Q4 2023 Ionis Pharmaceuticals Inc Earnings Call

February 21, 2024

Operator: All participants will be in listen only mode, should you need assistance please signal our conference specialist by pressing the star key followed by zero. After todays presentation, there will be an opportunity to ask questions, to ask a question you may press star then one on your telephone keypad, to withdraw your question, please press star then two. As a reminder, this call is being recorded, at this time I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations to lead off the call. Please begin.

Operator: All participants will be in listen only mode, should you need assistance please signal our conference specialist by pressing the star key followed by zero.

After todays presentation, there will be an opportunity to ask questions to ask a question you May Press Star then one on your telephone keypad to withdraw your question. Please press Star then two.

Operator: After todays presentation, there will be an opportunity to ask questions, to ask a question you may press star then one on your telephone keypad, to withdraw your question, please press star then two. As a reminder, this call is being recorded, at this time I would like to turn the call over to Wade Walke, Senior Vice President of Investor Relations to lead off the call. Please begin.

As a reminder, this call is being recorded at this time I would like to turn the call over to Wade Walke Senior Vice President of Investor Relations to lead off the call. Please begin.

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

Wade Walke: Thank you Megan, before we begin I encourage everyone to go to the investors section of the Ionis website to view the press release and 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. With me this morning are Brent Monia, Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Hougen, Our Chief Financial Officer, Eric Swayze, our Executive Vice President of Research, Eugene Schneider Clinical Chief Clinical Development Officer, and Onaiza Cadoret Chief Global Product Strategy and Operations Officer will also join us for the Q&A portion of the call. I'd 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. With that I'll turn the call over to Brett.

When we begin I encourage everyone to go to the investors section of the <unk> website to view the press release and 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.

Wade Walke: 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 Brent Monia, Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Hougen, Our Chief Financial Officer, Eric Swayze, our Executive Vice President of Research, Eugene Schneider Clinical Chief Clinical Development Officer, and Onaiza Cadoret Chief Global Product Strategy and Operations Officer will also join us for the Q&A portion of the call. I'd 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. With that I'll turn the call over to Brett.

Also posted slides on our website that accompany today's call.

With me. This morning are Brent ammonia, Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Hougen, Our Chief Financial Officer, Eric.

Wade Walke: With me this morning are Brent Monia, Chief Executive Officer, Richard Geary, Chief Development Officer, and Beth Hougen, Our Chief Financial Officer, Eric Swayze, our Executive Vice President of Research, Eugene Schneider Clinical Chief Clinical Development Officer, and Onaiza Cadoret Chief Global Product Strategy and Operations Officer will also join us for the Q&A portion of the call. I'd 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. With that I'll turn the call over to Brett.

Eric Swayze, our executive Vice President of research Eugene Schneider clinical Chief clinical development Officer, and <unk>, Chief Global product strategy and operations Officer will also join us for the Q&A portion of the call.

Wade Walke: And Onaiza Cadoret Chief Global Product Strategy and Operations Officer will also join us for the Q&A portion of the call.

Wade Walke: I'd 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. With that I'll turn the call over to Brett.

I'd 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.

Wade Walke: 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. With that I'll turn the call over to Brett.

Detail with that I'll turn the call over to Brett.

Brett P. Monia: Thanks, Wade and good morning, everybody and thanks for joining us today. At <unk>, we are proud of our scientific heritage, we have United groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines. And now that we have validated the broad applicability of our RNA targeting platform. We're on the brink of independently delivering our medicines directly to patients. Over the next several years, we expect to successfully launch multiple medicines on our own while continuing to expand our technology. So that we can address the needs of even more patients. This will be a key driver of our next phase of growth and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Aon is and we're already off to a great start in 2024 in fact, just yesterday the FDA granted breakthrough therapy designation to <unk> for Fcs. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Aon has discovered medicines Cal Saudi for side, one AOS and window for <unk> Polyneuropathy. <unk> is the first drug approved to treat a genetic form of ALS. It was granted accelerated approval in the U S. Early last year for patients with sard when AOS. And we were also pleased to cap off a highly successful year with the approval of <unk> for <unk> Polyneuropathy in late December. The way new launch is well underway in the U S through our co commercialization partnership with Astrazeneca and we're executing on our strategy to bring <unk> to patients globally with additional potential approvals in Europe, and Canada, This year and more regulatory submissions and approvals on the way. Based on our strong overall profile, including highly positive phase III data, which we reported last year together with the freedom of simple at home monthly self administration. We believe is very well positioned to become the therapy of choice for <unk> patients who remain underserved by current therapies.

Brett P. Monia: Thanks, Wade, good morning everybody and thanks for joining us today. At Ionis, we are proud of our scientific heritage, we have united groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines. And now that we have validated the broad applicability of our RNA targeting platform, we're on the brink of independently delivering our medicines directly to patients. Over the next several years, we expect to successfully launch multiple medicines on our own, while continuing to expand our technology so that we can address the needs of even more patients. This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

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

And on 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.

At <unk>, we are proud of our scientific heritage, we have United groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines.

Brett P. Monia: At Ionis, we are proud of our scientific heritage, we have united groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines. And now that we have validated the broad applicability of our RNA targeting platform, we're on the brink of independently delivering our medicines directly to patients. Over the next several years, we expect to successfully launch multiple medicines on our own, while continuing to expand our technology so that we can address the needs of even more patients. This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett P. Monia: And now that we have validated the broad applicability of our RNA targeting platform, we're on the brink of independently delivering our medicines directly to patients. Over the next several years, we expect to successfully launch multiple medicines on our own, while continuing to expand our technology so that we can address the needs of even more patients. This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett P. Monia: And now that we have validated the broad applicability of our RNA targeting platform, we're on the brink of independently delivering our medicines directly to patients.

And now that we have validated the broad applicability of our RNA targeting platform. We're on the brink of independently delivering our medicines directly to patients.

<unk> detail.

That I will turn the call over to Brett.

Brett P. Monia: Over the next several years, we expect to successfully launch multiple medicines on our own, while continuing to expand our technology so that we can address the needs of even more patients. This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Over the next several years, we expect to successfully launch multiple medicines on our own while continuing to expand our technology. So that we can address the needs of even more patients.

Brett: Thanks, Wade and good morning, everybody and thanks for joining us today.

Brett: At <unk>, we are proud of our scientific heritage, we have United groundbreaking science and technology with a relentless passion to discover and develop new transformational medicines.

This will be a key driver of our next phase of growth and we're committed to investing in all capabilities needed to accomplish this.

Brett P. Monia: This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this. Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett P. Monia: This will be a key driver of our next phase of growth, and we're committed to investing in all capabilities needed to accomplish this.

Brett: And now that we have validated the broad applicability of our RNA targeting platform. We're on the brink of independently delivering our medicines directly to patients.

Last year was a remarkable year for Aon is and we're already off to a great start in 2024 in fact, just yesterday the FDA granted breakthrough therapy designation to <unk> for Fcs.

Brett P. Monia: Last year was a remarkable year for Ionis and we're already off to a great start in 2024, in fact just yesterday, the FDA granted breakthrough therapy designation to Olezarsen for FCS. This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett: Over the next several years, we expect to successfully launch multiple medicines on our own while continuing to expand our technology. So that we can address the needs of even more patients.

This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence showing that the therapy may offer substantial improvement over available treatments.

Brett P. Monia: This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence, showing that the therapy may offer substantial improvement over available treatments. Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett: This will be a key driver of our next phase of growth and we're committed to investing in all capabilities needed to accomplish this.

Brett: Last year was a remarkable year for Aon is and we're already off to a great start in 2024 and in fact, just yesterday the FDA granted breakthrough therapy designation to <unk> for Fcs.

Brett P. Monia: Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023. First we received two FDA approvals for Ionis discovered medicines Qalsody for SOD1 ALS and Wainua for ATTR Polyneuropathy. Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023.

First we received two FDA approvals for Aon has discovered medicines Cal Saudi for side, one AOS and window for <unk> Polyneuropathy.

Brett: This is a very important outcome as breakthrough therapy designation is designed to expedite development and review of therapies intended to treat serious conditions that have preliminary clinical evidence showing that the therapy may offer substantial improvement over available treatments.

Brett P. Monia: Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS. And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett P. Monia: Qalsody is the first drug approved to treat a genetic form of ALS, it was granted accelerated approval in the US early last year for patients with SOD1 ALS.

<unk> is the first drug approved to treat a genetic form of ALS. It was granted accelerated approval in the U S. Early last year for patients with sard when AOS.

Brett: Before we get to all the other exciting things planned for this year I'll first recap some of our key achievements in 2023.

Brett P. Monia: And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December. The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

Brett P. Monia: And we were also pleased to cap off a highly successful year with the approval of Wainua for ATTR Polyneuropathy in late December.

And we were also pleased to cap off a highly successful year with the approval of <unk> for <unk> Polyneuropathy in late December.

Brett: First we received two FDA approvals for Aon has discovered medicines Cal Saudi for <unk>, AOS and window for <unk> Polyneuropathy.

Brett P. Monia: The Wainua launch is well underway in the US through our co-commercialization partnership with Astrazeneca, and we're executing on our strategy to bring Wainua to patients globally, with the additional potential approvals in Europe, and Canada this year and more regulatory submissions and approvals on the way.

The way new launch is well underway in the U S through our co commercialization partnership with Astrazeneca and we're executing on our strategy to bring <unk> to patients globally with additional potential approvals in Europe, and Canada, This year and more regulatory submissions and approvals on the way.

Brett: <unk> is the first drug approved to treat a genetic form of ALS. It was granted accelerated approval in the U S. Early last year for patients with <unk> ALS.

Brett P. Monia: Based on our strong overall profile, including highly positive phase III data, which we reported last year together with the freedom of simple at home monthly self administration. We believe is very well positioned to become the therapy of choice for <unk> patients who remain underserved by current therapies. With a larger <unk> cardiomyopathy indication, we continue to advance our cardio transform study as planned. As the largest study ever conducted in this patient population cardio transform is positioned to be a landmark study designed to deliver a very rich dataset. We expect the data we generate to 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're very well positioned to bring renew it to patients in the U S and around the globe. We also recently delivered positive phase III top line data Readouts for two additional important medicines, <unk> and FCS and <unk> in HIV. And the phase III balance study in patients with FCS Osrs's showed significant triglyceride reductions substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the U S and EU this year positioning <unk> for potential approval in the U S. By the end of the year, assuming we get priority review. With this timing, we expect <unk> to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the phase III <unk> study abdominal worsened for the prophylactic treatment of hereditary angioedema. And the phase III study, Don <unk> and met the primary endpoint with a statistically significant reduction in the rate of <unk> attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing our regulatory submission to the FDA, which will include both every four weeks and every eight week dosing. We expect <unk> to be our second independent U S launch.

Brett P. Monia: Based on our strong overall profile, including highly positive Phase III data, which we reported last year, together with the freedom of simple at home monthly self administration, we believe Wainua is very well positioned to become the therapy of choice for ATTR patients who remain underserved by current therapies. With a larger ATTR cardiomyopathy indication, we continue to advance our CARDIO-TTRANSFORM study as planned, as the largest study ever conducted in this patient population CARDIO-TTRANSFORM is positioned to be a landmark study designed to deliver a very rich dataset. We expect the data we generate to enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we're very well positioned to bring Wainua to patients in the US and around the globe. We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE. In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

Based on our strong overall profile, including highly positive phase III data, which we reported last year together with the freedom of simple at home monthly self administration. We believe is very well positioned to become the therapy of choice for <unk> patients who remain underserved by current therapies.

Brett: And we are also pleased to cap off a highly successful year with the approval of <unk> for <unk> Polyneuropathy in late December.

Brett: The way new launch is well underway in the U S through our co commercialization partnership with Astrazeneca and we're executing on our strategy to bring <unk> to patients globally with the additional potential approvals in Europe, and Canada, This year and more regulatory submissions and approvals on the way.

With a larger <unk> cardiomyopathy indication, we continue to advance our cardio transform study as planned.

Brett P. Monia: With a larger ATTR cardiomyopathy indication, we continue to advance our CARDIO-TTRANSFORM study as planned, as the largest study ever conducted in this patient population CARDIO-TTRANSFORM is positioned to be a landmark study designed to deliver a very rich dataset. We expect the data we generate to enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we're very well positioned to bring Wainua to patients in the US and around the globe. We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE. In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

Brett: Based on strong overall profile, including highly positive phase III data, which we reported last year together with the freedom of simple at home monthly self administration. We believe we knew is very well positioned to become the therapy of choice for <unk> patients who remain underserved by current therapies.

As the largest study ever conducted in this patient population cardio transform is positioned to be a landmark study designed to deliver a very rich dataset.

Brett P. Monia: We expect the data we generate to enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape. And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we're very well positioned to bring Wainua to patients in the US and around the globe. We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE. In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

Brett P. Monia: We expect the data we generate to enable physicians and payers to make informed treatment decisions in this dynamic treatment landscape.

