to bring RENUA to patients in the U.S. and around the world.

Unknown Executive: We continue to advance our cardio transform study of renewal for the larger <unk> cardiomyopathy indication with the potential for date for data as early as 2025.

Brett P. Monia: Thanks, Wade. Good morning, everybody, and thanks for joining us today. 2024 is off to a great start for Ionis as we continue to execute on our vision to bring better futures to people with serious diseases. With the recent U.S. launch of our first Ionis co-branded medicine, WAINUA, Ionis Discovered Medicines are now reaching even more people living with serious diseases. We're on the cusp of independently delivering a steady stream of new transformational medicines to patients, beginning with our planned launches of olezarsen and donidalorsen. By uniting groundbreaking science and technology with a relentless passion to discover, develop, and deliver new transformational medicines to people in need, we believe Ionis is well positioned to unlock next-level value. The WAINUA launch for ATTR polyneuropathy is on track in the U.S. with our co-commercialization partner, AstraZeneca.

Brett Monia: Thanks, Wade. Good morning, everybody, and thanks for joining us today. 2024 is off to a great start for Ionis as we continue to execute on our vision to bring better futures to people with serious diseases. With the recent U.S. launch of our first Ionis co-branded medicine, WAINUA, Ionis Discovered Medicines are now reaching even more people living with serious diseases. We're on the cusp of independently delivering a steady stream of new transformational medicines to patients, beginning with our planned launches of olezarsen and donidalorsen. By uniting groundbreaking science and technology with a relentless passion to discover, develop, and deliver new transformational medicines to people in need, we believe Ionis is well positioned to unlock next-level value. The WAINUA launch for ATTR polyneuropathy is on track in the U.S. with our co-commercialization partner, AstraZeneca.

Our next plan launch is for OLEZARSEN in FCS a severe rare disease with no approved treatments in the U.S. OLEZARSEN is also in development for the much larger SHTG patient population with more than 3 million estimated patients in the U.S alone. By addressing these two indications, OLEZARSEN represents one of the most meaningful opportunities in our pipeline today.

Unknown Executive: The largest study ever conducted in this patient population the landmark cardio transform trial is on track to deliver the most comprehensive and robust dataset.

<unk> is also in development for the much larger S. H D. G patient population with more than 3 million estimated patients in the U S alone I. By addressing these two indications Ozark represents one of the most meaningful opportunities in our pipeline today.

Unknown Executive: We expect the data, we generate will enable physicians and payers to make informed treatment decisions and this dynamic treatment landscape.

By addressing these two indications Ozark represents one of the most meaningful opportunities in our pipeline today.

Unknown Executive: With Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in <unk> amyloidosis. We believe we are well positioned to bring we knew what the patients in the U S and around the globe.

Last month, we presented and published very positive phase III results for OLEZARSEN in FCS. In the phase III balance study in patients with FCS, OLEZARSEN showed substantial triglyceride reductions. Importantly for patients, physicians, and payers, OLEZARSEN also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis as well as a favorable safety and tolerability profile. Balance is truly groundbreaking as it is the first trial to demonstrate that reducing triglycerides can reduce the incidents of acute pancreatitis. In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in OLEZARSEN's potential for success in FCS and SHDG.

In the phase III balance study in patients with FCS. So it was ours and showed substantial triglyceride reductions importantly for patients physicians and payers <unk> also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis as well as a favorable safety and tolerability profile. Balance is truly groundbreaking as it is the first trial to demonstrate that reducing triglycerides can reduce the incidents of acute pancreatitis. In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides in this study 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in <unk> potential for <unk>. <unk> in FCS and S. H T G. Yeah.

Unknown Executive: Our next planned launch is for olizarcin and FCS, a severe rare disease with no approved treatments in the U.S. Olazarsan is also in development for the much larger SHTG patient population, with more than 3 million estimated patients in the U.S. alone. By addressing these two indications, OWSR represents one of the most meaningful opportunities in our pipeline today.

Unknown Executive: Our next planned launches for all of US are sitting in FCS is a severe rare disease with no approved treatments in the U S.

Unknown Executive: <unk> is also in development for the much larger S. H D. G patient population with more than 3 million estimated patients in the U S alone.

Balance is truly groundbreaking as it is the first trial to demonstrate that reducing triglycerides can reduce the incidents of acute pancreatitis. In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides in this study 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in <unk> potential for <unk>. <unk> in FCS and S. H T G. Yeah.

Unknown Executive: By addressing these two indications Ozark represents one of the most meaningful opportunities in our pipeline today.

Brett P. Monia: While it's early days in the launch, we're pleased with the collective team's progress. With approval decisions in Europe and Canada expected later this year and additional regulatory submissions already completed, we expect to soon bring WAINUA to even more patients around the globe. And based on WAINUA's strong efficacy profile, together with the freedom of simple at-home monthly self-administration, we believe WAINUA is poised to become the therapy of choice for ATTR patients. We continue to advance our CardioTransform study of WAINUA for the larger ATTR cardiomyopathy indication, with the potential for data as early as 2025. As the largest study ever conducted in this patient population, the landmark CardioTransform trial is on track to deliver the most comprehensive and robust data set. The expected data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape.

Brett Monia: While it's early days in the launch, we're pleased with the collective team's progress. With approval decisions in Europe and Canada expected later this year and additional regulatory submissions already completed, we expect to soon bring WAINUA to even more patients around the globe. And based on WAINUA's strong efficacy profile, together with the freedom of simple at-home monthly self-administration, we believe WAINUA is poised to become the therapy of choice for ATTR patients. We continue to advance our CardioTransform study of WAINUA for the larger ATTR cardiomyopathy indication, with the potential for data as early as 2025. As the largest study ever conducted in this patient population, the landmark CardioTransform trial is on track to deliver the most comprehensive and robust data set. The expected data we generate will enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape.

In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in OLEZARSEN's potential for success in FCS and SHTG.

Unknown Executive: Last month, we presented and published very positive phase 3 results for Olazarsan in FCS. In the phase 3 balance study, in patients with FCS, Olazarsan showed substantial triglyceride reduction. Importantly, for patients, physicians, and payers, Olazarsan also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis, as well as a favorable safety and tolerability profile. Balance is truly groundbreaking, as it is the first trial to demonstrate that reducing triglycerides can reduce the incidence of acute pancreatitis.

In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides in this study 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in <unk> potential for <unk>. <unk> in FCS and S. H T G. Yeah.

Unknown Executive: Last month, we presented and published very positive phase III results for <unk> in Fcs.

Unknown Executive: In the phase III balance study in patients with FCS or resource and showed substantial triglyceride reductions importantly for patients physicians and payers <unk> also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis as well as a favorable safety and tolerability profile.

<unk> in FCS and S. H T G. Yeah.

Yeah.

I am pleased to report that we submitted the NDA for OLEZARSEN in FCS with the FDA last month, putting Ionis one step closer to our first independent launch. Assuming priority review, we're on track for a potential U.S approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year. OLEZARSEN is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved OLEZARSEN could be the standard of care for both FCS and SHTG. Our ongoing phase III studies for SHTG continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase III studies in SHTG core in essence with a remaining studied court two expected to complete enrollment very soon. This puts us on track for SHTG phase III data mid next year.

Unknown Executive: Balance is truly groundbreaking as it is the first trial to demonstrate that reducing triglycerides can reduce the incidents of acute pancreatitis.

Assuming priority review, we're on track for a potential U S approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year. Ozark and is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved those are some could be the standard of care for both FCS and S. H T G. Our ongoing phase III studies for <unk> continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase III studies in S. H D. G core in essence with a remaining studied court two expected to complete enrollment very soon. Puts us on track for S. Hcg phase III data mid next year.

Unknown Executive: In addition to the Phase III Balance Study, we presented and published positive data from the BRIDGE Study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels, reinforcing our confidence in oligoxiracin's potential for success in FCS and SHTG. I'm pleased to report that we submitted the NDA for Olizarsin and FCS to the FDA last month, putting Ionis one step closer to our first independent launch. Assuming priority review, we're on track for a potential U.S. approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year.

Unknown Executive: In addition to the phase III balance study, we presented and published positive data from the bridge study in patients with high cardiovascular risk and moderately elevated triglycerides in this study 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels reinforcing our confidence in <unk> potential for success.

We're also preparing to file for regulatory approval in Europe later this year. Ozark and is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved those are some could be the standard of care for both FCS and S. H T G. Our ongoing phase III studies for <unk> continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase III studies in S. H D. G core in essence with a remaining studied court two expected to complete enrollment very soon. Puts us on track for S. Hcg phase III data mid next year.

Ozark and is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved those are some could be the standard of care for both FCS and S. H T G. Our ongoing phase III studies for <unk> continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase III studies in S. H D. G core in essence with a remaining studied court two expected to complete enrollment very soon. Puts us on track for S. Hcg phase III data mid next year.

Brett P. Monia: With AstraZeneca's global leadership in the commercialization of novel cardiovascular treatments coupled with our leadership in TTR amyloidosis, we believe we are well positioned to bring WAINUA to patients in the U.S. and around the globe. Our next planned launch is for olezarsen in FCS, a severe rare disease with no approved treatments in the U.S. Olezarsen is also in development for the much larger sHTG patient population, with more than 3 million estimated patients in the U.S. alone. By addressing these two indications, olezarsen represents one of the most meaningful opportunities in our pipeline today. Last month, we presented and published very positive phase 3 results for olezarsen in FCS. In the phase 3 BALANCE study in patients with FCS, olezarsen showed substantial triglyceride reductions.

Brett Monia: With AstraZeneca's global leadership in the commercialization of novel cardiovascular treatments coupled with our leadership in TTR amyloidosis, we believe we are well positioned to bring WAINUA to patients in the U.S. and around the globe. Our next planned launch is for olezarsen in FCS, a severe rare disease with no approved treatments in the U.S. Olezarsen is also in development for the much larger sHTG patient population, with more than 3 million estimated patients in the U.S. alone. By addressing these two indications, olezarsen represents one of the most meaningful opportunities in our pipeline today. Last month, we presented and published very positive phase 3 results for olezarsen in FCS. In the phase 3 BALANCE study in patients with FCS, olezarsen showed substantial triglyceride reductions.

Unknown Executive: FCS and S. H D G.

Our ongoing phase III studies for <unk> continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase III studies in S. H D. G core in essence with a remaining studied court two expected to complete enrollment very soon. Puts us on track for S. Hcg phase III data mid next year.

Unknown Executive: I'm pleased to report that we submitted the NDA for <unk> in FCS with the FDA last month, putting it on your own is one step closer to our first independent launch.

I am pleased to also report that we have now completed enrollment in two of the three phase III studies in S. H D. G core in essence with a remaining studied court two expected to complete enrollment very soon. Puts us on track for S. Hcg phase III data mid next year.

Unknown Executive: Assuming priority review, we're on track for a potential U S approval by the end of this year.

Unknown Executive: We're also preparing to file for regulatory approval in Europe later this year.

Puts us on track for S. Hcg phase III data mid next year.

Unknown Executive: Olazarsan is poised to be the first approved medicine for FCS in the United States, and our strong results to date further increase our confidence that, if approved, Olazarsan could be the standard of care for both FCS and SHTG. Our ongoing phase 3 studies for SHTG continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three Phase III studies in SHTG, CORE and ESSENCE, with our remaining study, CORE II, expected to complete enrollment very soon. This puts us on track for SHCG Phase 3 data mid-next year.

Unknown Executive: Oh source and is poised to be the first approved medicine for FCS in the United States and our strong results to date further increase our confidence that if approved those are some could be the standard of care for both FCS and S. H T G.

Following closely behind OLEZARSEN and FCS is our next expected commercial launch with DONIDALORSEN, our potentially first-in-class prophylactic treatment for hereditary angioedema. Early in the first quarter, we reported positive topline data from the phase III Oasis HAE study. DONIDALORSEN met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks. The study also met other important secondary endpoints and had a favorable safety and tolerability profile.

Early in the first quarter, we reported positive topline data from the phase III Oasis Hae's study. Don a divorce and met the primary endpoint with a statistically significant reduction in the rate of <unk> attacks in patients treated every four weeks and patients treated every eight weeks. <unk> also met other important secondary endpoints and had a favorable safety and Tolerability profile.

Unknown Executive: Our ongoing phase III studies for <unk> continued to progress well I'm.

Unknown Executive: I am pleased to also report that we have now completed enrollment in two of the three phase III studies next hcg core in essence with a remaining studied court to expected to complete enrollment very soon.

Don a divorce and met the primary endpoint with a statistically significant reduction in the rate of <unk> attacks in patients treated every four weeks and patients treated every eight weeks. <unk> also met other important secondary endpoints and had a favorable safety and Tolerability profile.

Brett P. Monia: Importantly, for patients, physicians, and payers, olezarsen also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis, as well as a favorable safety and tolerability profile. BALANCE is truly groundbreaking, as it is the first trial to demonstrate that reducing triglycerides can reduce the incidence of acute pancreatitis. In addition to the phase 3 BALANCE study, we presented and published positive data from the BRIDGE study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels, reinforcing our confidence in olezarsen's potential for success in FCS and sHTG. I'm pleased to report that we submitted the NDA for olezarsen in FCS with the FDA last month, putting IONIS one step closer to our first independent launch. Assuming priority review, we're on track for a potential U.S.

Brett Monia: Importantly, for patients, physicians, and payers, olezarsen also demonstrated substantial and clinically meaningful reductions in attacks of acute pancreatitis, as well as a favorable safety and tolerability profile. BALANCE is truly groundbreaking, as it is the first trial to demonstrate that reducing triglycerides can reduce the incidence of acute pancreatitis. In addition to the phase 3 BALANCE study, we presented and published positive data from the BRIDGE study in patients with high cardiovascular risk and moderately elevated triglycerides. In this study, 93% of patients with moderately elevated triglycerides at baseline achieved normal triglyceride levels, reinforcing our confidence in olezarsen's potential for success in FCS and sHTG. I'm pleased to report that we submitted the NDA for olezarsen in FCS with the FDA last month, putting IONIS one step closer to our first independent launch. Assuming priority review, we're on track for a potential U.S.

<unk> also met other important secondary endpoints and had a favorable safety and Tolerability profile.

Unknown Executive: This puts us on track for S. Hcg phase II data mid next year.

Unknown Executive: Following closely behind Olazarsan and FCS is our next expected commercial launch with Donna Dolorsan, our potentially first in-class prophylactic treatment for hereditary angioedema. Early in the first quarter, we reported positive top-line data from the Phase 3 OASIS-HAE study. Donna Doloresan met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks.

We're looking forward to presenting data from the phase III Oasis and Oasis plus studies in the late breaker oral session at the European Academy of Allergy and Clinical Immunology Congress [inaudible] Congress at the end of this month. Oasis plus includes an open label cohort for patients rolling over from the Phase III study in a separate cohort that we referred to as the switch study. The switch study is a first of its kind study evaluating patients who have transitioned to DONIDALORSEN from other prophylactic HAE medications. We plan to hold a webcast in conjunction with the clinical data presentation at Yaqui.

Unknown Executive: Following closely behind <unk> and FCS is our next expected commercial launch with Don endorsing our potentially first in class prophylactic treatment for hereditary angioedema.

Unknown Executive: Early in the first quarter, we reported positive topline data from the phase III Oasis study.

Oasis plus includes an open label cohort for patients rolling over from the Phase III study in a separate cohort that we referred to as the switch study. The switch study is a first of its kind study evaluating patients who have transitioned to dawn endorsement from other prophylactic HAE medications. We plan to hold a webcast in conjunction with the clinical data presentation at Yaqui.

Unknown Executive: Got a divorce and met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks.

The switch study is a first of its kind study evaluating patients who have transitioned to dawn endorsement from other prophylactic HAE medications. We plan to hold a webcast in conjunction with the clinical data presentation at Yaqui.

Unknown Executive: The study also met other important secondary endpoints and had a favorable safety and Tolerability profile.

We plan to hold a webcast in conjunction with the clinical data presentation at Yaqui.

Unknown Executive: This study also met other important secondary endpoints and had a favorable safety and tolerability profile. We're looking forward to presenting data from the Phase III OASIS and OASIS Plus studies at the Late Breaker Oral Session at the European Academy of Allergy and Clinical Immunology Congress, the EACI Congress, at the end of this month. OASIS-Plus 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, a first-of-its-kind study evaluating patients who have transitioned to donagloran from other prophylactic HAE medications.

Unknown Executive: We're looking forward to presenting data from the phase III Oasis and Oasis plus studies in the late breaker oral session at the European Academy of allergy and clinical Immunology Congress Yoki Congress at the end of this month.

With these positive data in hand, we are working to finalize our regulatory submission to the FDA, which will include both four week and eight week dosing options. Additionally, our European commercial partner Otsuka is preparing to file for marketing approval in Europe. Based on our phase III results and the long term efficacy and favorable safety data seen in the ongoing phase II open label extension study, we believe DONIDALORSEN if approved, could evolve the HAE prophylactic treatment paradigm.

Brett P. Monia: Approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year. Olezarsen is poised to be the first approved medicine for FCS in the United States, and our strong results to date further increase our confidence that, if approved, olezarsen could be the standard of care for both FCS and SHTG. Our ongoing phase 3 studies for SHTG continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase 3 studies in SHTG, CORE, and ESSENCE, with our remaining study, CORE II, expected to complete enrollment very soon. This puts us on track for SHTG phase 3 data mid-next year. Following closely behind olezarsen in FCS is our next expected commercial launch with donidalorsen, our potentially first-in-class prophylactic treatment for hereditary angioedema.

Brett Monia: Approval by the end of this year. We're also preparing to file for regulatory approval in Europe later this year. Olezarsen is poised to be the first approved medicine for FCS in the United States, and our strong results to date further increase our confidence that, if approved, olezarsen could be the standard of care for both FCS and SHTG. Our ongoing phase 3 studies for SHTG continue to progress well. I am pleased to also report that we have now completed enrollment in two of the three phase 3 studies in SHTG, CORE, and ESSENCE, with our remaining study, CORE II, expected to complete enrollment very soon. This puts us on track for SHTG phase 3 data mid-next year. Following closely behind olezarsen in FCS is our next expected commercial launch with donidalorsen, our potentially first-in-class prophylactic treatment for hereditary angioedema.

Unknown Executive: Oasis plus included an open label cohort for patients rolling over from the Phase III study in a separate cohort that we referred to as the switch study.

Based on our phase III results and the long term efficacy and favorable safety safety data seen in the ongoing phase II Open label extension study, we believe Donegal worse, and if approved could evolve the AJ prophylactic treatment paradigm.

Unknown Executive: Switch study is the first of its kind study evaluating patients who have transitioned to dawn endorsement from other prophylactic HAE medications.

Unknown Executive: We plan to hold a webcast in conjunction with the Clinical Data Presentation at IACU. With these positive data in hand, we're working to finalize our regulatory submission to the FDA, which will include both four-week and eight-week dosing options. Additionally, our European commercial partner, Atsuka, is preparing to file for marketing approval in Europe.

Unknown Executive: To hold a webcast in conjunction with the clinical data presentation at Yaqui.

Beyond our near term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise. Our leading neurology pipeline today includes 12 medicines and we remain on track to have six wholly owned neurology medicines in clinical development by the end of this year. We just recently added one of these medicines during neurology pipeline with the initiation of the orbit study, our first inpatient study for ion 356 targeting PLP One for PMT, a rare excellent recessive Luca dystrophy.

Unknown Executive: With these positive data in hand, we are working to finalize our regulatory submission to the FDA, which will include both four week and eight week dosing options.

Our leading neurology pipeline today includes 12 medicines and we remain on track to have six wholly owned neurology medicines in clinical development by the end of this year. We just recently added one of these medicines during neurology pipeline with the initiation of the orbit study. Our first inpatient study for ion $3 56 targeting P. L. P. One for PMT, a rare excellent recessive Luca dystrophy.

Unknown Executive: Additionally, our European commercial partner Otsuka is preparing to file for marketing approval in Europe.

Unknown Executive: Based on our Phase 3 results and the long-term efficacy and favorable safety data seen in the ongoing Phase 2 Open Label Extension Study, we believe Donovan-Glorison, if approved, could evolve the HAE prophylactic treatment paradigm. Beyond our near-term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise. Our leading neurology pipeline today includes 12 medicines, and we remain on track to have six wholly owned neurology medicines in clinical development by the end of this year.

We just recently added one of these medicines during neurology pipeline with the initiation of the orbit study. Our first inpatient study for ion $3 56 targeting P. L. P. One for PMT, a rare excellent recessive Luca dystrophy.

Unknown Executive: Yeah.

Unknown Executive: Based on our phase III results in the long term efficacy and favorable safety safety data seen in the ongoing phase II Open label extension study, we believe Donegal worse, and if approved could evolve the AJ prophylactic treatment paradigm.

Brett P. Monia: Early in Q1, we reported positive top-line data from the phase 3 OASIS HAE study. Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks. The study also met other important secondary endpoints and had a favorable safety and tolerability profile. We're looking forward to presenting data from the phase 3 OASIS and OASIS Plus studies in the late breaker oral session at the EAACI Congress, the EAACI Congress, at the end of this month. OASIS Plus 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. The SWITCH study is a first-of-its-kind study evaluating patients who have transitioned to donidalorsen from other prophylactic HAE medications.

Brett Monia: Early in Q1, we reported positive top-line data from the phase 3 OASIS HAE study. Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks. The study also met other important secondary endpoints and had a favorable safety and tolerability profile. We're looking forward to presenting data from the phase 3 OASIS and OASIS Plus studies in the late breaker oral session at the EAACI Congress, the EAACI Congress, at the end of this month. OASIS Plus 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. The SWITCH study is a first-of-its-kind study evaluating patients who have transitioned to donidalorsen from other prophylactic HAE medications.

In addition to our neurology franchise, we also reported positive phase II data for ion 224 our medicine targeting [inaudible] in development to treat metabolic dysfunction associated [inaudible] hepatitis or Nash. These data provided clinical evidence demonstrating for the first time that targeting [inaudible] two to reduce hepatic fat reduction can improve nash histological endpoints, including improving fibrosis. The study met its primary and key secondary endpoints, while also demonstrating that ion 224 was safe and well tolerated. These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license ion 224 to maximize its value for the millions of people living with nash today.

Unknown Executive: Beyond our near term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise.

Unknown Executive: Our leading neurology pipeline today includes 12 medicines and we remain on track to have six wholly owned neurology medicines in clinical development by the end of this year.

These data provided clinical evidence demonstrating for the first time that targeting <unk> two to reduce hepatic fat reduction can improve mash histological endpoints, including improving fibrosis. The study met its primary and key secondary endpoints, while also demonstrating the ion to two four was safe and well tolerated. These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license IMTT for a maximized its value for the millions of people living with Nash today. Yeah.

Unknown Executive: We just recently added one of these medicines to our neurology pipeline with the initiation of the ORBIT study, a first inpatient study for Ion 356, targeting PLP1 for PMD, a rare, excellent, recessive leukodystrophy. In addition to our neurology pipeline, we also reported positive Phase 2 data for ION224, our medicine targeting DGAD2, in development to treat metabolic dysfunction associated with steatohepati These data provided clinical evidence demonstrating for the first time that targeting DMAT2 to reduce hepatic fat production can improve MASH histological endpoints, including improving fibrosis, studying its primary and key secondary endpoints while also demonstrating that Ion 224 was safe and well-tolerated.

Unknown Executive: We just recently added one of these medicines to our neurology pipeline with the initiation of the orbit study. Our first inpatient study for ion $3 56 targeting <unk> one for PMT, a rare excellent recessive Luca dystrophy.

The study met its primary and key secondary endpoints, while also demonstrating the ion to two four was safe and well tolerated. These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license IMTT for a maximized its value for the millions of people living with Nash today. Yeah.

These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license IMTT for a maximized its value for the millions of people living with Nash today. Yeah.

Unknown Executive: In addition to our neurology franchise, we also reported positive phase II data for <unk> two for our medicines targeting <unk> two in development to treat metabolic dysfunction associated Seattle hepatitis or Nash.

Since this program is outside of our key focus areas, we intend to license IMTT for a maximized its value for the millions of people living with Nash today. Yeah.

Yeah.

Our accomplishments this year and the investments we're making over the next few years, 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 of value for all Ionis stakeholders.

Unknown Executive: These data provided clinical evidence demonstrating for the first time that targeting <unk> two to reduce hepatic fat reduction can improve mash histological endpoints, including improving fibrosis.

Brett P. Monia: We plan to hold a webcast in conjunction with the clinical data presentation at EAACI. With these positive data in hand, we're working to finalize our regulatory submission to the FDA, which will include both 4-week and 8-week dosing options. Additionally, our European commercial partner, Otsuka, is preparing to file for marketing approval in Europe. Based on our phase 3 results and the long-term efficacy and favorable safety data seen in the ongoing phase 2 open-label extension study, we believe donidalorsen, if approved, could evolve the HAE prophylactic treatment paradigm. Beyond our near-term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise. Our leading neurology pipeline today includes 12 medicines, and we remain on track to have 6 wholly-owned neurology medicines in clinical development by the end of this year.

Brett Monia: We plan to hold a webcast in conjunction with the clinical data presentation at EAACI. With these positive data in hand, we're working to finalize our regulatory submission to the FDA, which will include both 4-week and 8-week dosing options. Additionally, our European commercial partner, Otsuka, is preparing to file for marketing approval in Europe. Based on our phase 3 results and the long-term efficacy and favorable safety data seen in the ongoing phase 2 open-label extension study, we believe donidalorsen, if approved, could evolve the HAE prophylactic treatment paradigm. Beyond our near-term opportunities, we have made important progress in advancing additional areas of our rich pipeline, including our leading neurology franchise. Our leading neurology pipeline today includes 12 medicines, and we remain on track to have 6 wholly-owned neurology medicines in clinical development by the end of this year.

Unknown Executive: Study met its primary and key secondary endpoints, while also demonstrating the ion to two four was safe and well tolerated.

With that, I'd like to introduce Kyle Jenne, who recently rejoined Ionis to lead our global product strategy and spearhead our next phase of growth. With his extensive commercial and Biopharma leadership experience and familiarity and our programs, Kyle hit the ground running and has already seamlessly added value to our commercial and medical organizations during this very important time.

Unknown Executive: These results support advancing this program to the next stage of development. Since this program is outside of our key focus areas, we intend to license ION224 to maximize its value for the millions of people living with MASH today. Our accomplishments this year and the investments we're making over the next few years 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 patients.

Unknown Executive: These results support advancing this program to the next stage of development.

With his extensive commercial and Biopharma leadership experience and familiarity and our programs kind of hit the ground running and is already seamlessly added value to our commercial and medical organizations. During this very important time.

Unknown Executive: This program is outside of our key focus areas, we intend to license IMTT for it maximizes value for the millions of people living with Nash today.

Unknown Executive: <unk>.

Unknown Executive: Our accomplishments this year and the investments we're making over the next few years 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 of value for all Iona stakeholders.

After Kyle provides a brief update on the WAINUA launch and the status of our go-to-market activities for OLEZARSEN and DONIDALORSEN, Beth will review our financials, including our first quarter results and then I'll wrap things up before taking your questions. And with that, over to Kyle.

Unknown Executive: With that, I'd like to introduce Kyle Janais, who recently rejoined Ionis to lead our global product strategy and spearhead our next phase of growth. With his extensive commercial and biopharma leadership experience and familiarity with our programs, Kyle hit the ground running and has already seamlessly added value to our commercial and medical organizations during this very important time. After Kyle provides a brief update on the way NOAA launched and the status of our go-to-market activities for Olazarsan and Donovan-Doloresan, Beth will review our financials, including our first-quarter revenue, and then I'll wrap things up before taking your questions. And with that, over to Kyle.

Unknown Executive: With that I'd like to introduce Kyle <unk>, who recently rejoined islands to lead our global product strategy and spearhead our next phase of growth.

Kyle Jenne: Thank you Brett. I'm excited me back at Ionis working with a highly accomplished team with deep commercial experience, who are ready to bring our important medicines to patients in need. Over the last four years, we have approached our commercial build in a thoughtful and purposeful manner, focusing on hiring the right roles at the right time. We now have a team in place executing on the co-commercialization of WAINUA with AstraZeneca and preparing for the upcoming independent launches of OLEZARSEN and DONIDALORSEN. The capabilities we've established include medical affairs, as well as commercial expertise and marketing, market access, patient services commercial operations, and sales.

Kyle Janais: With his extensive commercial and Biopharma leadership experience and familiarity with our programs kind of hit the ground running and is already seamlessly added value to our commercial and medical organizations. During this very important time.

Brett P. Monia: We just recently added one of these medicines to our neurology pipeline with the initiation of the ORBIT study, a first inpatient study for ION356 targeting PLP1 for PMD, a rare X-linked recessive leukodystrophy. In addition to our neurology franchise, we also reported positive phase 2 data for ION224, our medicine targeting DGAT2, in development to treat metabolic dysfunction associated with steatohepatitis, or MASH. These data provided clinical evidence demonstrating, for the first time, that targeting DGAT2 to reduce hepatic fat production can improve MASH histological endpoints, including improving fibrosis. The study met its primary and key secondary endpoints while also demonstrating that ION224 was safe and well tolerated. These results support advancing this program to the next stage of development.

Brett Monia: We just recently added one of these medicines to our neurology pipeline with the initiation of the ORBIT study, a first inpatient study for ION356 targeting PLP1 for PMD, a rare X-linked recessive leukodystrophy. In addition to our neurology franchise, we also reported positive phase 2 data for ION224, our medicine targeting DGAT2, in development to treat metabolic dysfunction associated with steatohepatitis, or MASH. These data provided clinical evidence demonstrating, for the first time, that targeting DGAT2 to reduce hepatic fat production can improve MASH histological endpoints, including improving fibrosis. The study met its primary and key secondary endpoints while also demonstrating that ION224 was safe and well tolerated. These results support advancing this program to the next stage of development.

Over the last four years, we have approached our commercial build in a thoughtful and purposeful manner focusing on hiring the right roles at the right time. We now have a team in place executing on a co commercialization of <unk> with Astrazeneca and preparing for the upcoming independent launches of <unk> and Donny to Larsen. Capabilities. We've established include medical affairs, as well as commercial expertise and marketing market access patient services commercial operations and sales.

We now have a team in place executing on a co commercialization of <unk> with Astrazeneca and preparing for the upcoming independent launches of <unk> and Donny to Larsen. Capabilities. We've established include medical affairs, as well as commercial expertise and marketing market access patient services commercial operations and sales.

Kyle Janais: After Kyle provides a brief update on the way new launch and the status of our go to market activities for <unk> and Diamond to loosen that will review our financials, including our first quarter results and then I'll wrap things up before taking your questions and with that over to Kyle.

Capabilities. We've established include medical affairs, as well as commercial expertise and marketing market access patient services commercial operations and sales.

Kyle Janais: Thank you, Brett. I'm excited to be back at Ionis working with a highly accomplished team with deep commercial experience who are ready to bring our important medicines to patients in need. Over the last four years, we have approached our commercial build in a thoughtful and purposeful manner, focusing on hiring the right roles at the right time. We now have a team in place executing on the co-commercialization of Waynoa with AstraZeneca and preparing for the upcoming independent launches of Olazarsan and Donnie DeLorsi.

Kyle Janais: Thank you Brett I'm excited me back that I honest working with a highly accomplished team with deep commercial experience, who are ready to bring our important medicines to patients in need.

We also recently appointed the first Ionis national sales director to the team and are beginning to hire our field organization in preparation for the FCS launch. Following the U.S approval at the end of last year for WAINUA, we started bringing this important medicine to patients in the first quarter.

We also recently appointed the first Ionis national sales director to the team and are beginning to hire our field organization in preparation for the FCS launch.

Kyle Janais: Over the last four years, we have approached our commercial build in a thoughtful and purposeful manner focusing on hiring the right roles at the right time.

Following the U.S approval at the end of last year for WAINUA, we started bringing this important medicine to patients in the first quarter. As Brett noted, WAINUA represents Ionis' first co-branded medicine and is poised to be the treatment of choice for hereditary ATTR polyneuropathy based on its efficacy and safety profile and the ability to self administer. With an estimated 40,000 patients worldwide and fewer than 20% of patients on an approved treatment patients with hereditary ATTR polyneuropathy remain significantly under diagnosed and largely underserved. As a result, a high unmet need remains that we and AstraZeneca are uniquely positioned to address. Overall, the launch is tracking to plan based on predefined launch performance indicators.