We expect the data we generate to enable physicians and payers to make informed treatment decisions and this dynamic treatment landscape.

Brett P. Monia: And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in TTR amyloidosis, we believe we're very well positioned to bring Wainua to patients in the US and around the globe. We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE. In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

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

Brett: With a larger atti cardiomyopathy indication, we continue to advance our cardio transform study as planned.

Brett: As the largest study ever conducted in this patient population cardio transform is positioned to be a landmark study designed to deliver a very rich dataset.

We also recently delivered positive phase III top line data Readouts for two additional important medicines, <unk> and FCS and <unk> in HIV.

Brett P. Monia: We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE. In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

Brett P. Monia: We also recently delivered positive Phase III top line data readouts for two additional important medicines, Olezarsen in FCS and Donidalorsen in HAE.

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

Brett P. Monia: In Phase III balance study, in patients with FCS Olezarsen showed significant triglyceride reductions, substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile. We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

And the phase III balance study in patients with FCS Osrs's showed significant triglyceride reductions substantial reductions in acute pancreatitis events, and a favorable safety and tolerability profile.

Brett: And with Astrazeneca as global leadership in the commercialization of novel cardiovascular treatments, coupled with our leadership in <unk> amyloidosis, We believe we're very well positioned to bring renew with the patients in the U S and around the globe.

Brett P. Monia: We remain on track to file for marketing approval in the US and EU this year, positioning Olezarsen for potential approval in the US by the end of the year, assuming we get priority review. With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

We remain on track to file for marketing approval in the U S and EU this year positioning <unk> for potential approval in the U S. By the end of the year, assuming we get priority review.

Brett: We also recently delivered positive phase III top line data Readouts for two additional important medicines, <unk> and FCS and <unk> in HIV.

Brett P. Monia: With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch. We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

Brett P. Monia: With this timing, we expect Olezarsen to be our next approved medicine, and our first independent launch.

With this timing, we expect <unk> to be our next approved medicine, and our first independent launch.

Brett: And the phase III balance study in patients with FCS Osrs and showed significant triglyceride reductions substantial reductions in acute pancreatitis events and a favorable safety and tolerability profile.

Brett P. Monia: We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HAE study of Donidalorsen for the prophylactic treatment of hereditary angioedema. In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

We're also pleased with the positive top line data, we reported last month from the phase III <unk> study abdominal worsened for the prophylactic treatment of hereditary angioedema.

We remain on track to file for marketing approval in the U S and EU this year positioning <unk> for potential approval in the U S. By the end of the year, assuming we get priority review.

Brett P. Monia: In the Phase III study, Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile. With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

And the phase III study, Don <unk> and met the primary endpoint with a statistically significant reduction in the rate of <unk> attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile.

Brett: With this timing, we expect <unk> to be our next approved medicine, and our first independent launch.

Brett P. Monia: With these positive data now in hand, we're preparing a regulatory submission to the FDA, which will include both every four weeks and every eight week dosing, we expect Donidalorsen to be our second independent US launch.

With these positive data now in hand, we're preparing our regulatory submission to the FDA, which will include both every four weeks and every eight week dosing.

Brett: We're also pleased with the positive top line data, we reported last month from the Phase III Oasis HK study abdominal portion for the prophylactic treatment of hereditary angioedema.

Brett P. Monia: We expect <unk> to be our second independent U S launch. Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe. Based on our phase II results in a durable efficacy and favorable safety data seen long term in the ongoing phase II open label extension study, we believe <unk> could be an attractive new treatment option for patients with HCA. We look forward to presenting the full phase II data for both <unk> and <unk> later this year. We also made significant progress expanding our rich phase III pipeline. Last year, we began the year with six medicines in phase III development and this year, we began with nine medicines in phase III. These new phase III additions include <unk>, our wholly owned medicine for Alexander disease, and two partner programs appear version for chronic HBV and ion as FBL Rx for Iga nephropathy. We also continued to make great strides last year in advancing our industry, leading RNA targeting technology. We advanced our first bicycle S irna muscle targeting like a drug for a heart failure indication into preclinical development, which astrazeneca license in the fourth quarter. And we expect to advance additional medicines utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier. Most recently, we established a new partnership with Victoria to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. <unk> adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today I honest is at a key inflection point with the recent approvals of two medicines three positive phase III readouts of numerous upcoming phase III Readouts expected over the next couple of years. At the same time, we've also made great progress across the rest for the rest of our rich pipeline and advance our leading technology for our future medicines. All of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: We expect Donidalorsen to be our second independent US launch. Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe. Based on our phase II results in a durable efficacy and favorable safety data seen long term in the ongoing phase II open label extension study, we believe <unk> could be an attractive new treatment option for patients with HCA. We look forward to presenting the full phase II data for both <unk> and <unk> later this year. We also made significant progress expanding our rich phase III pipeline. Last year, we began the year with six medicines in phase III development and this year, we began with nine medicines in phase III. These new phase III additions include <unk>, our wholly owned medicine for Alexander disease, and two partner programs appear version for chronic HBV and ion as FBL Rx for Iga nephropathy. We also continued to make great strides last year in advancing our industry, leading RNA targeting technology. We advanced our first bicycle S irna muscle targeting like a drug for a heart failure indication into preclinical development, which astrazeneca license in the fourth quarter. And we expect to advance additional medicines utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier. Most recently, we established a new partnership with Victoria to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. <unk> adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today I honest is at a key inflection point with the recent approvals of two medicines three positive phase III readouts of numerous upcoming phase III Readouts expected over the next couple of years. At the same time, we've also made great progress across the rest for the rest of our rich pipeline and advance our leading technology for our future medicines. All of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: We expect Donidalorsen to be our second independent US launch.

We expect <unk> to be our second independent U S launch.

Brett: And the phase III study <unk> <unk> met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every four weeks or every eight weeks, along with a favorable safety and tolerability profile.

Brett P. Monia: Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe. Based on our Phase III results and a durable efficacy and favorable safety data seen long term in the ongoing Phase II open label extension study, we believe Donidalorsen could be an attractive new treatment option for patients with HAE. We look forward to presenting the full Phase III data for both Olezarsen and Donidalorsen later this year, we also made significant progress expanding our rich Phase III pipeline. Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III. These new Phase III additions include Zilganersen, our wholly owned medicine for Alexander's Disease, and two partner programs, Bepirovirsen for chronic HBV and IONIS-FB-Lrx for IgA Nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe.

Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe.

Brett P. Monia: Based on our Phase III results and a durable efficacy and favorable safety data seen long term in the ongoing Phase II open label extension study, we believe Donidalorsen could be an attractive new treatment option for patients with HAE. We look forward to presenting the full Phase III data for both Olezarsen and Donidalorsen later this year, we also made significant progress expanding our rich Phase III pipeline. Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III. These new Phase III additions include Zilganersen, our wholly owned medicine for Alexander's Disease, and two partner programs, Bepirovirsen for chronic HBV and IONIS-FB-Lrx for IgA Nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Based on our phase II results in a durable efficacy and favorable safety data seen long term in the ongoing phase II open label extension study, we believe <unk> could be an attractive new treatment option for patients with HCA.

Brett: With these positive data now in hand, we're preparing our regulatory submission to the FDA, which will include both every four week and every eight week dosing.

We look forward to presenting the full phase II data for both <unk> and <unk> later this year.

Brett P. Monia: We look forward to presenting the full Phase III data for both Olezarsen and Donidalorsen later this year, we also made significant progress expanding our rich Phase III pipeline. Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III. These new Phase III additions include Zilganersen, our wholly owned medicine for Alexander's Disease, and two partner programs, Bepirovirsen for chronic HBV and IONIS-FB-Lrx for IgA Nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: We look forward to presenting the full Phase III data for both Olezarsen and Donidalorsen later this year, we also made significant progress expanding our rich Phase III pipeline.

Brett: We expect <unk> to be our second independent U S launch.

We also made significant progress expanding our rich phase III pipeline.

Brett: Additionally, our partner Otsuka is preparing to submit for marketing approval in Europe.

Brett P. Monia: Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III. These new Phase III additions include Zilganersen, our wholly owned medicine for Alexander's Disease, and two partner programs, Bepirovirsen for chronic HBV and IONIS-FB-Lrx for IgA Nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: Last year, we began the year with six medicines in Phase III development, and this year, we began with nine medicines in Phase III.

Last year, we began the year with six medicines in phase III development and this year, we began with nine medicines in phase III.

These new phase III additions include <unk>, our wholly owned medicine for Alexander disease, and two partner programs appear version for chronic HBV and ion as FBL Rx for Iga nephropathy.

Brett P. Monia: These new Phase III additions include Zilganersen, our wholly owned medicine for Alexander's Disease, and two partner programs, Bepirovirsen for chronic HBV and IONIS-FB-Lrx for IgA Nephropathy. We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett: We look forward to presenting the full phase II data for both <unk> and <unk> later this year.

Brett P. Monia: We also continued to make great strides last year in advancing our industry-leading RNA targeting technology, we advanced our first Bicycle siRNA muscle targeting [Inaudible] drug for a heart failure indication into preclinical development, which AstraZeneca licensed in the fourth quarter. And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

We also continued to make great strides last year in advancing our industry, leading RNA targeting technology.

Brett: We also made significant progress expanding our rich phase III pipeline.

Brett: Last year, we began the year with six medicines in phase III development and this year, we began with nine medicines in phase III.

We advanced our first bicycle S irna muscle targeting like a drug for a heart failure indication into preclinical development, which astrazeneca license in the fourth quarter.

Brett: These new phase III additions include Zildjian Ehrsson, our wholly owned medicine for Alexander disease, and two partner programs that peer version for chronic HBV and ion as FPL, our extra Iga nephropathy.

Brett P. Monia: And we expect to advance additional medicines, utilizing our muscle targeting technology this year. We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: And we expect to advance additional medicines, utilizing our muscle targeting technology this year.

And we expect to advance additional medicines utilizing our muscle targeting technology this year.

Brett P. Monia: We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier, most recently, we established a new partnership with Vect-Horus to utilize their novel protein based approaches to systemically deliver our medicines to the CNS. This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier.

Brett: We also continued to make great strides last year in advancing our industry, leading RNA targeting technology.

Most recently, we established a new partnership with Victoria to utilize their novel protein based approaches to systemically deliver our medicines to the CNS.

Brett: We advanced our first bicycle SA RNA muscle targeting like a drug for a heart failure indication into preclinical development, which astrazeneca license in the fourth quarter.

Brett P. Monia: This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases. Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases.

<unk> adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases.

Brett: And we expect to advance additional medicines utilizing our muscle targeting technology this year.

Brett P. Monia: Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024. Today Ionis is at a key inflection point, with the recent approvals of two medicines, three positive Phase III readouts, and numerous upcoming Phase III readouts expected over the next couple of years. And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett: We also made substantial progress in our efforts to deliver our CNS medicines across the blood brain barrier.

Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024.

Brett: Most recently we have.

Today I honest is at a key inflection point with the recent approvals of two medicines three positive phase III readouts of numerous upcoming phase III Readouts expected over the next couple of years.

Brett: That was a new partnership with victorious utilize their novel protein based approaches to systemically deliver our medicines to the CNS.

Brett P. Monia: And at the same time, we've also made great progress across the [Inaudible] for the rest of our rich pipeline, and advance our leading technology for our future medicines, all of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett: This adds to our multi pronged approach to traverse the blood brain barrier with our novel treatments to further strengthen our leadership position in treating CNS diseases.

At the same time, we've also made great progress across the rest for the rest of our rich pipeline and advance our leading technology for our future medicines.

Brett: Our accomplishments throughout 2023 provide great momentum and position us well for a catalyst rich 2024.

Brett P. Monia: All of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

All of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett: Today I honest is at a key inflection point with the recent approvals of two medicines three positive phase III readouts in numerous upcoming phase III Readouts expected over the next couple of years.

Brett P. Monia: We will continue to focus on building and advancing our wholly owned pipeline, which will position us to deliver even more medicines directly to patients. We expect that the investments we're making over the next few years will drive an outsized opportunity to earn multibillion dollar revenue from our proprietary pipeline, generating next level of value for all Ionis stakeholders. And with that, I'll turn the call over to Richard to discuss our recent pipeline progress, next step we'll review our 2023 financial results and provide our 2024 financial guidance. Then I'll wrap things up before taking your questions. Richard.

Brett P. Monia: We will continue to focus on building and advancing our wholly owned pipeline, which will position us to deliver even more medicines directly to patients.

We will continue to focus on building and advancing our wholly owned pipeline, which will position us to deliver even more medicines directly to patients.

We expect that the investments we're making over the next few years will drive an outsized opportunity to earn multibillion dollar revenue from our proprietary pipeline generating next level of value for all <unk> stakeholders and with that I'll turn the call over to Richard to discuss our recent pipeline progress next step will review our. 2023 financial results and provide our 2024 financial guidance. Then I'll wrap things up before taking your questions rich. Richard.