Following the U S approval at the end of last year for a new App, we started bringing this important medicine to patients in the first quarter.

Kyle Janais: We now have a team in place executing on the co commercialization of <unk> with Astrazeneca and preparing for the upcoming independent launches of <unk> and Donny to Larsen.

As Brett noted, WAINUA represents Ionis' first co-branded medicine and is poised to be the treatment of choice for hereditary ATTR polyneuropathy based on its efficacy and safety profile and the ability to self administer. With an estimated 40,000 patients worldwide and fewer than 20% of patients on an approved treatment patients with hereditary ATTR polyneuropathy remain significantly under diagnosed and largely underserved. As a result, a high unmet need remains that we and AstraZeneca are uniquely positioned to address. Overall, the launch is tracking to plan based on predefined launch performance indicators.

Brett P. Monia: Since this program is outside of our key focus areas, we intend to license ION224 to maximize its value for the millions of people living with MASH today. Our accomplishments this year and the investments we're making over the next few years 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'd like to introduce Kyle Jenne, who recently rejoined Ionis to lead our global product strategy and spearhead our next phase of growth. With his extensive commercial and biopharma leadership experience and familiarity with our programs, Kyle hit the ground running and has already seamlessly added value to our commercial and medical organizations during this very important time.

Brett Monia: Since this program is outside of our key focus areas, we intend to license ION224 to maximize its value for the millions of people living with MASH today. Our accomplishments this year and the investments we're making over the next few years 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'd like to introduce Kyle Jenne, who recently rejoined Ionis to lead our global product strategy and spearhead our next phase of growth. With his extensive commercial and biopharma leadership experience and familiarity with our programs, Kyle hit the ground running and has already seamlessly added value to our commercial and medical organizations during this very important time.

Kyle Janais: The capabilities we've established include medical affairs, as well as commercial expertise in marketing, market access, patient services, commercial operations, and sales. We have also recently appointed the first Ionis National Sales Director to the team and are beginning to hire our field organization in preparation for the FCS launch. Following the U.S. approval at the end of last year for Waynua, we started bringing this important medicine to patients in the first quarter. As Brett noted, Waynewis represents Ionis' first co-branded medicine and is poised to be the treatment of choice for hereditary ATTR polyneuropathy based on its efficacy and safety profile and the ability to self-administer. With an estimated 40,000 patients worldwide and fewer As a result, a high unmet need remains that we in AstraZeneca are uniquely positioned to address. Overall, the launch is tracking to plan based on predefined launch performance indicators.

Kyle Janais: Capabilities. We've established include medical affairs, as well as commercial expertise and marketing market access patient services commercial operations and sales.

With an estimated 40000 patients worldwide and fewer than 20% of patients on an approved treatment patients with hereditary <unk> polyneuropathy. Remains significantly under diagnosed and largely underserved. As a result of high unmet need remains that we and astrazeneca are uniquely positioned to address overall the launch is tracking to plan based on predefined launch performance indicators.

Kyle Janais: We also recently appointed the first I honest national sales director to the team and are beginning to hire our field organization in preparation for the FCS launch.

Remains significantly under diagnosed and largely underserved. As a result of high unmet need remains that we and astrazeneca are uniquely positioned to address overall the launch is tracking to plan based on predefined launch performance indicators.

Kyle Janais: Following the U S approval at the end of last year for a new App, we started bringing this important medicine to patients in the first quarter.

As a result of high unmet need remains that we and astrazeneca are uniquely positioned to address overall the launch is tracking to plan based on predefined launch performance indicators.

Kyle Janais: As Bret noted when newest.

Kyle Janais: Represents <unk> first co branded medicine and is poised to be the treatment of choice for hereditary <unk> polyneuropathy based on its efficacy and safety profile and the ability to self administer.

We are seeing good uptake among patients, some of whom are new to this class of medicine, and some of whom have switched from other brands. The cross functional teams at Ionis and AstraZeneca are working well together and the early phase of the launch is benefiting from the expertise of both organizations. Under our co- commercialization partnership with AstraZeneca, we have a one customer team approach that is designed to drive broad uptake. We are leading the patient support aspect of the launch while AstraZeneca is leading the other customer facing commercial and medical teams.

The cross functional teams that ion honest and Astrazeneca are working well together in the early phase of the launch is benefiting from the expertise of both organizations. Under our co commercialization partnership with Astrazeneca, we have a one customer team approach that is designed to drive broad uptake. We are leading the patient support aspect of the launch while astrazeneca is leading the other customer facing commercial and medical teams.

Kyle Janais: With an estimated 40000 patients worldwide and fewer than 20% of patients on an approved treatment patients with hereditary <unk> polyneuropathy.

Brett P. Monia: After Kyle provides a brief update on the WAINUA launch and the status of our go-to-market activities for olezarsen and donidalorsen, Beth will review our financials, including our first quarter results. And then I'll wrap things up before taking your questions. And with that, over to Kyle.

Brett Monia: After Kyle provides a brief update on the WAINUA launch and the status of our go-to-market activities for olezarsen and donidalorsen, Beth will review our financials, including our first quarter results. And then I'll wrap things up before taking your questions. And with that, over to Kyle.

Under our co commercialization partnership with Astrazeneca, we have a one customer team approach that is designed to drive broad uptake. We are leading the patient support aspect of the launch while astrazeneca is leading the other customer facing commercial and medical teams.

Under our co- commercialization partnership with AstraZeneca, we have a one customer team approach that is designed to drive broad uptake. We are leading the patient support aspect of the launch while AstraZeneca is leading the other customer facing commercial and medical teams.

Kyle Janais: <unk> significantly under diagnosed and largely underserved.

Kyle Janais: As a result of high unmet need remains that we and astrazeneca are uniquely positioned to address overall the launch is tracking to plan based on predefined launch performance indicators we.

Kyle Jenne: Thank you, Brett. I'm excited to be back at Ionis, working with a highly accomplished team with deep commercial experience who are ready to bring our important medicines to patients in need. Over the last four years, we have approached our commercial build in a thoughtful and purposeful manner, focusing on hiring the right roles at the right time. We now have a team in place executing on the co-commercialization of Wainua with AstraZeneca and preparing for the upcoming independent launches of Olezarsen and Donidalorsen. The capabilities we've established include medical affairs, as well as commercial expertise in marketing, market access, patient services, commercial operations, and sales. We also recently appointed the first Ionis national sales director to the team and are beginning to hire our field organization in preparation for the FCS launch. Following the U.S.

Kyle Janais: We are seeing good uptake among patients, some of whom are new to this class of medicine, and some of whom have switched from other brands. The cross-functional teams at Ionis and AstraZeneca are working well together, and the early phase of the launch is benefiting from the expertise of both organizations. Under our co-commercialization partnership with AstraZeneca, we have a one-customer team approach that's designed to drive broad uptake. We are leading the patient support aspect of the launch, while AstraZeneca is leading the other customer-facing commercial and medical team.

The combined team is working together seamlessly with a shared goal to make WAINUA the preferred choice for newly diagnosed patients with ATTR polyneuropathy. Prescribers and patients are recognizing WAINUA's strong clinical profile and value of the ability to easily self administer WAINUA from their home. We are pleased with the initial phase of the launch and expect to continue reaching a growing number of patients as more prescribers learn about the value that WAINUA brings. Establishing our co-commercialization partnership with AstraZeneca for WAINUA was an important step to efficiently prepare Ionis for our upcoming independent commercial launches of OLEZARSEN and DONIDALORSEN. 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 expect the approval of OLEZARSEN for FCS by the end of this year assuming priority review.

Kyle Janais: We are seeing good uptake among patients some of whom are new to this class of medicine, and some of whom have switched from other brands.

Kyle Janais: The cross functional teams that ion <unk> and Astrazeneca are working well together in the early phase of the launch is benefiting from the expertise of both organizations.

Prescribers and patients are recognizing we knew a strong clinical profile and value of the ability to easily self administer window from their home. We are pleased with the initial phase of the launch and expect to continue reaching a growing number of patients as more prescribers aren't about the value that we know are brings establish. Establishing our co commercialization partnership with Astrazeneca for <unk>. It was an important step to efficiently prepare eye on us for our upcoming independent commercial launches of <unk> and dawn into Larson. We are developing <unk> for two indications the rare Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We expect the approval of <unk> for FCS by the end of this year assuming priority review.

Kyle Janais: Under our co commercialization partnership with Astrazeneca, we have a one customer team approach that is designed to drive broad uptake. We are leading the patient support aspect of the launch while astrazeneca is leading the other customer facing commercial and medical teams.

Establishing our co commercialization partnership with Astrazeneca for <unk>. It was an important step to efficiently prepare eye on us for our upcoming independent commercial launches of <unk> and dawn into Larson. We are developing <unk> for two indications the rare Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We expect the approval of <unk> for FCS by the end of this year assuming priority review.

Establishing our co-commercialization partnership with AstraZeneca for WAINUA was an important step to efficiently prepare Ionis for our upcoming independent commercial launches of OLEZARSEN and DONIDALORSEN. 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 expect the approval of OLEZARSEN for FCS by the end of this year assuming priority review.

It was an important step to efficiently prepare eye on us for our upcoming independent commercial launches of <unk> and dawn into Larson. We are developing <unk> for two indications the rare Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We expect the approval of <unk> for FCS by the end of this year assuming priority review.

Kyle Janais: The combined team is working together seamlessly with a shared goal to make Waynua the preferred choice for newly diagnosed patients with ATTR polyneuropathy. Physicians and patients are recognizing Waynua's strong clinical profile and value the ability to easily self-administer Waynua from their home.

Kyle Janais: The combined team is working together seamlessly with a shared goal to make way know us the preferred choice for newly diagnosed patients with <unk> polyneuropathy.

We are developing <unk> for two indications the rare Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We expect the approval of <unk> for FCS by the end of this year assuming priority review.

Kyle Jenne: Approval at the end of last year for WAINUA, we started bringing this important medicine to patients in Q1. As Brett noted, WAINUA represents Ionis's first co-branded medicine and is poised to be the treatment of choice for hereditary ATTR polyneuropathy based on its efficacy and safety profile and the ability to self-administer. With an estimated 40,000 patients worldwide and fewer than 20% of patients on an approved treatment, patients with hereditary ATTR polyneuropathy remain significantly underdiagnosed and largely underserved. As a result, a high unmet need remains that we and AstraZeneca are uniquely positioned to address. Overall, the launch is tracking the plan based on predefined launch performance indicators. We are seeing good uptake among patients, some of whom are new to this class of medicine and some of whom have switched from other brands.

Kyle Janais: Prescribers and patients are recognizing we knew a strong clinical profile and value of the ability to easily self administer window from their home. We are pleased with the initial phases of the launch and expect to continue reaching a growing number of patients as more prescribers aren't about the value that we know are brings establish.

Kyle Janais: We are pleased with the initial phase of the launch and expect to continue reaching a growing number of patients as more prescribers learn about the value that we know it brings. Establishing our co-commercialization partnership with AstraZeneca for Waynua was an important step to efficiently prepare Ionis for our upcoming independent commercial launches of Ola Zarson and Donnie DeLorso. We are developing olazarsan for two indications The Rare FCS Indication and the Broader SHTG Indication with Anticipated First Mover Advantage in Both Settings

Last month, we presented the positive FCS phase III data, which were simultaneously published in the New England Journal of Medicine. These data generated very positive feedback from key opinion leaders. They were especially impressed with the reduction in acute pancreatitis attacks. Additionally, they were encouraged that the reductions in triglycerides translated to substantial reductions in hospitalizations and inpatient hospital days supporting the potential for OLEZARSEN to make a profound difference in the lives of people with FCS. And we expect that these data will also be very important in securing access with payers. And I'm happy to report that we recently initiated an expanded access program for OLEZARSEN in the U.S, enabling patients to have access to treatment ahead of potential approval. Our launch preparations are well underway for FCS. We are building for this launch using the substantial capabilities we've already established for WAINUA. Our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing FCS through disease education.

Kyle Janais: Establishing our co commercialization partnership with Astrazeneca for <unk>.

These data generated very positive feedback from key opinion leaders they were especially impressed with the reduction in acute pancreatitis attacks. Additionally, they were encouraged that the reductions in triglycerides translated to substantial reductions in hospitalizations and inpatient hospital days supporting the potential for <unk> to make a pro. Difference in the lives of people with Fcs. And we expect that these data will also be very important in securing access with Payors and I'm happy to report that we recently initiated an expanded access program for <unk> in the U S. Enabling patients to have access to treatment ahead of potential approval. Our launch. Preparations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

Kyle Janais: It was an important step to efficiently prepare eye on us for our upcoming independent commercial launches of <unk> and on into <unk>.

Kyle Janais: We are developing <unk> for two indications the rare Fcs indication and the broader <unk> indication with anticipated first mover advantage in both settings. We expect the approval of <unk> for FCS by the end of this year assuming priority review.

Kyle Janais: We expect the approval of Olazarsan for FCS by the end of this year, assuming priority review. Last month, we presented positive FCS Phase 3 data, which were simultaneously published in the New England Journal of Medicine. These data generated very positive feedback from key opinion leaders, who were especially impressed with the reduction in acute pancreatitis attacks.

Difference in the lives of people with Fcs. And we expect that these data will also be very important in securing access with Payors and I'm happy to report that we recently initiated an expanded access program for <unk> in the U S. Enabling patients to have access to treatment ahead of potential approval. Our launch. Preparations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

And we expect that these data will also be very important in securing access with Payors and I'm happy to report that we recently initiated an expanded access program for <unk> in the U S. Enabling patients to have access to treatment ahead of potential approval. Our launch. Preparations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

Kyle Janais: Last month, we presented the positive FCS phase III data, which were science simultaneously published in the New England Journal of Medicine.

Kyle Jenne: The cross-functional teams at Ionis and AstraZeneca are working well together, and the early phase of the launch is benefiting from the expertise of both organizations. Under our co-commercialization partnership with AstraZeneca, we have a one-customer team approach that's designed to drive broad uptake. We are leading the patient support aspect of the launch, while AstraZeneca is leading the other customer-facing commercial and medical teams. The combined team is working together seamlessly with a shared goal to make WAINUA the preferred choice for newly diagnosed patients with ATTR polyneuropathy. Prescribers and patients are recognizing WAINUA's strong clinical profile and value the ability to easily self-administer WAINUA from their home. We are pleased with the initial phase of the launch and expect to continue reaching a growing number of patients as more prescribers learn about the value that WAINUA brings.

Kyle Janais: These data generated very positive feedback from key opinion leaders they were especially impressed with the reduction in acute pancreatitis attacks. Additionally, they were encouraged that the reductions in triglycerides translated to substantial reductions in hospitalizations and inpatient hospital days supporting the potential for <unk> to make a profit.

Our launch. Preparations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

Our launch preparations are well underway for FCS. We are building for this launch using the substantial capabilities we've already established for WAINUA. Our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing FCS through disease education.

Preparations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

Kyle Janais: Additionally, they were encouraged that the reductions in triglycerides translated to substantial reductions in hospitalizations and inpatient hospital days, supporting the potential for olizarsin to make a profound difference in the lives of people with FCS, and we expect that these data will also be very important in securing access with payers. And I'm happy to report that we recently initiated an expanded access program for Olazarsan in the U.S., enabling patients to have access to treatment ahead of potential approval. Our launch preparations are well underway for FCS. We are building for this launch using the substantial capabilities we've already established for WNUA.

Kyle Janais: Sound difference in the lives of people with Fcs.

Kyle Janais: And we expect that these data will also be very important in securing access with Payors and I'm happy to report that we recently initiated an expanded access program for <unk> in the U S. Enabling patients to have access to treatment ahead of potential approval.

We have conducted extensive market research to identify the physicians most likely to diagnose FCS and treat patients with OLEZARSEN. These are the physicians that we will focus on initially after launch. Additionally, we aim to build meaningful relationships with patients and health care professionals through a differentiating omnichannel strategy and by leveraging our omni channel capabilities, we expect to efficiently broaden our access to a larger base of treating physicians and accelerate the patient journey process. We are building a world class patient and caregiver support team to help patients through every step of their treatment journey.

These are the physicians that we will focus on initially after launch. Additionally, we aim to build meaningful relationships with patients and health care professionals through a differentiating omnichannel strategy and by leveraging our omni channel capabilities, we expect to efficiently broaden our access to a larger base of treating physicians and accelerate the patient.

Kyle Janais: Our launch.

Kyle Janais: Separations are well underway for FCS we are building for this launch using a substantial capabilities. We've already established for window up our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing Fcs through disease education.

Kyle Janais: Our medical affairs team has been connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing FCS through disease education. We have conducted extensive market research to identify the physicians most likely to diagnose FCS and treat patients with ulcerative colitis. These are the positions that we will focus on initially after launch.

Kyle Jenne: Establishing our co-commercialization partnership with AstraZeneca for WAINUA was an important step to efficiently prepare Ionis for our upcoming independent commercial launches of olezarsen and donidalorsen. 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 expect the approval of olezarsen for FCS by the end of this year, assuming priority review. Last month, we presented the positive FCS phase 3 data, which were simultaneously published in the New England Journal of Medicine. These data generated very positive feedback from key opinion leaders. They were especially impressed with the reduction in acute pancreatitis attacks. Additionally, they were encouraged that the reductions in triglycerides translated to substantial reductions in hospitalizations and inpatient hospital days, supporting the potential for olezarsen to make a profound difference in the lives of people with FCS.

Journey process. We are building a world class patient and caregiver support team to help patients through every step of their treatment journey.

We are building a world class patient and caregiver support team to help patients through every step of their treatment journey. This includes helping patients to understand their disease, be informed about their medication and provide the appropriate support for access and reimbursement programs. The goal of this team is to provide a seamless customer experience that helps patients initiate treatment and remain on therapy long term. With our national sales director in place, we plan to hire our customer facing account champion team leading up to the launch. The team will be sized appropriately for this rare disease population and focus on FCS disease education, product information, and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers, integrated delivery networks, and other essential reimbursement channels. And as we prepare for the SHTG indication, we plan to further scale all of these capabilities to realize the full potential of OLEZARSEN.

We are building a world class patient and caregiver support team to help patients through every step of their treatment journey.

Kyle Janais: We have conducted extensive market research to identify the physicians, most likely to diagnose Fcs and treat patients with <unk>.

This includes helping patients to understand their disease, be informed about their medication and provide the appropriate support for access and reimbursement programs. The goal of this team is to provide a seamless customer experience that helps patients initiate treatment and remain on therapy long term. With our national sales director in place, we plan to hire our customer facing account champion team leading up to the launch. The team will be sized appropriately for this rare disease population and focus on FCS disease education, product information, and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers, integrated delivery networks, and other essential reimbursement channels.

Kyle Janais: These are the physicians that we all focus on initially after launch. Additionally, we aim to build meaningful relationships with patients and health care professionals through a differentiating omnichannel strategy.

Kyle Janais: Additionally, we aim to build meaningful relationships with patients and healthcare professionals through a differentiating omni-channel strategy. And by leveraging our omni-channel capabilities, we expect to efficiently broaden our access to a larger base of treating physicians and accelerate the patient journey. We are building a world-class patient and caregiver support team to help patients through every step of their treatment journey. This includes helping patients to understand their disease, be informed about their medication, and provide the appropriate support for access and reimbursement programs.

With our national sales director in place, we plan to hire our customer facing account champion team leading up to the launch the. The team will be sized appropriately for this rare disease population and focus on FCS disease education product information and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers integrated delivery networks and.

Kyle Janais: By leveraging our omnichannel capabilities, we expect to efficiently broaden our access to a larger base of treating physicians and accelerate the patient journey process.

The team will be sized appropriately for this rare disease population and focus on FCS disease education product information and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers integrated delivery networks and.

Kyle Janais: We are building a world class patient and caregiver support team to help patients through every step of their treatment journey.

Kyle Janais: This includes helping patients to understand their disease be informed about their medication and provide the appropriate support for access and reimbursement programs. The goal of this team is to provide a seamless customer experience that helps patients initiate treatment and remain on therapy long term.

And as we prepare for the SHTG indication, we plan to further scale all of these capabilities to realize the full potential of OLEZARSEN. DONIDALORSEN for the prophylactic treatment of HAE is our next planned launch after OLEZARSEN. And just like OLEZARSEN, we recently initiated an expanded access program for DONIDALORSEN in the US so that patients have access to treatment ahead of potential approval. HAE is an attractive opportunity for Ionis. There are more than 20,000 patients with HAE in the U.S and Europe. Within the U.S, prophylactic treatment is well accepted by patients and physicians. We know where this concentrated base of treating physicians are and they are primarily located in large centers of excellence. Many patients with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience. We plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

And as we prepare for the SHTG indication, we plan to further scale all of these capabilities to realize the full potential of OLEZARSEN.

And as we prepare for the <unk> indication we plan to further scale all of these capabilities to realize the full potential of <unk>. Don into Lorson for the prophylactic treatment of HCA is our next planned launch after <unk> and. And just cycle as <unk>, we recently initiated an expanded access program for <unk> in the U S. So that patients have access to treatment ahead of potential approval.

Kyle Jenne: We expect that these data will also be very important in securing access with payers. I'm happy to report that we recently initiated an expanded access program for olezarsen in the US, enabling patients to have access to treatment ahead of potential approval. Our launch preparations are well underway for FCS. We are building for this launch using the substantial capabilities we've already established for WAINUA. Our medical affairs team has been out connecting with physicians for nearly three years, improving disease awareness and urgency around identifying and diagnosing FCS through disease education. We have conducted extensive market research to identify the physicians most likely to diagnose FCS and treat patients with olezarsen. These are the physicians that we will focus on initially after launch. Additionally, we aim to build meaningful relationships with patients and healthcare professionals through a differentiating omnichannel strategy.

Kyle Janais: The goal of this team is to provide a seamless customer experience that helps patients initiate treatment and remain on therapy long term. With our National Sales Director in place, we plan to hire our customer-facing account champion team leading up to the launch.

Kyle Janais: With our national sales director in place, we plan to hire our customer facing account champion team leading up to the launch the.

DONIDALORSEN for the prophylactic treatment of HAE is our next planned launch after OLEZARSEN. And just like OLEZARSEN, we recently initiated an expanded access program for DONIDALORSEN in the US so that patients have access to treatment ahead of potential approval. HAE is an attractive opportunity for Ionis. There are more than 20,000 patients with HAE in the U.S and Europe. Within the U.S, prophylactic treatment is well accepted by patients and physicians. We know where this concentrated base of treating physicians are and they are primarily located in large centers of excellence. Many patients with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience. We plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

Don into Lorson for the prophylactic treatment of HCA is our next planned launch after <unk> and. And just cycle as <unk>, we recently initiated an expanded access program for <unk> in the U S. So that patients have access to treatment ahead of potential approval.

Kyle Janais: The team will be sized appropriately for this rare disease population and focus on FCS disease education, product information, and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers, integrated delivery networks, and other essential reimbursement channels. And as we prepare for the SHTG indication, we plan to further scale all of these capabilities to realize the full potential of all of our Donny DeLorsen for the prophylactic treatment of HAE is our next planned launch after Olazar.

Kyle Janais: The team will be sized appropriately for this rare disease population and focus on FCS disease education product information and reimbursement and access once approved. In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers integrated delivery networks and.

And just cycle as <unk>, we recently initiated an expanded access program for <unk> in the U S. So that patients have access to treatment ahead of potential approval.

HAE is an attractive opportunity for Ionis. There are more than 20,000 patients with HAE in the U.S and Europe. Within the U.S, prophylactic treatment is well accepted by patients and physicians. We know where this concentrated base of treating physicians are and they are primarily located in large centers of excellence. Many patients with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience. We plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

He is an attractive opportunity for ion us there are more than 20000 patients with <unk> in the U S and Europe within the U S. Prophylactic treatment is well accepted by patients and physicians, we know where this concentrated base of treating physicians are and they are primarily located in large centers of excellence many.

Kyle Janais: Other essential reimbursement channels.

Kyle Janais: And as we prepare for the <unk> indication we plan to further scale all of these capabilities to realize the full potential of <unk>.

Many patients with HCA are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience we plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

Kyle Janais: Don into Lorson for the prophylactic treatment of HCA is our next planned launch after <unk> and.

Kyle Janais: And just like Olazarsan, we recently initiated an expanded access program for Donnie Doloresan in the U.S. so that patients have access to treatment ahead of potential approval. H.A.E. is an attractive opportunity for Ionis because there are more than 20,000 patients with H.A.E. in the U.S. and Europe.

Kyle Janais: And just cycle as <unk>, we recently initiated an expanded access program for <unk> in the U S. So that patients have access to treatment ahead of potential approval.

Kyle Jenne: By leveraging our omnichannel capabilities, we expect to efficiently broaden our access to a larger base of treating physicians and accelerate the patient journey process. We are building a world-class patient and caregiver support team to help patients through every step of their treatment journey. This includes helping patients to understand their disease, be informed about their medication, and provide the appropriate support for access and reimbursement programs. The goal of this team is to provide a seamless customer experience that helps patients initiate treatment and remain on therapy long term. With our national sales director in place, we plan to hire our customer-facing account champion team leading up to the launch. The team will be sized appropriately for this rare disease population and focus on FCS disease education, product information, and reimbursement and access once approved.

Kyle Janais: He is an attractive opportunity for ion us there are more than 20000 patients with <unk> in the U S and Europe within the U S. Prophylactic treatment is well accepted by patients and physicians, we know where this concentrated base of treating physicians are and they are primarily located in large centers of excellence.

Based on the phase III results, we anticipate DONIDALORSEN could evolve the HAE prophylactic treatment paradigm and address the unmet needs of patients. Patients tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability and administration profile and we believe that DONIDALORSEN could be that medicine. DONIDALORSEN has the potential to extend dosing intervals to every four to eight weeks using an auto injector. The current standard of care is dosed every two to four weeks using a vial and syringe. We're looking forward to the upcoming phase III Oasis HAE and Oasis plus data presentations for DONIDALORSEN at the end of this month.

Kyle Janais: Within the U.S., prophylactic treatment is well accepted by patients and physicians. We know where this concentrated base of treating physicians is, and they are primarily located in large centers of expertise. Many patients with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience. We plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

Patients tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability and administration profile and we believe that <unk> could be that medicine. <unk> has the potential to extend dosing intervals to every four to eight weeks using an auto injector. The current standard of care is dosed every two to four weeks using a vial and syringe. We're looking forward to the upcoming phase III Oasis AJ. Oasis plus data presentations for <unk> at the end of this month.

Kyle Janais: Many patients with HCA are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience we plan to build an efficiently sized field team to reach prescribers and support the needs of these patients.

DONIDALORSEN has the potential to extend dosing intervals to every four to eight weeks using an auto injector. The current standard of care is dosed every two to four weeks using a vial and syringe. We're looking forward to the upcoming phase III Oasis HAE and Oasis plus data presentations for DONIDALORSEN at the end of this month.

<unk> has the potential to extend dosing intervals to every four to eight weeks using an auto injector. The current standard of care is dosed every two to four weeks using a vial and syringe. We're looking forward to the upcoming phase III Oasis AJ. Oasis plus data presentations for <unk> at the end of this month.

We're looking forward to the upcoming phase III Oasis AJ. Oasis plus data presentations for <unk> at the end of this month.

Kyle Janais: Based on the Phase 3 results, we anticipate that Donnie Delorsin could evolve the HEE prophylactic treatment paradigm and address the unmet needs of patients. Patients tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability and administration profile, and we believe that Donny D'Lorsan could be that medicine. Donnie Doloresan has the potential to extend dosing at intervals to every four to eight weeks using an auto-injector. The current standard of care is dosed every two to four weeks using a vial and syringe.

Kyle Janais: Based on the phase III results, we anticipate danita lorson could evolve DHA prophylactic treatment paradigm and address the unmet needs of patients.

Oasis plus data presentations for <unk> at the end of this month.

The Oasis plus presentations will include open label extension data in patients treated up to one and a half years. In addition, we will be presenting data from the first of its kind switch study, which we believe will be very informative for physicians and patients for two important reasons. First, we expect these data will assist physicians in understanding how to manage patients effectively when switching to DONIDALORSEN. And second, these data will include a patient preference survey answering the important question do you prefer DONIDALORSEN or your prior treatment. With positive phase III and long term phase II OLE data together with every four or eight week self administration, we believe DONIDALORSEN could be an important new prophylactic treatment for HAE if approved.

Kyle Janais: <unk> tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability and administration profile and we believe that <unk> could be that medicine.

Kyle Jenne: In addition, we are also expanding our market access capabilities with trade and distribution and account management teams to interact directly with payers, integrated delivery networks, and other essential reimbursement channels. As we prepare for the sHTG indication, we plan to further scale all of these capabilities to realize the full potential of olezarsen. Donidalorsen, for the prophylactic treatment of HAE, is our next planned launch after olezarsen. And just like olezarsen, we recently initiated an expanded access program for donidalorsen in the US so that patients have access to treatment ahead of potential approval. HAE is an attractive opportunity for IONIS. There are more than 20,000 patients with HAE in the US and Europe. Within the US, prophylactic treatment is well accepted by patients and physicians. We know where this concentrated base of treating physicians are, and they are primarily located in large centers of excellence.

Kyle Janais: <unk> has the potential to extend dosing intervals to every four to eight weeks using an auto injector. The current standard of care is dosed every two to four weeks using a vial and syringe.

<unk> patients effectively when switching to <unk> and second these data will include a patient preference survey answering the important question do you before Dani <unk> or do you or your prior treatment. With positive phase III in long term phase II <unk> data together with every four or eight week self administration, we believe <unk> could be an important new prophylactic treatment for <unk> if approved.

Kyle Janais: We're looking forward to the upcoming Phase 3 OASIS-HAE and OASIS Plus data presentations for Donnie Lawerson at the end of this month. The OASIS Plus presentations will include open-label extension data in patients treated up to one and a half years. In addition, we will be presenting data from a first-of-its-kind switch study, which we believe will be very informative for physicians and patients for two important reasons. First, we expect these data will assist physicians in understanding how to manage patients effectively when switching to Donnie Delorsin.

Kyle Janais: We're looking forward to the upcoming phase III Oasis AJ.

Kyle Janais: Oasis plus data presentations for <unk> at the end of this month.

With positive phase III in long term phase II <unk> data together with every four or eight week self administration, we believe <unk> could be an important new prophylactic treatment for <unk> if approved.

Kyle Janais: The Oasis plus presentations will include open label extension data in patients treated up to one and a half years and.

Kyle Janais: In addition, we will be presenting data from the first of its kind switch study, which we believe will be very informative for physicians and patients for two important reasons first we expect these data will assist physicians and understanding how to manage patients effectively when switching to <unk> and second these data will include a patient preference surge.

I'm pleased to say that we are right where we should be in preparing for our upcoming launches. Our commercial infrastructure 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. This is a very exciting time for Ionis and I'm proud to be a part of it. Now over to Beth.

Kyle Janais: And second, these data will include a patient preference survey answering the important question, do you prefer Donnie Delorsin or your prior treatment? With positive Phase 3 and long-term Phase 2 OLE data, together with every 4 or 8 weeks of self-administration, we believe Donnie Lorsen could be an important new prophylactic treatment for HAP if approved. I'm pleased to say that we are right where we should be in preparing for our upcoming launches. Our commercial infrastructure is in place, and we will be ready to begin delivering our medicines to people in need as these new therapies come to market. This is a very exciting time for Ionis, and I'm proud to be a part of it. Now, over to Beth. Thank you, Kyle.

Beth Hougen: Thank you Kyle and I couldn't agree more. This really is an exciting time at Ionis as we launch our first co-commercialized medicine and we are closer than ever to bringing a steady cadence of our own medicine to the market. Our first quarter financial results reflect our progress toward achieving this important goal. We earned revenues of $119 million in the first quarter. Half of our revenue was from commercial products comprised primarily of substantial [inaudible] royalties. Our commercial revenue also included the addition of royalties from the U.S launch of WAINUA. The other half of our revenue was from programs under our R&D collaborations, reflecting the value that our pipeline and technology continued to generate.