Brett P. Monia: We expect that the investments we're making over the next few years will drive an outsized opportunity to earn multibillion dollar revenue from our proprietary pipeline, generating next level of value for all Ionis stakeholders. And with that, I'll turn the call over to Richard to discuss our recent pipeline progress, next step we'll review our 2023 financial results and provide our 2024 financial guidance. Then I'll wrap things up before taking your questions. Richard.

Brett: And at the same time, we've also made great progress across the rest for the rest of our rich pipeline and advance our leading technology for our future medicines.

All of which sets us up to bring a steady cadence of new transformational medicines to patients for years to come.

Brett P. Monia: And with that, I'll turn the call over to Richard to discuss our recent pipeline progress, next step we'll review our 2023 financial results and provide our 2024 financial guidance. Then I'll wrap things up before taking your questions. Richard.

Brett: We will continue to focus on building and advancing our wholly owned pipeline, which will position us to deliver even more medicines directly to patients.

2023 financial results and provide our 2024 financial guidance.

Brett P. Monia: Then I'll wrap things up before taking your questions. Richard.

Then I'll wrap things up before taking your questions rich.

Brett: We expect that the investments we're making over the next few years will drive an outsized opportunity to earn multibillion dollar revenue from our proprietary pipeline generating next level of value for all Iona stakeholders and with that I'll turn the call over to Richard to discuss our recent pipeline progress next step will review our two.

Richard.

Richard S. Geary: Well, thank you Brad. Many notable pipeline achievements in 2000 2030 some. Some of which you've heard with the highlight being the approval in December of way Noah in the U S for patients with <unk> Polyneuropathy. <unk> was approved based on the neuro T transform. Results. And week 35. In this study we knew a demonstrated powerful and sustained GTR suppression stopped neuropathy disease progression and improve neuropathy impairment and quality of life. These highly positive results were reinforced at week 66, and <unk> 85, and as the only approved medicine for the treatment of ATR Polyneuropathy thing can be self administered via auto injector. We believe <unk> is well positioned to reach newly diagnosed patients and patients who remain unknown. <unk> by current therapies. <unk> robust profile also supports our confidence in the potential to benefit patients in a much larger ATT, our cardiomyopathy patient population. Our conviction was reinforced with the data we presented at Hff's say late last year that showed improvement in cardiac structure and function in a predefined cardiac subpopulation of patients in neuro T transform. And in January additional data was published in the Journal of American Heart Association. Showing encouraging results in a cohort of patients with hereditary <unk> cardiomyopathy myopathy from the neuro <unk> transform study. With over 1400 patients cardio T transform is the largest and most comprehensive study ever conducted in <unk> cardiomyopathy patients. We designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilize. We are also conducting advanced cardiac imaging sub studies as part of our overall program.

Richard S. Geary: Well, thank you Brett, we had many notable pipeline achievements in 2023, some of which you've heard with the highlight being the approval in December of Wainua in the US for patients with ATTR Polyneuropathy. Wainua was approved based on the NEURO-TTransform results in week 35, in this study Wainua demonstrated powerful and sustained GTR suppression, stopped neuropathy disease progression and improved neuropathy impairment and quality of life. These highly positive results were reinforced at week 66, and at 85, and is the only approved medicine for the treatment of ATTR Polyneuropathy that can be self administered via auto injector. We believe Wainua is well positioned to reach newly diagnosed patients and patients who remain under served by current therapies. Wainua's robust profile also supports our confidence in the potential to benefit patients in a much larger ATTR cardiomyopathy patient population. Our conviction was reinforced with the data we presented at HFSA late last year that showed improvement in cardiac structure and function in a pre-defined cardiac subpopulation of patients in NEURO-TTransform. And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

Many notable pipeline achievements in 2000 2030 some.

Some of which you've heard with the highlight being the approval in December of way Noah in the U S for patients with <unk> Polyneuropathy.

<unk> was approved based on the neuro T transform.

Richard: 'twenty three financial results and provide our 2024 financial guidance.

Richard S. Geary: Wainua was approved based on the NEURO-TTransform results in week 35, in this study Wainua demonstrated powerful and sustained GTR suppression, stopped neuropathy disease progression and improved neuropathy impairment and quality of life. These highly positive results were reinforced at week 66, and at 85, and is the only approved medicine for the treatment of ATTR Polyneuropathy that can be self administered via auto injector. We believe Wainua is well positioned to reach newly diagnosed patients and patients who remain under served by current therapies. Wainua's robust profile also supports our confidence in the potential to benefit patients in a much larger ATTR cardiomyopathy patient population. Our conviction was reinforced with the data we presented at HFSA late last year that showed improvement in cardiac structure and function in a pre-defined cardiac subpopulation of patients in NEURO-TTransform. And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

Results.

And week 35.

Richard: And then I'll wrap things up before taking your questions.

In this study we knew a demonstrated powerful and sustained GTR suppression stopped neuropathy disease progression and improve neuropathy impairment and quality of life.

Richard: Richard.

Richard: Well, thank you Brad.

Richard: Many notable pipeline achievements in 2023 some.

Some of which you've heard with the highlight being the approval in December of why Noah in the U S for patients with <unk> Polyneuropathy.

Richard S. Geary: These highly positive results were reinforced at week 66, and at 85, and is the only approved medicine for the treatment of ATTR Polyneuropathy that can be self administered via auto injector. We believe Wainua is well positioned to reach newly diagnosed patients and patients who remain under served by current therapies. Wainua's robust profile also supports our confidence in the potential to benefit patients in a much larger ATTR cardiomyopathy patient population. Our conviction was reinforced with the data we presented at HFSA late last year that showed improvement in cardiac structure and function in a pre-defined cardiac subpopulation of patients in NEURO-TTransform. And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

These highly positive results were reinforced at week 66, and <unk> 85, and as the only approved medicine for the treatment of ATR Polyneuropathy thing can be self administered via auto injector. We believe <unk> is well positioned to reach newly diagnosed patients and patients who remain unknown.

Richard: Renewal was approved based on the neuro T transform.

Richard: Results in week 35.

Richard S. Geary: We believe Wainua is well positioned to reach newly diagnosed patients and patients who remain under served by current therapies. Wainua's robust profile also supports our confidence in the potential to benefit patients in a much larger ATTR cardiomyopathy patient population. Our conviction was reinforced with the data we presented at HFSA late last year that showed improvement in cardiac structure and function in a pre-defined cardiac subpopulation of patients in NEURO-TTransform. And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

Richard S. Geary: We believe Wainua is well positioned to reach newly diagnosed patients and patients who remain under served by current therapies.

Richard: In this study we knew a demonstrated powerful and sustained GTR suppression stopped neuropathy disease progression and improve neuropathy impairment and quality of life.

<unk> by current therapies.

<unk> robust profile also supports our confidence in the potential to benefit patients in a much larger ATT, our cardiomyopathy patient population.

Richard S. Geary: Wainua's robust profile also supports our confidence in the potential to benefit patients in a much larger ATTR cardiomyopathy patient population.

Richard: He is highly positive results were reinforced at week 66, and <unk> 85, and as the only approved medicine for the treatment of ATR Polyneuropathy thing can be self administered via auto injector. We believe <unk> is well positioned to reach newly diagnosed patients and patients who remain under.

Richard S. Geary: Our conviction was reinforced with the data we presented at HFSA late last year that showed improvement in cardiac structure and function in a pre-defined cardiac subpopulation of patients in NEURO-TTransform. And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

Our conviction was reinforced with the data we presented at Hff's say late last year that showed improvement in cardiac structure and function in a predefined cardiac subpopulation of patients in neuro T transform.

Served by current therapies.

Richard S. Geary: And in January additional data was published in the Journal of American Heart Association showing encouraging results in a cohort of patients with hereditary ATTR cardiomyopathy from the NEURO-TTransform study. With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

And in January additional data was published in the Journal of American Heart Association.

Richard: Why newest robust profile also supports our confidence in the potential to benefit patients in a much larger <unk> cardiomyopathy patient population.

Showing encouraging results in a cohort of patients with hereditary <unk> cardiomyopathy myopathy from the neuro <unk> transform study.

Richard: Our conviction was reinforced with the data we presented at Hff's say late last year that showed improvement in cardiac structure and function in a predefined cardiac subpopulation of patients in neuro T transform.

Richard S. Geary: With over 1,400 patients, CARDIO-TTransform is the largest and most comprehensive study ever conducted in ATTR cardiomyopathy patients, we designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

With over 1400 patients cardio T transform is the largest and most comprehensive study ever conducted in <unk> cardiomyopathy patients.

Richard: And in January additional data was published in the Journal of American Heart Association.

We designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape.

Richard: Showing encouraging results in a cohort of patients with hereditary <unk> cardiomyopathy myopathy from the neuro <unk> transform study.

Richard S. Geary: This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilizers.

This includes generating data for key subgroups, such as patients on a stabilizer and those naive to stabilize.

Richard: With over 1500 patients cardio T transform is the largest and most comprehensive study ever conducted in <unk> cardiomyopathy patients.

Richard S. Geary: We are also conducting advanced cardiac imaging sub studies as part of our overall program. These include an MRI sub study and its integrity sub study. We believe these data will generate even more valuable data. The potential benefits of <unk> in cardiomyopathy patients by evaluating how we knew is affecting changes in the heart itself. The FDA recently granted <unk> fast track designation for the treatment of <unk> cardiomyopathy, which can expedite the regulatory review process. Receiving this designation further reinforces our confidence in why new has potential to be a transformational treatment in this underserved and growing patient population. With cardio T transform fully enrolled we remain on track for data as early as 2025. <unk> is poised to be the first medicine that we bring to market independently. With the positive phase III results from the balance study in patients with Fcs. We are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted <unk>. Both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of Fcs. As a reminder, in the balance study the 80 milligram dose of <unk> and demonstrated statistically significant reductions in triglycerides robust target engagement and a favorable safety and tolerability profile. Most importantly, <unk> demonstrated unprecedented substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology annual scientific sessions in early April. Based on these positive data, although <unk> is positioned to become the standard of care for patients with Fcs. We're excited to bring this important medicine to patients with <unk> first potential approval late this year, assuming priority review. We're also developing <unk> for patients with severe hypertrichosis redeeming our <unk>, our ongoing phase III studies for assets TG are progressing nicely and we remain on track for data next year. Following closely behind <unk>. As Don at Dolores. Which we anticipate will be our second independent launch assuming approval.

Richard S. Geary: We are also conducting advanced cardiac imaging sub-studies as part of our overall program, these include an MRI sub-study and a integrity sub-study. We believe these data will generate even more valuable data about the potential benefits of Wainua in cardiomyopathy patients, by evaluating how Wainua is affecting changes in the heart itself. The FDA recently granted Wainua fast track designation for the treatment of ATTR cardiomyopathy, which can expedite the regulatory review process. Receiving this designation further reinforces our confidence in Wainua's potential to be a transformational treatment in this underserved and growing patient population. With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025. Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: We are also conducting advanced cardiac imaging sub-studies as part of our overall program, these include an MRI sub-study and a integrity sub-study.

We are also conducting advanced cardiac imaging sub studies as part of our overall program.

These include an MRI sub study and its integrity sub study.

Richard: We designed this study to generate a rich dataset that we believe will be key for physicians and payers in this evolving and dynamic treatment landscape. This.

Richard S. Geary: We believe these data will generate even more valuable data about the potential benefits of Wainua in cardiomyopathy patients, by evaluating how Wainua is affecting changes in the heart itself. The FDA recently granted Wainua fast track designation for the treatment of ATTR cardiomyopathy, which can expedite the regulatory review process. Receiving this designation further reinforces our confidence in Wainua's potential to be a transformational treatment in this underserved and growing patient population. With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025. Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

We believe these data will generate even more valuable data.

The potential benefits of <unk> in cardiomyopathy patients by evaluating how we knew is affecting changes in the heart itself.

Richard: This includes generating data for key subgroups, such as patients on a stabilizer and.

Richard: And those naive to stabilizers. We're also conducting advanced cardiac imaging sub studies as part of our overall program.

Richard S. Geary: The FDA recently granted Wainua fast track designation for the treatment of ATTR cardiomyopathy, which can expedite the regulatory review process. Receiving this designation further reinforces our confidence in Wainua's potential to be a transformational treatment in this underserved and growing patient population. With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025. Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: The FDA recently granted Wainua fast track designation for the treatment of ATTR cardiomyopathy, which can expedite the regulatory review process.

The FDA recently granted <unk> fast track designation for the treatment of <unk> cardiomyopathy, which can expedite the regulatory review process.

Richard: These include an MRI sub study and its integrity sub study.

Richard S. Geary: Receiving this designation further reinforces our confidence in Wainua's potential to be a transformational treatment in this underserved and growing patient population. With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025. Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: Receiving this designation further reinforces our confidence in Wainua's potential to be a transformational treatment in this underserved and growing patient population.

Receiving this designation further reinforces our confidence in why new has potential to be a transformational treatment in this underserved and growing patient population.

Richard: We believe these data will generate even more valuable data about the potential benefits of <unk> in cardiomyopathy patients by evaluating how we knew is affecting changes in the heart itself.