Beth: <unk> answering the important question do you have before Dani <unk> or do you or your prior treatment.

Kyle Jenne: Many patients with HAE are unsatisfied with their current treatments and looking for an option that reduces frequency and severity of attacks with attractive tolerability and convenience. We plan to build an efficiently sized field team to reach prescribers and support the needs of these patients. Based on the Phase 3 results, we anticipate donidalorsen could evolve the HAE prophylactic treatment paradigm and address the unmet needs of patients. Patients tell us that they would welcome a medicine that provides strong efficacy along with an attractive tolerability administration profile. We believe that donidalorsen could be that medicine. Donidalorsen has the potential to extend dosing at intervals to every 4 to 8 weeks using an autoinjector. The current standard of care is dosed every 2 to 4 weeks using a vial and syringe.

Beth: With positive phase III in long term phase II <unk> data together with every four or eight week self administration, we believe <unk> could be an important new prophylactic treatment for <unk> if approved.

And we are closer than ever to bringing a steady cadence of our own medicine to the market. Our first quarter financial results reflect our progress toward achieving this in part in the call. We earned revenues of $119 million in the first quarter. Half of our revenue was from commercial products comprised primarily of substantial stay lots of royalties. Our commercial revenue also included the addition of royalties from the U S line simply Neil. The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Our first quarter financial results reflect our progress toward achieving this in part in the call. We earned revenues of $119 million in the first quarter. Half of our revenue was from commercial products comprised primarily of substantial stay lots of royalties. Our commercial revenue also included the addition of royalties from the U S line simply Neil. The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Kyle Janais: <unk>.

Beth: I am pleased to say that we are right, where we should be in preparing for our upcoming launches our commercial infrastructure 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.

We earned revenues of $119 million in the first quarter. Half of our revenue was from commercial products comprised primarily of substantial stay lots of royalties. Our commercial revenue also included the addition of royalties from the U S line simply Neil. The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Half of our revenue was from commercial products comprised primarily of substantial stay lots of royalties. Our commercial revenue also included the addition of royalties from the U S line simply Neil. The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Kyle Janais: This is a very exciting time for eye on us and I am proud to be a part of it now over to Beth. Thank you Kyle and I Couldnt agree more this really is an exciting time at <unk> as we launch our first co commercialize medicine.

Our commercial revenue also included the addition of royalties from the U S line simply Neil. The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Beth: Thank you, Kyle. And I couldn't agree more.

The other half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

Beth: And we are closer than ever to bringing a steady cadence of our own medicine to the market.

Our non-GAAP operating expenses modestly increased year over year, as we continue to invest our capital resources towards growth opportunities. As expected, our SG&A expenses increased as we and AstraZeneca initiated the launch of WAINUA in the U.S and as we made investments ahead of the OLZARSEN and DONIDALORSEN launches. Our R&D expenses also increased due to the timing of our late stage program activities. We expect our R&D expenses to stabilize this year as several late stage studies have ended. And we ended the first quarter with cash and investments of $2.2 billion. Our first quarter results keep us on track to meet our 2024 financial guidance.

Beth: This really is an exciting time at Ionis as we launch our first co-commercialized medicine, and we are closer than ever to bringing a steady cadence of our own medicines to the market. Our first quarter financial results reflect our progress toward achieving this important goal. We earned revenues of $119 million in the first quarter.

Kyle Jenne: We're looking forward to the upcoming phase 3 OASIS HAE and OASIS Plus data presentations for donidalorsen at the end of this month. The OASIS Plus presentations will include open-label extension data in patients treated up to one and a half years. In addition, we will be presenting data from the first of its kind switch study, which we believe will be very informative for physicians and patients for two important reasons. First, we expect these data will assist physicians in understanding how to manage patients effectively when switching to donidalorsen. And second, these data will include a patient preference survey answering the important question, "Do you prefer donidalorsen or your prior treatment?" With positive phase 3 and long-term phase 2 OLE data together with every 4 or 8-week self-administration, we believe donidalorsen could be an important new prophylactic treatment for HAE if approved.

Beth: Our first quarter financial results reflect our progress toward achieving this in part in the call.

Beth: We earned revenues of $119 million in the first quarter.

As expected our SG&A expenses increased as we and Astrazeneca initiated the launch of <unk> in the U S and as we made investments ahead of the oldest and gone into less and launch it. Our R&D expenses also increased due to the timing of our late stage program activities.

Beth: Half of our revenue was from commercial products comprised primarily of substantial Spinraza royalties. Our commercial revenue also included the addition of royalties from the U.S. launch of We Knew. The other half of our revenue was from programs under our R&D collaborations, reflecting the value that our pipeline and technology continue to generate. Our non-GAAP operating expenses modestly increased year over year as we continued to invest our capital resources toward growth opportunities. As expected, our SG&A expenses increased as we and AstraZeneca initiated the launch of We Knew It in the U.S., and as we made investments ahead of the Ola Zarson and Diana Doloresan launches.

Beth: Half of our revenue was from commercial products comprised primarily of substantial.

Beth: Our royalties.

Beth: Our commercial revenue also included the addition of royalties from the U S lines simply new App.

Our R&D expenses also increased due to the timing of our late stage program activities.

Beth: Half of our revenue is from programs under our R&D collaborations, reflecting the value in our pipeline and technology continued to January.

We expect R&D expenses to stabilize this year at several late stage studies have ended.

And we ended the first quarter with cash and investments of $2 $2 billion.

Beth: Our non-GAAP operating expenses modestly increased year over year, as we continued to invest our capital resources towards growth opportunities.

Our first quarter results keep us on track to meet our 2024 financial guidance. Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestone, license fees, and R&D funding from partners. For example, we will earn $20 million if [inaudible] is approved in the EU and $30 million if WAINUA is approved in the EU. Additionally, we expect our royalty revenue to grow as the WAINUA launch ramps up and as the [inaudible] launch gets underway assuming approval.

Our first quarter results keep us on track to meet our 2024 financial guidance.

Beth: As expected our SG&A expenses increased as we and Astrazeneca initiated the launch of <unk> in the U S and as we made investments ahead of the <unk> launch it.

Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestone, license fees, and R&D funding from partners. For example, we will earn $20 million if [inaudible] is approved in the EU and $30 million if WAINUA is approved in the EU. Additionally, we expect our royalty revenue to grow as the WAINUA launch ramps up and as the [inaudible] launch gets underway assuming approval. We continue to project our full year 2024 operating expenses to increase in the mid to high single digit percent range compared to 2023, excluding the impact of one time costs last year.

Beth: Our R&D expenses also increased due to the timing of our late-stage program activities. We expect our R&D expenses to stabilize this year as several late-stage studies have ended. And we ended the first quarter with cash and investments of $2.2 billion.

Beth: Our R&D expenses also increased due to the timing of our late stage program activities. We expect our R&D expenses to stabilize this year at several late stage studies have ended.

Kyle Jenne: I'm pleased to say that we are right where we should be in preparing for our upcoming launches. Our commercial infrastructure 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. This is a very exciting time for Ionis, and I'm proud to be a part of it. Now over to Beth.

For example, we will add $20 million if <unk> is approved in the EU and $30 million. If we knew it is approved in the EU. Additionally, we expect our royalty revenue to grow as the renewal launch ramps up and as the Cal side I E. The launch gets underway assuming approval.

Additionally, we expect our royalty revenue to grow as the renewal launch ramps up and as the Cal side I E. The launch gets underway assuming approval.

Beth: And we ended the first quarter with cash and investments of $2 2 billion.

Beth: Our first quarter results keep us on track to meet our 2024 financial guidelines. Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestones, license fees, and R&D funding from partners. For example, we will earn $20 million if CalSATI is approved in the EU and $30 million if WENUA is approved in the EU. Additionally, we expect our royalty revenue to grow as the WENUA launch ramps up and as the CalSATI EU launch gets underway, assuming approval.

Beth: Our first quarter results keep us on track to meet our 2024 financial guidance.

Elizabeth L. Hougen: Thank you, Kyle. I couldn't agree more. This really is an exciting time at Ionis as we launch our first co-commercialized medicine. We are closer than ever to bringing a steady cadence of our own medicines to the market. Our Q1 financial results reflect our progress toward achieving this important goal. We earned revenues of $119 million in Q1. Half of our revenue was from commercial products comprised primarily of substantial SPINRAZA royalties. Our commercial revenue also included the addition of royalties from the U.S. launch of WAINUA. The other half of our revenue was from programs under our R&D collaborations reflecting the value that our pipeline and technology continue to generate. Our non-GAAP operating expenses modestly increased year-over-year as we continued to invest our capital resources toward growth opportunities.

Beth Hougen: Thank you, Kyle. I couldn't agree more. This really is an exciting time at Ionis as we launch our first co-commercialized medicine. We are closer than ever to bringing a steady cadence of our own medicines to the market. Our Q1 financial results reflect our progress toward achieving this important goal. We earned revenues of $119 million in Q1. Half of our revenue was from commercial products comprised primarily of substantial SPINRAZA royalties. Our commercial revenue also included the addition of royalties from the U.S. launch of WAINUA. The other half of our revenue was from programs under our R&D collaborations reflecting the value that our pipeline and technology continue to generate. Our non-GAAP operating expenses modestly increased year-over-year as we continued to invest our capital resources toward growth opportunities.

We continue to project our full year 2024 operating expenses to increase in the mid to high single digit percent range compared to 2023, excluding the impact of one time costs last year. This increase will be driven primarily from SG&A expenses as we continue investing in our go to market activities to support our planned independent launches and our minority portion of WAINUA's sales and marketing costs, which are in the high teens to low 20% range. We expect to end the year with $1.7 billion in cash and investments. And as we invest in the substantial opportunities before us today that we expect we'll unlock next level value. So as you can see, we delivered a solid first quarter and now I'd like to provide you with a compelling financial vision of our clear path to drive increased value.

We continue to project our full year 2020 for operating expenses to increase in the mid to high single digit percent range compared to 2023, excluding the impact of one time costs flat share.

Beth: Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestone and license fees and R&D funding from partners.

This increase will be driven primarily from SG&A expenses as we continue investing in our go to market activities to support our planned independent launches and our minority portion of WAINUA's sales and marketing costs, which are in the high teens to low 20% range. We expect to end the year with $1.7 billion in cash and investments. And as we invest in the substantial opportunities before us today that we expect we'll unlock next level value. So as you can see, we delivered a solid first quarter and now I'd like to provide you with a compelling financial vision of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly-owned programs, we have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us, we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

Beth: For example, we will add $20 million if <unk> is approved in the EU and $30 million. If we knew it is approved in the EU. Additionally, we expect our royalty revenue to grow as the renewal launch ramps up and as the Cal side EU launch gets underway assuming approval.

Thanks, Sharon in the high teens to low 20% range. We expect to end the year with $1 $7 billion in cash and investments. And as we invest in a substantial opportunities before us today that we expect well I'm not next level value. So as you can see we delivered a solid first quarter and now I'd like to provide you with a compelling financial division of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

We expect to end the year with $1 $7 billion in cash and investments. And as we invest in a substantial opportunities before us today that we expect well I'm not next level value. So as you can see we delivered a solid first quarter and now I'd like to provide you with a compelling financial division of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

Beth: We continue to project our full year 2024 operating expenses to increase in the mid to high single digit percent range compared to 2023, excluding the impact of one-time costs last year. This increase will be driven primarily by SG&A expenses as we continue investing in our go-to-market activities to support our planned independent launches and our minority portion of Wynua's sales and marketing costs, which are in the high teens to low 20% range.

Beth: We continue to project our full year 2020 for operating expenses to increase in the mid to high single digit percent range compared to 2023, excluding the impact of one time costs flat share.

And as we invest in a substantial opportunities before us today that we expect well I'm not next level value. So as you can see we delivered a solid first quarter and now I'd like to provide you with a compelling financial division of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

So as you can see we delivered a solid first quarter and now I'd like to provide you with a compelling financial division of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

Beth: This increase will be driven primarily from SG&A expenses as we continue investing in our go to market activities to support our planned independent launches and our minority portion of when U S sales and marketing costs.

Elizabeth L. Hougen: As expected, our SG&A expenses increased as we and AstraZeneca initiated the launch of WAINUA in the U.S. and as we made investments ahead of the olezarsen and donidalorsen launches. Our R&D expenses also increased due to the timing of our late-stage program activities. We expect our R&D expenses to stabilize this year as several late-stage studies have ended. We ended the first quarter with cash and investments of $2.2 billion. Our first quarter results keep us on track to meet our 2024 financial guidance. Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestones, license fees, and R&D funding from partners. For example, we will earn $20 million if QALSODY is approved in the EU and $30 million if WAINUA is approved in the EU.

Beth Hougen: As expected, our SG&A expenses increased as we and AstraZeneca initiated the launch of WAINUA in the U.S. and as we made investments ahead of the olezarsen and donidalorsen launches. Our R&D expenses also increased due to the timing of our late-stage program activities. We expect our R&D expenses to stabilize this year as several late-stage studies have ended. We ended the first quarter with cash and investments of $2.2 billion. Our first quarter results keep us on track to meet our 2024 financial guidance. Looking ahead, we project our revenues in subsequent quarters to be modestly higher compared to the first quarter based on anticipated regulatory milestones, license fees, and R&D funding from partners. For example, we will earn $20 million if QALSODY is approved in the EU and $30 million if WAINUA is approved in the EU.

With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

With a rich pipeline that includes a growing number of wholly-owned programs, we have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us, we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

Beth: Karen in the high teens to low 20% range.

Beth: We expect to end the year with $1.7 billion in cash and investment, and as we invest in the substantial opportunities before us today, we expect will unlock next-level value. As you can see, we delivered a solid first quarter, and now I'd like to provide you with a compelling financial vision of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly owned programs, we have a clear path to positive cash flow, powered by sustained revenue growth. To fully realize the opportunities before us, we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

To fully realize the opportunities before us we will continue to make significant investments over the next few years. We are investing efficiently in four key areas.

Beth: We expect to end the year with $1 7 billion in cash and investments and as we invest in a substantial opportunities before us today that we expect.

We are investing efficiently in four key areas.

Beth: Next level value.

First, as you just heard from Kyle, we are making significant investments in the launch of WAINUA in the United States. To execute on a successful launch for this important medicine, we built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for OLEZARSEN and DONIDALORSEN. As we prepare for these launches over the next couple of years, we will scale our capabilities and increase our go to market activities in line with the combined multibillion dollar revenue potential that these medicines represent.

Beth: So as you can see we delivered a solid first quarter and now I'd like to provide you with a compelling financial division of our clear path to drive increased value.

To execute on a successful launch for this important medicine, we built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for all those assays and dining to worsen. As we prepare for these launches over the next couple of years, we will scale, our capabilities and increase our go to market activities in line with the combined multibillion dollar revenue potential that these medicines represent.

Beth: With a rich pipeline that includes a growing number of wholly owned programs. We have a clear path to positive cash flow powered by sustained revenue growth.

As we prepare for these launches over the next couple of years, we will scale, our capabilities and increase our go to market activities in line with the combined multibillion dollar revenue potential that these medicines represent.

Beth: To fully realize the opportunities before us we will continue to make significant investments over the next few years.

Beth: We are investing efficiently in four key areas.

Elizabeth L. Hougen: Additionally, we expect our royalty revenue to grow as the WAINUA launch ramps up and as the QALSODY EU launch gets underway assuming approval. We continue to project our full year 2024 operating expenses to increase in the mid- to high single-digit % range compared to 2023, excluding the impact of one-time costs last year. This increase will be driven primarily from SG&A expenses as we continue investing in our go-to-market activities to support our planned independent launches and our minority portion of WAINUA's sales and marketing costs, which are in the high teens to low 20% range. We expect to end the year with $1.7 billion in cash and investments. And as we invest in the substantial opportunities before us today that we expect will unlock next-level value. So as you can see, we delivered a solid first quarter.

Beth Hougen: Additionally, we expect our royalty revenue to grow as the WAINUA launch ramps up and as the QALSODY EU launch gets underway assuming approval. We continue to project our full year 2024 operating expenses to increase in the mid- to high single-digit % range compared to 2023, excluding the impact of one-time costs last year. This increase will be driven primarily from SG&A expenses as we continue investing in our go-to-market activities to support our planned independent launches and our minority portion of WAINUA's sales and marketing costs, which are in the high teens to low 20% range. We expect to end the year with $1.7 billion in cash and investments. And as we invest in the substantial opportunities before us today that we expect will unlock next-level value. So as you can see, we delivered a solid first quarter.

Beth: First, as you just heard from Kyle, we are making significant investments in the launch of WENUA in the United States. To execute on a successful launch for this important medicine, we have built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for Olisarsen and Donnie DeLorsen. As we prepare for these launches over the next couple of years, we will scale our capabilities and increase our go-to-market activities in line with the combined, multibillion-dollar revenue potential that these medicines represent.

Beth: First as you just heard from Kyle we are making significant investments in the launch of <unk> in the United States.

Second, we will continue to invest in advancing our late stage medicines. We expect that our level of investment in this area will be relatively stable over the next few years because first of all, all of our large phase III studies today are at or near full enrollment, which is the heaviest period of investment. And we have concluded several studies recently and are now able to re allocate R&D resources from these programs to our third area of investment, or earlier stage wholly-owned program. Our investments in advancing these programs set us up to deliver our next wave of medicines to patients.

We expect that our level of investment in this area will be relatively stable over the next few years. First of all all of our large phase III studies today are at or near full enrollment. Is the heaviest period of investment. And we have concluded several studies recently and are now able to re allocate R&D resources from these programs to our third area of investment. Earlier stage wholly owned program. Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth: To execute on a successful launch for this important medicine, we built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for all those assays and Donny Larson.

First of all all of our large phase III studies today are at or near full enrollment. Is the heaviest period of investment. And we have concluded several studies recently and are now able to re allocate R&D resources from these programs to our third area of investment. Earlier stage wholly owned program. Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Is the heaviest period of investment. And we have concluded several studies recently and are now able to re allocate R&D resources from these programs to our third area of investment. Earlier stage wholly owned program. Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth: As we prepare for these launches over the next couple of years, we will scale, our capabilities and increase our go to market activities in line with the combined multibillion dollar revenue potential that these medicines represent.

And we have concluded several studies recently and are now able to re allocate R&D resources from these programs to our third area of investment. Earlier stage wholly owned program. Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Earlier stage wholly owned program. Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth: Second, we will continue to invest in advancing our late-stage benefits. We expect that our level of investment in this area will be relatively stable over the next few years because, first of all, all of our large phase three studies today are at or near full enrollment, which is the heaviest period of investment. We have concluded several studies recently and are now able to reallocate R&D resources from these programs to our third area of investment, our earlier stage wholly owned program.

Our investment in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth: Second we will continue to invest in advancing our late stage medicines.

Beth: We expect that our level of investment in this area will be relatively stable over the next few years because first of all all of our large phase III studies today are at or near full enrollment, which is the heaviest period of investments and we have concluded several studies recently and are now able to be Alex.

And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile. With these investments, we have an outsized opportunity to deliver medicines to patients in need, which in turn positions us to earn multibillion dollar revenue and achieve positive cash flow on a sustained basis. This slide depicts these opportunities and as you can see, we have many medicines that can power our revenue growth. Beyond our upcoming launches for OLAZARSEN for FCS and DONIDALORSEN for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of OLAZARSEN, our wholly-owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine we expect to bring to patients over the near to mid term, including ZILGANERSEN for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

With these investments we have an outsized opportunity to deliver medicines to patients in need which in turn positions us to earn multibillion dollar revenue and achieve positive cash flow on a sustained basis. This slide depicts these opportunity and as you can see we have many medicines that can power our revenue growth. Beyond our upcoming launches for <unk> for FCS and Donna to worsen for HLA, we have several additional wholly owned medicines in development that could reach patients over the next several years. This includes our planned launch of <unk>, our wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha nursing for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Elizabeth L. Hougen: Now I'd like to provide you with a compelling financial vision of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly-owned programs, we have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us, we will continue to make significant investments over the next few years. We are investing efficiently in four key areas. First, as you just heard from Kyle, we are making significant investments in the launch of WAINUA in the United States. To execute on a successful launch for this important medicine, we built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for olezarsen and donidalorsen.

Beth Hougen: Now I'd like to provide you with a compelling financial vision of our clear path to drive increased value. With a rich pipeline that includes a growing number of wholly-owned programs, we have a clear path to positive cash flow powered by sustained revenue growth. To fully realize the opportunities before us, we will continue to make significant investments over the next few years. We are investing efficiently in four key areas. First, as you just heard from Kyle, we are making significant investments in the launch of WAINUA in the United States. To execute on a successful launch for this important medicine, we built key commercial functions and are gaining important experience that we can leverage as we prepare for our upcoming launches for olezarsen and donidalorsen.

Beth: Kate R&D resources from these programs to our third area of investment are earlier stage wholly owned program.

This slide depicts these opportunities and as you can see, we have many medicines that can power our revenue growth. Beyond our upcoming launches for OLAZARSEN for FCS and DONIDALORSEN for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of OLAZARSEN, our wholly-owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine we expect to bring to patients over the near to mid term, including ZILGANERSEN for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

This slide depicts these opportunities and as you can see, we have many medicines that can power our revenue growth. Beyond our upcoming launches for OLEZARSEN for FCS and DONIDALORSEN for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of OLEZARSEN, our wholly-owned medicine for the treatment of severe high triglycerides that has blockbuster potential.

This slide depicts these opportunity and as you can see we have many medicines that can power our revenue growth. Beyond our upcoming launches for <unk> for FCS and Donna to worsen for HLA, we have several additional wholly owned medicines in development that could reach patients over the next several years. This includes our planned launch of <unk>, our wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha nursing for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Beth: Our investments in advancing these programs set us up to deliver our next wave of medicines to patients. And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles. With these investments, we have an outsized opportunity to deliver medicines to patients in need, which in turn positions us to earn multi-billion dollar revenues and achieve positive cash flow on a sustained basis. This slide depicts these opportunities, and as you can see, we have many medicines that can power our revenue growth.

Beth: Our investments in advancing these programs set us up to deliver our next wave of medicines to patients.

Beyond our upcoming launches for <unk> for FCS and Donna to worsen for HLA, we have several additional wholly owned medicines in development that could reach patients over the next several years. This includes our planned launch of <unk>, our wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha nursing for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Beth: And finally, we are investing in cutting edge technologies to ensure we continue to deliver innovative medicines with competitive profile.

Beth: With these investments we have an outsized opportunity to deliver medicines to patients in need which in turn positions us to earn multibillion dollar revenue and achieve positive cash flow on a sustained basis.

This includes our planned launch of <unk>, our wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha nursing for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine we expect to bring to patients over the near to mid term, including ZILGANERSEN for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha nursing for Alexander disease, which is currently in phase III development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

Beth: This slide depicts these opportunity and as you can see we have many medicines that can power our revenue growth.

Elizabeth L. Hougen: As we prepare for these launches over the next couple of years, we will scale our capabilities and increase our go-to-market activities in line with the combined multi-billion dollar revenue potential that these medicines represent. Second, we will continue to invest in advancing our late-stage medicine. We expect that our level of investment in this area will be relatively stable over the next few years because, first of all, all of our large Phase 3 studies today are at or near full enrollment, which is the heaviest period of investment. And we have concluded several studies recently and are now able to reallocate R&D resources from these programs to our third area of investment, our earlier stage wholly-owned programs. Our investments in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth Hougen: As we prepare for these launches over the next couple of years, we will scale our capabilities and increase our go-to-market activities in line with the combined multi-billion dollar revenue potential that these medicines represent. Second, we will continue to invest in advancing our late-stage medicine. We expect that our level of investment in this area will be relatively stable over the next few years because, first of all, all of our large Phase 3 studies today are at or near full enrollment, which is the heaviest period of investment. And we have concluded several studies recently and are now able to reallocate R&D resources from these programs to our third area of investment, our earlier stage wholly-owned programs. Our investments in advancing these programs set us up to deliver our next wave of medicines to patients.

Beth: Beyond our upcoming launches for Olazarsan for FCS and Donna Doloresan for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of Oluzar, a wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential. Additionally, we have a growing pipeline of potential groundbreaking disease-modifying neurology medicines we expect to bring to patients over the near-to-midterm, including Zilkonercin for Alexander disease, which is currently in Phase 3 development.

Beth: Beyond our upcoming launches for <unk> for FCS and Donna to listen for HCA. We have several additional wholly owned medicines in development that could reach patients over the next several years.

We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

These include PELACARSEN, a first-in-class investigational medicine that Novartis is developing to address the millions of patients with LP [inaudible] driven cardiovascular disease. Data and a regulatory submission for PELACARSEN are planned for next year. The [inaudible] is an investigational medicine that GSK is developing in a large phase III programs to treat the millions of patients with HBV infection. And of course, we have WAINUA with the ATTR polyneuropathy launch on track and our landmark cardio transform study progressing well. We believe that WAINUA has the potential to become the preferred treatment for ATTR in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments and that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

Beth: This includes our planned launch of <unk>, our wholly owned medicine for the treatment of severe high triglycerides that has blockbuster potential.

Beth: Additionally, we have a growing pipeline of potential groundbreaking disease modifying neurology medicine, we expect to bring to patients over the near to mid term, including Zilkha Nordson for Alexander disease, which is currently in phase III development.

Data and a regulatory submission for Pellekar are planned for next year. The peer person an investigational medicine that GSK is developing in a large phase III programs to treat the millions of patients with HBV infection. And of course, we have renewals with the <unk> Polyneuropathy launch on track and our landmark cardio transform steady progressing well, we believe that we knew it has the potential to become the preferred treatment for <unk> in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

The peer person an investigational medicine that GSK is developing in a large phase III programs to treat the millions of patients with HBV infection. And of course, we have renewals with the <unk> Polyneuropathy launch on track and our landmark cardio transform steady progressing well, we believe that we knew it has the potential to become the preferred treatment for <unk> in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

Beth: We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones, assuming continued advancement. These include Pelicarsin, a first-in-class investigational medicine that Novartis is developing to address the millions of patients with Lp little a driven cardiovascular disease. Data and a regulatory submission for Pellicarson are planned for next year.

Beth: We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement.

And of course, we have WAINUA with the ATTR polyneuropathy launch on track and our landmark cardio transform study progressing well. We believe that WAINUA has the potential to become the preferred treatment for ATTR in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments and that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

And of course, we have renewals with the <unk> Polyneuropathy launch on track and our landmark cardio transform steady progressing well, we believe that we knew it has the potential to become the preferred treatment for <unk> in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

Beth: These include pellet Carson a first in class investigational medicine that Novartis is developing to address the millions of patients with LP literally driven cardiovascular disease.

Elizabeth L. Hougen: And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles. With these investments, we have an outsized opportunity to deliver medicines to patients in need, which in turn positions us to earn multi-billion-dollar revenues and achieve positive cash flow on a sustained basis. This slide depicts these opportunities. As you can see, we have many medicines that can power our revenue growth. Beyond our upcoming launches for olezarsen for FCS and donidalorsen for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of olezarsen, our wholly-owned medicine for the treatment of severe high triglycerides that has blockbuster potential.

Beth Hougen: And finally, we are investing in cutting-edge technologies to ensure we continue to deliver innovative medicines with competitive profiles. With these investments, we have an outsized opportunity to deliver medicines to patients in need, which in turn positions us to earn multi-billion-dollar revenues and achieve positive cash flow on a sustained basis. This slide depicts these opportunities. As you can see, we have many medicines that can power our revenue growth. Beyond our upcoming launches for olezarsen for FCS and donidalorsen for HAE, we have several additional wholly-owned medicines in development that could reach patients over the next several years. This includes our planned launch of olezarsen, our wholly-owned medicine for the treatment of severe high triglycerides that has blockbuster potential.

All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

Beth: Data and a regulatory submission for <unk> are planned for next year.

Beth: The peer-to-peer and investigational medicine that GSK is developing in a large phase 3 program to treat millions of patients with HBV infection. And, of course, we have Waynua, with the ATTR polyneuropathy launch on track and our landmark CardioTransform study progressing well. We believe that Waynua has the potential to become the preferred treatment for ATTR in this substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments.

And that's in addition to royalties up to the mid 20% range. And all of this is on top of our substantial and sustainable current revenues.

Beth: The peer berson and investigational medicine that GSK is developing in a large phase III programs to treat the millions of patients with HBV infection.

And all of this is on top of our substantial and sustainable current revenues.

Beth: And of course, we have renewals with the <unk> Polyneuropathy launch on track and our landmark cardio transform steady progressing well.

So as you can see, over the next few years, we plan to make strategic investments in our commercial opportunities and advancing our rich pipeline and in our technology. We expect these investments to power strong revenue growth and positive cash flow as our medicines reach more patients in need positioning us to deliver next level of value for all Ionis stakeholders for years to come. And with that, I'll turn the call back to Brett.

Beth: We believe that we knew and has the potential to become the preferred treatment for <unk> in the substantial and growing market.

Beth: All of these programs combined could generate up to $6 billion in milestone payments.

And need positioning us to deliver next to that next level of value for all and stakeholders for years to come and with that I'll turn the call back to Beth.

Beth: And that's in addition to royalties up to this mid-20% range. And all of this is on top of our substantial and sustainable current revenue. As you can see, over the next few years, we plan to make strategic investments in our commercial opportunities, in Advancing Our Rich Pipeline, and in Our Technology. We expect these investments to power strong revenue growth and positive cash flow as our medicines reach 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 to Brett. Thank you, Beth.

Beth: And that's in addition to royalties up to the mid 20% range.

Beth: And all of this is on top of our substantial and sustainable current revenues.

Brett P. Monia: Thank you Beth. Indeed, Ionis is well positioned to continue building on our positive momentum as we execute on all our strategic priorities. We have 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. We've established Ionis as a leader in [inaudible] therapeutics with several approved drugs and one of the richest mid and late stage pipelines in the industry. Our pipeline is delivering. We achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. We've prioritized building our wholly-owned pipeline and we expect to advance several of these medicines into clinical development this year.

Indeed, I own this is well positioned to continue building on our positive momentum as we execute on all our strategic priorities. We have arrived where we are today, but being focused on a clear vision and a clear set of strategic objectives, which. Which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients. We've established <unk> as a leader in <unk> therapeutics with several approved drugs and one of the richest mid and late stage pipelines in the industry. Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. Prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

Elizabeth L. Hougen: Additionally, we have a growing pipeline of potential groundbreaking disease-modifying neurology medicines we expect to bring to patients over the near to mid-term, including zilganersen for Alexander disease, which is currently in phase 3 development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement. These include pelacarsen, a first-in-class investigational medicine that Novartis is developing to address the millions of patients with Lp(a)-driven cardiovascular disease. Data and a regulatory submission for pelacarsen are planned for next year. The bepirovirsen, an investigational medicine that GSK is developing in a large phase 3 program to treat the millions of patients with HBV infection. And of course, we have WAINUA, with the ATTR polyneuropathy launch on track and our landmark CardioTransform study progressing well.

Beth Hougen: Additionally, we have a growing pipeline of potential groundbreaking disease-modifying neurology medicines we expect to bring to patients over the near to mid-term, including zilganersen for Alexander disease, which is currently in phase 3 development. We also have multiple partnered programs that are poised to provide substantial future royalty revenue and sales milestones assuming continued advancement. These include pelacarsen, a first-in-class investigational medicine that Novartis is developing to address the millions of patients with Lp(a)-driven cardiovascular disease. Data and a regulatory submission for pelacarsen are planned for next year. The bepirovirsen, an investigational medicine that GSK is developing in a large phase 3 program to treat the millions of patients with HBV infection. And of course, we have WAINUA, with the ATTR polyneuropathy launch on track and our landmark CardioTransform study progressing well.

Beth: So as you can see over the next few years, we plan to make strategic investments in our commercial opportunities and advancing our rich pipeline and in our technology. We expect these investments to power strong revenue growth and positive cash flow as our medicine beach more patients.

We have arrived where we are today, but being focused on a clear vision and a clear set of strategic objectives, which.

Which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients. We've established <unk> as a leader in <unk> therapeutics with several approved drugs and one of the richest mid and late stage pipelines in the industry. Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. Prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

We've established <unk> as a leader in <unk> therapeutics with several approved drugs and one of the richest mid and late stage pipelines in the industry. Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. Prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

Brett: In need positioning us to deliver next to that next level value for all and its stakeholders for years to come and with that I'll turn the call back to Beth.

Brett P. Monia: Our pipeline is delivering. We achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. We've prioritized building our wholly-owned pipeline and we expect to advance several of these medicines into clinical development this year.

Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. Prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

Brett: Indeed, Ionis is well positioned to continue building on our positive momentum as we execute on all our strategic priorities. 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 conceive, discover, and develop directly to patients. We've established Ionis as a leader in oligonucleotide therapeutics, with several approved drugs and one of the richest mid- and late-stage pipelines in the industry.

Brett: Thank you Beth.

Brett: Indeed, <unk> is well positioned to continue building on our positive momentum as we execute on all our strategic priorities.

Prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

Brett: We've arrived where we are today, but being focused on a clear vision and a clear set of strategic objectives.

Brett: Which include building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients.

In parallel, our partnered programs are progressing on track with key phase III data readouts planned this year, and important phase III readouts next year and beyond. We're extending our leadership position in oligonucleotide therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery. All of this sets us up to continue bringing a steady cadence of new medicines, transformational medicines to patients for years to come.

Brett: We've established <unk> as a leader in OLED nucleotide therapeutics with several approved drugs and one of the richest mid and late stage pipelines in the industry.

We're extending our leadership position in Oregon nucleotide therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery. All of this sets us up to continue bringing a steady cadence of new medicines transformational medicines to patients for years to come.

Elizabeth L. Hougen: We believe that WAINUA has the potential to become the preferred treatment for ATTR in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid-20% range. And all of this is on top of our substantial and sustainable current revenues. So as you can see, over the next few years, we plan to make strategic investments in our commercial opportunities, in advancing our rich pipeline, and in our technology. We expect these investments to power strong revenue growth and positive cash flow as our medicines reach 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 to Beth.

Beth Hougen: We believe that WAINUA has the potential to become the preferred treatment for ATTR in the substantial and growing market. All of these programs combined could generate up to $6 billion in milestone payments. And that's in addition to royalties up to the mid-20% range. And all of this is on top of our substantial and sustainable current revenues. So as you can see, over the next few years, we plan to make strategic investments in our commercial opportunities, in advancing our rich pipeline, and in our technology. We expect these investments to power strong revenue growth and positive cash flow as our medicines reach 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 to Brett.

Brett: Our pipeline is delivering. We achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term. We've prioritized building our wholly owned pipeline, and we expect to advance several of these medicines into clinical development this year. In parallel, our partner programs are progressing on track with key Phase 2 data readouts planned this year and important Phase 3 readouts next year and beyond.

Brett: Our pipeline is delivering we achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on the strong momentum in the near term, we prioritize building our wholly owned pipeline and we expect to advance several of these medicines into clinical development. This year.

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

We're looking forward to sharing our progress as we build on our recent achievements and accomplish all our strategic objectives. And with that, I'll now open the call up for questions. Keith, we can take questions now.

Brett: In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year, an important phase III Readouts next year and beyond.

we can take questions now.

Brett: We're extending our leadership position in oligonucleotide therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas, and opening up new areas for drug discovery. All of this sets us up to continue bringing transformational medicines to patients for years to come.

Brett: We're extending our leadership position in Oregon nucleotide therapeutics by expanding and diversifying our technology further optimizing our capabilities for existing therapeutic areas and opening up new areas for drug discovery.

Operator: Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad.

If you are using a speaker phone, please pick up your handset before pressing the keys. If at anytime your question has been addressed and you would like to withdraw it, please press star then two. At this time, we will pause momentarily to assemble the roster.

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

Operator: And our first question comes from [inaudible] with Guggenheim Securities.

Brett: We're looking forward to sharing our progress as we build on our recent achievements and accomplish all our strategic goals. And with that, I'll now open the call to questions. Steve, we can take questions now. Yes, thank you. We will now begin the question and answer session. To ask a question, you may press star then 1 on your telephone keyboard. If you are using a speakerphone, please raise your hands before pressing the button. If at any time your question has been addressed, and you would like to withdraw,

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

Unknown: Hey, good morning and thanks for taking the questions. Firstly on DONIDALORSEN and OLEZARSEN, between the expanded access the OLE and switch, how many FCS and HAE patients do you currently have on therapy who could be low hanging fruits for the early commercial adoption? So for OLEZARSEN, virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rolled over into the open label extension and they're continuing in that trial

Hey, good morning, and thanks for taking the questions. Firstly on <unk>. <unk>. Between the <unk> expanded access the oily and switch harmony FCS and <unk> patients do you currently have. On therapy, who could be low hanging fruits for the early commercial adoption. So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

Brett Monia: Thank you, Beth. Indeed, Ionis is well positioned to continue building on our positive momentum as we execute on all our strategic priorities. We have 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 conceive, discover, and develop directly to patients. We've established Ionis as a leader in oligonucleotide therapeutics with several approved drugs and one of the richest mid and late-stage pipelines in the industry. Our pipeline is delivering. We achieved multiple marketing approvals and positive key data readouts over the past year and are poised to build on this strong momentum in the near term. We've prioritized building our wholly-owned pipeline, and we expect to advance several of these medicines into clinical development this year.

Firstly on <unk>. <unk>. Between the <unk> expanded access the oily and switch harmony FCS and <unk> patients do you currently have. On therapy, who could be low hanging fruits for the early commercial adoption. So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

<unk>. Between the <unk> expanded access the oily and switch harmony FCS and <unk> patients do you currently have. On therapy, who could be low hanging fruits for the early commercial adoption. So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

Steve: With that I'll now open the call up for questions.

Between the <unk> expanded access the oily and switch harmony FCS and <unk> patients do you currently have. On therapy, who could be low hanging fruits for the early commercial adoption. So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

Brett: Yes.

Operator: Yes, thank you. We will now begin the question and answer session. To ask a question, you may press Star and then 1 on your telephone keypad. 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 it, please press Star then 2. At this time, we will pause momentarily to assemble the raw data. And the first question comes from Debjit Chattopadhyay with Guggenheim Securities.

Steve: We can take questions now thank.

Steve: Thank you we will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad.

On therapy, who could be low hanging fruits for the early commercial adoption. So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

Operator: Speaker phone please pick up your handset before pressing the keys. So anytime your question has been addressed I would like to withdraw it. Please press star then two.

Brett P. Monia: So for OLEZARSEN, virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rolled over into the open label extension and they're continuing in that trial in the open label extension now so that's a pretty good measure there. For the expanded access program for OLEZARSEN in FCS that's just getting started so it's early days, we will provide an update later on, but so far our reception has been very positive. A similar story for DONIDALORSEN, virtually all of the patients that completed the trial, which was the vast majority of them, well in excess of 90% of the patients completed the trial elected to roll over into the open label extension and they've stayed and they've remained in the open label extension. The EAP just got started I think last week.

So for <unk> in virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rollover into the open label extension and they're continuing in that trial.

Operator: Time, we will pause momentarily to assemble the roster.

Debjit D. Chattopadhyay: And our first question comes from David <unk> with Guggenheim Securities.

Debjit D. Chattopadhyay: Hey, good morning, and thanks for taking the questions.

in the open label extension now so that's a pretty good measure there. For the expanded access program for OLEZARSEN in FCS that's just getting started so it's early days, we will provide an update later on, but so far our reception has been very positive. A similar story for DONIDALORSEN, virtually all of the patients that completed the trial, which was the vast majority of them, well in excess of 90% of the patients completed the trial elected to roll over into the open label extension and they've stayed and they've remained in the open label extension. The EAP just got started I think last week. Got it. And one quick one, are there any part D dynamics we should be monitoring with respect to WAINUA launch versus [inaudible].

Debjit D. Chattopadhyay: Firstly on <unk>.

For the expanded access program for <unk> in FCS is just getting started so it's. It's early days, we will provide an update later on but so far our reception has been very positive. A similar story for Donna the worst downturn to worsen. Virtually all of the patients that completed the trial, which was the vast majority of them well in excess of 90% of the patients completing the trial. <unk> to roll over into the open label extension. And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Debjit D. Chattopadhyay: Between the <unk> expanded access the oily and switch harmony FCS and <unk> patients do you currently have.

It's early days, we will provide an update later on but so far our reception has been very positive. A similar story for Donna the worst downturn to worsen. Virtually all of the patients that completed the trial, which was the vast majority of them well in excess of 90% of the patients completing the trial. <unk> to roll over into the open label extension. And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Debjit D. Chattopadhyay: On therapy, who could be low hanging fruits for the early commercial adoption.

Brett Monia: In parallel, our partnered programs are progressing on track with key phase 2 data readouts planned this year and important phase 3 readouts next year and beyond. We're extending our leadership position in oligonucleotide therapeutics by expanding and diversifying our technology, further optimizing our capabilities for existing therapeutic areas, and opening up new areas for drug discovery. All of this sets us up to continue bringing a steady cadence of new medicines, transformational medicines, to patients for years to come. We're looking forward to sharing our progress as we build on our recent achievements and accomplish all our strategic objectives. And with that, I'll now open the call up for questions. Keith, we can take questions now.

A similar story for Donna the worst downturn to worsen. Virtually all of the patients that completed the trial, which was the vast majority of them well in excess of 90% of the patients completing the trial. <unk> to roll over into the open label extension. And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Unknown Executive: So, for Olazarsan, virtually all of the patients, which was approximately 60 patients or so, Eugene, in the phase 3 study, rolled over into the open label extension, and they're continuing in that trial in the open label extension now. So that's, I mean, that's a pretty good measure there.

Virtually all of the patients that completed the trial, which was the vast majority of them well in excess of 90% of the patients completing the trial. <unk> to roll over into the open label extension. And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Debjit D. Chattopadhyay: So for <unk>.

Unknown Executive: Virtually all of the patients, which was approximately 60 patients or so Eugene in the phase III study rolled over into the open label extension and they're continuing in that trial.

<unk> to roll over into the open label extension. And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

And they've stayed and they've remained in the open label extension. The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Unknown Executive: The open label extension now so thats I mean, thats a pretty good measure there.

Unknown Executive: The Extended Access Program for all those ARSEN and FCS is just getting started, so it's early days. We'll provide an update later on, but so far, reception has been very positive. Similar story for Donna DeLorsen. Donna DeLorsen, virtually all of the patients that completed the trial, which was the vast majority, well in excess of 90% of the patients completed the trial, elected to roll over into the open label extension, and they've stayed, and they've remained in the open label extension. The EAP has just got started, I think.

The EAP is just got started with I think last week are down of course. Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Unknown Executive: For the expanded access program for <unk> in FCS is just getting started so.

Got it. And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

And one quick one are there any part D dynamics, we should be monitoring with respect to <unk> launch. Versus a M beautiful.

Unknown: Got it. And one quick one, are there any part D dynamics we should be monitoring with respect to WAINUA launch versus [inaudible].

Unknown Executive: It's early days, we will provide an update later on but so far the reception has been very positive.

Unknown Executive: Similar story for Donna the worrisome onto Lorson.

Versus a M beautiful.

Unknown Executive: Virtually all of the patients that completed the trial, which was the vast majority.

Kyle Jenne: Yes, I'd be happy to talk about that. Thanks for the question. So first I will just say the launch is going really well. The payers are covering the medication as expected. There's experience in this space already with polyneuropathy and so the criteria for use is largely understood from the majority of payers. On the part D side of things, we are continuing to navigate that very efficiently. AstraZeneca is leading the way on the market access side of things and they're doing a fantastic job and our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket support where appropriate for commercial patients and supporting them just through the regular reimbursement process that you would expect and also working directly with the offices. So overall, I think the payer landscape is positive, the patient experience is very positive and we're continuing to execute the launch very effectively.

Operator: Yes. Thank you. We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please raise up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw it, please press star, then two. At this time, we will pause momentarily to assemble the roster. And the first question comes from Dipaji Chavapadhyay with Guggenheim Securities.

Unknown Executive: <unk> in excess of 90% of the patients completing the trial elected to rollover into the open label extension.

First I will just say the launch is going really well the payers are covering the medication as expected theres experience in this space already with Polyneuropathy and so the criteria for uses largely understood from the majority of payers. On the part D side of things, we are continuing to navigate that very efficiently. Astrazeneca is leading the way on the market access side of things and they're doing a fantastic job. In our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket.

Unknown Executive: And they've stayed and they remained in the open label extension.

Unknown Executive: The EAP is just got started with I think last week are down in the world.

On the part D side of things, we are continuing to navigate that very efficiently. Astrazeneca is leading the way on the market access side of things and they're doing a fantastic job. In our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket.

Speaker Change: Got it and one quick one.

Unknown Executive: Any part D dynamics, we should be monitoring with respect to <unk> launch.

Astrazeneca is leading the way on the market access side of things and they're doing a fantastic job. In our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket.

Debjit Chattopadhyay: Hey. Good morning, and thanks for taking the questions. Firstly, on donidalorsen and olezarsen, between the expanded access, the OLE, and switch, how many FCS and HAE patients do you currently have on therapy who could be low-hanging fruits for the early commercial adoption?

Unknown Executive: Versus <unk>.

In our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket.

Unknown Executive: Yeah, I'd be happy to talk about that. Thanks for the question. So first, I'll just say the launch is going really well. The payers are covering the medication as expected. There's experience in the space already with polyneuropathy, and so the criteria for use are largely understood by the majority of payers. On the Part D side of things, we're continuing to navigate that very efficiently. AstraZeneca is leading the way on the market access side of things, and they're doing a fantastic job.

Unknown Executive: Well.

Unknown Executive: Happy to talk about that thanks for the question. So first I'll just say the launch is going really well.

<unk>, where appropriate for commercial patients and supporting them just the regular reimbursement process that you would expect and also working directly with the offices. So overall I think the payer landscape is positive the patient experience is very positive and we're continuing to execute the launch very effectively.

Unknown Executive: The payers are covering the medication as expected.

Unknown Executive: <unk> in this space already with Polyneuropathy and so the criteria for uses largely understood from the majority of payers.

Brett Monia: So for olezarsen, virtually all of the patients, which was approximately 60 patients or so, Eugene, in the phase 3 study rolled over into the open-label extension, and they're continuing in that trial in the open-label extension now. So I mean, that's a pretty good measure there. For the expanded access program for olezarsen and FCS, that's just getting started. So it's early days. We'll provide an update later on. But so far, reception has been very positive. Similar story for donidalorsen. Donidalorsen, virtually all of the patients that completed the trial, which was the vast majority, well, an excess of 90% of the patients completed the trial, elected to roll over into the open-label extension. And they've stayed, and they've remained in the open-label extension. The EAP just got started, I think, last week for donidalorsen.

Unknown Executive: On the part D side of things, we are continuing to navigate that very efficiently.

Unknown: Got it, thank you.

Operator: Thank you. And the next question comes from Gary Nachman with Raymond James.

Unknown Executive: Astrazeneca is leading the way on the market access side of things and they are doing a fantastic job.

Unknown Executive: And our patient services program is really supporting patients effectively to educate them on the process and also provide out-of-pocket support where appropriate for commercial patients and supporting them just through the regular reimbursement process that you would expect and also working directly with the offices. So overall, I think the payer landscape is positive. The patient experience is very positive, and we're continuing to execute the launch very effectively.

Gary Nachman: Thanks guys. So on OLEZARSEN, when will you know the exact review timeline for FCS? I know you're assuming a priority review, but when will that be confirmed? And then talk a bit more about the commercial launch preparations for OLEZARSEN for FCS, how big of a team will you need overall? And describe some of these synergies with the infrastructure already built in there for WAINUA how that could be leveraged.

Unknown Executive: In our patient services program is really supporting patients effectively to educate them on the process and also provide out of pocket.

Unknown Executive: <unk>, where appropriate for commercial patients and supporting them just through the regular reimbursement process that you would expect and also working directly with the offices. So overall I think the payer landscape is positive the patient experience is very positive and we're continuing to execute the launch very effectively.

And then talk a bit more about the commercial launch preparations for <unk> for FCS how big of a team will you need overall. And describe some of these synergies with the infrastructure already built in there for we knew how that could be leveraged.

And describe some of these synergies with the infrastructure already built in there for we knew how that could be leveraged.

Brett P. Monia: Thanks, Gary. I'll take the first one and Kyle could talk a little bit about [inaudible] and plans for commercialization and maybe Jonathan can jump in too. So we expect to hear from the FDA 60 days or so after we submitted and we submitted in April. We submitted in April and it's 60 day timeline for that. Once we hear from the FDA, we will expect to hear about our PDUFA date whether or not are they are expecting to have an outcome, we don't expect to have an outcome, but that would be information that would come in that update. And thirdly, whether we receive priority review as well in addition [inaudible] when we hear from the FDA on the acceptance of the NDA. Kyle, can you talk a little bit about the launch for FCS?

Speaker Change: Got it thank you.

Unknown Executive: Thank you. The next question comes from Gary Nachman with Raymond James.

I'll take the first one and Kyle. Could you talk a little bit about that. And plans for commercialization, maybe Jonathan can jump into. So the we.

Unknown Executive: Thank you and the next question comes from Gary Nachman with Raymond James.

Could you talk a little bit about that. And plans for commercialization, maybe Jonathan can jump into. So the we.

And plans for commercialization, maybe Jonathan can jump into. So the we.

Unknown Executive: Thanks, guys. So on Olazarsan, when will you know the exact review timeline for FCS? I know you're assuming a priority review, but when will that be confirmed? And then we can talk a bit more about the commercial launch preparations for Olazarsan for FCS. How big of a team will you need overall? And describe some of the synergies with the infrastructure already built in there for Waynua and how that could be leveraged.

Gary Nachman: Thanks, guys. So <unk> Lowell you know the exact review timeline for FCS I know youre, assuming a priority review, but when will that be confirmed.

So the we.

We expect to hear from the FDA. 60 days or so after we submitted and we submitted in March. At earn April sorry, we submitted in April and into 60 day timeline for that. Once we hear from the FDA, we will expect to.

Debjit Chattopadhyay: Got it. And one quick one. Are there any Part D dynamics we should be monitoring with respect to Wainua launch versus Amvuttra?

60 days or so after we submitted and we submitted in March. At earn April sorry, we submitted in April and into 60 day timeline for that. Once we hear from the FDA, we will expect to.

Unknown Executive: And then talk a bit more about the commercial launch preparations for <unk> for FCS how big of a team will you need overall.

At earn April sorry, we submitted in April and into 60 day timeline for that. Once we hear from the FDA, we will expect to.

Unknown Executive: And describe some of these synergies with the infrastructure already built in there for <unk>, how that could be leveraged.

Once we hear from the FDA, we will expect to.

Operator: Yeah. I'd be happy to talk about that. Thanks for the question. So first, I'll just say the launch is going really well. The payers are covering the medication as expected. There's experience in the space already with polyneuropathy. And so the criteria for use is largely understood from the majority of payers. On the Part D side of things, we're continuing to navigate that very efficiently. AstraZeneca is leading the way on the market access side of things, and they're doing a fantastic job. And our patient services program is really supporting patients effectively to educate them on the process and also provide out-of-pocket support where appropriate for commercial patients and supporting them just through the regular reimbursement process that you would expect and also working directly with the offices. So overall, I think the payer landscape is positive. The patient experience is very positive.

Kyle Jenne: Yeah. I'd be happy to talk about that. Thanks for the question. So first, I'll just say the launch is going really well. The payers are covering the medication as expected. There's experience in the space already with polyneuropathy. And so the criteria for use is largely understood from the majority of payers. On the Part D side of things, we're continuing to navigate that very efficiently. AstraZeneca is leading the way on the market access side of things, and they're doing a fantastic job. And our patient services program is really supporting patients effectively to educate them on the process and also provide out-of-pocket support where appropriate for commercial patients and supporting them just through the regular reimbursement process that you would expect and also working directly with the offices. So overall, I think the payer landscape is positive. The patient experience is very positive.

Here about our <unk> date. Whether or not. Or are they are expecting to have an AD com. We don't expect to have an outcome, but that would be information that would come in that uptake.

Unknown Executive: Thanks, Gary. I'll take the first one, and Kyle can talk a little bit about the field preparation and plans for commercialization. Maybe Jonathan can jump in, too. So we expect to hear from the FDA 60 days or so after we submit it, and we submitted it in March – or in April, sorry. We submitted it in April, and it's a 60-day timeline for that. Once we hear from the FDA, we'll expect to hear about our PDUFA date.

Whether or not. Or are they are expecting to have an AD com. We don't expect to have an outcome, but that would be information that would come in that uptake.

Speaker Change: Thanks, Gary.

Or are they are expecting to have an AD com. We don't expect to have an outcome, but that would be information that would come in that uptake.

Speaker Change: I'll take the first one and Kyle.

Speaker Change: Could you talk a little bit about.

Unknown Executive: The field <unk>.

Speaker Change: Plans for commercialization, maybe Jonathan can jump into.

And thirdly, a whether we receive priority. View as well. In addition, today and we will announce all of that at the same when we can. When we hear from the FDA on the acceptance of the NDA.

Unknown Executive: So the we.

Unknown Executive: We expect to hear from the FDA.

View as well. In addition, today and we will announce all of that at the same when we can. When we hear from the FDA on the acceptance of the NDA.

In addition, today and we will announce all of that at the same when we can. When we hear from the FDA on the acceptance of the NDA.

Unknown Executive: 60 days or so after we submitted we submitted in March.

When we hear from the FDA on the acceptance of the NDA.

Unknown Executive: At earn April sorry, we submitted in April and has a 60 day timeline for that.

Kyle Jenne: Yes, I'll talk about the synergies and then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go to market strategy there. But the synergies with WAINUA, I think what's important within the organization is first of all we've been very calculated and very measured in terms of the way that we build the internal infrastructure so that we are efficient and being smart about the capabilities that we're building and the timing of that build. We've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up so things like the CRM and data and analytics and those types of infrastructures are in place. Our market access team is doing a fantastic job of doing market insights work and understanding the way that the market is anticipated to look from a payer standpoint, and trade and channel and distribution.

Launch for FCS, Yes, I'll talk about the synergies and then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go to market strategy, there, but the synergies with way new I think what's important within.

Unknown Executive: Once we hear from the FDA, we will expect to.

Unknown Executive: Here about our <unk> date.

Unknown Executive: Whether or not they're expecting to have an ad come, we don't expect to have an ad come, but that would be information that would come in that update. Thirdly, whether we receive priority review as well in addition to that. And we'll announce all that when we hear from the FDA on the acceptance of the NDA. Kyle, talk a little bit about the launch for FCS.

Unknown Executive: Whether or not we.

Kyle Janais: Are they are expecting to have an AD com, we don't expect to have an outcome, but that would be information that would come in that update.

Within the organization is first of all we've been very calculated and very measured in terms of the way that we build the internal infrastructure. So that we are efficient. And being smart about the capabilities that we're building and the timing of that build. What we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up so things like the CRM and data and analytics and those types of infrastructures are in place. Our market access team is doing a fantastic job of doing market insights work in understanding the way that the market is anticipated to look from a payer standpoint, and trade and channel and distribution.

Unknown Executive: And thirdly a.

And being smart about the capabilities that we're building and the timing of that build. What we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up so things like the CRM and data and analytics and those types of infrastructures are in place. Our market access team is doing a fantastic job of doing market insights work in understanding the way that the market is anticipated to look from a payer standpoint, and trade and channel and distribution.

Unknown Executive: Whether we received priority review as well.

Operator: We're continuing to execute the launch very effectively.

Kyle Jenne: We're continuing to execute the launch very effectively.

What we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up so things like the CRM and data and analytics and those types of infrastructures are in place. Our market access team is doing a fantastic job of doing market insights work in understanding the way that the market is anticipated to look from a payer standpoint, and trade and channel and distribution.

Unknown Executive: In addition, today and we will announce all of that is when we when we hear from the FDA on the acceptance of the NDA.

Debjit Chattopadhyay: Got it. Thank you.

Operator: Thank you. And the next question comes from Gary Nachman with Raymond James.

Kyle Janais: I'll talk a little bit about the <unk>.

Kyle Janais: Yeah, I'll talk about the synergies, and then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go-to-market strategy there. But the synergies with Waynua, I think what's important within the organization is, first of all, we've been very calculated and very measured in terms of the way that we build the internal infrastructure so that we're efficient and smart about the capabilities that we're building and the timing of that build.

Kyle Janais: Launched for FCS, Yes, I'll talk about the synergies and then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go to market strategy, there, but the synergies with way Noah I think what's important within the organization is first of all we've been very calculated and very measured in terms of the way that we build the internal infrastructure. So that we are efficient.

Gary Nachman: Thanks, guys. So on olezarsen, when will you know the exact review timeline for FCS? I know you're assuming a priority review, but when will that be confirmed? And then talk a bit more about the commercial launch preparations for olezarsen for FCS. How big of a team will you need overall? And describe some of the synergies with the infrastructure already built in there for WAINUA, how that could be leveraged.

Our market access team is doing a fantastic job of doing market insights work in understanding the way that the market is anticipated to look from a payer standpoint, and trade and channel and distribution.

Kyle Janais: But we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up, so things like the CRM and data and analytics and those types of infrastructures are in place. Our market access team is doing a fantastic job of doing market insights work and understanding the way that the market is anticipated to look from a payer standpoint in trade, channel, and distribution.

Jonathan: And being smart about the capabilities that we're building and the timing of that build.

And finally, and really importantly is the medical affairs group. We established that team a little over three years ago. That team has been interacting with KOLs, they've had strong presence at the congresses, there's been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean overall, I think what you're hearing is the capacity and the ability and the infrastructure and the timing of all of this is really coming together nicely and the execution I've been very impressed with and very pleased with where we're at right now. So Jonathan maybe specific to FCS.

Kyle Janais: What we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group has stood up so things like the CRM and data and analytics and those types of infrastructures are in place.

Brett Monia: Thanks, Gary. I'll take the first one, and Kyle could talk a little bit about the field prep and plans for commercialization. Maybe Jonathan could jump into. So we expect to hear from the FDA 60 days or so after we submitted, and we submitted it in March or in April, sorry. We submitted it in April, and it's a 60-day timeline for that. Once we hear from the FDA, we'll expect to hear about our PDUFA date, whether or not they're expecting to have an adcom. We don't expect to have an adcom, but that would be information that would come in that update. And thirdly, whether we receive priority review as well in addition to that. And we'll announce all that when we hear from the FDA on the acceptance of the NDA. Kyle, talk a little bit about the launch for FCS.

That team has been interacting. With Kols they've had strong presence at the Congress is theres been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean overall I think what you're hearing is the capacity. City, and the ability and the infrastructure and the timing of all of this is really coming together nicely and the execution I've been very impressed with and very pleased with where we're at right now so Jonathan maybe specific to Fcs.

With Kols they've had strong presence at the Congress is theres been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean overall I think what you're hearing is the capacity. City, and the ability and the infrastructure and the timing of all of this is really coming together nicely and the execution I've been very impressed with and very pleased with where we're at right now so Jonathan maybe specific to Fcs.

Kyle Janais: Our market access team is doing a fantastic job of doing market insights work in understanding the way that the market is anticipated to look from a payer standpoint, and trade channel and distribution and.

City, and the ability and the infrastructure and the timing of all of this is really coming together nicely and the execution I've been very impressed with and very pleased with where we're at right now so Jonathan maybe specific to Fcs.

Kyle Janais: And finally, and really important, is the medical affairs group. We established that team a little over three years ago. And that team has been interacting with KOLs. They've had a strong presence at Congresses. There's been a lot of data collection and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So, I mean, overall, I think what you're hearing is, you know, the capacity and the ability and the infrastructure and the timing of all of this is really coming together nicely. And the execution, I've been very impressed with and very pleased with where we're at right now. So, Jonathan, maybe specific to FCS. Yeah, I think they're

Kyle Janais: And finally, and really importantly is the medical Affairs group, we established that team a little over three years ago.

Jonathan Birchall: Yes, I think there are, as Kyle alluded to, a lot of synergies between the capabilities we've built to support the WAINUA launch, particularly around areas such as patient services that will transfer very relevantly to the FCS launch. Bit of background as I'm sure you're aware, the FCS launch is a rare disease. They're a relatively small number of patients who are managed by a relatively small number of HCP's. So as you can imagine, the footprint or the scale of our commercial build will meet the needs of those customer groups, that customer group and indeed, those patients. So given the rare disease nature, it will be appropriately built to service that population.

Kyle Janais: That team has been interacting with.

Kyle Janais: With Kols they've had strong presence at Congresses, there's been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean overall I think what you're hearing is.

Transfer. Very relevantly to the FCS launch. I'm bit of background as I'm sure you're aware the FCS launch is a rare disease, they're a relatively small number of patients who are managed by a relatively small number of hcp's. So as you can imagine the footprint or the scale of our commercial build will meet.

Very relevantly to the FCS launch. I'm bit of background as I'm sure you're aware the FCS launch is a rare disease, they're a relatively small number of patients who are managed by a relatively small number of hcp's. So as you can imagine the footprint or the scale of our commercial build will meet.

I'm bit of background as I'm sure you're aware the FCS launch is a rare disease, they're a relatively small number of patients who are managed by a relatively small number of hcp's. So as you can imagine the footprint or the scale of our commercial build will meet.

Kyle Janais: The capacity and the ability and the infrastructure and the timing of all of this is really coming together nicely and the execution I've been very impressed with and very pleased with where we're at right now so Jonathan maybe specific to FCS yes.

Operator: Yeah. I'll talk about the synergies. Then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go-to-market strategy there. But the synergies with WAINUA, I think what's important within the organization is, first of all, we've been very calculated and very measured in terms of the way that we build the internal infrastructure so that we're efficient and being smart about the capabilities that we're building and the timing of that build. But we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group is stood up, so things like the CRM, data, and analytics, and those types of infrastructures are in place.

Kyle Jenne: Yeah. I'll talk about the synergies. Then I'll turn it over to Jonathan to talk about some of the field force sizing and the thinking around the go-to-market strategy there. But the synergies with WAINUA, I think what's important within the organization is, first of all, we've been very calculated and very measured in terms of the way that we build the internal infrastructure so that we're efficient and being smart about the capabilities that we're building and the timing of that build. But we've currently got in place marketing capabilities, which I think are very robust with strong leadership and experience in the marketing capacity. Our commercial operations group is stood up, so things like the CRM, data, and analytics, and those types of infrastructures are in place.

Jonathan: Yeah, I think there are, as Kyle alluded to, a lot of synergies between the capabilities we've built to support the Waynewa launch, particularly around areas such as patient services, that'll transfer very relevantly to the FCS launch. A bit of background, as I'm sure you're aware, FCS is a rare disease. There are a relatively small number of patients who are managed by a relatively small number of So as you can imagine, the footprint or the scale of our commercial build will meet the needs of that customer group and indeed those patients. So given the rare disease nature, it'll be appropriately built to service that population.

Jonathan: Yes, I think there is.

The needs of those customer groups that customer group and indeed, those patients so given given the rare disease nature. It will be appropriately built to service that population.

Jonathan: <unk> alluded to a lot of synergies between the capabilities, we built to support that were newer loans, particularly around areas such as patient services.

Jonathan: Transfer.

Jonathan: Very relevantly to the FCS launch.

Gary Nachman: Alright, great. And then on DONI, just describe the latest thinking on the data you'll be including in the NDA and how are you thinking about positioning the drug from a competitive standpoint in terms of switches versus getting naive patients in that market and Kyle, how big of an expert you'll need there from a commercial standpoint relative to OLEZARSEN. Thank you.

Jonathan: I'm bit of background as Im sure Youre aware the FCS launch is a rare disease. They are a relatively small number of patients who are managed by a relatively small number of hcp's. So as you can imagine the footprint or the scale of our commercial build will meet.

Relative to all of us Thank you.

Jonathan: The needs of those customer groups that customer group and indeed, those patients so given given the rare disease nature. It will be appropriately built to service that population.