Richard S. Geary: With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025. Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: With CARDIO-TTransform fully enrolled we remain on track for data as early as 2025.

With cardio T transform fully enrolled we remain on track for data as early as 2025.

Richard: Yeah.

Richard: The FDA recently granted <unk> fast track designation for the treatment of <unk> cardiomyopathy, which can expedite the regulatory review process.

Richard S. Geary: Olezarsen is poised to be the first medicine we bring to market independently, with the positive Phase III results from the balance study in patients with FCS we are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

<unk> is poised to be the first medicine that we bring to market independently.

With the positive phase III results from the balance study in patients with Fcs.

Receiving this designation further reinforces our confidence in why newest potential to be a transformational treatment in this underserved and growing patient population.

We are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted <unk>.

Richard S. Geary: Additionally, we're pleased that the FDA has granted Olazarsen both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of FCS. As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard: With cardio T transform fully enrolled we will.

Both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of Fcs.

Remain on track for data as early as 2025.

Richard: <unk> is poised to be the first medicine that we bring to market independently.

As a reminder, in the balance study the 80 milligram dose of <unk> and demonstrated statistically significant reductions in triglycerides robust target engagement and a favorable safety and tolerability profile.

Richard S. Geary: As a reminder, in the balance study, the 80 milligram dose of Olazarsen demonstrated statistically significant reductions in triglycerides, robust target engagement, and a favorable safety and tolerability profile. Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

The positive phase III results from the balance study in patients with Fcs.

Richard: We are preparing our NDA and MAA submissions. Additionally, we're pleased that the FDA has granted osrs in.

Most importantly, <unk> demonstrated unprecedented substantial and clinically meaningful reductions in acute pancreatitis attacks.

Richard S. Geary: Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks. We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: Most importantly, Olazarsen demonstrated unprecedented, substantial and clinically meaningful reductions in acute pancreatitis attacks.

Both orphan drug designation and breakthrough therapy designation, which can help expedite the review of this new medicine for the treatment of Fcs.

Richard S. Geary: We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April. Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard S. Geary: We are looking forward to presenting the balance study data at the American College of Cardiology Annual Scientific Sessions in early April.

We are looking forward to presenting the balance study data at the American College of Cardiology annual scientific sessions in early April.

Richard: As a reminder, in the balance study the 80 milligram dose of <unk> demonstrated statistically significant reductions in triglycerides robust target engagement and a favorable safety and tolerability profile.

Richard S. Geary: Based on these positive data, Olazarsen is positioned to become the standard of care for patients with FCS. We're excited to bring this important medicine to patients with Olazarsen's first potential approval late this year, assuming priority review. We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Based on these positive data, although <unk> is positioned to become the standard of care for patients with Fcs.

We're excited to bring this important medicine to patients with <unk> first potential approval late this year, assuming priority review.

Richard: Most importantly, <unk> demonstrated unprecedented substantial and clinically meaningful reductions in acute pancreatitis attacks.

We're also developing <unk> for patients with severe hypertrichosis redeeming our <unk>, our ongoing phase III studies for assets TG are progressing nicely and we remain on track for data next year.

Richard: We are looking forward to presenting the balance study data at the American College of Cardiology annual scientific sessions in early April.

Richard S. Geary: We're also developing Olazarsen for patients with severe hypertriglyceridemia or sHTG, our ongoing Phase III studies for sHTG are progressing nicely, and we remain on track for data next year.

Richard: Based on these positive data, although <unk> is positioned to become the standard of care for patients with Fcs.

Following closely behind <unk>.

Richard S. Geary: Following closely behind <unk>. As Don at Dolores. Which we anticipate will be our second independent launch assuming approval. <unk> has the potential to be an attractive new prophylactic treatment option for hereditary angioedema patients many of whom continue to experience unpredictable painful and severe attacks. Despite currently available prophylactic treatments. In the recently reported phase III Oasis Hai results Don into loss and demonstrated statistically significant reductions in the rate of attacks in HAE patients. Treated every four or every eight weeks. In addition, Donna Dolores and achieve statistical significance on the extensive set of secondary endpoints in the Q4 week dose group and key secondary endpoints in the Q eight week group. Which we expect to be key differentiators for Donald or send in the prophylactic market. <unk> also demonstrated a favorable safety and Tolerability profile in this study and Additionally, we are encouraged that following completion of the treatment period and the phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive phase III results build on the positive durable results, we have seen in the phase II and phase III OLED studies in the Phase two open label extension study Donna Dolores and demonstrated substantial reductions in HAE attacks. Sustained and durable over two years in addition to a favorable safety and Tolerability profile. We anticipate Don at the Larson could evolve DHA prophylactic treatment paradigm, and what I mean by that based on the phase III results down at Dolores and has the potential to expand extend dosing intervals. Monthly or every two months using an auto injector. From the current standard of care, which is dosed every two to four weeks using a vial and syringe and with an attractive efficacy safety and Tolerability profile demonstrated in the <unk>. Our Acis H AE phase III study, we expect <unk> to be a treatment of choice for many patients. We're busy preparing the NDA, which will include both four week and eight week dosing options. Additionally, otsuka is preparing to submit for marketing approval in Europe and we're pleased that we just recently received orphan drug designation for Donna Larson.

Richard S. Geary: Following closely behind Olezarsen is Donidalorsen, which we anticipate will be our second independent launch, assuming approval. Donidalorsen has the potential to be an attractive new prophylactic treatment option for hereditary angioedema patients, many of whom continue to experience unpredictable, painful and severe attacks despite currently available prophylactic treatments. In the recently reported Phase III Oasis HAE results Donidalorsen demonstrated statistically significant reductions in the rate of attacks in HAE patients treated every four or every eight weeks. In addition, Donidalorsen achieves statistical significance on the extensive set of secondary endpoints in the Q4 week, dose group and key secondary endpoints in the Q8 week group, which we expect to be key differentiators for Donidalorsen in the prophylactic market. Donidalorsen also demonstrated a favorable safety and tolerability profile in this study. And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients. We're busy preparing the NDA, which will include both four week and eight week dosing options.

Richard S. Geary: Following closely behind Olezarsen is Donidalorsen, which we anticipate will be our second independent launch, assuming approval.

Richard: We're excited to bring this important medicine to patients with <unk> first potential approval late this year, assuming priority review.

As Don at Dolores.

Which we anticipate will be our second independent launch assuming approval.

Richard S. Geary: Donidalorsen has the potential to be an attractive new prophylactic treatment option for hereditary angioedema patients, many of whom continue to experience unpredictable, painful and severe attacks despite currently available prophylactic treatments. In the recently reported Phase III Oasis HAE results Donidalorsen demonstrated statistically significant reductions in the rate of attacks in HAE patients treated every four or every eight weeks. In addition, Donidalorsen achieves statistical significance on the extensive set of secondary endpoints in the Q4 week, dose group and key secondary endpoints in the Q8 week group, which we expect to be key differentiators for Donidalorsen in the prophylactic market. Donidalorsen also demonstrated a favorable safety and tolerability profile in this study. And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

<unk> has the potential to be an attractive new prophylactic treatment option for hereditary angioedema patients many of whom continue to experience unpredictable painful and severe attacks. Despite currently available prophylactic treatments.

Richard: We're also developing <unk> for patients with severe hypertrichosis redeeming our <unk>, our ongoing phase III studies for <unk> are progressing nicely and we remain on track for data next year.

Richard S. Geary: In the recently reported Phase III Oasis HAE results Donidalorsen demonstrated statistically significant reductions in the rate of attacks in HAE patients treated every four or every eight weeks. In addition, Donidalorsen achieves statistical significance on the extensive set of secondary endpoints in the Q4 week, dose group and key secondary endpoints in the Q8 week group, which we expect to be key differentiators for Donidalorsen in the prophylactic market. Donidalorsen also demonstrated a favorable safety and tolerability profile in this study. And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

Richard: Following closely behind <unk>.

In the recently reported phase III Oasis Hai results Don into loss and demonstrated statistically significant reductions in the rate of attacks in HAE patients.

Richard: As Don at Dolores.

Richard: Which we anticipate will be our second independent launch assuming approval.

Richard: <unk> has the potential to be an attractive new prophylactic treatment option for hereditary angioedema patients many of whom continue to experience unpredictable painful and severe attacks. Despite currently available prophylactic treatments.

Richard S. Geary: In addition, Donidalorsen achieves statistical significance on the extensive set of secondary endpoints in the Q4 week, dose group and key secondary endpoints in the Q8 week group, which we expect to be key differentiators for Donidalorsen in the prophylactic market. Donidalorsen also demonstrated a favorable safety and tolerability profile in this study. And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

Treated every four or every eight weeks.

In addition, Donna Dolores and achieve statistical significance on the extensive set of secondary endpoints in the Q4 week dose group and key secondary endpoints in the Q eight week group.

Richard: In the recently reported phase III Oasis Hai results Don into Larsen demonstrated statistically significant reductions in the rate of attacks in HAE patients.

Which we expect to be key differentiators for Donald or send in the prophylactic market.

Richard S. Geary: Donidalorsen also demonstrated a favorable safety and tolerability profile in this study. And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

Richard S. Geary: Donidalorsen also demonstrated a favorable safety and tolerability profile in this study.

<unk> also demonstrated a favorable safety and Tolerability profile in this study and Additionally, we are encouraged that following completion of the treatment period and the phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension.

Richard S. Geary: And additionally we are encouraged to following completion of the treatment period in the Phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension. These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

Richard: Treated every four or every eight weeks.

In addition, Donna Dolores and achieve statistical significance on the extensive set of secondary endpoints in the Q4 week dose group and key secondary endpoints in the Q eight week group.

Richard S. Geary: These positive Phase III results build on the positive durable results we have seen in the Phase II and Phase III [Inaudible] studies, in the Phase II open label extension study Donidaorsen demonstrated substantial reductions in HAE attacks that were sustained and durable over two years in addition to a favorable safety and tolerability profile. We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

These positive phase III results build on the positive durable results, we have seen in the phase II and phase III OLED studies in the Phase two open label extension study Donna Dolores and demonstrated substantial reductions in HAE attacks.

We expect to be key differentiators for Donna doors and in the prophylactic market.

Richard: <unk> also demonstrated a favorable safety and Tolerability profile in this study and Additionally, we are encouraged that following completion of the treatment period in the phase III study over 90% of the randomized patients entered the ongoing Oasis plus open label extension.

Sustained and durable over two years in addition to a favorable safety and Tolerability profile.

Richard S. Geary: We anticipate Donidalorsen could evolve the HAE prophylactic treatment paradigm, and what I mean by that, based on the Phase III results, Donidalorsen has the potential to extend dosing intervals to monthly or every two months using an auto injector from the current standard of care, which is dosed every two to four weeks using a vial and syringe. And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

We anticipate Don at the Larson could evolve DHA prophylactic treatment paradigm, and what I mean by that based on the phase III results down at Dolores and has the potential to expand extend dosing intervals.

Richard: These positive phase III results build on the positive durable results, we have seen in the phase II and phase III OLED studies in the Phase two open label extension study dawn of Dolores and demonstrated substantial reductions in HAE attacks that were sustained and durable over two.

Monthly or every two months using an auto injector.

From the current standard of care, which is dosed every two to four weeks using a vial and syringe and with an attractive efficacy safety and Tolerability profile demonstrated in the <unk>.

Richard: Two years in addition to a favorable safety and Tolerability profile.

Richard S. Geary: And with an attractive efficacy safety and tolerability profile demonstrated in the OASIS HAE Phase III study, we expect Donidolarsen to be a treatment of choice for many HAE patients.

We anticipate non at Dolores could evolve.

Richard: Hey, prophylactic treatment paradigm, and what I mean by that based on the phase III results down at a loss and has the potential to expand extend dosing intervals to monthly or every two months using an auto injector.

Our Acis H AE phase III study, we expect <unk> to be a treatment of choice for many patients.

Richard S. Geary: We're busy preparing the NDA, which will include both four week and eight week dosing options, additionally, Otsuka is preparing to submit for marketing approval in Europe, and we're pleased for we just recently received Orphan drug designation for Donidalorsen in the EU. We're really looking forward to presenting the Phase III OASIS data at a Medical Congress by mid-year, along with the Phase III results, we're also planning to present results from the OASIS plus study. The OASIS plus study includes an open label cohort for patients rolling over from the Phase III study, and a separate cohort that we referred to as the switch study. The switch study is evaluating patients who have transitioned to Donidolarson from other prophylactic HAE medications. Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed. Spinraza a leading medicine for the treatment of SMA, Wainua, which was just recently approved for ATTR Polyneuropathy, and Qalsody approved to treat SOD1 ALS patients in the US last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

We're busy preparing the NDA, which will include both four week and eight week dosing options. Additionally, otsuka is preparing to submit for marketing approval in Europe and we're pleased that we just recently received orphan drug designation for Donna Larson.