Operator: Our market access team is doing a fantastic job of doing market insights work and understanding the way that the market is anticipated to look from a payer standpoint in trade, channel, and distribution. And finally, and really importantly, is the medical affairs group. We established that team a little over three years ago. And that team has been interacting with KOLs. They've had strong presence at congresses. There's been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean, overall, I think what you're hearing is the capacity, the ability, the infrastructure, and the timing of all of this is really coming together nicely. And the execution, I've been very impressed with and very pleased with where we're at right now. So Jonathan, maybe specific to FCS?

Kyle Jenne: Our market access team is doing a fantastic job of doing market insights work and understanding the way that the market is anticipated to look from a payer standpoint in trade, channel, and distribution. And finally, and really importantly, is the medical affairs group. We established that team a little over three years ago. And that team has been interacting with KOLs. They've had strong presence at congresses. There's been a lot of data and dissemination. We've collected a lot of information externally and brought that knowledge back into the organization as well. So I mean, overall, I think what you're hearing is the capacity, the ability, the infrastructure, and the timing of all of this is really coming together nicely. And the execution, I've been very impressed with and very pleased with where we're at right now. So Jonathan, maybe specific to FCS?

Kyle Jenne: Yeah, let me start by talking a little bit about the market. We strongly believe based on the profile of DONIDALORSEN that we'll be able to evolve the prophylactic treatment paradigm. This is a very competitive market as you just outlined, it as a switch market right. A lot of these patients are already identified, they're currently being treated and we anticipate switch in a switch data that we're going to going to rollout at the end of the month to be very, very relevant in this space and also innovative and different.

Talking a little bit about the market. Strongly believe based on the profile of <unk> and that will be able to evolve the prophylaxis prophylactic treatment paradigm. This is a very competitive market as you just outlined it as a switch market right. A lot of these patients are already identified they're currently being treated. We anticipate. Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

Strongly believe based on the profile of <unk> and that will be able to evolve the prophylaxis prophylactic treatment paradigm. This is a very competitive market as you just outlined it as a switch market right. A lot of these patients are already identified they're currently being treated. We anticipate. Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

Unknown Executive: All right, great. And then, on Donny, just describe the latest thinking on the data you'll be including in the NDA, and how you're thinking about positioning the drug from a competitive standpoint in terms of switches versus getting naive patients in that market. And Kyle, how big of an effort you'll need there from a commercial standpoint relative to olizarsin. Thank you.

Speaker Change: Alright, Great and then on Dani just described the latest thinking on the data youll be including in the NDA and how are you thinking about positioning the drug from a competitive standpoint in terms of switches versus getting naive patients in that market and how big of an expert youll need there from a commercial standpoint.

This is a very competitive market as you just outlined it as a switch market right. A lot of these patients are already identified they're currently being treated. We anticipate. Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

We anticipate. Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

Unknown Executive: Relative to all of us Thank you.

The prevalence overall, we're looking at 20,000 plus patients between the U.S and EU. And the data sets in terms of differentiation and the way that we're going to go about this really support a couple of things, number one, the primary endpoint, obviously around reduced rates of HAE attacks. But the durability of that I think is really, really important to note in the data. We've got four or eight week dosing, that's differentiated versus the competition. We've got a safe and tolerable therapy. And the switch data and being able to show patient preference is going to be really critical I think, not only to patients, but also to prescribers in terms of how to do this and to payers in terms of what is the cost of doing this and how do we do this effectively to make sure that it's efficient in terms of making that transition. So overall, I think between the data and the marketplace and the way things are setting up, we're going to be really poised to do a great job here in this space. In terms of the commercial size, we're probably going to be competitive in terms of the sizing, 50 to 100 ballpark in terms of field infrastructure. And I expect to be able to start putting that team in place later this year pending the regulatory timelines and process that will be outlined later.

Unknown Executive: Yeah, let me start by talking a little bit about the market. You know, we strongly believe, based on the profile of Donnie Delorsen, that we'll be able to evolve the prophylactic treatment paradigm. This is a very competitive market, as you just outlined. It is a switch market, right?

Speaker Change: Yes, let me start by.

Unknown Executive: Talking a little bit about the market.

And the data sets in terms of differentiation in the way that we're going to go about this really support a couple of things number one the primary endpoint, obviously around reduced rates of HAE attacks. But the durability of that I think is really really important. To note in the data. We've got four or eight week dosing, that's differentiated versus the competition, we've got a safe and tolerable therapy, and the switch data and being able to show patient preference is going to be really critical I think not only to patients, but also to prescribers in terms of how to do this and to payer.

Unknown Executive: Strongly believe with based on the profile of <unk> and that will be able to evolve the prophylaxis prophylactic treatment paradigm.

Unknown Executive: This is a very competitive market as you just outlined it as a switch market right a lot of these patients are alright.

Jonathan Birchall: Yeah. I think there are, as Kyle alluded to, a lot of synergies between the capabilities we've built to support the WAINUA launch, particularly around areas such as patient services that'll transfer very relevantly to the FCS launch. A bit of background, as I'm sure you're aware, the FCS launch is a rare disease. There are a relatively small number of patients who are managed by a relatively small number of HCPs. So as you can imagine, the footprint or the scale of our commercial build will meet the needs of that customer group and indeed those patients. So given the rare disease nature, it'll be appropriately built to service that population.

But the durability of that I think is really really important. To note in the data. We've got four or eight week dosing, that's differentiated versus the competition, we've got a safe and tolerable therapy, and the switch data and being able to show patient preference is going to be really critical I think not only to patients, but also to prescribers in terms of how to do this and to payer.

Kyle Janais: A lot of these patients are already identified, and they're currently being treated. And we anticipate switch and the switch data that we're going to roll out at the end of the month to be very, very relevant in this space and also innovative and different. The prevalence overall, we're looking at 20,000 plus patients between the U.S. and the EU. And the data sets, in terms of differentiation and the way that we're going to go about this, really support a couple of things.

To note in the data. We've got four or eight week dosing, that's differentiated versus the competition, we've got a safe and tolerable therapy, and the switch data and being able to show patient preference is going to be really critical I think not only to patients, but also to prescribers in terms of how to do this and to payer.

Kyle Janais: <unk> identified they're currently being treated.

We've got four or eight week dosing, that's differentiated versus the competition, we've got a safe and tolerable therapy, and the switch data and being able to show patient preference is going to be really critical I think not only to patients, but also to prescribers in terms of how to do this and to payer.

Kyle Janais: We anticipate.

Kyle Janais: Switch in a switch data that we're going to going to rollout at the end of the month to be very very relevant in this space and also innovative and different.

Kyle Janais: The prevalence overall, we're looking at 20000 plus patients had between the us and EU.

Kyle Janais: The data sets in terms of differentiation in the way that we're going to go about this really support a couple of things number one the primary endpoint, obviously around reduced rates of HAE attacks.

In terms of what is the cost of doing this and how do we do this effectively to make sure that it's efficient in terms of making that transition. So overall I think we did. Between the data in the marketplace and the way things are setting up were going to be really poised to do a great job here in this space.

Kyle Janais: Number one, the primary endpoint, obviously around reduced rates of HAE attacks. But the durability of that, I think, is really, really important to note in the data. We've got four or eight-week dosing, and that's differentiated versus the competition. We've got a safe and tolerable therapy, and the switch data and being able to show patient preference are going to be really critical, I think. Not only to patients but also to prescribers in terms of how to do this, and to payers in terms of what the cost of doing this is, and how do we do this effectively to make sure that it's efficient in terms of making that transition.

Kyle Janais: But the durability of that I think is really really important.

Between the data in the marketplace and the way things are setting up were going to be really poised to do a great job here in this space.

Kyle Janais: To note in the data.

Kyle Janais: We've got four or eight week dosing, that's differentiated versus the competition, we've got a safe and tolerable therapy, and the switch data and being able to show patient preference is going to be really critical I think.

In terms of the commercial size. We're probably be competitive in terms of the sizing 50 to 100 ballpark in terms of field infrastructure. And I expect. To be able to start putting that team in place later this year pending the regulatory timelines and process. It will be outlined later.

In terms of the commercial size, we're probably going to be competitive in terms of the sizing, 50 to 100 ballpark in terms of field infrastructure. And I expect to be able to start putting that team in place later this year pending the regulatory timelines and process that will be outlined later.

We're probably be competitive in terms of the sizing 50 to 100 ballpark in terms of field infrastructure. And I expect. To be able to start putting that team in place later this year pending the regulatory timelines and process. It will be outlined later.

Gary Nachman: All right. Great. And then on donidalorsen, just describe the latest thinking on the data you'll be including in the NDA and how you're thinking about positioning the drug from a competitive standpoint in terms of switches versus getting naive patients in that market. And Kyle, how big of an effort you'll need there from a commercial standpoint relative to olezarsen? Thank you.

And I expect. To be able to start putting that team in place later this year pending the regulatory timelines and process. It will be outlined later.

Kyle Janais: Not only to patients, but also to prescribers in terms of how to do this and to payers in terms of what is the cost of doing this and how do we do this effectively to make sure that it's efficient in terms of making that transition.

To be able to start putting that team in place later this year pending the regulatory timelines and process. It will be outlined later.

Brett P. Monia: Yeah, and regarding Gary the NDA--Thanks Kyle. We plan to submit for approval both for every four week dosing as well as every eight week dosing will include the open label extension data for the safety database is necessary for approval. We're also expecting to include instructions based on the switch data on how physicians will be able to switch patients from an existing prophylactic over two predominant [inaudible]. And related to that, we're very much looking forward to sharing in depth switch data along with the phase II open label extension data and the phase III data at Yakui on May 31st of this month. The switch data is absolutely the first prospective study ever conducted in patients with HAE switching them from one prophylactic to another and we're looking forward to sharing data, not only on how well patients are protected from HAE attacks compared to baseline rates, but also compliance, how long they stay on treatment and the preference that whether patient preferred DONIDALORSEN over the previous treatment and why they choose that. So it's a very important study, the first of its kind and it's also a litmus test for the market in the United States, which is a switch market.

Kyle Janais: So, you know, overall, I think that between the data and the marketplace and the way things are setting up, we're going to be really poised to do a great job here in this space. In terms of the commercial size, you know, we'll probably be competitive in terms of the sizing, you know, 50 to 100 ballpark in terms of field infrastructure, and, you know, I expect to be able to start putting that team in place later this year, pending the regulatory timelines and process that will be outlined later. Yeah.

Plan to submit for approval both for every four week dosing as well as every eight week dosing will include the open label extension data. For the safety. Database is necessary for approval. We're also expecting to include instructions are based on the switch data on how. Physicians will be able to switch patients from an existing prophylactic over two predominant divorce and related to that we're very much looking forward to sharing in depth switch data along with the open label Phase II Open label extension data in the phase III data at <unk> on May 31st.

Kyle Janais: Overall I think.

Kyle Janais: Between the data in the marketplace and the way things are setting up were going to be really poised to do a great job here in this space.

Operator: Yeah. Let me start by talking a little bit about the market. We strongly believe, based on the profile of donidalorsen, that we'll be able to evolve the prophylactic treatment paradigm. This is a very competitive market, as you just outlined. It is a switch market, right? A lot of these patients are already identified. They're currently being treated. And we anticipate switch and the switch data that we're going to roll out at the end of the month to be very, very relevant in this space and also innovative and different. The prevalence overall, we're looking at 20,000+ patients between the US and the EU. And the datasets in terms of differentiation and the way that we're going to go about this really support a couple of things. Number one, the primary endpoint, obviously, around reduced rates of HAE attacks.

Kyle Jenne: Yeah. Let me start by talking a little bit about the market. We strongly believe, based on the profile of donidalorsen, that we'll be able to evolve the prophylactic treatment paradigm. This is a very competitive market, as you just outlined. It is a switch market, right? A lot of these patients are already identified. They're currently being treated. And we anticipate switch and the switch data that we're going to roll out at the end of the month to be very, very relevant in this space and also innovative and different. The prevalence overall, we're looking at 20,000+ patients between the US and the EU. And the datasets in terms of differentiation and the way that we're going to go about this really support a couple of things. Number one, the primary endpoint, obviously, around reduced rates of HAE attacks.

For the safety. Database is necessary for approval. We're also expecting to include instructions are based on the switch data on how. Physicians will be able to switch patients from an existing prophylactic over two predominant divorce and related to that we're very much looking forward to sharing in depth switch data along with the open label Phase II Open label extension data in the phase III data at <unk> on May 31st.

Kyle Janais: In terms of the commercial size.

Database is necessary for approval. We're also expecting to include instructions are based on the switch data on how. Physicians will be able to switch patients from an existing prophylactic over two predominant divorce and related to that we're very much looking forward to sharing in depth switch data along with the open label Phase II Open label extension data in the phase III data at <unk> on May 31st.

Kyle Janais: We'll probably be competitive in terms of the sizing 50 to 100 ballpark in terms of field infrastructure.

Physicians will be able to switch patients from an existing prophylactic over two predominant divorce and related to that we're very much looking forward to sharing in depth switch data along with the open label Phase II Open label extension data in the phase III data at <unk> on May 31st.

Kyle Janais: And I expect to be able to start putting that team in place later this year pending the regulatory timelines and process. It will be outlined later.

Unknown Executive: Yeah, and regarding Gary, the NDA, thanks Kyle, we plan to submit for approval both for every four-week dose as well as every eight-week dose. We'll include open-label extension data to support the safety, you know, databases necessary for approval. We're also expecting to include instructions based on the switch data on how physicians will be able to switch patients from an existing prophylactic over to dominant to dominant dolorsan. And related to that, we're very much looking forward to sharing in depth the switch data along with the open-label phase three open-label extension data and phase three data at IACHI on May 31st this month.

Speaker Change: Yeah and regarding Gary the NDA. Thanks, Kyle we plan to submit for approval both for every four week dosing as well as every eight week dosing will include the open label extension data.

Of this month. Switch data.

Brett P. Monia: The switch data is absolutely the first prospective study ever conducted in patients with HAE switching them from one prophylactic to another and we're looking forward to sharing data, not only on how well patients are protected from HAE attacks compared to baseline rates, but also compliance, how long they stay on treatment and the preference that whether patient preferred DONIDALORSEN over the previous treatment and why they choose that. So it's a very important study, the first of its kind and it's also a litmus test for the market in the United States, which is a switch market.

Switch data.

It is really is absolutely the first prospective study ever conducted in patients with HAE switching them from one prophylactic to another and we're looking forward to sharing data not only on how well patients are protected from a J attacks compared to baseline rates, but also compliance how long they stay on treatment. And our preference that weather patient preferred donegal worsened over the previous treatment and why. They choose that so it's very important study the first of its kind and it's also a litmus test for the market in the United States, which which is a switch market.

Unknown Executive: For the safety.

Unknown Executive: Database is necessary for approval. We're also expecting to include instructions based on the switch data on how.

Operator: But the durability of that, I think, is really, really important to note in the data. We've got 4 or 8-week dosing. That's differentiated versus the competition. We've got a safe and tolerable therapy. And the switch data and being able to show patient preference is going to be really critical, I think, not only to patients, but also to prescribers in terms of how to do this and to payers in terms of what is the cost of doing this and how do we do this effectively to make sure that it's efficient in terms of making that transition. So overall, I think that between the data and the marketplace and the way things are setting up, we're going to be really poised to do a great job here in this space.

Kyle Jenne: But the durability of that, I think, is really, really important to note in the data. We've got 4 or 8-week dosing. That's differentiated versus the competition. We've got a safe and tolerable therapy. And the switch data and being able to show patient preference is going to be really critical, I think, not only to patients, but also to prescribers in terms of how to do this and to payers in terms of what is the cost of doing this and how do we do this effectively to make sure that it's efficient in terms of making that transition. So overall, I think that between the data and the marketplace and the way things are setting up, we're going to be really poised to do a great job here in this space.

Unknown Executive: Physicians will be able to switch patients from an existing prophylactic over two predominant divorce and related to that we're very much looking forward to sharing in depth switch data along with the open label Phase II open label extension data in the phase III data at Yockey.

And our preference that weather patient preferred donegal worsened over the previous treatment and why. They choose that so it's very important study the first of its kind and it's also a litmus test for the market in the United States, which which is a switch market.

They choose that so it's very important study the first of its kind and it's also a litmus test for the market in the United States, which which is a switch market.

Unknown Executive: <unk> 31.

Unknown Executive: The switch data is really, is absolutely the first prospective study ever conducted in patients with HAE, switching them from one prophylactic to another, and we're looking forward to sharing data not only on how well patients are protected from HAE attacks compared to baseline rates, but also compliance, how long they stay on treatment, and a preference for whether patients prefer dominant to dolorsan over their previous treatment and why they choose that. So it's a very important study, it's the first of its kind, and it's also a litmus test for the market in the United States, which is a switch.

Unknown Executive: Of this month.

Unknown Executive: Switch data.

Unknown Executive: It is really is absolutely the first prospective study ever conducted in patients with HPE switching them from one prophylactic to another and we're looking forward to sharing data not only on how well patients are protected from a J attacks compared to baseline rates, but also compliance how long they stay on treatment.

Gary Nachman: Great. Very helpful. Thank you.

Operator: Thank you. And the next question comes from Jessica Fye with JP Morgan.

Jessica Fye: Hey, guys. Good afternoon, thanks for taking my questions. On that path to sustained positive cash flow, can you talk a little bit about over what time horizon do you see the company being able to achieve that? And then just a quick second one. For ion 541 your taxing two asset for ALS, can you set the stage for what to watch for in those phase II results and just remind me the timing for that readout? Thank you.

Yeah. Let's see on that path to sustained positive cash flow can you talk a little bit about over what time horizon do you see the company being able to achieve that. And then just a quick. Second one for IR 504, one you're taxing to asset for ALS can you set the stage for what to watch for in those phase II results and just to remind me the timing for that readout. Thank you.

Unknown Executive: And our preference that whether patients preferred donegal worsen over the previous treatment and why.

Let's see on that path to sustained positive cash flow can you talk a little bit about over what time horizon do you see the company being able to achieve that. And then just a quick. Second one for IR 504, one you're taxing to asset for ALS can you set the stage for what to watch for in those phase II results and just to remind me the timing for that readout. Thank you.

Operator: In terms of the commercial size, we'll probably be competitive in terms of the sizing, 50 to 100 ballpark in terms of field infrastructure. I expect to be able to start putting that team in place later this year pending the regulatory timelines and process that will be outlined later.

Kyle Jenne: In terms of the commercial size, we'll probably be competitive in terms of the sizing, 50 to 100 ballpark in terms of field infrastructure. I expect to be able to start putting that team in place later this year pending the regulatory timelines and process that will be outlined later.

Unknown Executive: They choose that so it is very important study so first of its kind and it's also a litmus test for the market in the United States, which is a switch market.

And then just a quick. Second one for IR 504, one you're taxing to asset for ALS can you set the stage for what to watch for in those phase II results and just to remind me the timing for that readout. Thank you.

Second one for IR 504, one you're taxing to asset for ALS can you set the stage for what to watch for in those phase II results and just to remind me the timing for that readout. Thank you.

Unknown Executive: Great. Very helpful. Thank you. Thank you. And the next question comes from Jessica Fye with J.P. Morgan. Hey guys, good afternoon. Thanks for taking my questions. On that path to success,

Speaker Change: Great very helpful. Thank you.

Unknown Executive: Thank you. And the next question comes from Jessica Fye of J.P. Morgan.

Jessica Fye: Thank you.

Brett Monia: Yeah. And regarding Gary, the NDA, thanks, Kyle. We plan to submit for approval both for every four-week dosing as well as every eight-week dosing. We'll include the open label extension data to support the safety database as necessary for approval. We're also expecting to include instructions based on the switch data on how physicians will be able to switch patients from an existing prophylactic over to donidalorsen. And related to that, we're very much looking forward to sharing in-depth the switch data along with the phase 3 open label extension data, and the phase 3 data at EAACI on 31 May of this month. The switch data is absolutely the first prospective study ever conducted in patients with HAE, switching them from one prophylactic to another.

Unknown Executive: Next question comes from Jessica Fye with Jpmorgan.

Beth Hougen: Sure Jess. Hi, good morning. So as you think about Ionis, as you think about our opportunities, obviously, we've got a substantial opportunity ahead of us with the rich pipeline that we have, particularly the late stage pipeline, multibillion dollar revenue opportunity. It's going to take us a few years of continued investment to bring those drugs through development, through the regulatory process and launch those medicines and we want those launches obviously to be ramping, but it's really the strength of multiple sources of revenue are sustained and substantial base of revenue today, the ability for that to grow, the ability for them partnered programs to reach the market and generate substantial royalties and sales milestones.

Jessica Fye: Hey, guys. Good afternoon, thanks for taking my questions.

Jessica Fye: On that path to sustained positive cash flow can you talk a little bit about over what time horizon do you see the company being able to achieve that.

Multibillion dollar revenue opportunity. It's going to take US a few years of continued investment to bring those drags through through development through the regulatory process and and launch those medicines. And we want those launches and obviously to be ramping.

It's going to take US a few years of continued investment to bring those drags through through development through the regulatory process and and launch those medicines. And we want those launches and obviously to be ramping.

Jessica Fye: Then just a quick.

Jessica Fye: Second one for ion $5 for one year on taxing to asset for ALS can you set the stage for what to watch for in those phase II results and just to remind me the timing for that readout. Thank you.

And we want those launches and obviously to be ramping.

Unknown Executive: Sure, Jess. Hi. Good morning.

But it's really the strength of multiple sources of revenue are sustained and substantial base of revenue today, the ability for that to grow the ability for them partnered programs to reach the market and generate substantial royalties and sales milestones.

Jessica Fye: Sure Jeff Hi, Good morning, So as you think about <unk> as you think about our opportunities.

Unknown Executive: Obviously, we've got a substantial opportunity ahead of us with the rich pipeline that we have particularly the late stage pipeline.

Brett Monia: And we're looking forward to sharing data not only on how well patients are protected from HAE attacks compared to baseline rates but also compliance, how long they stay on treatment, and a preference, whether patients prefer donidalorsen over their previous treatment and why they choose that. So it's a very important study. It's the first of its kind. And it's also a litmus test for the market in the United States, which is a switch market.

Unknown Executive: Multi billion dollar revenue opportunity.

Unknown Executive: It's going to take US a few years of continued investment to bring those drugs through development through the regulatory process and analyze those medicines.

And then to build on that with our product revenues with our wholly-owned medicines, as those come to market and those launches ramp up that will really drive the positive cash flow. And I think what's important to remember that Ionis which is very unique for us versus others in our space is that we're not that far away. Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generates cash for the company and helps offset our investments today. We anticipate that will continue and that means that the delta that we have to cover when we finally get these products to market is actually fairly, fairly modest and a very, very achievable goal for us. So hopefully that gives you a perspective on how to think about it.

Jessica Fye: And we want those launches and obviously to be ramping.

Jessica Fye: But it's really the strength of multiple sources of revenue are sustained and substantial base of revenue today, the ability for that to grow the ability for them partnered programs to reach the market and generate substantial royalties and sales milestones.

Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generates. Cash for the company and helps offset our investments today, we anticipate that will continue and that means that the delta that we have to cover when we when we finally get these products to market is actually. A fairly fairly modest and very very achievable goal for us. So hopefully that gives you a perspective on how to think about it.

Unknown Executive: So as you think about Ionis, you think about our opportunities. Obviously, we've got a substantial opportunity ahead of us with the rich pipeline that we have, particularly the late stage pipeline, multi-billion dollar revenue opportunity. The ability for those programs to reach the market and generate substantial royalties and sales milestones. And then to build on that with our product revenues, with our wholly owned medicines, as those come to market and those launches ramp up, that will really drive positive cash flow.

Gary Nachman: Great. Very helpful. Thank you.

Cash for the company and helps offset our investments today, we anticipate that will continue and that means that the delta that we have to cover when we when we finally get these products to market is actually. A fairly fairly modest and very very achievable goal for us. So hopefully that gives you a perspective on how to think about it.

Operator: Thank you. And the next question, Jessica Fye with JP Morgan.

Unknown Executive: And then to build on that with our product revenues with our wholly owned medicines as those come to market and those launches ramp up that will really drive the positive cash flow and I think what's important to remember about ion is which is very unique for us versus others in our space is that we're not that far away.

Jessica Fye: Hey, guys. Good afternoon. Thanks for taking my questions. Let's see. On that path to sustained positive cash flow, can you talk a little bit about over what time horizon you see the company being able to achieve that? And then just a quick second one. For Ionis Pharmaceuticals, Inc. Brett Monia, your Qalsody asset for ALS. Can you set the stage for what to watch for in those phase 2 results and just remind me the timing for that readout? Thank you.

A fairly fairly modest and very very achievable goal for us. So hopefully that gives you a perspective on how to think about it.

Unknown Executive: And I think what's important to remember about Ionis, which is very unique for us compared to others in our space, is that we're not that far away. Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generates cash for the company and helps offset our investments today. We anticipate that will continue, and that means that the delta that we have to cover when we finally get these products to market is actually fairly modest and a very achievable goal for us. So hopefully, that gives you a perspective on how to think about it.

We're looking forward to your other question Jess of having data results from the phase II study for [inaudible] two in non genetic AOS around mid year this year. Eugene, please comment on what we're looking for.

Unknown Executive: Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generate cash.

Having data results from the phase II study for <unk> two in non genetic AOS around mid year. This year using a cup. Please comment on what we're looking for. Yes.

Unknown Executive: Cash for the company and helps offset our investments today.

Yes.

Eugene Schneider: Thanks for the question Jess. First thing, patient experience and primarily this is a safety study, it's a dose ranging study we are assessing safety of increasing doses of [inaudible] in patients with sporadic ALS as Brett said. So really the key goal of this study is to demonstrate and assess safety of various dose levels of [inaudible] medicine. Obviously Biogen is looking at other surrogates of ALS progression and those have been well described such as [inaudible] so of course, there will be some of those exploratory endpoints that are used to assess whether there is any activity on key ALS progression measures. Based on the Cal Saudi outcome [inaudible] will obviously be a key measure in that they will also be exploratory measures of I'm sure ALS functional rating scale in other sub domains within there. Fairly short study.

Unknown Executive: We anticipate that will continue and that means that the delta that we have to cover when we when we finally get these products to market is actually.

Elizabeth Hougen: Sure, Jess. Hi. Good morning. So as you think about IONIS, you think about our opportunities. Obviously, we've got a substantial opportunity ahead of us with the rich pipeline that we have, particularly the late-stage pipeline, multibillion-dollar revenue opportunity. It's going to take us a few years of continued investment to bring those drugs through development, through the regulatory process, and launch those medicines. And we want those launches then, obviously, to be ramping. But it's really the strengths of multiple sources of revenue, our sustained and substantial base of revenue today, the ability for that to grow, the ability for partnered programs to reach the market and generate substantial royalties and sales milestones, and then to build on that with our product revenues with our wholly-owned medicines as those come to market and those launches ramp up that will really drive the positive cash flow.

Beth Hougen: Sure, Jess. Hi. Good morning. So as you think about IONIS, you think about our opportunities. Obviously, we've got a substantial opportunity ahead of us with the rich pipeline that we have, particularly the late-stage pipeline, multibillion-dollar revenue opportunity. It's going to take us a few years of continued investment to bring those drugs through development, through the regulatory process, and launch those medicines. And we want those launches then, obviously, to be ramping. But it's really the strengths of multiple sources of revenue, our sustained and substantial base of revenue today, the ability for that to grow, the ability for partnered programs to reach the market and generate substantial royalties and sales milestones, and then to build on that with our product revenues with our wholly-owned medicines as those come to market and those launches ramp up that will really drive the positive cash flow.

Our first thing patient experience and primarily this is a safety study, it's a dose ranging study or. Or <unk>. We are assessing. Safety of <unk>. Increasing doses of. Our all ago in patients with sporadic ALS.

Or <unk>. We are assessing. Safety of <unk>. Increasing doses of. Our all ago in patients with sporadic ALS.

We are assessing. Safety of <unk>. Increasing doses of. Our all ago in patients with sporadic ALS.

Unknown Executive: Fairly fairly modest and very very achievable goal for us. So hopefully that gives you a perspective on how to think about it.

Safety of <unk>. Increasing doses of. Our all ago in patients with sporadic ALS.

Increasing doses of. Our all ago in patients with sporadic ALS.

Our all ago in patients with sporadic ALS.

Unknown Executive: We're looking forward to the other part of your question, your other question, Jess, and having data results from the Phase 2 study for Ataxin-2 in non-genetic ALS around mid-year this year. Eugene, please comment on what we're looking for.

Unknown Executive: Looking forward to the other.

As Brett said, so really the key goal of this study is to demonstrate safety. Various dose levels of interest vehicle medicine.

Eugene: Part of your credit your other question Jess.

Unknown Executive: Having data results from the phase II study for <unk> two in non genetic AOS around mid year this year Eugene.

Various dose levels of interest vehicle medicine.

We're obviously or Biogen is looking at other sort. Surrogates of. Bill is progression and those have been well described such as north <unk>. So of course, there will be some of those exploratory. <unk> that are used to assess whether there is any. Activity on key AOS progression measures. Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there. Fairly shorts. Yeah. Okay. Yeah.

Unknown Executive: Thanks for your question, Jess. It's our first-in-patient experience, and primarily this is a safety study. It's a dose-ranging study where we're obviously assessing safety of increasing doses of oligo in patients with sporadic ALS as As Brett said, so really, the key goal of that study is to demonstrate and assess safety of various dose levels of intrathecal medicine, or obviously, or Biogen is looking at other surrogates of, ALS progression, and those have been well described, such as neurofilament, so of course, there will be some of those exploratory Endpoints that are used to assess whether there is any, activity on key ALS progressions.

Eugene: Please comment on what we're looking for.

Unknown Executive: Yes.

Surrogates of. Bill is progression and those have been well described such as north <unk>. So of course, there will be some of those exploratory. <unk> that are used to assess whether there is any. Activity on key AOS progression measures. Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there. Fairly shorts. Yeah. Okay. Yeah.

Speaker Change: Thanks for the question Jeff.

Unknown Executive: Our first thing patient experience and primarily this is a safety study, it's a dose ranging study or.

Bill is progression and those have been well described such as north <unk>. So of course, there will be some of those exploratory. <unk> that are used to assess whether there is any. Activity on key AOS progression measures. Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there. Fairly shorts. Yeah. Okay. Yeah.

Unknown Executive: We're obviously assessing safety of <unk>.

<unk> that are used to assess whether there is any. Activity on key AOS progression measures. Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there. Fairly shorts. Yeah. Okay. Yeah.

Unknown Executive: Increasing doses of.

Unknown Executive: Our all ago in patients with sporadic ALS.

Activity on key AOS progression measures. Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there.

Okay. Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there.

Unknown Executive: As Brett said, so really the key goal of this study is to demonstrate and assess safety.

Brett P. Monia: Based on the [inaudible] will obviously be a key measure in that they will also be exploratory measures of I'm sure ALS functional rating scale in other sub domains within there.

Based on the Cal Saudi outcome North on my wife's name of obviously be a key measure in that they will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there.

Unknown Executive: Various dose levels of interest vehicle.

Unknown Executive: Medicine.

Unknown Executive: We're obviously or Biogen is looking at other sort.

Elizabeth Hougen: I think what's important to remember about Ionis, which is very unique for us versus others in our space, is that we're not that far away. Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generates cash for the company and helps offset our investments today. We anticipate that will continue. And that means that the delta that we have to cover when we finally get these products to market is actually fairly modest and a very achievable goal for us. So hopefully, that gives you a perspective on how to think about it.

Beth Hougen: I think what's important to remember about Ionis, which is very unique for us versus others in our space, is that we're not that far away. Unlike a lot of companies who are launching their first medicines, we already have a very substantial base of revenue that generates cash for the company and helps offset our investments today. We anticipate that will continue. And that means that the delta that we have to cover when we finally get these products to market is actually fairly modest and a very achievable goal for us. So hopefully, that gives you a perspective on how to think about it.

Unknown Executive: Surrogates of.

Fairly shorts. Yeah. Okay. Yeah.

Unknown Executive: Bill is progression and those have been well described such as north <unk>. So of course, there will be some of those exploratory.

Yeah. Okay. Yeah.

Okay.

Eugene Schneider: Fairly short study.

Yeah.

Operator: Thank you. And the next question comes from Joseph Stringer with Needham and Company.

Unknown Executive: Endpoints that are used to assess whether there is any.

Joseph Stringer: Hi, thanks for taking our questions. Just a follow up on DONIDALORSEN in the switch study. You mentioned a patient survey and some other data, but maybe can you put a little bit finer point on what data specifically you'll need to see from the switch study that would resonate most from a commercial uptake perspective. Well, I'll start and Kyle can jump in. It's really the totality of the data Joey. First of all, we will share data with current treatments that are available on the market today, so it won't just be one treatment that we're switching and we're going to be looking at patients that have been on previously been on [inaudible] or other prophylactic treatments what their baseline attack rates were coming into the study and then how the AKE rate evolves as patients continue to be on DONIDALORSEN treatment. That's very important to have that data for the commercial launch.

Hi, Thanks for taking our questions just a follow up on Donny Dolores and in the switch study you mentioned. Our patient survey and some other. Data, but maybe can you put a little bit. Finer point on what data specifically, you'll need to see from the switch study that would. <unk> most from a commercial uptake. Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Unknown Executive: Activity on key AOS progression measures.

Unknown Executive: Based on the CALSATI outcome, NORFILM and LightChain will obviously be a key measure in that. There will also be exploratory measures of, I'm sure, the ALS functional rating scale and other subdomains. Great.

Unknown Executive: Yes.

Unknown Executive: Based on the Cal Saudi outcome north on the right team of obviously be a key.

Our patient survey and some other. Data, but maybe can you put a little bit. Finer point on what data specifically, you'll need to see from the switch study that would. <unk> most from a commercial uptake. Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Data, but maybe can you put a little bit. Finer point on what data specifically, you'll need to see from the switch study that would. <unk> most from a commercial uptake. Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Unknown Executive: And then there will also be exploratory measures of I'm sure AOS functional rating scale in other sub domains within there.

Finer point on what data specifically, you'll need to see from the switch study that would. <unk> most from a commercial uptake. Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Unknown Executive: There's a fairly short slide. Thank you. And the next question comes from Joseph Stringer with Needham and Company. Hi, thanks for taking our questions.

<unk> most from a commercial uptake. Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Unknown Executive: Fairly shorts.

Brett Monia: We're looking forward to the other part of your other question, Jess, having data results from the phase 2 study for TAXN2 in non-genetic ALS around midyear this year. Eugene, please comment on what we're looking for.

Unknown Executive: Yes.

Perspective. Well I'll start and Carl can jump in. It's really the totality of the data Joey. We're gonna. First of all we will share data.

Well I'll start and Carl can jump in. It's really the totality of the data Joey.

Unknown Executive: Thank you. The next question comes from Joseph Stringer with Needham & Company.

Unknown Executive: Thank you and the next question comes from Joseph Stringer with Needham <unk> Company.

It's really the totality of the data Joey.

We're gonna. First of all we will share data.

Joseph Stringer: Hi, Thanks for taking our questions just to follow up on Donny Dolores and in the switch study you mentioned.

We're gonna. First of all we will share data.

First of all we will share data.

Eugene Schneider: Yeah. Thanks for your question, Jess. It's our first-in-patient experience. Primarily, this is a safety study. It's a dose-ranging study. We're obviously assessing safety of increasing doses of oligo in patients with sporadic ALS, as Brett said. Really, the key goal of that study is to demonstrate and assess safety of various dose levels of intrathecal medicine. Obviously, Biogen is looking at other surrogates of ALS progression. Those have been well described, such as neurofilament. Of course, there will be some of those exploratory endpoints that are used to assess whether there is any activity on key ALS progression measures.

Current treatment. Current treatments are available on the market today. So it won't just be one treatment that we're switching and we're going to be looking at. Patients that have been on previously been on tech zero or the data or other prophylactic treatments. What their baseline attack rates were coming into the study and then how the a J E T. Right.

Joseph Stringer: Our patient survey and some other.

Current treatments are available on the market today. So it won't just be one treatment that we're switching and we're going to be looking at. Patients that have been on previously been on tech zero or the data or other prophylactic treatments. What their baseline attack rates were coming into the study and then how the a J E T. Right.

Joseph Stringer: Data, but maybe can you put a little bit.

Joseph Stringer: Finer point on what data specifically you will need to see from the switch study that would <unk>.

Patients that have been on previously been on tech zero or the data or other prophylactic treatments. What their baseline attack rates were coming into the study and then how the a J E T. Right.

Joseph Stringer: Resonate most from a commercial uptake.

What their baseline attack rates were coming into the study and then how the a J E T. Right.

Unknown Executive: Perspective.

Unknown Executive: I'll start, and Kyle can jump in. It's really the totality of the data, Joey. We're going to, first of all, share data with current treatments that are current treatments that are available on the market today. So it won't just be one treatment that we switch to. We're going to be looking at the patients that have previously been on TAC0 or Lidale or other prophylactic treatments, what their baseline HAE attack rates were coming into the study, and then how that HAE attack rate changes as patients continue to be on tongue dilution treatment.

Joseph Stringer: Well I'll start and Carl can jump in.

Right.

continue to be on DONIDALORSEN treatment. That's very important to have that data for the commercial launch. Second, as I mentioned, we're going to also ask patients, which they prefer in the trial and why and that'll be a survey that we're looking forward to sharing in the study is as well. And then thirdly, and very importantly, we will be able to have the data in the instructions in the algorithms if you will which are different for different prophylactic treatments on how much time it takes before DONIDALORSEN and will you know, how much time they need to be on and wean off existing prophylactic treatments and then move on to DONIDALORSEN based on previous treatments. But it is really important right Kyle to have this data for the launch of DONIDALORSEN.

continue to be on DONIDALORSEN treatment. That's very important to have that data for the commercial launch.

Unknown Executive: It's really the totality of the data Joey.

Kyle Janais: We're gonna.

Second, as I mentioned, we're going to also ask patients, which they prefer in the trial and why and that'll be a survey that we're looking forward to sharing in the study is as well. And then thirdly, and very importantly, we will be able to have the data in the instructions in the algorithms if you will which are different for different prophylactic treatments on how much time it takes before DONIDALORSEN and will you know, how much time they need to be on and wean off existing prophylactic treatments and then move on to DONIDALORSEN based on previous treatments. But it is really important right Kyle to have this data for the launch of DONIDALORSEN.

Unknown Executive: First of all we will share data.

As I mentioned. We're going to also ask patients, which they prefer. In the trial and why and that'll be a survey that we're looking forward to sharing and <unk>.

Unknown Executive: Yes.

Unknown Executive: Current treatment.

We're going to also ask patients, which they prefer. In the trial and why and that'll be a survey that we're looking forward to sharing and <unk>.

Unknown Executive: Current treatments are available on the market today. So it won't just be one treatment that we're switching we're going to be looking at.

In the trial and why and that'll be a survey that we're looking forward to sharing and <unk>.

Unknown Executive: Patients have been on previously been on tech zero or the data or other prophylactic treatments.

Study is as well and then thirdly, and very importantly, we will be able to have the data in the instructions in the out the algorithms. If you will which are different for different prophylactic treatments.

Unknown Executive: What their baseline attack rates were coming into the study and then how the a J.

Brett Monia: Yeah. I think based on the CalSATI outcome, neurofilament light chain will obviously be a key measure in that. There will also be exploratory measures of, I'm sure, ALS functional rating scale and other subdomains within there.

Unknown Executive: Attack.

Unknown Executive: Right.

On how much time it takes to before we're done doors and will you know how much time, they need to be on and wean off existing prophylactic treatments and then move on to Don indoors. Based on previous periods, but it is really important right Kyle. This data for the. Launched on tonnage.

Unknown Executive: Evolves as patients continue to be on Donaldson treatment, that's very important for the commercial to have that data for the commercial launch second.

Unknown Executive: That's very important for the commercial to have that data for the commercial launch. Second, as I mentioned, we're also going to ask patients which they prefer in the trial and why. That'll be a survey that we're looking forward to sharing in the study as well. Then, thirdly, and very importantly, we'll be able to have the data, the instructions, and the algorithms, if you will, which are different for different prophylactic treatments, on how much time it takes before Donna Dolores and how much time they need to be on and weaned off existing prophylactic treatments before moving on to Donna Dolores.

Eugene Schneider: It is a fairly short study.

Unknown Executive: As I mentioned.

Based on previous periods, but it is really important right Kyle. This data for the. Launched on tonnage.

Brett Monia: Thank you.

Eugene Schneider: Yep.

Unknown Executive: We're going to also ask patients.

This data for the. Launched on tonnage.

Unknown Executive: They prefer.

Launched on tonnage.

Unknown Executive: In the trial.

Operator: Thank you. The next question, Joey Stringer with Needham & Company.

Unknown Executive: Why.

Brett P. Monia: Yeah, I think first it's highly differentiated. This hasn't been done before and I think that differentiation is going to help us. This is an unsatisfied market right. I mean, we already see that patients are moving between therapies as it is right now and they're moving because they're either not adequately controlled or they're having breakthroughs or sometimes it's because of the way that the delivery mechanism works for the treatment that they are on. And so when we're thinking about the data it's going to be helpful for us to know in a very formal way the feedback from patients number one. And number two to help inform physicians about how to do this safely and effectively. And finally on the payer side, payers want to make sure that they're not paying for multiple medications at the same time and so this will help us with the payer messaging as well to talk about how to effectively get onto DONIDALORSEN, stay on DONIDALORSEN without them having to have multiple therapies overlapping or that they're having to pay for and cover for these patients.

Unknown Executive: <unk>, we're looking forward to sharing in the study as well and then thirdly and very importantly, we will be able to have the data in the instructions and the algorithms. If you will which are different for different prophylactic treatments.

Joseph Stringer: Hi. Thanks for taking our questions. Just to follow up on donidalorsen in the SWITCH study, you mentioned a patient survey and some other data. But maybe can you put a little bit finer point on what data specifically you will need to see from the SWITCH study that would resonate most from a commercial uptake perspective?

Unknown Executive: On how much time, it takes to before <unk> will.

Sometimes it's because of the way that the delivery mechanism works for the treatment that they are on and so when we're thinking about the data it's going to be helpful. For us to know in a very formal way the feedback from patients number one. And number two to help inform physicians about how to do this safely and effectively and finally on the payer side payers want to make sure that they're not paying for multiple medications at the same time and so this will help us with the payer messaging as well to talk about how to effectively get onto dining tillerson and stay on Dolores and without them having to have multiple therapy. These overlapping or that they're having to pay for and cover for these patients.

Unknown Executive: How much time, they need to be on and wean off existing prophylactic treatments and move on to Don indoors.

Unknown Executive: Based on previous treatments, but it's really important right Kyle.

Unknown Executive: To have this data for the.

Unknown Executive: The launch done.

Brett Monia: Well, I'll start, and Kyle could jump in. It's really the totality of the data, Joey. First of all, we will share data with current treatment that are current treatments that are available on the market today. So it won't just be one treatment that we're switching. We're going to be looking at patients that have previously been on Takhzyro or Orladuyo or other prophylactic treatments, what their baseline HAE attack rates were coming into the study, and then how that HAE attack rate evolves as patients continue to be on donidalorsen treatment. That's very important to have that data for the commercial launch. Second, as I mentioned, we're going to also ask patients which they prefer in the trial and why. And that'll be a survey that we're looking forward to sharing in the study as well.

Kyle Janais: Yeah, I think first that it's highly differentiated. This hasn't been done before, and I think that differentiation is going to help us. This is an unsatisfied market, right?

Speaker Change: Yes, I think first it's highly differentiated this hasn't been done before and I think that differentiation is going to help us. This is an unsatisfied market right. I mean, we already see that patients are moving between therapies as it is right now and they are moving because they're either not adequately controlled or theyre, having breakthroughs or some.

And number two to help inform physicians about how to do this safely and effectively and finally on the payer side payers want to make sure that they're not paying for multiple medications at the same time and so this will help us with the payer messaging as well to talk about how to effectively get onto dining tillerson and stay on Dolores and without them having to have multiple therapy. These overlapping or that they're having to pay for and cover for these patients.

Kyle Janais: <unk>, it's because of the way that the delivery mechanism works for the treatment that they are on and so when we're thinking about the data it's going to be helpful for us to know.

These overlapping or that they're having to pay for and cover for these patients.

Kyle Janais: I mean, we already see that patients are moving between therapies as it is right now, and they're moving because they're either not adequately controlled, or they're having breakthroughs, or sometimes it's because of the way that the delivery mechanism works for the treatment that they're on. And so when we're thinking about the data, you know, it's going to be helpful for us to know in a very formal way the feedback from patients, number one, and number two, to help inform physicians about how to do this safely and effectively.

Joseph Stringer: Great. Thanks for taking our questions.

Kyle Janais: And finally, on the payer side, you know, payers want to make sure that they're not paying for multiple medications at the same time. And so this will help us with the payer messaging as well to talk about how to effectively get on Donnie Delorsin and stay on Donnie Delorsin without them having to have multiple therapies overlapping or that they're having to pay for and cover for these patients.

Okay.

Kyle Janais: Very formal way the feedback from patients number one.

Operator: Thank you. And the next question comes from Jason Gerberry with Bank of America.

Kyle Janais: And number two to help inform physicians about how to do this safely and effectively and finally on the payer side payers want to make sure that they're not paying for multiple medications at the same time and so this will help us with the payer messaging as well to talk about how to effectively get onto dining <unk> stay on Donny to larsen without them having to have multiple.

Jason Gerberry: Hey, guys. Thanks for taking my questions. Two for me. Can you comment on the phase III SHTG trials and how pancreatitis events are accruing on a blinded basis versus events you've seen in other trials or your best estimate of what that event rate may look like. And then my second question is around TTR cardiomyopathy and the potential for combination therapy. Alnylam was pretty adamant that payers will cover a stabilizer and a silencer and generic [inaudible] leaving go generic this decade, so I'm just curious like what work you've done around combo that it will get covered and that there is an attainable clinical bar for combo. I know there's a lot in that but if you can address that. Alright, before handing it over to Kyle and Jonathan about this dynamic TTR cardiomyopathy market, combination monotherapy, let me comment on the SHTG. So as a reminder, Jason,

Two for me just can you comment on the phase III <unk> trials and how. Pancreatitis events are. Craig on a blinded basis versus. <unk> seen in other trials are your best estimate of what that event rate. May look like and then my second question is around the TR cardiomyopathy and the potential for combination therapy.

Pancreatitis events are. Craig on a blinded basis versus. <unk> seen in other trials are your best estimate of what that event rate. May look like and then my second question is around the TR cardiomyopathy and the potential for combination therapy.

Craig on a blinded basis versus. <unk> seen in other trials are your best estimate of what that event rate. May look like and then my second question is around the TR cardiomyopathy and the potential for combination therapy.

<unk> seen in other trials are your best estimate of what that event rate. May look like and then my second question is around the TR cardiomyopathy and the potential for combination therapy.

Kyle Janais: PS overlapping or that they're having to pay for and cover for these patients.

Brett Monia: And then thirdly, and very importantly, we'll be able to have the data, the instructions, and the algorithms, if you will, which are different for different prophylactic treatments on how much time it takes before donidalorsen will how much time they need to be on and wean off existing prophylactic treatments and move on to donidalorsen based on previous treatments. But it's really important, right, Kyle, to have this data for the launch of donidalorsen?

May look like and then my second question is around the TR cardiomyopathy and the potential for combination therapy.

Kyle Janais: Yeah.

Speaker Change: Great. Thanks for taking our questions.

Unknown Executive: Thank you. The next question comes from Jason Gerberry with Bank of America.

<unk> was pretty adamant that just payers will cover a stabilizer and a silencer and generic question feminists, leaving go generic this decade. So I'm just curious like what work you've done. Around combo that it will get covered and that there is an attainable clinical bar for combo I know, there's a lot in that but if. If you can address that. Alright, before handing it over to Carl and Jonathan about the dynamic. Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Kyle Janais: Thank you and the next question comes from Joseph <unk>, Joseph Sorry, Jason <unk> with Bank of America.

Unknown Executive: Hey guys, thanks for taking my questions. Two for me: can you comment on the Phase 3 SHTG trials and how acute pancreatitis events are accruing on a blinded basis versus My second question is around TTR cardiomyopathy and the potential for combination therapy. On Island, they seem pretty adamant that payers won't cover a stabilizer and a silencer, and there are questions, you know, if tofaminis will even go generic this decade. So I'm just curious about what work you've done around combo that, you know, it'll get covered, and that there's an attainable clinical bar for combo. I know there's a lot in that, but I'd love it if you could address that. Thanks.

Jason Gerberry: Oh, Hey, guys. Thanks for taking my questions.

So I'm just curious like what work you've done. Around combo that it will get covered and that there is an attainable clinical bar for combo I know, there's a lot in that but if. If you can address that. Alright, before handing it over to Carl and Jonathan about the dynamic. Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Unknown Executive: Two for me just can you comment on the phase III <unk> trials and how <unk>.

Around combo that it will get covered and that there is an attainable clinical bar for combo I know, there's a lot in that but if. If you can address that. Alright, before handing it over to Carl and Jonathan about the dynamic. Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Unknown Executive: Pancreatitis events are coming.

Unknown Executive: <unk> on a blinded basis versus.

If you can address that. Alright, before handing it over to Carl and Jonathan about the dynamic. Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Unknown Executive: <unk> seen in other trials are your best estimate of what that event rate.

Operator: Yeah. I think first, it's highly differentiated. This hasn't been done before. And I think that differentiation is going to help us. This is an unsatisfied market, right? I mean, we already see that patients are moving between therapies as it is right now. And they're moving because they're either not adequately controlled or they're having breakthroughs. Or sometimes it's because of the way that the delivery mechanism works for the treatment that they're on. And so when we're thinking about the data, it's going to be helpful for us to know in a very formal way the feedback from patients, number one, and number two, to help inform physicians about how to do this safely and effectively. And finally, on the payer side, payers want to make sure that they're not paying for multiple medications at the same time.

Kyle Jenne: Yeah. I think first, it's highly differentiated. This hasn't been done before. And I think that differentiation is going to help us. This is an unsatisfied market, right? I mean, we already see that patients are moving between therapies as it is right now. And they're moving because they're either not adequately controlled or they're having breakthroughs. Or sometimes it's because of the way that the delivery mechanism works for the treatment that they're on. And so when we're thinking about the data, it's going to be helpful for us to know in a very formal way the feedback from patients, number one, and number two, to help inform physicians about how to do this safely and effectively. And finally, on the payer side, payers want to make sure that they're not paying for multiple medications at the same time.

Alright, before handing it over to Carl and Jonathan about the dynamic. Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Brett P. Monia: Alright, before handing it over to Kyle and Jonathan about this dynamic TTR cardiomyopathy market, combination monotherapy, let me comment on the SHTG. So as a reminder, Jason, we saw remarkable reductions in acute pancreatitis in our FCS balance study for OLEZARSEN. Not only was the reduction substantial, the number of events in the placebo group were much more than we anticipated going into that study point. I guess, a very important point that I want to emphasize is that we don't really know people, it's not really understood well what the AP event rates are in FCS or SHTG is these trials that we're conducting that are going to add a lot of light, shed a lot of light onto what the true AP events are for both FCS and SHTG. Virtually all of the AP events that occurred in the FCS study were in the placebo group.

Unknown Executive: They look like and then my second question is around TR cardiomyopathy, and the potential for combination therapy.

Ctr cardiomyopathy market combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

we saw remarkable reductions in acute pancreatitis in our FCS balance study for OLEZARSEN. Not only was the reduction substantial, the number of events in the placebo group were much more than we anticipated going into that study point. I guess, a very important point that I want to emphasize is that we don't really know people, it's not really understood well what the AP event rates are in FCS or SHTG is these trials that we're conducting that are going to add a lot of light, shed a lot of light onto what the true AP events are for both FCS and SHTG. Virtually all of the AP events that occurred in the FCS study were in the placebo group.

Unknown Executive: <unk> is pretty adamant that just payers will cover a stabilizer on a silencer and generic questions feminists, leaving go generic this decade.

Not only was whereas the reduction substantial the number of events in the placebo group were much more than we anticipated going into that study to point I guess, a very important point that I want to emphasize. We don't really know people, it's not really understood well what the event rates are in FCS or S. Http. It as these trials that we're conducting that are going to add a lot of light shed a lot of light onto what the true <unk> events are for both FCS and S. H T G. Virtually all of the AP events that occurred in the FCS study were in the placebo group.

Unknown Executive: So I'm just curious like what work you've done.

Unknown Executive: Around combo that it will get covered and that there is an attainable clinical bar for combo I know, there's a lot in that but if.

Unknown Executive: If you can address that.

Unknown Executive: Alright, before handing over to Kyle and Jonathan about the dynamic TTR cardiomyopathy market combination monotherapy, let me comment on the SHTG. So, as a reminder, Jason, we saw remarkable reductions in acute pancreatitis in our FCS balance study for Olitz-Arson.

Speaker Change: Alright, before handing over to Carl and Jonathan about the dynamic.

We don't really know people, it's not really understood well what the event rates are in FCS or S. Http. It as these trials that we're conducting that are going to add a lot of light shed a lot of light onto what the true <unk> events are for both FCS and S. H T G. Virtually all of the AP events that occurred in the FCS study were in the placebo group.

Unknown Executive: TR cardiomyopathy marketed combination monotherapy, let me comment on the <unk>. So as a reminder, Jason.

Operator: This will help us with the payer messaging as well to talk about how to effectively get on to donidalorsen and stay on donidalorsen without them having to have multiple therapies overlapping or that they're having to pay for and cover for these patients.

Kyle Jenne: This will help us with the payer messaging as well to talk about how to effectively get on to donidalorsen and stay on donidalorsen without them having to have multiple therapies overlapping or that they're having to pay for and cover for these patients.

Unknown Executive: We saw a remarkable reductions in acute pancreatitis in our FCS balance study for for <unk>.

Unknown Executive: Not only was the reduction substantial, the number of AP events in the placebo group were much more than we anticipated going into that study. Point, I guess, a very important point that I want to emphasize, is that we don't really know people it's not really understood well what the AP event rates are in FCS or SHTG is these trials that we're conducting that are going to add a lot of light shed a lot of light on to what the true AP events are for both FCS and SHTG virtually all of the AP events that occurred in the SDS study were in the placebo.

Virtually all of the AP events that occurred in the FCS study were in the placebo group.

Unknown Executive: Not only was.

Unknown Executive: Whereas the reduction substantial the number of events in the placebo group were much more than we anticipated going into that study to point I guess, a very important point that I want to emphasize is that we don't really know people, who is not really understood well what the event rates are in Fcs or S. Http.

Certainly in SHTG, we would expect and do expect fewer AP events compared to FCS based on the fact that the mean triglyceride reductions are lower in SHTG than they are in FCS. But with that said, we have many patients in our SHTG trial that are in the thousands in the FCS range in this study, but the main reduction TG levels will be less and therefore, you would expect the rate of AP events to be a bit lower in SHTG. With that said, we are seeing blinded manner AP events and they are accumulating pretty robustly in this study. If we can replicate anything like what we saw in FCS, the majority of those patients we would expect to be in the placebo group because OLEZARSEN is expected to reduce triglycerides even better from a magnitude standpoint in SHTG versus FCS. So the balance FCS study certainly gave us more confidence in a positive AP outcome and in the study. Just a reminder, the primary endpoint is triglyceride reductions, AP events in the SHTG study is a key secondary.

Joseph Stringer: Great. Thank you for taking our questions.

Operator: Thank you. And the next question comes from Jason, sorry, Jason Gerberry with Bank of America.

Gary Nachman: Oh, hey, guys. Thanks for taking my questions. Two for me. Just can you comment on the phase 3 sHTG trials and how acute pancreatitis events are accruing on a blinded basis versus events you've seen in other trials or your best estimate of what that event rate may look like? And then my second question is around TTR, cardiomyopathy, and the potential for combination therapy. On Ionis, it seems pretty adamant that just payers won't cover a stabilizer and a silencer. And there are questions if tafamidis will even go generic this decade. So I'm just curious what work you've done around combo that it'll get covered and that there's an attainable clinical bar for combo. I know there's a lot in that, but I'd just love it if you can address that. Thanks.

Jason Gerberry: Oh, hey, guys. Thanks for taking my questions. Two for me. Just can you comment on the phase 3 sHTG trials and how acute pancreatitis events are accruing on a blinded basis versus events you've seen in other trials or your best estimate of what that event rate may look like? And then my second question is around TTR, cardiomyopathy, and the potential for combination therapy. On Ionis, it seems pretty adamant that just payers won't cover a stabilizer and a silencer. And there are questions if tafamidis will even go generic this decade. So I'm just curious what work you've done around combo that it'll get covered and that there's an attainable clinical bar for combo. I know there's a lot in that, but I'd just love it if you can address that. Thanks.

But with that said we have many patients in our <unk> trial that are in the thousands in the FCS range. In this study, but the main reduction mean TG levels will be less and therefore, you would expect the rate of AP. Events to be a bit lower. S H T G. With that said we are seeing. Blinded manner 80 events and they are accumulating. Pretty robustly in this study.

Unknown Executive: It is these trials that we're conducting that are going to add a lot of light shed a lot of light onto what the true <unk> events are for both FCS and S. H T G.

Events to be a bit lower. S H T G. With that said we are seeing. Blinded manner 80 events and they are accumulating. Pretty robustly in this study.

Unknown Executive: Virtually all of the events that occurred in the FCS study were in the placebo group.

S H T G. With that said we are seeing. Blinded manner 80 events and they are accumulating. Pretty robustly in this study.

With that said we are seeing. Blinded manner 80 events and they are accumulating. Pretty robustly in this study.

Unknown Executive: Certainly, in SHTG, we would expect and do expect fewer AP events just based on, as compared to FCS, based on the fact that the mean triglyceride reductions are lower in SHTG than they are in FCS. But with that said, we have many patients in our SHTG trial that are in the thousands in the FCS range in the study. But the mean reduction; mean TG levels will be less. And therefore, you would expect the rate of AP events to be a bit lower in SHTG.

Blinded manner 80 events and they are accumulating. Pretty robustly in this study.

Unknown Executive: Certainly in <unk>, we would expect and do expect fewer AP events, just based on compared to FCS based on the fact that the mean triglyceride reductions are lower and S. H D. G than they are in Fcs.

Pretty robustly in this study.

If we can replicate any anything like what we saw in FCS. The majority of those patients we would expect to be in the placebo group because the <unk> is expected to reduce triglycerides even better. From a magnitude standpoint, and S. H T G versus FCS so at the balance FCS study, certainly gave us more confidence and a and a positive AP. Outcome and in the study get reminder, the primary endpoint is triglyceride reductions AP events in the <unk> study is a key secondary.

Unknown Executive: But with that said we have many patients in our <unk> trial that are in the thousands in the FCS range. In this study, but the mean reduction mean TG levels will be less and therefore, you would expect the rate of AP events to be a bit lower and S. H T. G I.

From a magnitude standpoint, and S. H T G versus FCS so at the balance FCS study, certainly gave us more confidence and a and a positive AP. Outcome and in the study get reminder, the primary endpoint is triglyceride reductions AP events in the <unk> study is a key secondary.

Brett Monia: All right. Before handing over to Kyle and Jonathan about the dynamic TTR cardiomyopathy market, combination monotherapy, let me comment on the SHTG. So as a reminder, Jason, we saw remarkable reductions in acute pancreatitis in our FCS BALANCE study for olezarsen. Not only was the reduction substantial, the number of AP events in the placebo group were much more than we anticipated going into that study. The point, I guess, a very important point that I want to emphasize is that we don't really know. It's not really understood well what the AP event rates are in FCS or SHTG. It is these trials that we're conducting that are going to add a lot of light, shed a lot of light onto what the true AP events are for both FCS and SHTG.

Unknown Executive: With that said, we are seeing AP events in a blinded manner, and they're accumulating pretty robustly in the study. If we can replicate anything like what we saw in FCS, the majority of those patients would expect to be in the placebo group because olozarsin is expected to produce triglycerides even better from a magnitude standpoint in SHTG versus FCS. So the balanced FCS study certainly gave us more confidence in a positive AP outcome in the study. Jonathan, do you want to comment on the changing dynamics in TTR cardiomyopathy, how we're seeing monotherapy combination play out?

Outcome and in the study get reminder, the primary endpoint is triglyceride reductions AP events in the <unk> study is a key secondary.

Unknown Executive: With that said we are seeing.

Jonathan: Blended manner <unk> events and they are accumulating.

Jonathan: Pretty robustly in this study.

Jonathan: If we can replicate any anything like what we saw in FCS. The majority of those patients we would expect to be in the placebo group because the <unk> is expected to produce triglycerides even better.

Jonathan, do you want to comment on the changing dynamics in TTR cardiomyopathy, how we are seeing monotherapy combination play out?

Jonathan Birchall: Yes, I think the specific question for me around the payers willingness to cover the combo and I guess my first point it is very difficult to answer the question given that we don't yet have any data and therefore don't really understand the profile of the combination. That said, I think there are plenty of other therapy areas, whether it's [inaudible] work in Hep C where treatments were seven figures, plenty of oncology drugs, where there are very expensive combinations that are still covered by payers. What I can tell you specifically with regards to cardio transform and the combination usage is the market research that we've completed has shown there is a willingness from payers to cover the combination. Obviously, the caveat to that is it'll be data dependent but so long as with data from what's effectively the largest study in this area, we are fairly confident that if we are able to demonstrate the benefit that that will then ultimately be covered by the payers. And we're very well positioned to demonstrate added benefit in combination based on the design of our trial, the size of our trial and the percentage of patients we have on [inaudible] versus monotherapy.

Jonathan: From a magnitude standpoint in <unk> versus FCS so at the balance FCS study certainly gave us more confidence in a in a positive outcome.

His willingness. To cover the combo and I guess my first point it is very difficult to answer the question given that we don't yet have any data and therefore don't really understand the profile of the combination. That said I think there are plenty of other therapy areas, whether it's giving us working in Hep C where. Treatments were seven figures plenty of oncology drugs, whether a very expensive combinations. Still covered by payers and what I can tell you specifically with regards to to cardio transform. Combination usages. Our market research that we've.

To cover the combo and I guess my first point it is very difficult to answer the question given that we don't yet have any data and therefore don't really understand the profile of the combination. That said I think there are plenty of other therapy areas, whether it's giving us working in Hep C where. Treatments were seven figures plenty of oncology drugs, whether a very expensive combinations. Still covered by payers and what I can tell you specifically with regards to to cardio transform. Combination usages. Our market research that we've.

Unknown Executive: Outcome.

Jonathan: In the study reminder, the primary endpoint is triglyceride reductions.

That said I think there are plenty of other therapy areas, whether it's giving us working in Hep C where. Treatments were seven figures plenty of oncology drugs, whether a very expensive combinations. Still covered by payers and what I can tell you specifically with regards to to cardio transform. Combination usages. Our market research that we've.

Jonathan: Events in the <unk> study is a key secondary.

Unknown Executive: Jonathan you want to comment on the changing dynamics in GTO cardiomyopathy, how we are seeing monotherapy combination play out.

Treatments were seven figures plenty of oncology drugs, whether a very expensive combinations. Still covered by payers and what I can tell you specifically with regards to to cardio transform. Combination usages. Our market research that we've.

Brett Monia: Virtually all of the AP events that occurred in the FCS study were in the placebo group. Certainly, in SHTG, we would expect and do expect fewer AP events compared to FCS based on the fact that the mean triglyceride reductions are lower in SHTG than they are in FCS. But with that said, we have many patients in our SHTG trial that are in the thousands in the FCS range in the study. But the mean TG levels will be less. And therefore, you would expect the rate of AP events to be a bit lower in SHTG. With that said, we are seeing in a blinded manner AP events. And they're accumulating pretty robustly in the study.

Jonathan: Yeah, I think the specific question for me around that is about the combo. And I guess my first point is very difficult to answer the question, given that we don't yet have any data and therefore don't really understand the profile of the combination. That said, I think there are plenty of other therapy areas, whether it's Gilead's work in Hep C, where treatments cost seven figures, or plenty of oncology drugs where there are very expensive combinations that are still covered by payers.

Still covered by payers and what I can tell you specifically with regards to to cardio transform. Combination usages. Our market research that we've.

Jonathan: Yes, I think the specific question for me around that.

Jonathan: Hi, his willingness.

Jonathan: To cover the combo and I guess my first point it is very difficult to answer the question given that we don't yet have any data and therefore don't really understand the profile of the combination.