Richard S. Geary: Additionally, otsuka is preparing to submit for marketing approval in Europe and we're pleased that we just recently received orphan drug designation for Donna Larson. In the EU. We're really looking forward to presenting the phase III Oasis data at a medical Congress by mid year, along with the Phase III results. We're also planning to present results from the Oasis plus study. <unk> plus study includes an open label cohort for patients rolling over from the Phase III study and a separate cohort we referred to as the switch study. The switch study is evaluating patients who have transitioned to Donna Dawson from other prophylactic HAE medications. Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed spin rozzer as a leading medicine for the treatment of SMA when a new law. Which was just recently approved. <unk> Polyneuropathy. And Cal Saudi approved to treat <unk> patients in the U S last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development. Including Int 707 for prion disease, which recently began clinical testing. Among our partnered neurology programs late last year, we completed enrollment in the phase two Halo study for ion 58 to <unk>. Inpatients with Angelman syndrome. We also shared some encouraging initial observations from this study at the fast meeting in November. These data included a reduction in slow wave EEG delta activity and approximately 70% of patients and an increase in faster frequency rhythms and over 80% of the patients both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution. This improvement in EEG activities. Seeds, what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline and overall functioning on the total bayley score a direct measure of functioning across multiple domains. And on the Angelman syndrome.

Richard: From the current standard of care, which is dosed every two to four weeks using a vial and syringe and with an attractive efficacy safety and Tolerability profile demonstrated in.

In the EU.

Richard: Our <unk> <unk> phase III study, we expect <unk> to be a treatment of choice for many patients.

Richard S. Geary: We're really looking forward to presenting the Phase III OASIS data at a Medical Congress by mid-year, along with the Phase III results, we're also planning to present results from the OASIS plus study. The OASIS plus study includes an open label cohort for patients rolling over from the Phase III study, and a separate cohort that we referred to as the switch study. The switch study is evaluating patients who have transitioned to Donidolarson from other prophylactic HAE medications. Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed. Spinraza a leading medicine for the treatment of SMA, Wainua, which was just recently approved for ATTR Polyneuropathy, and Qalsody approved to treat SOD1 ALS patients in the US last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

We're really looking forward to presenting the phase III Oasis data at a medical Congress by mid year, along with the Phase III results. We're also planning to present results from the Oasis plus study.

Richard: We're busy preparing the NDA, which will include both four week and eight week dosing options. Additionally, otsuka is preparing to submit for marketing approval in Europe and we're pleased that we just recently received orphan drug designation for Donna Larson.

<unk> plus study includes an open label cohort for patients rolling over from the Phase III study and a separate cohort we referred to as the switch study.

Richard S. Geary: The OASIS plus study includes an open label cohort for patients rolling over from the Phase III study, and a separate cohort that we referred to as the switch study. The switch study is evaluating patients who have transitioned to Donidolarson from other prophylactic HAE medications. Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed. Spinraza a leading medicine for the treatment of SMA, Wainua, which was just recently approved for ATTR Polyneuropathy, and Qalsody approved to treat SOD1 ALS patients in the US last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Richard S. Geary: The OASIS plus study includes an open label cohort for patients rolling over from the Phase III study, and a separate cohort that we referred to as the switch study.

The switch study is evaluating patients who have transitioned to Donna Dawson from other prophylactic HAE medications.

In the EU.

We're really looking forward to presenting the phase III Oasis data at a medical Congress by midyear along with the Phase III results. We're also planning to present results from the Oasis plus study.

Richard S. Geary: The switch study is evaluating patients who have transitioned to Donidolarson from other prophylactic HAE medications. Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed. Spinraza a leading medicine for the treatment of SMA, Wainua, which was just recently approved for ATTR Polyneuropathy, and Qalsody approved to treat SOD1 ALS patients in the US last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Richard S. Geary: The switch study is evaluating patients who have transitioned to Donidolarson from other prophylactic HAE medications.

Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed spin rozzer as a leading medicine for the treatment of SMA when a new law.

Richard S. Geary: Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed.

Richard: The Oasis plus study includes an open label cohort for patients rolling over from the Phase III study in a separate cohort we referred to as the switch study.

Richard S. Geary: Spinraza a leading medicine for the treatment of SMA, Wainua, which was just recently approved for ATTR Polyneuropathy, and Qalsody approved to treat SOD1 ALS patients in the US last year. Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Which was just recently approved.

<unk> Polyneuropathy.

Richard: The switch study is evaluating patients who have transitioned to Donna Dawson from other prophylactic HAE medications.

And Cal Saudi approved to treat <unk> patients in the U S last year.

Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases.

Richard S. Geary: Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases. By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Richard S. Geary: Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases.

Richard: Turning now to our leading neurology franchise, which today includes three marketed breakthrough medicines that we discovered and developed spin rozzer as a leading medicine for the treatment of SMA.

By the end of this year, we expect to have six wholly owned neurology medicines in clinical development.

Richard S. Geary: By the end of this year, we expect to have six wholly owned neurology medicines in clinical development, including ION717 for Prion disease, which recently began clinical testing. Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Richard: When a new law, which was just recently approved.

Four ATR Polyneuropathy and Cal Saudi approved to treat <unk> patients in the U S last year.

Including Int 707 for prion disease, which recently began clinical testing.

Richard S. Geary: Among our partnered neurology programs, late last year we completed enrollment in the Phase 1/2 HALOS study for ION582 in patients with Angelman syndrome, we also shared some encouraging initial observations from this study at the FAST meeting in November. These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Among our partnered neurology programs late last year, we completed enrollment in the phase two Halo study for ion 58 to <unk>.

Richard: Behind our approved neurology medicines is a robust and growing clinical pipeline of medicines to treat both rare and broad neurological diseases.

Inpatients with Angelman syndrome.

We also shared some encouraging initial observations from this study at the fast meeting in November.

Richard: By the end of this year, we expect to have six wholly owned neurology medicines in clinical development.

Richard S. Geary: These data included a reduction in slow wave EEG delta activity in approximately 70% of patients, and an increase in faster frequency rhythms in over 80% of the patients, both compared to baseline activities. While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

These data included a reduction in slow wave EEG delta activity and approximately 70% of patients and an increase in faster frequency rhythms and over 80% of the patients both compared to baseline activities.

Richard: Including eye on 71, 7% for prion disease, which recently began clinical testing.

Richard: Among our partnered neurology programs late last year, we completed enrollment in the phase one two Halo study for ion 582 in.

Richard S. Geary: While direct comparisons are difficult and should be viewed with caution, this improvement in EEG activities exceeds what is observed in natural history studies over the same time period. Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

While direct comparisons are difficult and should be viewed with caution.

In patients with Angelman syndrome.

Richard: We also shared some encouraging initial observations from this study at the fast meeting in November.

This improvement in EEG activities.

Seeds, what is observed in natural history studies over the same time period.

Richard: These data included a reduction in slow wave EEG delta activity and approximately 70% of patients and an increase in faster frequency rhythms and over 80% of the patients both compared to baseline activities.

Richard S. Geary: Also a majority of patients in the study showed improvement compared to baseline, and overall functioning on the total Bayley score a direct measure of functioning across multiple domains, and on the Angelman syndrome CGI changed scale, which captures clinical impression of the patient.

Also a majority of patients in the study showed improvement compared to baseline and overall functioning on the total bayley score a direct measure of functioning across multiple domains.

And on the Angelman syndrome.

Richard S. Geary: And on the Angelman syndrome. CGI changed scale, which captures clinical impression of the patient. We look forward to reporting more data from the Halo study by mid year. With the successes, we've achieved to date and the breadth of the pipeline in development it. It's clear that our neurology franchise set setting us apart as a leader in this space. The Angelman study is one of several mid stage data Readouts. We have planned for 2024 that if positive could further add to our rich phase III pipeline and bolster our ability to deliver a steady cadence of transformative medicines to patients for years to come. This year, we're looking forward to many key catalysts, including detailed phase III data presentations and regulatory submissions for <unk> and Donna Dawson. Several expected marketing approvals decisions for way Noah in various countries. And potential launch of <unk>, assuming priority review and approval late this year. We will keep you updated on our progress throughout the year. And with that I'll turn it over to Beth. Richard. 2023 was a strong year underscored by similarly strong financial results. In which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring lean Nuer OLED. Oh, the dioxin and Donna to me. Market. As a result, we delivered a non-GAAP operating loss of $247 million. A significant improvement compared to 2022, and our 2023 guidance. By significantly we significantly exceeded 2023 revenue guidance by more than $200 million, earning revenues of $325 million and $788 million for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue. <unk> from the business development successes, we achieved last year. We earned $479 million of R&D revenue in 2023, which included revenue from our new collaborations with Astrazeneca Roche and Novartis and. In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy.

Richard S. Geary: And on the Angelman syndrome. CGI changed scale, which captures clinical impression of the patient.

Richard: While direct comparisons are difficult and should be viewed with caution.

CGI changed scale, which captures clinical impression of the patient.

Richard: This improvement in EEG activities.

Richard S. Geary: We look forward to reporting more data from the HALO study by mid year. With the successes we've achieved to date, and the breadth of the pipeline in development, its clear that our neurology franchise sets us apart as a leader in this space. The Angelman study is one of several mid-stage data readouts we have planned for 2024 that if positive, could further add to our rich Phase III pipeline and bolster our ability to deliver a steady cadence of transformative medicines to patients for years to come. This year, we're looking forward to many key catalysts, including detailed Phase III data presentations and regulatory submissions for Olezarsen and Donidolarsen, several expected marketing approvals decisions for Wainua in various countries, and potential launch of Olezarsen assuming priority review and approval late this year. We will keep you updated on our progress throughout the year, and with that I'll turn it over to Beth. Richard. 2023 was a strong year underscored by similarly strong financial results. In which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring lean Nuer OLED. Oh, the dioxin and Donna to me. Market. As a result, we delivered a non-GAAP operating loss of $247 million. A significant improvement compared to 2022, and our 2023 guidance. By significantly we significantly exceeded 2023 revenue guidance by more than $200 million, earning revenues of $325 million and $788 million for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue. <unk> from the business development successes, we achieved last year. We earned $479 million of R&D revenue in 2023, which included revenue from our new collaborations with Astrazeneca Roche and Novartis and.

We look forward to reporting more data from the Halo study by mid year.

Richard: <unk> what is observed in natural history studies over the same time period.

Richard: Also a majority of patients in the study showed improvement compared to baseline and overall functioning on the total bayley score a direct measure of functioning across multiple domains.

With the successes, we've achieved to date and the breadth of the pipeline in development it.

It's clear that our neurology franchise set setting us apart as a leader in this space.

Richard: And on the Angelman syndrome.

The Angelman study is one of several mid stage data Readouts. We have planned for 2024 that if positive could further add to our rich phase III pipeline and bolster our ability to deliver a steady cadence of transformative medicines to patients for years to come.

Richard S. Geary: The Angelman study is one of several mid-stage data readouts we have planned for 2024 that if positive, could further add to our rich Phase III pipeline and bolster our ability to deliver a steady cadence of transformative medicines to patients for years to come. This year, we're looking forward to many key catalysts, including detailed Phase III data presentations and regulatory submissions for Olezarsen and Donidolarsen, several expected marketing approvals decisions for Wainua in various countries, and potential launch of Olezarsen assuming priority review and approval late this year. We will keep you updated on our progress throughout the year, and with that I'll turn it over to Beth.

Richard: CGI changed scale, which captures clinical impression of the patient.

Richard: We look forward to reporting more data from the Halo study by mid year.

Richard: With the successes, we've achieved to date and the breadth of the pipeline in development. It's.

This year, we're looking forward to many key catalysts, including detailed phase III data presentations and regulatory submissions for <unk> and Donna Dawson.

Richard: It's clear that our neurology franchise setting us apart as a leader in this space.

Richard S. Geary: This year, we're looking forward to many key catalysts, including detailed Phase III data presentations and regulatory submissions for Olezarsen and Donidolarsen, several expected marketing approvals decisions for Wainua in various countries, and potential launch of Olezarsen assuming priority review and approval late this year. We will keep you updated on our progress throughout the year, and with that I'll turn it over to Beth.

Richard: The Angelman study is one of several mid stage data Readouts. We have planned for 2024 that if positive could further add to our rich phase III pipeline and bolster our ability to deliver a steady cadence of transformative medicines to patients for years to come.

Several expected marketing approvals decisions for way Noah in various countries.

And potential launch of <unk>, assuming priority review and approval late this year.

We will keep you updated on our progress throughout the year.

Richard S. Geary: We will keep you updated on our progress throughout the year, and with that I'll turn it over to Beth.

And with that I'll turn it over to Beth.

Richard: This year, we're looking forward to many key catalysts, including detailed phase III data presentations and regulatory submissions for <unk>.

Richard.

2023 was a strong year underscored by similarly strong financial results.