Combination usages. Our market research that we've.

Our market research that we've.

Completed as shown there is there is a willingness from payers. To cover the combination obviously, the caveat to that is it'll be data dependent but so long as with. And data from what's effectively the largest study. A study in this area, we are fairly confident that if we are able to demonstrate the benefit that that will then ultimately be covered by the payers and we're very well positioned. Is to demonstrate a added benefiting combination based on the design of our trial the size of our trial and the. And the percentage of patients we have in onto families versus monotherapy.

To cover the combination obviously, the caveat to that is it'll be data dependent but so long as with. And data from what's effectively the largest study. A study in this area, we are fairly confident that if we are able to demonstrate the benefit that that will then ultimately be covered by the payers and we're very well positioned. Is to demonstrate a added benefiting combination based on the design of our trial the size of our trial and the. And the percentage of patients we have in onto families versus monotherapy.

Jonathan: That said I think there are plenty of other therapy areas, whether it's giving us working in Hep C. Wet.

And data from what's effectively the largest study. A study in this area, we are fairly confident that if we are able to demonstrate the benefit that that will then ultimately be covered by the payers and we're very well positioned. Is to demonstrate a added benefiting combination based on the design of our trial the size of our trial and the. And the percentage of patients we have in onto families versus monotherapy.

Jonathan: At treatments were seven figures plenty of oncology drugs, whether a very expensive combinations.

A study in this area, we are fairly confident that if we are able to demonstrate the benefit that that will then ultimately be covered by the payers and we're very well positioned. Is to demonstrate a added benefiting combination based on the design of our trial the size of our trial and the. And the percentage of patients we have in onto families versus monotherapy.

Jonathan: Still covered by payers.

Jonathan: And what I can tell you specifically with regard to cardio transform and the combination usage is that the market research that we've completed has shown that there is a willingness from payers to cover the combination. Obviously, the caveat to that is it'll be data-dependent. But so long as we have data from what's effectively the largest study in this area, we're fairly confident that, if we're able to demonstrate the benefit, that that'll then ultimately be covered by the payers.

Brett P. Monia: And we're very well positioned to demonstrate added benefit in combination based on the design of our trial, the size of our trial and the percentage of patients we have on [inaudible] versus monotherapy.

Jonathan: I can't tell you specifically with regards to the cardio transform.

Is to demonstrate a added benefiting combination based on the design of our trial the size of our trial and the. And the percentage of patients we have in onto families versus monotherapy.

Jonathan: Combination usages.

Brett Monia: If we can replicate anything like what we saw in FCS, the majority of those patients we would expect to be in the placebo group because the olezarsen is expected to produce triglycerides even better from a magnitude standpoint in sHTG versus FCS. So the BALANCE study certainly gave us more confidence in a positive AP outcome in the study. Reminder, the primary endpoint is triglyceride reductions. AP events in the sHTG study is a key secondary. Jonathan, you want to comment on the changing dynamics in TTR cardiomyopathy, how we're seeing monotherapy combination play out?

Jonathan: Our market research that we've.

Jonathan: Completed as shown there is there is a willingness from payers.

And the percentage of patients we have in onto families versus monotherapy.

Jonathan: To cover the combination obviously, the caveat to that it will be data dependent but so long as with.

Jason Gerberry: Got it. Thank you.

Operator: Thank you. And next question comes from Yanan Zhu with Wells Fargo.

Jonathan: Data from what's effectively the largest study.

Yanan Zhu: Great. Thanks for taking our questions. Maybe to follow up on ATTR cardiomyopathy, just curious any color on the blinded event rate any update there and any thinking about the primary endpoint analysis. And also, as a competitor readout their data, what are the key data points that you will be focused on learning? Thanks. So thank you Yanan. So the blinded event rates in the cardio transform trial are tracking well. They're on track for what we expected and when I say that I'm referring to both mortality as well as hospitalizations and the nature of those hospitalizations we're looking at very carefully. And there are no changes to our plans on primary endpoint or timing. As we said in our presentation, as early as next year is still on track. The study were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost very much on the blinded event rate to drive the decision with our partner AstraZeneca on when to read this study out. We're very much looking forward to the readout of the first silencer in ATT cardiomyopathy from our phase III trial later this year. If we learn something from it, it could influence our timing for reading out the study. We're very much looking forward to it and I really can't say much more about it than that at this point.

Jonathan: A study in this area we are fairly confident that we if we are able to demonstrate the benefit that that will then ultimately be covered by the payers and we're very well positioned.

On the blinded event rate any update there and any thinking about the primary endpoint analysis and also as a competitor readout. The data. What are the key data points and that you will be focused on. Learning thanks. So thank you again, so the blinded event rates in the cardio transform trial are tracking well, they're on track for what we expected and that when I say that I'm, referring to both mortality as well as hospitalizations and the nature of those hot. Utilization is we're looking at very quickly very carefully. And and Theres no changes to our plans on primary endpoint or timing as we said in our. In our presentation. Early as next year is still on track. The study we were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost <unk>. Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>. This study out we're very much looking forward to the readout of the first silence or NTT or cardiomyopathy from our phase III trial. Later this year, if we learn something from it could influence that. You know, our our timing for reading out the study. Much looking forward to it. And I really can't go say much more about it than that at this point.

Unknown Executive: And we're very well positioned to demonstrate an added benefit in combination based on the design of our trial, the size of our trial, and the percentage of patients we have on tefaminase versus monoclonal.

Unknown Executive: Bye.

Unknown Executive: To demonstrate added benefiting combination based on the design of our trial the size of our trial and the <unk>.

The data. What are the key data points and that you will be focused on. Learning thanks. So thank you again, so the blinded event rates in the cardio transform trial are tracking well, they're on track for what we expected and that when I say that I'm, referring to both mortality as well as hospitalizations and the nature of those hot. Utilization is we're looking at very quickly very carefully. And and Theres no changes to our plans on primary endpoint or timing as we said in our. In our presentation. Early as next year is still on track. The study we were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost <unk>. Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>. This study out we're very much looking forward to the readout of the first silence or NTT or cardiomyopathy from our phase III trial. Later this year, if we learn something from it could influence that. You know, our our timing for reading out the study. Much looking forward to it. And I really can't go say much more about it than that at this point.

What are the key data points and that you will be focused on. Learning thanks.

Unknown Executive: And the percentage of patients we have in onto families versus monotherapy.

Kyle Jenne: So thank you Yanan. So the blinded event rates in the cardio transform trial are tracking well. They're on track for what we expected and when I say that I'm referring to both mortality as well as hospitalizations and the nature of those hospitalizations we're looking at very carefully. And there are no changes to our plans on primary endpoint or timing. As we said in our presentation, as early as next year is still on track. The study were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost very much on the blinded event rate to drive the decision with our partner AstraZeneca on when to read this study out. We're very much looking forward to the readout of the first silencer in ATT cardiomyopathy from our phase III trial later this year. If we learn something from it, it could influence our timing for reading out the study. We're very much looking forward to it and I really can't say much more about it than that at this point.

Speaker Change: Got it thank you.

Learning thanks.

Jonathan Birchall: Yeah. I think the specific question for me around the payer's willingness to cover the combo. I guess my first point is it's very difficult to answer the question given that we don't yet have any data and therefore don't really understand the profile of the combination. That said, I think there are plenty of other therapy areas, whether it's Gilead's work in Hep C where their treatments were seven figures, plenty of oncology drugs where there are very expensive combinations that are still covered by payers. What I can tell you specifically with regards to CardioTransform and the combination usage is the market research that we've completed has shown that there is a willingness from payers to cover the combination. Obviously, the caveat to that is it'll be data-dependent.

Unknown Executive: Thank you. And the next question comes from Yanan Zhu with Wells Fargo.

Yanan Zhu: Thank you and next question comes from Yanan, Zhu with Wells Fargo.

So thank you again, so the blinded event rates in the cardio transform trial are tracking well, they're on track for what we expected and that when I say that I'm, referring to both mortality as well as hospitalizations and the nature of those hot. Utilization is we're looking at very quickly very carefully. And and Theres no changes to our plans on primary endpoint or timing as we said in our. In our presentation. Early as next year is still on track. The study we were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost <unk>. Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>. This study out we're very much looking forward to the readout of the first silence or NTT or cardiomyopathy from our phase III trial. Later this year, if we learn something from it could influence that. You know, our our timing for reading out the study. Much looking forward to it. And I really can't go say much more about it than that at this point.

Unknown Executive: Great. Thanks for taking our questions. Maybe to follow up on ATTR cardiomyopathy, just curious, any color on the blinded event rate? Any update there? And any thoughts about the primary endpoint analysis? And also, when a competitor reads out their data, what are the key data points that you will be focused on learning?

Yanan Zhu: Great. Thanks for taking our questions maybe to follow up on <unk> cardiomyopathy, just curious any color on the blinded event rate.

Unknown Executive: Right, there and any thinking about the primary endpoint analysis and also as a competitor readout.

Utilization is we're looking at very quickly very carefully. And and Theres no changes to our plans on primary endpoint or timing as we said in our. In our presentation.

And and Theres no changes to our plans on primary endpoint or timing as we said in our. In our presentation.

Unknown Executive: The data.

Unknown Executive: What are the key data points and.

Unknown Executive: You will be focused on.

In our presentation.

Speaker Change: Learning thanks.

Early as next year is still on track. The study we were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost <unk>. Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>.

Unknown Executive: Thanks.

Speaker Change: So thank you Ian.

The study we were to go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost <unk>. Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>.

Unknown Executive: So the blinded event rates in the cardio transform trial are tracking well they are on track for what we expected.

Very much on the blinded event rate to drive the decision without with our partner Astrazeneca on <unk>.

Unknown Executive: When I say that I'm, referring to both mortality as well as hospitalizations.

This study out we're very much looking forward to the readout of the first silence or NTT or cardiomyopathy from our phase III trial. Later this year, if we learn something from it could influence that. You know, our our timing for reading out the study. Much looking forward to it. And I really can't go say much more about it than that at this point.

Unknown Executive: Hospitalizations and the nature of those hospitalizations, we're looking at very quickly very carefully.

Jonathan Birchall: But so long as we have data from what's effectively the largest study in this area, we're fairly confident that if we're able to demonstrate the benefit, that that'll then ultimately be covered by the payers.

Unknown Executive: And <unk>.

Speaker Change: And there's no changes to our plans on primary endpoint or timing as we said in our.

You know, our our timing for reading out the study. Much looking forward to it. And I really can't go say much more about it than that at this point.

Unknown Executive: In our presentation.

Much looking forward to it. And I really can't go say much more about it than that at this point.

Unknown Executive: As early as next still on track.

And I really can't go say much more about it than that at this point.

Brett Monia: Yeah. And we're very well positioned to demonstrate added benefit in combination based on the design of our trial, the size of our trial, and the percentage of patients we have on tafamidis versus monotherapy.

Unknown Executive: Everywhere you go towards completion of 140 weeks of treatment that would be mid year 2026, and we're focused almost very much on the blinded event rate to drive that decision with our partner Astrazeneca <unk> study out we're very much looking forward to the readout of the first silencer and Ctr cardiomyopathy from our phase.

Yanan Zhu: Great. If I may ask a follow up on the Angelman syndrome readout, what might be the venue and how do we think about the relative importance of the biomarker EEG versus clinical endpoints like CGI and 84 when we learn the data? Thank you.

Unknown Executive: So, thank you, Yanan. So, the blinded event rates in the CardioTransform trial are tracking well. They're on track for what we expected. And when I say that, I'm referring to both mortality as well as hospitalizations and the nature of those hospitalizations.

What might be the venue. How do we. Think about the relative importance of the biomarker EEG versus clinical endpoints like CGI in 84 when we. Really the data thank you.

How do we. Think about the relative importance of the biomarker EEG versus clinical endpoints like CGI in 84 when we. Really the data thank you.

Think about the relative importance of the biomarker EEG versus clinical endpoints like CGI in 84 when we. Really the data thank you.

Unknown Executive: We're looking at it very quickly, very carefully, and there are no changes to our plans for the primary endpoint or timing. As we said in our presentation, as early as next year, we're still on track to study where to go to completion, 140 weeks of treatment, that would be mid-year 2020. And we're focused very much on the blinded event rate to drive the decision with our partner AstraZeneca on when to read the study out.

Gary Nachman: Got it. Thank you.

Jason Gerberry: Got it. Thank you.

Operator: Thank you. The next question, Yanan Zhu with Wells Fargo.

Unknown Executive: We're very much looking forward to the readout of the first silencer in TTR cardiomyopathy from a phase three trial later this year. If we learn something from it, it could influence our timing for reading out the study. We're very much looking forward to it, and really can't say much more about it than that.

Unknown Executive: <unk> trial later this year, if we learn something from it could influence that.

Yanan Zhu: Great. Thanks for taking our questions. Maybe to follow up on ATTR cardiomyopathy, just curious, any color on the blinded event rate, any update there, and any thinking about the primary endpoint analysis. And also, as a competitor reads out their data, what are the key data points that you will be focused on learning? Thanks.

Really the data thank you.

Brett P. Monia: Yeah, Eugene will comment on the clinical endpoints biomarker EEG and the other in daily [inaudible] et cetera. We haven't settled on how and when exactly we will report out the next step for the Angelman program. As you know Yanan, Biogen has an option to license this program. And as we've said before, when we do announce the next step for the program when the when the data reads out we're also planning to comment on what Biogen's plans are for the next steps with the option for the program.

Unknown Executive: R R.

Unknown Executive: Our timing for reading out the study, we're very much looking forward to it.

Unknown Executive: And I really can't go say much more about it than that at this point.

We don't we haven't. Settled on how and when exactly we will report out. The next step for the Angelman program as you know and Biogen has an option to license this program. And as we've said before. When we do announce the next step for the program when the when the when the data reads out. So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

Settled on how and when exactly we will report out. The next step for the Angelman program as you know and Biogen has an option to license this program. And as we've said before. When we do announce the next step for the program when the when the when the data reads out. So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

Unknown Executive: Great. If I may ask a follow-up question on Andelman syndrome readout, what might be the venue, and how do we think about the relative importance of the EEG biomarker versus clinical endpoints like CGI and Bayley-4 when we, you know, get the data? Thank you.

Speaker Change: Great. If I may ask a follow up on <unk> syndrome readout.

The next step for the Angelman program as you know and Biogen has an option to license this program. And as we've said before. When we do announce the next step for the program when the when the when the data reads out. So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

Speaker Change: What might be the venue and how do we think.

Speaker Change: Think about the relative importance of the biomarker EEG versus clinical.

And as we've said before. When we do announce the next step for the program when the when the when the data reads out. So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

When we do announce the next step for the program when the when the when the data reads out. So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

Speaker Change: <unk> CGI and <unk> 84.

Brett Monia: So thank you, Yanan. So the blinded event rates in the CardioTransform trial are tracking well. They're on track for what we expected. And when I say that, I'm referring to both mortality, as well as hospitalizations, and the nature of those hospitalizations. We're looking at it very carefully. And there's no changes to our plans on primary endpoint or timing. As we said in our presentation, as early as next year is still on track. The study, where it'll go to its completion 140 weeks, the treatment would be midyear 2026. And we're focused almost very much on the blinded event rate to drive the decision with our partner, AstraZeneca, on when to read the study out. We're very much looking forward to the readout of the first silencer in TTR cardiomyopathy from a phase 3 trial later this year.

Speaker Change: Really the data thank you.

So we're also planning to comment on where Biogen plans are for the next steps with the option and for the program.

Unknown Executive: Yeah, Eugene will comment on the clinical endpoints, biomarker EEG and other in Bayley-4, etc. We don't, we have not settled on how and when exactly we will report out the next step for the ANGELWINS program. As you know, Yanan Biogen has an option to license this program.

Speaker Change: Yes, Eugene will comment on the clinical endpoints biomarker EEG and the other in daily for et cetera.

As far as forum, we have not settled on that either. There is an Angelman conference in August of this year, which we regularly attend each year that could be a forum but we haven't made any firm decisions. And of course, if Biogen license this program they will be in the driver's seat to make those calls ultimately. Eugene, talk a little bit about the endpoints that we're looking at in Angelman?

We have not settled on that either. There is an Angelman conference in August of this year, which we regularly attend each year that could be a form but we haven't we haven't made any firm decisions and of course, if biogen licensed this is the program they will be in the driver's seat to make. Those calls ultimately.

Speaker Change: We don't we haven't.

Eugene: Settled on how and when exactly we will report out.

There is an Angelman conference in August of this year, which we regularly attend each year that could be a form but we haven't we haven't made any firm decisions and of course, if biogen licensed this is the program they will be in the driver's seat to make. Those calls ultimately.

Eugene: The next step for the Angelman program as you know Biogen has an option to license this program.

Unknown Executive: And as we've said before, when we do announce the next step of the program, when the data reads out, we're also planning to comment on what Biogen's plans are for the next steps of the option for the program. As far as forum, we have not settled on that either. There is an Angel Mints conference in August of this year, which we regularly attend each year. That could be a forum, but we haven't made any firm decisions.

Eugene: And as we've said before.

Those calls ultimately.

Unknown Executive: When we do announce the next step of the program when the when the data reads out will also we're also planning to comment on where Biogen plans are for the next steps with the option for the program.

Eugene Schneider: Yeah, sure. Thanks for your question Yanan. So of course, this is truly a learning study for us and as such we're really exploring a range of different outcomes including of course, EEG which has quite a bit of data both through natural history as well as some of the early data that was shared with the community. Importantly of course, the clinical assessments that include standard scales you mentioned [inaudible] of course, Vineland is another very common scale used in neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation and symptoms of Angelman and that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the impact that our drug may have on all of those features of this pretty complex disorder.

Yes. So of course, we're this is a. Truly a learning study for us and as such we're really exploring a range of different outcomes including of. Of course, <unk>, which has. Quite a bit of data both through natural history as well as some of the early <unk>. Data that was shared with the community. Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Truly a learning study for us and as such we're really exploring a range of different outcomes including of. Of course, <unk>, which has. Quite a bit of data both through natural history as well as some of the early <unk>. Data that was shared with the community. Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: As far as forum.

Unknown Executive: We have not settled on that either.

Of course, <unk>, which has. Quite a bit of data both through natural history as well as some of the early <unk>. Data that was shared with the community. Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: There is an Angelman conference in August of this year, which we regularly attend each year that could be a form but we haven't we haven't made any firm decisions and of course, if biogen licensed the program there will be in the driver's seat.

Quite a bit of data both through natural history as well as some of the early <unk>. Data that was shared with the community. Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Brett Monia: If we learn something from it, it could influence our timing for reading out the study. We're very much looking forward to it. And I really can't say much more about it than that at this point.

Data that was shared with the community. Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: And, of course, if Biogen licenses the program, they'll be in the driver's seat to make those calls. Eugene, can you talk a little bit about the endpoints that we're looking at in Angelman's? Yeah, sure. Thanks for your question, Yanan.

Importantly of course, the clinical assessments that include standard. Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Eugene: Those calls ultimately.

Scales. You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Eugene: Can you talk a little bit about the endpoints that we're looking at in England's yes sure. Thanks for your question Liana.

You mentioned Bailey for of course, Vineland is another very common scale use and neurodevelopmental disorders. But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: Thanks for your question, Yanan. Yeah, so of course, we're, this is truly a learning study for us. And as such, we're really exploring a range of different outcomes, including, of course, EEG, which has built up quite a bit of data, both through natural history, as well as some of the early data that was shared with the community. But importantly, of course, the clinical assessments that include standard scales that you mentioned. Bayley-4, for example, is another very common scale used in neurodevelopmental disorders.

Yanan Zhu: Great. If I may ask a follow-up on Angelman syndrome readout, what might be the venue? And how do we think about the relative importance of the biomarker EEG versus clinical endpoints like CGI and Bayley IV when we learn the data? Thank you.

Unknown Executive: Yes. So of course, we're this is a.

Unknown Executive: Truly a learning study for us and as such we're really exploring a range of different outcomes including of.

But we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms for Angela. And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: Of course, <unk>, which has.

Unknown Executive: Still quite a bit of data both through natural history as well as some of the early <unk>.

And that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the. Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: Data that was shared with the community.

Brett Monia: Yeah. Eugene will comment on the clinical endpoints, biomarker, EEG, and Bayley IV, etc. We have not settled on how and when exactly we will report out the next step for the Angelman program. As you know, Yanan, Biogen has an option to license this program. And as we've said before, when we do announce the next step for the program, when the data reads out, we're also planning to comment on what Biogen's plans are for the next steps if they option in for the program. As far as forum, we have not settled on that either. There is an Angelman conference in August of this year, which we regularly attend each year. That could be a forum. But we haven't made any firm decisions. And of course, if Biogen licenses the program, they'll be in the driver's seat to make those calls ultimately.

Impacted our drug may have on all of those features of this pretty complex disorder.

Unknown Executive: Importantly of course, the clinical assessments that include standard.

Unknown Executive: Scales.

Yanan Zhu: Got it. Thank you.

Unknown Executive: You mentioned daily for of course volume land is another very common scale youth and Neurodevelopmental disorders, but we're also looking at other aspects of this disease essentially covering a very broad range of presentation on symptoms.

Operator: Thank you. And the next question comes from [inaudible] with RBC.

Unknown Executive: But we're also looking at other aspects of this disease, essentially covering a very broad range of... Presentation and Symptoms for Angel Line, and that includes things like sleep and behavior and other things. So we're truly trying to learn as much as possible about the impact that our drug may have on all of those features of this pretty complex disease.

Unknown: Oh, great. Thanks so much for taking my questions and congrats on all the progress. Maybe one TCR cardiomyopathy [inaudible] if I may, what was your reaction to AstraZeneca powering their phase III trial for the monoclonal antibody in thousand patients? Basically we now have Alnylam with 665 patients, your trial is 1,400 patients and AstraZeneca's monoclonal antibody has 1,000 patients. Does this mean that Alnylam is underpowered, you are overpowered and the monoclonal antibody is [inaudible] powered? Any thoughts there much appreciated. And then maybe on [inaudible], what's the latest thinking on this target? Roche is clearly very excited about it and even willing to run the cardiovascular trial, while the [inaudible] your target is not getting the same amount of airtime that it once did. Am I off here and if so, what's next for this program?

Unknown Executive: Got it. Thank you.

What was your reaction to Astrazeneca power in their phase III trial for the monoclonal antibody <unk> thousand patients basically we now have a balance you'll just be a 665 patients. Your trial is for 300 patients and Astrazeneca is a monoclonal antibody that tower foundations does this mean you said no islands underpowered you are overpowered. And I'm going to fly antibodies. The purpose is powered any thoughts there much appreciate it and then maybe what's the latest thinking on this targeted Roche is clearly very excited about it and even willing to run the cardiovascular trial, while the skill set your target is not getting the same amount of airtime than it once did.

Unknown Executive: For agile one and that includes things like sleep behavior and other things. So we're truly trying to learn as much as possible about the.

Unknown Executive: Impacted our drug may have on all of those.

Unknown Executive: Features of this pretty complex disorder.

Unknown Executive: Got it thank you.

And I'm going to fly antibodies. The purpose is powered any thoughts there much appreciate it and then maybe what's the latest thinking on this targeted Roche is clearly very excited about it and even willing to run the cardiovascular trial, while the skill set your target is not getting the same amount of airtime than it once did.

Unknown Executive: Thank you. And the next question comes from Luca Issi with RBC.

Unknown Executive: Okay.

Unknown Executive: Thank you and the next question comes from Luca <unk> with RBC.

Unknown Executive: Oh, great. Thanks so much for taking the question and congratulations on the progress. Maybe one on TTR cardiomyopathy. Eugene, if I may, what was your reaction to AstraZeneca powering their phase three trial for their monoclonal antibody at 1000 patients? Basically, we now have Alnilam Helios B in 665 patients, your trial is 1400 patients, and AstraZeneca's monoclonal antibody at 1000 patients. Does this mean that Alnilam is underpowered, you are overpowered, and the monoclonal antibody is underpowered?

Luca Issi: Oh, great. Thanks, so much for taking my question.

Unknown Executive: That's on the progress, making one TCR cardiomyopathy gene if I may.

Unknown Executive: What was your reaction to Astrazeneca powering their phase III trial for the monoclonal antibody <unk> thousand patients basically we now have a balance sheet be a 665 patients. Your trial is for 200 patients and Astrazeneca is a monoclonal antibody that consultation does this mean you said no islands underpowered you are overpowered.

Brett Monia: Eugene, talk a little bit about the endpoints that we're looking at in Angelman's.

Eugene Schneider: Yeah. Sure. Thanks. We have a question, Yanan. Yeah. So of course, this is truly a learning study for us. And as such, we're really exploring a range of different outcomes, including, of course, EEG, which has built quite a bit of data both through natural history as well as some of the early data that was shared with the community. But importantly, of course, the clinical assessments that include standard scales that you mentioned, Bayley IV, of course, Vineland is another very common scale used in neurodevelopmental disorders. But we're also looking at other aspects of this disease, essentially covering a very broad range of presentation and symptoms for Angelman. And that includes things like sleep and behavior and other things. So we're truly trying to learn as much as possible about the impact that our drug may have on all of those features of this pretty complex disorder.

Am I off here and if so, what's next for this program? And then finally on HAE, I think on page 17, you're citing that this asset obviously includes near elimination of attacks, wondering if you can comment on whether that applies to both Q4W and QAW or only Q4W? Thanks so much. A lot to unpack there on the questions on trial design. We're not that close to AstraZeneca's antibody [inaudible] cardiomyopathy Luca. And so the size of their study, the powering assumptions that went into that all that is not in our area. We of course talk to them pretty regularly about how these two mechanisms could synergize down the road or so, but certainly we're not involved in design of their trial.

Am I off here and if so, what's next for this program?

And then finally on HAE, I think on page 17, you're citing that this asset obviously includes near elimination of attacks, wondering if you can comment on whether that applies to both Q4W and QAW or only Q4W? Thanks so much.

Unknown Executive: And then maybe on AGT: what's the latest thinking on this target? Roche is clearly very excited about it and even willing to run a cardiovascular outcome trial while he feels that your target is not getting the same amount of airtime that it once did. Am I off here? And if so, what's next for this program?

Speaker Change: In a minute.

Eugene: The purpose of power any thoughts there much appreciated and then maybe on <unk>.

Q <unk>. Thanks, so much. No comment. A lot to unpack there. On the margin. Questions trial design so. We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

Unknown Executive: What's the latest thinking on this targeted Roche is clearly very excited about it and even willing to run a cardiovascular outcome trial, while steel said youre targeted not getting the same amount of airtime than it once did.

No comment. A lot to unpack there. On the margin. Questions trial design so. We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

Brett P. Monia: A lot to unpack there on the questions on trial design. We're not that close to AstraZeneca's antibody [inaudible] cardiomyopathy Luca. And so the size of their study, the powering assumptions that went into that all that is not in our area. We of course talk to them pretty regularly about how these two mechanisms could synergize down the road or so, but certainly we're not involved in the design of their trial. I don't think--Kyle, any assumptions or anything?

A lot to unpack there. On the margin. Questions trial design so. We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

On the margin. Questions trial design so. We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

Questions trial design so. We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

We're not that close to Astrazeneca is a antibody. The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

Unknown Executive: Am I off here and if so what's next service program and then finally on <unk> I think on page 17, you're citing that this assets. Obviously includes mirror eliminations of attacks wondering if you can comment on whether that applies to both Q4 W. H U a W or all of these.

The <unk> for <unk> cardiomyopathy Luca. And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

And. So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

So the size of their studied the powering assumptions that went into that all that is not. In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

In our area, we were of course talk to them. We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

We regularly about. How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

How these two mechanisms crude synergize down the road or so, but certainly we're not involved in design of their trial.

Q4 W: Q4 W. Thanks, so much.

Unknown Executive: I'm out; I'm out.

Speaker Change: No comment.

Unknown Executive: So we're not that close to AstraZeneca's antibody depleter for TTR Cardamom and Pluluca. And so, you know, the size of their study, the powering assumptions that went into that, all that, it's not in our area. We, of course, talk to them pretty regularly about, you know, how these two mechanisms could synergize down the road or so, but certainly we're not involved in the design of their trial. I don't think, you know, towering assumptions, anything.

No, just on our trial, as you know, we spoke about it a lot and certainly we feel pretty confident in our assumptions that are based on emerging data so that's what I feel comfortable speaking about. I can't speculate what others used in their assumptions. It's a different mechanism. We believe in our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our cardio transform study. With that, I can't really, I don't want to comment anymore on what others are doing. HGT, no change.

Kyle Jenne: No, just on our trial, as you know, we spoke about it a lot and certainly we feel pretty confident in our assumptions that are based on emerging data so that's what I feel comfortable speaking about. I can't speculate what others used in their assumptions.

Unknown Executive: A lot to unpack there.

<unk> anything no just just on our trial as you know we spoke about it a lot and certainly we feel pretty confident in our assumptions that are based on emerging data. But I feel comfortable speaking about account speculate what others used in their assumptions with a different mechanism. We believe that our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our in our cardio transform study. With that I can't really I don't want to comment anymore on the others are doing HGT. No change.

Unknown Executive: On the motion.

Unknown Executive: Questions trial design so.

Yanan Zhu: Got it. Thank you.

Unknown Executive: We're not that close to Astrazeneca is.

Operator: Thank you. The next question comes from Luke Issey with RBC.

Unknown Executive: Antibody depleter for TTM cardiomyopathy Luca.

But I feel comfortable speaking about account speculate what others used in their assumptions with a different mechanism. We believe that our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our in our cardio transform study. With that I can't really I don't want to comment anymore on the others are doing HGT. No change.

Luca Issi: Oh, great. Thanks so much for taking the question. And congrats on the progress. Maybe one on ATTR cardiomyopathy, Eugene, if I may. What was your reaction to AstraZeneca powering their phase 3 trial for their monoclonal antibody at 1,000 patients? Basically, we now have Alnylam, Helios-B, at 665 patients. Your trial is 1,400 patients. And AstraZeneca's monoclonal antibody at 1,000 patients. Does this mean that Alnylam is underpowered? You are overpowered? And the monoclonal antibody is appropriately powered? Any thoughts there? Much appreciated. And then maybe on AGT, what's the latest thinking on this target? Roche is clearly very excited about it and even willing to run a cardiovascular outcome trial while it feels that your target is not getting the same amount of airtime that it once did. Am I off here? And if so, what's next for this program?

Unknown Executive: And.

Unknown Executive: So the size of their studied the powering assumptions that went into that all of that it's not.

Brett P. Monia: It's a different mechanism. We believe in our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our cardio transform study. With that, I can't really, I don't want to comment anymore on what others are doing. HGT, no change.

Unknown Executive: In our area where of course talk to them.

Unknown Executive: We regularly about.

Unknown Executive: How these two mechanisms crude synergize down the road or so, but certainly we're not involved in the design of their trial.

With that I can't really I don't want to comment anymore on the others are doing HGT. No change.

Unknown Executive: Powering.

Unknown Executive: No, just on our trial, as you know, we spoke about it a lot. And certainly, we feel pretty confident in our assumptions that are based on emerging data. So that's what I feel comfortable speaking about. I can't speculate what others use in their assumptions. It's a different mechanism, we believe.

No change.

HGT, no change. We are continuing to progress our plans as we've stated earlier that we plan to partner this program and we're still planning to do that and we're making progress. For HAE, we know, as we will share with you and Yakui at the end of this month, every four week and every eight week dosing showed a highly statistically significant benefit in reducing attack rates but every four week dosing had a greater reduction in attacks. So when we referred to near elimination then certainly every four week data comes closest to that in every eight week dosing.

Unknown Executive: <unk> anything no just just on our trial as you know we spoke about it a lot and certainly we feel pretty confident in our assumptions that are based on emerging data.

We are continuing to progress our plans as we've stated earlier that we plan to partner this program and we're still planning to do that and we're making progress. For HAE, we know, as we will share with you and Yakui at the end of this month, every four week and every eight week dosing showed a highly statistically significant benefit in reducing attack rates but every four week dosing had a greater reduction in attacks. So when we referred to near elimination then certainly every four week data comes closest to that in every eight week dosing.

Unknown Executive: But I feel comfortable speaking about account speculate what others used in their assumptions with a different mechanism. We believe that our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our in our cardio transform study.

For HCA. No. As we will share with you and Yoki. At the end of this month. Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in attacks. So when we referred to near elimination them certainly.

Unknown Executive: It's a different mechanism, but we believe in our trial design. We believe that we have the right size of the trial design and the makeup and the demographics of our cardio transforms. With that, I can't really, I don't want to comment anymore on what others are doing. AGT, no change; we are continuing to progress our plans, as we've stated earlier that we plan to partner with this program, and we're still planning to do that, and we're making progress.

No. As we will share with you and Yoki. At the end of this month. Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in attacks. So when we referred to near elimination them certainly.

As we will share with you and Yoki. At the end of this month. Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in attacks. So when we referred to near elimination them certainly.

At the end of this month. Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in attacks. So when we referred to near elimination them certainly.

Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in attacks. So when we referred to near elimination them certainly.

Luca Issi: And then finally, on HE, I think on page 17, you're citing that this asset obviously includes near eliminations of attacks. Wondering if you can comment on whether that applies to both Q4W and Q8W or only Q4W. Thanks so much.

Unknown Executive: With that I can't really I don't want to comment anymore on what others are doing HGT.

Unknown Executive: No change.

Unknown Executive: Our continuing to progress our plans as we've stated earlier that we plan to partner this program and we're still planning to do that and we're making we're making progress.

Every four week data comes closest. To that in every eight week dosing.

To that in every eight week dosing.

Unknown: Got it. Thanks so much.

Unknown Executive: For HAE, we know, as we will share with you at IACHI at the end of this month, both every four-week and every eight-week dosing showed a highly statistically significant benefit in reducing HAE attack rates, but every four-week dosing had a greater reduction in HAE attacks. So when we refer to near elimination, certainly, every four-week data comes closest to that, closer to that than every eight-week.

Unknown Executive: For HCA.

Brett Monia: Oh, a lot to unpack there. Luke, thanks for the questions.

Operator: Thank you. And the next question comes from Salveen Richter with Goldman Sachs.

Unknown Executive: We know we as we will share with you.

Eugene Schneider: My comment on the questions.

Brett Monia: My comment on the questions.

Brett Monia: Trial design. So we're not that close to AstraZeneca's antibody depleter for TTR cardiomyopathy, Luke. And so the size of their study, the powering assumptions that went into that, all that, it's not in our area. We're, of course, talk to them pretty regularly about how these two mechanisms could synergize down the road or so. But certainly, we're not involved in the design of their trial. I don't think powering assumptions, anything.

Unknown: Thanks for taking our question. This is [inaudible] on for Salveen. Just a follow up on the previous commentary about the Medicare part D side. How are you thinking about the possibility that there could be a higher level of scrutiny, especially in cardiomyopathy given the entrance of another stabilizer potentially this year? Thank you. For the Medicare D population, I mean things are evolving a little bit right with the IRA regulations and things that have come into play.

Unknown Executive: Yoki AR.

Unknown Executive: At the end of this month.

A follow up on my previous commentary about the Medicare part D side. How are you thinking about the possibility that there could be a higher level of scrutiny, especially inquiry. Cardiomyopathy. At the entrance of another stabilize or potentially this year. That's kind of what I'm thinking. Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Unknown Executive: Boat every four week in every eight week dosing showed a highly statistically significant benefit in reducing attack rates by every four week dosing had a greater reduction in AG and so when we referred to near elimination them certainly.

How are you thinking about the possibility that there could be a higher level of scrutiny, especially inquiry. Cardiomyopathy. At the entrance of another stabilize or potentially this year. That's kind of what I'm thinking. Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Cardiomyopathy. At the entrance of another stabilize or potentially this year. That's kind of what I'm thinking. Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

At the entrance of another stabilize or potentially this year. That's kind of what I'm thinking. Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Unknown Executive: Every four week data comes closest.

Unknown Executive: Mostly to that in every eight week dosing.

That's kind of what I'm thinking. Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Speaker Change: Got it thanks, so much.

Kyle Jenne: For the Medicare D population, I mean things are evolving a little bit right with the IRA regulations and things that have come into play. And historically, there's been quite a bit of distinction around the out-of-pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that. I think where we're at right now with Medicare part D is a much more favorable position than we have been historically and it's only anticipated to get better in the coming years. So out-of-pocket expenses are going to be limited for those patients either 3,000 or so dollars this year and it goes down to 2,000 or so dollars next year and then there's also the ability to spread those costs over time, so it's not a one time assessment for the patient, which I think is very positive. So when we're thinking about WAINUA

Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Unknown Executive: Thank you. And the next question comes from Salveen Richter with Goldman Sachs.

Unknown Executive: Got it. Thanks so much. Thank you. And the next question comes from Salveen Richter with Goldman Sachs. Thanks for speaking on that question.

Speaker Change: Thank you and our next question comes from <unk> Richter with Goldman Sachs.

Eugene Schneider: No. Just on our trial, as you know, we spoke about it a lot. And certainly, we feel pretty confident in our assumptions that are based on emerging data. So that's what I feel comfortable speaking about. I can't speculate what others use in their assumptions and what.

Salveen Richter: Thanks for taking my question. This is Tommy on for Celgene.

And historically, there's been quite a bit of distinction around the out-of-pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that. I think where we're at right now with Medicare part D is a much more favorable position than we have been historically and it's only anticipated to get better in the coming years. So out-of-pocket expenses are going to be limited for those patients either 3,000 or so dollars this year and it goes down to 2,000 or so dollars next year and then there's also the ability to spread those costs over time, so it's not a one time assessment for the patient, which I think is very positive. So when we're thinking about WAINUA

Salveen Richter: A follow up on my previous commentary about the Medicare part D side.

Salveen Richter: Good how are you thinking about the possibility that there could be a higher level of scrutiny, especially in Korea and.

I think where we're at right now with Medicare part D is a much more favorable position than we have been historically and it's only anticipated to get better. In the coming years, so out of pocket expenses are going to be limited for those patients either 3000, or so dollars. This year and it goes down in 2000, or so dollars next year and. Then theres also the ability to spread those costs over time, so it's not a one time. Assessment for the patient, which I think is very positive so when we're thinking about.

Brett Monia: It's a different mechanism. We believe in our trial design. We believe that we have the right size of the trial design and the makeup and the demographics in our CardioTransform study. With that, I don't want to comment anymore on what others are doing. AGT, no change. We are continuing to progress our plans as we've stated earlier that we plan to partner this program. And we're still planning to do that. And we're making progress. For HAE, we know, as we will share with you at the EAACI at the end of this month, both every four-week and every eight-week dosing showed highly statistically significant benefit in reducing HAE attack rates. But every four-week dosing had a greater reduction in HAE attacks. So when we refer to near elimination, certainly, every four-week data comes closer to that than every eight-week dosing.

Unknown Executive: Cardiomyopathy.

Salveen Richter: And there's another stabilizer potentially this year thank.

In the coming years, so out of pocket expenses are going to be limited for those patients either 3000, or so dollars. This year and it goes down in 2000, or so dollars next year and. Then theres also the ability to spread those costs over time, so it's not a one time. Assessment for the patient, which I think is very positive so when we're thinking about.

Salveen Richter: Thank you.

Salveen Richter: I don't know if they can.

Unknown Executive: For the Medicare D population, I mean, things are evolving a little bit, right, with the IRA regulations and things that have come into play. And historically, there was quite a bit of distinction around the out-of-pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that. I think where we're at right now with Medicare Part D is a much more favorable position than we have been historically, and it's only anticipated to get better in the coming years.

Salveen Richter: Or for the Medicare D population, I mean things are evolving a little bit right with the IRS regulations and things that have come into play.

Then theres also the ability to spread those costs over time, so it's not a one time. Assessment for the patient, which I think is very positive so when we're thinking about.

Assessment for the patient, which I think is very positive so when we're thinking about.

Unknown Executive: Historically, there has been quite a bit of distinction around the out of pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that.

Kyle Jenne: So when we're thinking about WAINUA and other programs that we have that will go through the Medicare part D channel, I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately. And keep in mind, it's not just about our treatment for Medicare part D but it's a combination of all of the therapies that those patients are on that will hit that ultimate cap of $3,000 or $2000, respectively. So I think we're well positioned in a good place to the reimbursement channels to allow patients to have access and appropriate access to our treatments.

and other programs that we have that will go through the Medicare part D channel, I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately. And keep in mind, it's not just about our treatment for Medicare part D but it's a combination of all of the therapies that those patients are on that will hit that ultimate cap of $3,000 or $2000, respectively. So I think we're well positioned in a good place to the reimbursement channels to allow patients to have access and appropriate access to our treatments. Okay, thank you.

Unknown Executive: I think where we're at right now with Medicare part D is a much more favorable position than we have been historically and it's only anticipated to get better in the coming years. So out of pocket expenses are going to be limited for those patients either 3000, or so dollars. This year and it goes down in 2000 or so dollars next year.

Unknown Executive: So out-of-pocket expenses are going to be limited for those patients, either $3,000 or so this year, and it goes down to $2,000 or so next year. And then there's also the ability to spread those costs over time, so it's not a one-time expense for the patient, which I think is very positive. So, when we're thinking about, you know, WENUA and other programs that we have that will go through the Medicare Part D channel, I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately.

Cap of 3000 or $2000, respectively. So I think we're well positioned in a good place to the reimbursement channels to. Allow patients to have access and appropriate access to our treatments.

Unknown Executive: Then theres also the ability to spread those costs over time, so it's not a one time.

Allow patients to have access and appropriate access to our treatments.

Unknown Executive: Assessment for the patient, which I think is very positive so when we're thinking about.

Thank you.

Unknown: Okay, thank you.

Unknown Executive: <unk> and other programs that we have that will go through the Medicare part D Channel I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately and keep in mind, it's not just about our treatment for Medicare part D. But it's a combination of all of the therapies that those patients are on that we'll hit that ultimate <unk>.

Luca Issi: Got it. Thanks so much.

Operator: Thank you. And the next question comes from David Lebowitz with Citi. Please go ahead Mr. Lebowitz, your line is live.

Operator: Thank you. The next question, Salveen Richter with Goldman Sachs.

Okay. Please go ahead Mr. Lewis Your line is live.

Unknown Executive: And keep in mind, it's not just about our treatment for Medicare Part D, but it's a combination of all of the therapies that those patients are on that will hit that ultimate cap of $3,000 or $2,000, respectively. So, I think we're well positioned and in a good place through the reimbursement channels to allow patients to have access and appropriate access to our treatment. Thank you.

Please go ahead Mr. Lewis Your line is live.

Salveen Richter: Thanks for taking the question. This is Tommy on for Salveen. So just to follow up on the previous commentary about the Medicare Part D design, how are you thinking about the possibilities that there could be a higher level of scrutiny, especially in cardiomyopathy given the entrance of another stabilizer potentially this year? Thank you.

[Analyst] (Goldman Sachs): Thanks for taking the question. This is Tommy on for Salveen. So just to follow up on the previous commentary about the Medicare Part D design, how are you thinking about the possibilities that there could be a higher level of scrutiny, especially in cardiomyopathy given the entrance of another stabilizer potentially this year? Thank you.

David N. Lebowitz: Hello, would you be able to comment on ion 224 and you get to as far as the data that you recently presented and what you think about that therapy given the [inaudible] Nash landscape? Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported earlier this year on [inaudible] patients with Nash. This is the first time our targeted [inaudible] triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat based on this mechanism. We were very pleasantly surprised to see not only that, we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis, positive reduction in fibrosis in these patients. First time ever a treatment that blocks fat synthesis was shown to actually achieve this.

Comment on IL, two to four and you get to. As far as the data that you recently presented and what you think about that therapy given the. Burgeoning Nash landscape. Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported. Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Unknown Executive: Cap of 3000 or $2000, respectively. So I think we're well positioned to navigate in a good place to the reimbursement channels to.

As far as the data that you recently presented and what you think about that therapy given the. Burgeoning Nash landscape. Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported. Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Burgeoning Nash landscape. Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported. Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Unknown Executive: Allow patients to have access and appropriate access to our treatments.

Brett P. Monia: Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported earlier this year on [inaudible] patients with Nash. This is the first time our targeted [inaudible] triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat based on this mechanism. We were very pleasantly surprised to see not only that, we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis, positive reduction in fibrosis in these patients. First time ever a treatment that blocks fat synthesis was shown to actually achieve this.

Sure David. Yeah, we couldn't have been more pleased with the phase II data we reported. Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Speaker Change: Thank you.

Yeah, we couldn't have been more pleased with the phase II data we reported. Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Brett Monia: Tom, go ahead and take that.

Unknown Executive: Thank you. And the next question comes from David Lebowitz with Citi. Please go ahead and leave with your lines live.

Unknown Executive: Thank you and the next question comes from David Leibowitz with Citi.

Eugene Schneider: For the Medicare D population, I mean, things are evolving a little bit, right, with the IRA regulations and things that have come into play. And historically, there's been quite a bit of distinction around the out-of-pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that. I think where we're at right now with Medicare Part D is a much more favorable position than we have been historically. And it's only anticipated to get better in the coming years. So out-of-pocket expenses are going to be limited for those patients, either $3,000 or so this year. It goes down to $2,000 or so next year. And then there's also the ability to spread those costs over time. So it's not a one-time assessment for the patient, which I think is very positive.

Kyle Jenne: For the Medicare D population, I mean, things are evolving a little bit, right, with the IRA regulations and things that have come into play. And historically, there's been quite a bit of distinction around the out-of-pocket expenses for patients and the way that those had to be paid in terms of timing and timelines around that. I think where we're at right now with Medicare Part D is a much more favorable position than we have been historically. And it's only anticipated to get better in the coming years. So out-of-pocket expenses are going to be limited for those patients, either $3,000 or so this year. It goes down to $2,000 or so next year. And then there's also the ability to spread those costs over time. So it's not a one-time assessment for the patient, which I think is very positive.

Earlier this year on you got two in patients with Nash. This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

David Lebowitz: Please go ahead Mr. Lewis Your line is live.

This is the first time. Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

Our targeted debt to Fox by targeting do you get through a buck in the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

David Lebowitz: Hello would you be able to.

David Lebowitz: Comment on IL, two to four and you get to.

We certainly expected robust reductions in liver fat on them based on this mechanism. We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

David Lebowitz: As far as the data that you recently presented and what you think about that therapy given the.

We were very pleasantly surprised to see not only that we also saw reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis are positive.

David Lebowitz: Burgeoning Nash landscape.

Unknown Executive: Sure, David. Yeah, we couldn't have been more pleased with the Phase 2 data we reported earlier this year on DGAD2 in patients with MASH. You know, this is the first time, so our target is DGAD2. By targeting DGAD2, we're blocking the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat based on this mechanism, but we were very pleasantly surprised to see not only that, but we also saw reductions in MASH resolution, that is, inflammation of the liver by biopsy, as well as a turnaround in fibrosis, a positive reduction in fibrosis in these patients.

David Lebowitz: Sure David.

Unknown Executive: Yes, we couldnt be more pleased with the phase II data we reported.

First time ever a treatment that blocks fat synthesis was shown to actually achieve this. As we mentioned, this program as exciting as it is, doesn't fit really well within our focus for our wholly-owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with a partner and that's what we're doing, we're moving towards partnering this program to take it to the next step or stage of development, which could certainly be a phase III program. There's certainly interest and those conversations are progressing pretty well. It's early in the discussions, but they are progressing well.

First time ever a treatment that blocks fat synthesis was shown to actually achieve this.

Unknown Executive: Earlier this year on.

Unknown Executive: You got two in patients with Nash.

In these patients. First time ever a treatment that blocks trace fat synthesis was shown to actually achieve this. As we mentioned this program is exciting as it is doesn't fit really well within our focus. For our wholly owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with it. With a partner. And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

First time ever a treatment that blocks trace fat synthesis was shown to actually achieve this. As we mentioned this program is exciting as it is doesn't fit really well within our focus. For our wholly owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with it. With a partner. And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: This is the first time, so our targeted <unk> to <unk> by targeting to get to a buck in the triglyceride synthesis pathway in the liver.

As we mentioned, this program as exciting as it is, doesn't fit really well within our focus for our wholly-owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with a partner and that's what we're doing, we're moving towards partnering this program to take it to the next step or stage of development, which could certainly be a phase III program. There's certainly interest and those conversations are progressing pretty well. It's early in the discussions, but they are progressing well.

Eugene Schneider: So when we're thinking about WAINUA and other programs that we have that will go through the Medicare Part D channel, I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately. And keep in mind, it's not just about our treatment for Medicare Part D, but it's a combination of all of the therapies that those patients are on that will hit that ultimate cap of $3,000 or $2,000, respectively. So I think we're well positioned and in a good place through the reimbursement channels to allow patients to have access and appropriate access to our treatments.

Kyle Jenne: So when we're thinking about WAINUA and other programs that we have that will go through the Medicare Part D channel, I think we're very encouraged that we'll be able to work effectively within that system and support patients appropriately. And keep in mind, it's not just about our treatment for Medicare Part D, but it's a combination of all of the therapies that those patients are on that will hit that ultimate cap of $3,000 or $2,000, respectively. So I think we're well positioned and in a good place through the reimbursement channels to allow patients to have access and appropriate access to our treatments.

As we mentioned this program is exciting as it is doesn't fit really well within our focus. For our wholly owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with it. With a partner. And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: We certainly expected robust reductions in liver fat based on this mechanism.

For our wholly owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best with it. With a partner. And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: We were very pleasantly surprised to see not only that resources are reductions in Nash resolution that is inflammation of the liver by biopsy as well as a turnaround of fibrosis positive.

With a partner. And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

And that's what we're doing is we're moving towards partnering this program. To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: Reduction in fibrosis.

Unknown Executive: And.

To take it to the next step or stage of development, which could certainly be a phase III program. Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: In these patients.

Unknown Executive: First time ever a treatment that blocks trace fat synthesis was shown to actually achieve this.

Unknown Executive: As we mentioned, this program, as exciting as it is, doesn't fit really well within our focus at Ionis. We're a wholly owned pipeline for neurology and cardiovascular and maybe specialty rare opportunities. So we think this program fits best with a partner, and that's what we're doing; we're moving toward partnering this program to take it to the next step of the stage of development, which could certainly be a phase three program

Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Unknown Executive: As we mentioned this program is exciting as it is doesn't fit really well within our focus is on.

Salveen Richter: Thank you.

[Analyst] (Goldman Sachs): Thank you.

Operator: Thank you. And the next question, David Lieberowitz with Citi. Please go ahead, Mr. Lieberowitz. Your line is live.

Thanks for taking my question. Pleasure, David. And maybe we have time for one last question before wrapping things up. Yes, and that last one comes from [inaudible] with BMO. Hello, everyone and thanks for taking our question and congrats on the progress. Can you remind us what is the [inaudible] and when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2024? Also any comments around the commercial opportunity of that program would be helpful. Thank you.

Thanks for taking my question. Pleasure, David. And maybe we have time for one last question before wrapping things up. Yes, and that last one comes from [inaudible] with BMO.

Thanks for taking my question. Pleasure, David. And maybe we have time for one last question before wrapping things up.

David N. Lebowitz: Thanks for taking my question.

Unknown Executive: <unk>.

Brett P. Monia: Pleasure, David. And maybe we have time for one last question before wrapping things up.

Unknown Executive: For our wholly owned pipeline in neurology in cardiovascular and maybe specialty rare opportunities. So we think this program fits best.

Pleasure, David and maybe we have time for one last question before wrapping things up yes on that last one comes from <unk> <unk> with BMO. Hello, everyone and thanks for taking our question and congrats on the Falcon is can you remind us what is the spot the sofa Sop up loosening their PV and when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2020 for Australia. So it's not out of the commercial opportunity of that program would be helpful. Thank you.

Operator: Yes, and that last one comes from [inaudible] with BMO.

David Lebowitz,: Hello. Would you be able to comment on Ionis Pharmaceuticals, Inc., Brett Monia, Q2, Q4, and DGAT2 as far as the data that you recently presented and what you think about that therapy given the burgeoning national landscape?

Unknown Executive: With a partner.

Unknown: Hello, everyone and thanks for taking our question and congrats on the progress. Can you remind us what is the [inaudible] and when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2024? Also any comments around the commercial opportunity of that program would be helpful. Thank you.

Unknown Executive: And that's what we're doing is we're moving towards partnering this program.

Hello, everyone and thanks for taking our question and congrats on the Falcon is can you remind us what is the spot the sofa Sop up loosening their PV and when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2020 for Australia. So it's not out of the commercial opportunity of that program would be helpful. Thank you.

Unknown Executive: To take it to the next step or stage of development, which could certainly be a phase III program.

Unknown Executive: There's certainly interest, and those conversations are progressing pretty well. It's early in the discussions, but they're progressing. Thanks for taking my question. My pleasure, David. And maybe we have time for one last question before we wrap things up. Yes, and that last question comes from Kostas Biliouris with BMI. Hello everyone, thanks for taking our question and congrats on the progress. Can you remind us what the status of Sapa Blursen is in PV?

Unknown Executive: Theres certainly interest and those conversations are progressing pretty well it's early in the discussions, but they are progressing well.

Brett Monia: Sure, David. Yeah. We couldn't have been more pleased with the phase 2 data we reported earlier this year on DGAT2 in patients with MASH. This is the first time so our target is DGAT2. By targeting DGAT2, we're blocking the triglyceride synthesis pathway in the liver. We certainly expected robust reductions in liver fat based on this mechanism. We were very pleasantly surprised to see not only that, we also saw reductions in NASH resolution. That is inflammation of the liver by biopsy as well as a turnaround of fibrosis, positive reduction in fibrosis in these patients. First time ever a treatment that blocks fat synthesis was shown to actually achieve this. As we mentioned, this program, as exciting as it is, doesn't fit really well within our focus at Ionis for our wholly-owned pipeline in neurology and cardiovascular and maybe specialty rare opportunities.

So it's not out of the commercial opportunity of that program would be helpful. Thank you.

Kostas Biliouris: Thanks for taking my question.

Kostas Biliouris: Pleasure, David and maybe we have time for one last question before wrapping things up yes on that last one is now comes from <unk> <unk> with BMO.

Brett P. Monia: Thank you [inaudible]. Yeah, the [inaudible] program in Polycythemia Vera Phase II continues to progress well. I think we've said before it's an open label study and we've said before that we're clearly seeing evidence of robust activity efficacy in this study. And what we're doing in this phase II study that is reductions in hematocrit red cell counts normalizing in many cases in many patients. And what we're doing is dose ranging to understand what the right dose regimen will be for a potential advancement into phase III development. So we're looking forward to sharing that data potentially this year. It continues.

Unknown Executive: Yes, and that last one comes from Kostas Biliouris with BMO.

Kostas Biliouris: Hello, everyone and thanks for taking our question and congrats on the Falcon is can you remind us what is the spot the sofa Sop up loosening the PV and when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2024.

I think we've said before it's an open label study and we have been. We've said before that we're clearly seeing evidence of robust activity efficacy in this study. And what we're doing in this phase II study that is reductions in hematocrit. Red cell counts. Normalizing in many cases in many patients. And what we're doing is is dose ranging to understand what the right dose.

We've said before that we're clearly seeing evidence of robust activity efficacy in this study. And what we're doing in this phase II study that is reductions in hematocrit. Red cell counts. Normalizing in many cases in many patients. And what we're doing is is dose ranging to understand what the right dose.

And what we're doing in this phase II study that is reductions in hematocrit. Red cell counts. Normalizing in many cases in many patients. And what we're doing is is dose ranging to understand what the right dose.

Red cell counts. Normalizing in many cases in many patients. And what we're doing is is dose ranging to understand what the right dose.

Normalizing in many cases in many patients. And what we're doing is is dose ranging to understand what the right dose.

Kostas Biliouris: Also any thoughts around the commercial opportunity of that program would be helpful. Thank you.

And what we're doing is is dose ranging to understand what the right dose.

Unknown Executive: Thank you, Kostas. Yeah, yeah, the SAPA Blurson program in polycythemia vera phase 2 continues to progress well. I think we've said before, it's an open-label study, and we've been, we've said before that we're clearly seeing evidence of robust activity and efficacy in this study. What we're doing in this phase 2 study, that is, you know, reductions in hematocrit red cell counts, normalizing in many cases in many patients.

regimen will be for a potential advancement into phase III development. So we're looking forward to sharing that data potentially this year. It continues. As far as the market opportunity, it's a great question. We're assessing that now. We don't have an answer for you. It's a very interesting area and our commercial organization is well on its way in doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Ionis or as our partner. We're going to try to provide an update by the end of the year on the program.

regimen will be for a potential advancement into phase III development. So we're looking forward to sharing that data potentially this year. It continues.

Kostas Biliouris: Thank you Cosmos, yes. This <unk> program in Polycythemia Vera Phase two continues to progress well.

So we're looking forward to sharing that data potentially.

Unknown Executive: I think we've said before it's an open label study.

As far as the market opportunity, it's a great question. We're assessing that now. We don't have an answer for you. It's a very interesting area and our commercial organization is well on its way in doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Ionis or as our partner. We're going to try to provide an update by the end of the year on the program.

This year. It continues. As far as the market opportunity is a great question. We're assessing that now we don't have an answer for you. It's a it's a very interesting air. Area. Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

It continues. As far as the market opportunity is a great question. We're assessing that now we don't have an answer for you. It's a it's a very interesting air. Area. Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

Unknown Executive: We've said before that.

As far as the market opportunity is a great question. We're assessing that now we don't have an answer for you. It's a it's a very interesting air. Area. Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

Unknown Executive: We're clearly seeing evidence of robust activity efficacy in this study and.

It's a it's a very interesting air. Area. Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

Unknown Executive: What we're doing in this phase II study that is reductions in hematocrit.

Brett Monia: So we think this program fits best with a partner. And that's what we're doing, is we're moving towards partnering this program to take it to the next stage of development, which could certainly be a phase 3 program. There's certainly interest. And those conversations are progressing pretty well. It's early in the discussions, but they're progressing well.

Area. Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Aon as our partner. We're going to try to provide an update by the end of the year on the program.

Unknown Executive: Red cell counts.

Unknown Executive: Normalizing in many cases and many patients and what we're doing is dose ranging to understand what the right dose.

Unknown Executive: And what we're doing is dose ranging to understand what the right dose and dose regimen will be for potential advancement into phase 3. So we're looking forward to sharing that data, possibly this year.

Unknown Executive: And dose treat dose dose regimen will be for a potential advancement into phase III development.

We're going to try to provide an update by the end of the year on the program.

Unknown Executive: So we're looking forward to sharing that data potentially.

So thanks for the question [inaudible] and thanks everybody for joining us today who participated on our call. We plan to continue all this great momentum throughout the year. We're focused on next level of value for our shareholders and all stakeholders. We're also looking forward to providing a comprehensive overview recap of the phase [inaudible] data and we're presenting at Yakui on May 31st so stay tuned for that and we're looking forward to the webcast as well on that day. We hope you can join us on the webcast. Until then, thank you everybody for joining in and have a great day.

Unknown Executive: As far as the market opportunity is concerned, it's a great question. We're assessing that now. But we don't have an answer for you.

Unknown Executive: This year it.

Unknown Executive: It continues.

David Lebowitz,: Thanks for taking my question.

Unknown Executive: As far as the market opportunity is a great question. We're assessing that now we don't have an answer for you.

Brett Monia: Pleasure, David. Maybe we have time for one last question before wrapping things up.

You know focused on next level of value for our shareholders and all stakeholders.

Unknown Executive: It's a it's a very interesting area.

Operator: Yes. And that last one comes from Costa Spillaris with BMO.

Unknown Executive: And our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at the owners or the partner, we're going to try to provide an update by the end of the year on the program.

We're also looking forward to providing a comprehensive overview recap of the phase <unk> data and we're presenting our yoki on may 31st So stay tuned for that and we are and we're looking forward to the webcast as well on that day. We hope you can enjoy that join us on the webcast and until then thank you everybody for joining in and have a great day.

Kostas Biliouris,: Hello, everyone. Thanks for taking our question and congrats on the progress. Can you remind us what is the status of sapablursen in PV? And when should we expect updates from this program given the increasing activity in that space and the multiple readouts in 2024? Also, any thoughts around the commercial opportunity of that program would be helpful. Thank you.

We hope you can enjoy that join us on the webcast and until then thank you everybody for joining in and have a great day.

Unknown Executive: It's a very interesting area, and our commercial organization is well on its way to doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Ionis or with a partner. Thanks for the question, Kostas, and thanks, everybody, for joining us today who participated in our call. We plan to continue all this great momentum throughout the year, you know, focused on next-level value for our shareholders and all stakeholders.

Speaker Change: Thanks for the question cost us and thanks, everybody for joining us today.

Operator: Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Unknown Executive: Participating on our call we plan to continue all this great momentum throughout the year.

Eugene Schneider: Thank you, Costa. Yeah. Yeah. The sapablursen program in polycythemia vera, phase 2, continues to progress well. I think we've said before, it's an open-label study. And we've said before that we're clearly seeing evidence of robust activity, efficacy in this study. And what we're doing in this phase 2 study, that is reductions in hematocrit, red cell counts, normalizing in many cases, in many patients. And what we're doing is dose ranging to understand what the right dose and dose regimen will be for a potential advancement into phase 3 development. So we're looking forward to sharing that data potentially this year. It continues. As far as the market opportunity, it's a great question. We're assessing that now. We don't have an answer for you. It's a very interesting area.

Brett Monia: Thank you, Costa. Yeah. Yeah. The sapablursen program in polycythemia vera, phase 2, continues to progress well. I think we've said before, it's an open-label study. And we've said before that we're clearly seeing evidence of robust activity, efficacy in this study. And what we're doing in this phase 2 study, that is reductions in hematocrit, red cell counts, normalizing in many cases, in many patients. And what we're doing is dose ranging to understand what the right dose and dose regimen will be for a potential advancement into phase 3 development. So we're looking forward to sharing that data potentially this year. It continues. As far as the market opportunity, it's a great question. We're assessing that now. We don't have an answer for you. It's a very interesting area.

Unknown Executive: You know focused on next level of value for our shareholders and all stakeholders.

Unknown Executive: We're also looking forward to providing a comprehensive overview of the Phase III Donald and Lawrence data we're presenting at IACI on May 31st, so stay tuned for that. And we're looking forward to the webcast as well on that day. We hope you can join us on the webcast. And until then, thank you, everybody, for joining in, and have a great day.

Operator: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.

Unknown Executive: We're also looking forward to providing a comprehensive.

Operator: Overview recap of the phase <unk> data, we are presenting our yoki on may 31st so stay tuned for that and we are and we're looking forward to the webcast as well on that day.

Operator: We hope you can enjoy that join us on the webcast and until then thank you everybody for joining in and have a great day.

Operator: Goodbye.

Operator: Conference has now concluded. Thank you for attending today's presentation you may now disconnect.

Operator: [music].

Operator: Okay.

Eugene Schneider: Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Ionis or the partner. But we're going to try to provide an update by the end of the year on the program. So thanks for the question, Costa. And thanks, everybody, for joining us today who participated on our call. We plan to continue all this great momentum throughout the year focused on next-level value for our shareholders and all stakeholders. We're also looking forward to providing a comprehensive overview recap of the phase 3 donidalorsen data. We're presenting at EAACI on 31 May. So stay tuned for that. And we're looking forward to the webcast as well on that day.

Brett Monia: Our commercial organization is well on its way and doing all the market research for the opportunity in the United States and outside of the United States. So we have not decided on where this program fits best at Ionis or the partner. But we're going to try to provide an update by the end of the year on the program. So thanks for the question, Costa. And thanks, everybody, for joining us today who participated on our call. We plan to continue all this great momentum throughout the year focused on next-level value for our shareholders and all stakeholders. We're also looking forward to providing a comprehensive overview recap of the phase 3 donidalorsen data. We're presenting at EAACI on 31 May. So stay tuned for that. And we're looking forward to the webcast as well on that day.

Eugene Schneider: We hope you can join us on the webcast. And until then, thank you, everybody, for joining in. And have a great day.

Brett Monia: We hope you can join us on the webcast. And until then, thank you, everybody, for joining in. And have a great day.

Operator: Thank you. The conference is now concluded. Thank you for attending today's presentation. May now disconnect.

Q1 2024 Ionis Pharmaceuticals Inc Earnings Call

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