Elizabeth L. Hougen: Thank You Richard. 2023 was a strong year underscored by similarly strong financial results. In which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring lean Nuer OLED. Oh, the dioxin and Donna to me. Market. As a result, we delivered a non-GAAP operating loss of $247 million. A significant improvement compared to 2022, and our 2023 guidance. By significantly we significantly exceeded 2023 revenue guidance by more than $200 million, earning revenues of $325 million and $788 million for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue. <unk> from the business development successes, we achieved last year. We earned $479 million of R&D revenue in 2023, which included revenue from our new collaborations with Astrazeneca Roche and Novartis and. In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy. And $36 million for the licensing of ion 826, I dragged nearing clinical development designed to treat heart failure. Both of these in the fourth quarter. Our substantial R&D revenue, we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance. We also earned $309 million in commercial revenue with the majority coming from <unk>. Sales of spin off and our associated royalties were comparable year over year. And while fourth quarter sales were impacted by the timing of shipments in certain markets. It's been rather remained the global market leader in SMA. Importantly, with way newest FDA approval and recent launch we look forward to adding <unk> to our commercial revenue stream, which currently includes spin right that Cal Fannie take steady and we live right. Our non-GAAP operating expenses of $1 billion $35 million were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a noncash charge. Proceeded with the lease exit and the license fee, we paid to victorious in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million. As expected our operating expenses increased for the full year compared to 2022. We continued to advance key programs in our pipeline. The increase in our R&D expenses was due to increased clinical study costs. Which for higher because our phase III studies were fully enrolled are nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level ethylene moved numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the wave Mueller Olmesartan and Donna to alert and launch it. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our eye on its own and co commercialized medicine.

Elizabeth L. Hougen: Thank you Richard. 2023 was a strong year underscored by similarly strong financial results, in which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring Wainua, Olezarsen and Donidalorsen to market. As a result, we delivered a non-GAAP operating loss of $247 million dollars, a significant improvement compared to 2022, and our 2023 guidance. By significantly, we significantly exceeded 2023 revenue guidance by more than $200 million dollars, earning revenues of $325 million dollars and $788 million dollars for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

Elizabeth L. Hougen: Thank you Richard.

Richard: Several expected marketing approvals decisions for way Noah in various countries.

Elizabeth L. Hougen: 2023 was a strong year underscored by similarly strong financial results, in which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring Wainua, Olezarsen and Donidalorsen to market. As a result, we delivered a non-GAAP operating loss of $247 million dollars, a significant improvement compared to 2022, and our 2023 guidance. By significantly, we significantly exceeded 2023 revenue guidance by more than $200 million dollars, earning revenues of $325 million dollars and $788 million dollars for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

In which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring lean Nuer OLED.

Richard: And potential launch of <unk>, assuming priority review and approval late this year.

Oh, the dioxin and Donna to me.

Market.

Richard: We will keep you updated on our progress throughout the year.

As a result, we delivered a non-GAAP operating loss of $247 million.

Elizabeth L. Hougen: As a result, we delivered a non-GAAP operating loss of $247 million dollars, a significant improvement compared to 2022, and our 2023 guidance. By significantly, we significantly exceeded 2023 revenue guidance by more than $200 million dollars, earning revenues of $325 million dollars and $788 million dollars for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

Elizabeth L. Hougen: As a result, we delivered a non-GAAP operating loss of $247 million dollars, a significant improvement compared to 2022, and our 2023 guidance.

And with that I'll turn it over to Beth.

A significant improvement compared to 2022, and our 2023 guidance.

Beth: You mentioned.

Beth: 2023 was a strong year underscored by similarly strong financial results.

By significantly we significantly exceeded 2023 revenue guidance by more than $200 million, earning revenues of $325 million and $788 million for the fourth quarter and full year respectively.

Elizabeth L. Hougen: By significantly, we significantly exceeded 2023 revenue guidance by more than $200 million dollars, earning revenues of $325 million dollars and $788 million dollars for the fourth quarter and full year respectively. Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

Beth: In which we delivered substantial revenue, while simultaneously advancing our pipeline and preparing to bring lean nuer all.

Beth: <unk> and <unk> to market.

Beth: As a result, we delivered a non-GAAP operating loss of $247 million.

Elizabeth L. Hougen: Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022. These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

Elizabeth L. Hougen: Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022.

Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022.

Beth: A significant improvement compared to 2022, and our 2023 guidance.

Beth: By significantly we.

Elizabeth L. Hougen: These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year. We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

Elizabeth L. Hougen: These increases were primarily driven by increased R&D revenue, resulting from the business development successes we achieved last year.

These increases were primarily driven by increased R&D revenue.

Beth: Significantly exceeded 2023 revenue guidance by more than $200 million, earning revenues of $325 million and $788 million for the fourth quarter and full year respectively.

<unk> from the business development successes, we achieved last year.

Elizabeth L. Hougen: We earned $479 million dollars of R&D revenue in 2023, which included revenue from our new collaborations with Otsuka, Roche and Novartis.

We earned $479 million of R&D revenue in 2023, which included revenue from our new collaborations with Astrazeneca Roche and Novartis and.

Beth: Revenue more than doubled in the fourth quarter of 2023 and increased 34% for the full year, both compared to the same periods in 2022.

Elizabeth L. Hougen: In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy. And $36 million for the licensing of ion 826, I dragged nearing clinical development designed to treat heart failure. Both of these in the fourth quarter. Our substantial R&D revenue, we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance. We also earned $309 million in commercial revenue with the majority coming from <unk>. Sales of spin off and our associated royalties were comparable year over year. And while fourth quarter sales were impacted by the timing of shipments in certain markets. It's been rather remained the global market leader in SMA. Importantly, with way newest FDA approval and recent launch we look forward to adding <unk> to our commercial revenue stream, which currently includes spin right that Cal Fannie take steady and we live right. Our non-GAAP operating expenses of $1 billion $35 million were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a noncash charge. Proceeded with the lease exit and the license fee, we paid to victorious in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million. As expected our operating expenses increased for the full year compared to 2022. We continued to advance key programs in our pipeline. The increase in our R&D expenses was due to increased clinical study costs. Which for higher because our phase III studies were fully enrolled are nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level ethylene moved numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the wave Mueller Olmesartan and Donna to alert and launch it. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our eye on its own and co commercialized medicine. In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in. And cash and investments. Our ending cash was higher than projected primarily due to the significant payments from the business development transactions, we completed last year. And the successful convertible note refinancing we Opportunistically completed last June. Which provided us with cash earmarked to repay the remaining convertible notes due this year. We expect to carry the positive momentum generated by our strong 2023 performance into this year. Deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2020 for full year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue. Our total expected revenue for 2024 includes a sizable base of commercial revenue with spin rather as the cornerstone. We expect the resilience has been rather has demonstrated to continue at our royalties to reflect that. We're excited that we knew is on the market and the launch is off to a good start. Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the U S sales. With significant focus on patient identification and education, we are looking forward to adding initial weigh newer royalty revenue this year and. And as more new patients are identified and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs. This year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2020 for approximately $150 million to $175 million. We will consist of non cash amortization from partner payments, we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of <unk> and <unk>. License fees and R&D funding from our partners. Our 2020 for operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: In addition, we earned significant payments from AstraZeneca, including $50 million dollars for the US approval of Wainua for ATTR Polyneuropathy, and $36 million for the licensing of ION826, a drug nearing clinical development designed to treat heart failure, both of these in the fourth quarter. The substantial R&D revenue we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance. We also earned $309 million dollars in commercial revenue, with the majority coming from Spinraza. The sales of Spinraza and our associated royalties were comparable year over year, and while fourth quarter sales were impacted by the timing of shipments in certain markets, Spinraza remains the global market leader in SMA. Concordantly with Wainua's FDA approval and recent launch, we look forward to adding Wainua to our commercial revenue stream, which currently includes Spinraza, Qalsody, Tegsedi and Waylivra. Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Richard S. Geary: In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy. And $36 million for the licensing of ion 826, I dragged nearing clinical development designed to treat heart failure. Both of these in the fourth quarter. Our substantial R&D revenue, we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance. We also earned $309 million in commercial revenue with the majority coming from <unk>. Sales of spin off and our associated royalties were comparable year over year. And while fourth quarter sales were impacted by the timing of shipments in certain markets. It's been rather remained the global market leader in SMA. Importantly, with way newest FDA approval and recent launch we look forward to adding <unk> to our commercial revenue stream, which currently includes spin right that Cal Fannie take steady and we live right. Our non-GAAP operating expenses of $1 billion $35 million were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a noncash charge. Proceeded with the lease exit and the license fee, we paid to victorious in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million. As expected our operating expenses increased for the full year compared to 2022. We continued to advance key programs in our pipeline. The increase in our R&D expenses was due to increased clinical study costs. Which for higher because our phase III studies were fully enrolled are nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level ethylene moved numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the wave Mueller Olmesartan and Donna to alert and launch it. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our eye on its own and co commercialized medicine. In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in.

In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy.

Beth: These increases were primarily driven by increased R&D revenue, resulting from the business development successes, we achieved last year.

And $36 million for the licensing of ion 826, I dragged nearing clinical development designed to treat heart failure. Both of these in the fourth quarter.

Beth: We earned $479 million of R&D revenue in 2023, which included revenue from our new collaborations with Astrazeneca Roche and Novartis.

Elizabeth L. Hougen: The substantial R&D revenue we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance. We also earned $309 million dollars in commercial revenue, with the majority coming from Spinraza. The sales of Spinraza and our associated royalties were comparable year over year, and while fourth quarter sales were impacted by the timing of shipments in certain markets, Spinraza remains the global market leader in SMA. Concordantly with Wainua's FDA approval and recent launch, we look forward to adding Wainua to our commercial revenue stream, which currently includes Spinraza, Qalsody, Tegsedi and Waylivra. Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: The substantial R&D revenue we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance.

Our substantial R&D revenue, we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance.

Beth: In addition, we earn significant payments from astrazeneca, including $50 million for the U S approval of <unk> for <unk> Polyneuropathy and.

Elizabeth L. Hougen: We also earned $309 million dollars in commercial revenue, with the majority coming from Spinraza. The sales of Spinraza and our associated royalties were comparable year over year, and while fourth quarter sales were impacted by the timing of shipments in certain markets, Spinraza remains the global market leader in SMA. Concordantly with Wainua's FDA approval and recent launch, we look forward to adding Wainua to our commercial revenue stream, which currently includes Spinraza, Qalsody, Tegsedi and Waylivra. Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: We also earned $309 million dollars in commercial revenue, with the majority coming from Spinraza.

We also earned $309 million in commercial revenue with the majority coming from <unk>.

Elizabeth L. Hougen: The sales of Spinraza and our associated royalties were comparable year over year, and while fourth quarter sales were impacted by the timing of shipments in certain markets, Spinraza remains the global market leader in SMA. Concordantly with Wainua's FDA approval and recent launch, we look forward to adding Wainua to our commercial revenue stream, which currently includes Spinraza, Qalsody, Tegsedi and Waylivra. Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

And $36 million for the licensing of ion 826, I dragged nearing clinical development designed to treat heart failure. Both of these in the fourth quarter.

Sales of spin off and our associated royalties were comparable year over year.

And while fourth quarter sales were impacted by the timing of shipments in certain markets. It's been rather remained the global market leader in SMA.

Beth: Our substantial R&D revenue, we continued to generate reflects the value that our pipeline and technology are creating as numerous partnered programs advance.

Elizabeth L. Hougen: Concordantly with Wainua's FDA approval and recent launch, we look forward to adding Wainua to our commercial revenue stream, which currently includes Spinraza, Qalsody, Tegsedi and Waylivra. Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Importantly, with way newest FDA approval and recent launch we look forward to adding <unk> to our commercial revenue stream, which currently includes spin right that Cal Fannie take steady and we live right.

Beth: We also earned $309 million in commercial revenue with the majority coming from <unk>.

Elizabeth L. Hougen: Our non-GAAP operating expenses of $1 billion $35 million dollars were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a non-cash charge associated with the lease exit and the license fee we paid to Vect-Horus in the fourth quarter. Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Beth: Sales of spin off and our associated royalties were comparable year over year.

Our non-GAAP operating expenses of $1 billion $35 million were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a noncash charge.

Beth: And while fourth quarter sales were impacted by the timing of shipments in certain markets. It's been rather remained the global market leader in SMA.

Beth: Importantly, with Wayne you is FDA approval and recent launch we look forward to adding <unk> to our commercial revenue streams, which currently includes spin right that Cal Fannie take steady and we live right.

Proceeded with the lease exit and the license fee, we paid to victorious in the fourth quarter.

Elizabeth L. Hougen: Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars. As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million dollars.

Excluding those onetime expenses, our operating expenses were within our guidance range at $994 million.

Elizabeth L. Hougen: As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline. The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: As expected our operating expenses increased for the full year compared to 2022, as we continued to advance key programs in our pipeline.

Beth: Our non-GAAP operating expenses of $1 billion $35 million were slightly or approximately 4% above guidance, primarily due to certain onetime costs, including a noncash charge.

As expected our operating expenses increased for the full year compared to 2022.

Elizabeth L. Hougen: The increase in our R&D expenses was due to the increased clinical study costs, which for higher because our Phase III studies were fully enrolled, or nearly fully enrolled throughout last year. For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

We continued to advance key programs in our pipeline.

The increase in our R&D expenses was due to increased clinical study costs.

Beth: Proceeded with the lease exit and the license fee, we paid to Victoria and the fourth quarter.

Which for higher because our phase III studies were fully enrolled are nearly fully enrolled throughout last year.

Beth: Excluding those one time expenses, our operating expenses were within our guidance range at $994 million.

Elizabeth L. Hougen: For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development. Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development.

For the next several years, we expect our R&D expenses will stabilize near the current level ethylene moved numerous wholly owned medicine through development.

Beth: As expected our operating expenses increased for the full year compared to 2022.

Elizabeth L. Hougen: Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches. We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Elizabeth L. Hougen: Also as expected our SG&A expenses increased year over year as we invested ahead of the Wainua, Olezarsen and Donidalorsen launches.

Beth: We continue to advance key programs in our pipeline.

Also as expected our SG&A expenses increased year over year as we invested ahead of the wave Mueller Olmesartan and Donna to alert and launch it.

Beth: The increase in our R&D expenses was due to increased clinical study costs.

Elizabeth L. Hougen: We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our Ionis owned and co commercialized medicines.

Beth: Which for higher because our phase III studies were fully enrolled are nearly fully enrolled throughout last year.

We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our eye on its own and co commercialized medicine.

Beth: For the next several years, we expect our R&D expenses will stabilize near the current level as we move numerous wholly owned medicine through development.

Elizabeth L. Hougen: In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in. And cash and investments. Our ending cash was higher than projected primarily due to the significant payments from the business development transactions, we completed last year. And the successful convertible note refinancing we Opportunistically completed last June. Which provided us with cash earmarked to repay the remaining convertible notes due this year. We expect to carry the positive momentum generated by our strong 2023 performance into this year. Deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2020 for full year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue. Our total expected revenue for 2024 includes a sizable base of commercial revenue with spin rather as the cornerstone. We expect the resilience has been rather has demonstrated to continue at our royalties to reflect that. We're excited that we knew is on the market and the launch is off to a good start. Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the U S sales. With significant focus on patient identification and education, we are looking forward to adding initial weigh newer royalty revenue this year and. And as more new patients are identified and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs. This year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2020 for approximately $150 million to $175 million. We will consist of non cash amortization from partner payments, we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of <unk> and <unk>. License fees and R&D funding from our partners. Our 2020 for operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship. As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023. Excluding the impact of one time costs last year. Our planned expense growth will come almost entirely from increases in our SG&A expenses. But the way new launch underway. Our SG&A expenses will include our minority portion of Wayne newest sales and marketing costs. Or in the high teens to low 20% range. After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering ionosonde medicines to patients. Sept of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch all this arson for FCS assuming a profile. We expect to add the OLED <unk> in FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing down into lower sent to the market next year also assuming approval. Our projected R&D expenses reflect the important investments, we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity. This these programs represent for us and. And we can make these pipeline investments, while keeping R&D R&D expenses steady. Because of several of our late stage studies, and we can reallocate resources tied to our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million. Additionally, we project a year end cash balance of approximately $1 $7 billion. The vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: In addition, we exceeded our 2023 cash guidance by ending the year with $2.3 billion in cash and investments. Our ending cash was higher than projected, primarily due to the significant payments from the business development transactions we completed last year, and the successful convertible note refinancing we opportunistically completed last June, which provided us with cash earmarked to repay the remaining convertible notes due this year. We expect to carry the positive momentum generated by our strong 2023 performance into this year by deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2024 full-year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone. We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: In addition, we exceeded our 2023 cash guidance by ending the year with $2.3 billion in cash and investments.

In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in.

Richard S. Geary: In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in. And cash and investments. Our ending cash was higher than projected primarily due to the significant payments from the business development transactions, we completed last year. And the successful convertible note refinancing we Opportunistically completed last June. Which provided us with cash earmarked to repay the remaining convertible notes due this year. We expect to carry the positive momentum generated by our strong 2023 performance into this year. Deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2020 for full year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue. Our total expected revenue for 2024 includes a sizable base of commercial revenue with spin rather as the cornerstone. We expect the resilience has been rather has demonstrated to continue at our royalties to reflect that. We're excited that we knew is on the market and the launch is off to a good start. Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the U S sales. With significant focus on patient identification and education, we are looking forward to adding initial weigh newer royalty revenue this year and. And as more new patients are identified and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs. This year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2020 for approximately $150 million to $175 million. We will consist of non cash amortization from partner payments, we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of <unk> and <unk>. License fees and R&D funding from our partners. Our 2020 for operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship. As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023.

Also as expected our SG&A expenses increased year over year as we invested ahead of the Wayne Miller <unk>.

Elizabeth L. Hougen: Our ending cash was higher than projected, primarily due to the significant payments from the business development transactions we completed last year, and the successful convertible note refinancing we opportunistically completed last June, which provided us with cash earmarked to repay the remaining convertible notes due this year. We expect to carry the positive momentum generated by our strong 2023 performance into this year by deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2024 full-year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone. We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

And cash and investments.

Our ending cash was higher than projected primarily due to the significant payments from the business development transactions, we completed last year.

Beth: Donna to alert and launch it.

Beth: We expect our SG&A expenses to increase as we invest in our commercial infrastructure to support the launches of our eye on its owned and co commercialized medicine.

And the successful convertible note refinancing we Opportunistically completed last June.

Which provided us with cash earmarked to repay the remaining convertible notes due this year.

Beth: In addition, we exceeded our 2023 cask guidance by ending the year with $2 3 billion in.

Elizabeth L. Hougen: We expect to carry the positive momentum generated by our strong 2023 performance into this year by deploying our capital resources towards growth opportunities to unlock next level value. This is the foundation for our 2024 full-year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone. We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

We expect to carry the positive momentum generated by our strong 2023 performance into this year.

Beth: And cash and investments.

Beth: Our ending cash was higher than projected primarily due to the significant payments from business development transactions, we completed last year.

Deploying our capital resources towards growth opportunities to unlock next level value.

Elizabeth L. Hougen: This is the foundation for our 2024 full-year financial guidance, which we are pleased to announce today. We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone. We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: This is the foundation for our 2024 full-year financial guidance, which we are pleased to announce today.

Beth: And the successful convertible note refinancing we Opportunistically completed last June.

This is the foundation for our 2020 for full year financial guidance, which we are pleased to announce today.

Elizabeth L. Hougen: We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone. We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: We project to earn more than $575 million in revenue, our total expected revenue for 2024 includes a sizable base of commercial revenue with Spinraza as the cornerstone.

Beth: Which provided us with cash earmarked to repay the remaining convertible notes due this year.

We project to earn more than $575 million in revenue.

Beth: We expect to carry the positive momentum generated by our strong 2023 performance into this year.

Our total expected revenue for 2024 includes a sizable base of commercial revenue with spin rather as the cornerstone.

Elizabeth L. Hougen: We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that. We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: We expect the resilience Spinraza has demonstrated to continue and our royalties to reflect that.

Beth: Deploying our capital resources toward growth opportunities to unlock next level value.

We expect the resilience has been rather has demonstrated to continue at our royalties to reflect that.

Elizabeth L. Hougen: We're excited that Wainua is on the market and the launch is off to a good start, Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the US sales. With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Beth: This is the foundation for our 2020 for full year financial guidance, which we were pleased to announce today.

We're excited that we knew is on the market and the launch is off to a good start.

Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the U S sales.

Beth: We project to earn more than $575 million in revenue.

Beth: Our total expected revenue for 2024 includes a sizable base of commercial revenue, we spend rather as the cornerstone.

With significant focus on patient identification and education, we are looking forward to adding initial weigh newer royalty revenue this year and.

Elizabeth L. Hougen: With significant focus on patient identification and education, we are looking forward to adding initial Wainua royalty revenue this year, and as more new patients are identified, and the launch ramps up we expect revenue to grow. We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Beth: We expect the resilience has been rather has demonstrated to continue and our royalties to reflect that.

And as more new patients are identified and the launch ramps up we expect revenue to grow.

Beth: We're excited that way newness on the market and the launch is off to a good start.

We project meaningful R&D revenue from our partnered programs. This year, although we anticipate R&D revenue will be lower than it was last year.

Elizabeth L. Hougen: We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year. Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Elizabeth L. Hougen: We project meaningful R&D revenue from our partnered programs this year, although we anticipate R&D revenue will be lower than it was last year.

Beth: Astrazeneca is responsible for booking product sales and we will earn royalties in the mid 20% range on the U S sales.

Notably a significant portion of our R&D revenue in 2020 for approximately $150 million to $175 million.

Beth: With significant focus on patient identification and education, we are looking forward to adding initial weigh newer royalty revenue this year.

Elizabeth L. Hougen: Notably a significant portion of our R&D revenue in 2024, approximately $150 to $175 million dollars will consist of non cash amortization from partner payments we received in prior years. We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

We will consist of non cash amortization from partner payments, we received in prior years.

Beth: And as more new patients are identified and the launch ramps up we expect revenue to grow.

Beth: We project meaningful R&D revenue from our partnered programs. This year, although we anticipate R&D revenue will be lower than it was last year.

We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of <unk> and <unk>.

Elizabeth L. Hougen: We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of Wainua and Qalsody, license fees and R&D funding from our partners. Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Beth: Notably a significant portion of our R&D revenue in 2024.

License fees and R&D funding from our partners.

Elizabeth L. Hougen: Our 2024 operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Our 2020 for operating expense guidance reflects our commitment to independently bring our medicines to patients while also continuing to exercise sound fiscal stewardship.

Beth: Proximately $150 million to $175 million.

Beth: We will consist of non cash amortization from partner payments, we received in prior years.

Elizabeth L. Hougen: As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023. Excluding the impact of one time costs last year. Our planned expense growth will come almost entirely from increases in our SG&A expenses. But the way new launch underway. Our SG&A expenses will include our minority portion of Wayne newest sales and marketing costs. Or in the high teens to low 20% range. After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering ionosonde medicines to patients. Sept of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch all this arson for FCS assuming a profile. We expect to add the OLED <unk> in FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing down into lower sent to the market next year also assuming approval. Our projected R&D expenses reflect the important investments, we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity. This these programs represent for us and. And we can make these pipeline investments, while keeping R&D R&D expenses steady. Because of several of our late stage studies, and we can reallocate resources tied to our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million. Additionally, we project a year end cash balance of approximately $1 $7 billion. The vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million earmarked to address our remaining 2024 convertible notes that are coming due late this year. Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients. As more and more of our ion and phone medicines come to market, we expect the proportion of product revenue to increase significantly. Estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential. And following behind these are additional attractive opportunities coming from our prolific research engine. Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. That I will turn it back to Brent.

Elizabeth L. Hougen: As a result, we expect our 2024 operating expenses to increase in the mid-single-digit range compared to 2023, excluding the impact of one time costs last year. Our planned expense growth will come almost entirely from increases in our SG&A expenses, with the Wainua launch underway, our SG&A expenses will include our minority portion of Wainua's sales and marketing costs, which are in the high teens to low 20% range. After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering Ionis own medicines to patients except of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch, Olezarsen for FCS, assuming a profile, we expect to add the Olezarsen FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval. Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: As a result, we expect our 2024 operating expenses to increase in the mid-single-digit range compared to 2023, excluding the impact of one time costs last year.

Richard S. Geary: As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023. Excluding the impact of one time costs last year. Our planned expense growth will come almost entirely from increases in our SG&A expenses. But the way new launch underway. Our SG&A expenses will include our minority portion of Wayne newest sales and marketing costs. Or in the high teens to low 20% range. After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering ionosonde medicines to patients. Sept of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch all this arson for FCS assuming a profile. We expect to add the OLED <unk> in FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing down into lower sent to the market next year also assuming approval. Our projected R&D expenses reflect the important investments, we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity. This these programs represent for us and. And we can make these pipeline investments, while keeping R&D R&D expenses steady. Because of several of our late stage studies, and we can reallocate resources tied to our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million. Additionally, we project a year end cash balance of approximately $1 $7 billion. The vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million earmarked to address our remaining 2024 convertible notes that are coming due late this year. Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients.

Beth: We have the potential to earn cash generating revenue from regulatory milestones such as the EU approvals of <unk> and <unk>.

As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023.

Excluding the impact of one time costs last year.

Beth: License fees and R&D funding from our partners.

Elizabeth L. Hougen: Our planned expense growth will come almost entirely from increases in our SG&A expenses, with the Wainua launch underway, our SG&A expenses will include our minority portion of Wainua's sales and marketing costs, which are in the high teens to low 20% range. After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering Ionis own medicines to patients except of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch, Olezarsen for FCS, assuming a profile, we expect to add the Olezarsen FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval. Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Our planned expense growth will come almost entirely from increases in our SG&A expenses.

Beth: Our 2020 for operating expense guidance reflects our commitment to independently, bringing our medicines to patients while also continuing to exercise sound fiscal stewardship.

But the way new launch underway. Our SG&A expenses will include our minority portion of Wayne newest sales and marketing costs.

Beth: As a result, we expect our 2020 for operating expenses to increase in the mid single digit range compared to 2023.

Or in the high teens to low 20% range.

Elizabeth L. Hougen: After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering Ionis own medicines to patients except of course from the necessary field team. Today, our commercial organization is enthusiastically preparing for our first independent launch, Olezarsen for FCS, assuming a profile, we expect to add the Olezarsen FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval. Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering ionosonde medicines to patients.

Beth: Excluding the impact of one time costs last year.

Beth: Our planned expense growth will come almost entirely from increases in our SG&A expenses.

Sept of course from the necessary field team.

Beth: But the way new launch underway. Our SG&A expenses will include our minority portion of way newest sales and marketing costs.

Elizabeth L. Hougen: Today, our commercial organization is enthusiastically preparing for our first independent launch, Olezarsen for FCS, assuming a profile, we expect to add the Olezarsen FCS field team later this year. We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval. Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Today, our commercial organization is enthusiastically preparing for our first independent launch all this arson for FCS assuming a profile.

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

We expect to add the OLED <unk> in FCS field team later this year.

Beth: After having built our commercial capabilities over the last couple of years, we now have a fully integrated commercial organization capable of delivering ionosonde medicines to patients.

Elizabeth L. Hougen: We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval. Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: We're also scaling our capabilities as needed ahead of bringing Donidolarsen to the market next year, also assuming approval.

We're also scaling our capabilities as needed ahead of bringing down into lower sent to the market next year also assuming approval.

Elizabeth L. Hougen: Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities. We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: Our projected R&D expenses reflect the important investments we are making to grow our wholly owned pipeline and advance our next wave of opportunities.

Our projected R&D expenses reflect the important investments, we are making to grow our wholly owned pipeline and advance our next wave of opportunities.

Beth: <unk> of course for the necessary field team.

Beth: Today, our commercial organization is enthusiastically preparing for our first independent launch <unk> for FCS assuming a profile.

Elizabeth L. Hougen: We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity these programs represent for us. And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

We believe it's important to make investments today in our wholly owned programs because of the potential multibillion dollar revenue opportunity. This these programs represent for us and.

Beth: We expect to add the OLED darts in FCS field team later this year.

Beth: We're also scaling our capabilities as needed ahead of bringing down into lower sent to the market next year also assuming approval.

Elizabeth L. Hougen: And we can make these pipeline investments, while keeping R&D expenses steady, because there's several of our late stage studies that we can reallocate resources towards our earlier stage programs as they advance into later stages of development. With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

And we can make these pipeline investments, while keeping R&D R&D expenses steady.

Beth: Our projected R&D expenses reflect the important investments, we are making to grow our wholly owned pipeline and advance our next wave of opportunities.

Because of several of our late stage studies, and we can reallocate resources tied to our earlier stage programs as they advance into later stages of development.

Beth: We believe it's important to make investments today in our wholly owned programs because of the.

With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million.

Elizabeth L. Hougen: With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars. Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: With meaningful revenues and modest expense growth, we are projecting a non-GAAP operating loss of less than $475 million dollars.

Beth: The potential multibillion dollar revenue opportunity. This these programs represent for us and.

Additionally, we project a year end cash balance of approximately $1 $7 billion.

Elizabeth L. Hougen: Additionally, we project a year end cash balance of approximately $1.7 billion dollars, the vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities. In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Beth: And we can make these pipeline investments, while keeping R&D R&D expenses steady.

The vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities.

Beth: Because of several of our late stage study then we can reallocate resources toward our earlier stage programs as they advance into later stages of development.

Beth: With meaningful revenue and modest expense crowd, we are projecting a non-GAAP operating loss of less than $475 million.

In addition, we have $45 million earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Elizabeth L. Hougen: In addition, we have $45 million dollars earmarked to address our remaining 2024 convertible notes that are coming due late this year.

Beth: Additionally, we project a year end cash balance of approximately $1 $7 billion.

Elizabeth L. Hougen: Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients. As more and more of our Ionis own medicines come to market, we expect the proportion of product revenue to increase significantly. We estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential, and following behind these are additional attractive opportunities coming from our prolific research engine. Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. And with that I'll turn it back to Brett.

Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients.

Richard S. Geary: Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients. As more and more of our ion and phone medicines come to market, we expect the proportion of product revenue to increase significantly. Estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential. And following behind these are additional attractive opportunities coming from our prolific research engine. Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. That I will turn it back to Brent.

Beth: The vast majority of the projected year over year change in our cash reflects the investments we are making in our pipeline and our commercialization activities.

Elizabeth L. Hougen: As more and more of our Ionis own medicines come to market, we expect the proportion of product revenue to increase significantly. We estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential, and following behind these are additional attractive opportunities coming from our prolific research engine. Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. And with that I'll turn it back to Brett.

Elizabeth L. Hougen: As more and more of our Ionis own medicines come to market, we expect the proportion of product revenue to increase significantly.

As more and more of our ion and phone medicines come to market, we expect the proportion of product revenue to increase significantly.

Beth: In addition, we have $45 million earmarked to address our remaining 2024 convertible notes that are <unk>.

Elizabeth L. Hougen: We estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential, and following behind these are additional attractive opportunities coming from our prolific research engine. Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. And with that I'll turn it back to Brett.

Beth: Coming to late this year.

Estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential.

Beth: Looking beyond 2024, we expect to continue making significant investments in our commercial infrastructure to support our goal to expand our proprietary pipeline and independently deliver our medicines to patients as.

And following behind these are additional attractive opportunities coming from our prolific research engine.

Elizabeth L. Hougen: Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines. Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. And with that I'll turn it back to Brett.

Elizabeth L. Hougen: Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines.

Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines.

Beth: As more and more of our ion and phone medicines come to market, we expect the proportion of product revenue to increase significantly.

Elizabeth L. Hougen: Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver. And with that I'll turn it back to Brett.

Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow that we believe our pipeline can deliver.

Beth: Estimate that the programs in our pipeline today have a combined multibillion dollar peak sales potential.

Beth: And following behind these are additional attractive opportunities coming from our prolific made search engine.

Elizabeth L. Hougen: And with that I'll turn it back to Brett.

That I will turn it back to Brent.

Beth: Finally, we plan to continue to invest in technology that will enable us to expand our therapeutic opportunities and optimize delivery of our medicines.

Brett P. Monia: Thanks Beth. We're very proud of the remarkable progress we made last year and we're very much looking forward to building on this positive momentum this year. We have arrived at where we are today by being focused on a clear vision and a clear set of strategic objectives to achieve our vision. Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners. We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines. Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: Thanks Beth.

Brett P. Monia: We're very proud of the remarkable progress we made last year and we're very much looking forward to building on this positive momentum this year. We have arrived at where we are today by being focused on a clear vision and a clear set of strategic objectives to achieve our vision. Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners. We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines. Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: We're very proud of the remarkable progress we made last year and we're very much looking forward to building on this positive momentum this year.

We're very proud of the remarkable progress we made last year and we're very much looking forward to building on this positive momentum this year.

Our investments in 2024 and for the next few years reflect our plan to strategically deploy our resources to achieve the robust revenue growth and positive cash flow.

Brett P. Monia: We have arrived at where we are today by being focused on a clear vision and a clear set of strategic objectives to achieve our vision. Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners. We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines. Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: We have arrived at where we are today by being focused on a clear vision and a clear set of strategic objectives to achieve our vision.

We have arrived at where we are today by being focused on a clear vision and a clear set of strategic objectives to achieve our vision.

Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners.

Brett P. Monia: Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners. We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines. Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners.

Beth: We believe our pipeline can deliver.

Beth: That I will turn it back to Brent.

We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines.

Brent: Thanks Beth.

Brett P. Monia: We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines. Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: We have established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines.

We're very proud of the remarkable progress we made last year and we're very much looking forward to building on this positive momentum this year.

Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term.

Brett P. Monia: Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term. We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term.

Brent: We have arrived at where we are today, but I've been focused on a clear vision and a clear set of strategic objectives to achieve our vision.

Brent: Building and advancing our pipeline and delivering medicines that we can see discover and develop directly to patients is a top priority for our owners.

We also expect to add more wholly owned medicines to our pipeline this year and for many years to come.

Brett P. Monia: We also expect to add more wholly owned medicines to our pipeline this year and for many years to come. We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: We also expect to add more wholly owned medicines to our pipeline this year and for many years to come.

We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors.

Brett P. Monia: We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors. In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brent: We've established as a leader in cardiovascular and neurology drug discovery and development with one of the richest mid and late stage pipelines.

In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year.

Our pipeline is delivering we reported multiple positive key readouts over the past year and are positioned to deliver additional important results in the near term.

Brett P. Monia: In parallel our partnered programs are progressing on track with key phase III data Readouts planned this year. Important phase III Readouts next year and beyond. 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

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

Important phase III Readouts next year and beyond.

Brent: We also expect to add more wholly owned medicines to our pipeline this year and for many years to come.

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.

Brett P. Monia: 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. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brent: We are pleased that our first co commercialization launch if we knew it is off to a good start and we're very much looking forward to our upcoming independent launches for <unk> and Donny doors.

All of this sets us up to continue bringing a steady cadence of new.

Brett P. Monia: All of this sets us up to continue bringing a steady cadence of new. And potentially transformational medicines to the market for many years to come. As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: All of this sets us up to continue bringing a steady cadence of new. And potentially transformational medicines to the market for many years to come.

In parallel our partner programs are progressing on track with key phase III data Readouts planned this year.

And potentially transformational medicines to the market for many years to come.

As I mentioned at the start of this call I honest is at a key inflection point.

Brett P. Monia: As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts. To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brett P. Monia: As I mentioned at the start of this call I honest is at a key inflection point. We have great momentum and a substantial number of upcoming value driving catalysts.

Brent: Important phase III Readouts next year and beyond.

We have great momentum and a substantial number of upcoming value driving catalysts.

Brent: 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.

To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline.

Brett P. Monia: To support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for our stakeholders with financial responsibility and discipline. We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brent: All of this sets us up to continue bringing a steady cadence of new SMB.

Brent: Essentially transformational medicines to the market for many years to come.

Brett P. Monia: We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Brent: As I.

Brent: And at the start of this call I honest is at a key inflection point.

We have great momentum and a substantial number of upcoming value driving catalysts. This.

Operator: 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 pick up your handset before pressing the keys, to withdraw your question please press star then two. Our first question comes from Jason Gerberry with BOA. Please go ahead.

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

Support all of our strategic priorities, we will continue to make the necessary investments to ensure success and drive next level value for Iona stakeholders with financial responsibility and discipline.

Operator: If you are using a speakerphone, please pick up your handset before pressing the keys, to withdraw your question please press star then two. Our first question comes from Jason Gerberry with BOA. Please go ahead.

Operator: If you are using a speakerphone, please pick up your handset before pressing the keys, to withdraw your question please press star then two.

To withdraw your question. Please press Star then two.

Speaker Change: We're really looking forward to an outstanding year and sharing our progress along the way and with that we'll now pause and open the call up for questions.

Our first question comes from Jason <unk> with Bofa. Please go ahead.

Operator: Our first question comes from Jason Gerberry with BOA. Please go ahead.

Jason Gerberry: Thank you for taking my questions. So Brett mindful that you said CARDIO-TTransform will continue as planned, my questions are, how you're thinking about scenarios that will dictate whether you wait to on blind study in early first half '25 versus wait for the final analysis in 2026? And specifically if [Inaudible] were to miss on its overall population composite endpoint, but shows a favorable trend. How might you approach this timing consideration?

Jason Gerberry: Thank you for taking my questions.

Speaker Change: We will now begin the question and answer session.

Jason Gerberry: So Brett mindful that you said CARDIO-TTransform will continue as planned, my questions are, how you're thinking about scenarios that will dictate whether you wait to on blind study in early first half '25 versus wait for the final analysis in 2026? And specifically if [Inaudible] were to miss on its overall population composite endpoint, but shows a favorable trend. How might you approach this timing consideration?

So Brett mindful that you said cardio transform will continue as planned Mike.

Speaker Change: I'll ask a question you May press Star then one on your telephone keypad.

My questions are.

Speaker Change: You are using a speakerphone please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.

Just how youre thinking about scenarios that will dictate whether you wait two on blind. The study in early first half 'twenty five versus wait for the final analysis in 2026 and specifically.

Speaker Change: Our first question.

Jason Gerberry: And specifically if [Inaudible] were to miss on its overall population composite endpoint, but shows a favorable trend. How might you approach this timing consideration?

On island were to Miss on its overall population composite endpoint, but shows a favorable trend how might you approach this timing consideration.

Brett P. Monia: Thanks, Jason. We're not going to comment on other companies' programs, but what I will say is this. Nothing has changed in our plans to potentially read the CARDIO-TTransform study out early, it's the same plan that we laid out last year and earlier this year as well. The key driving factor that will weigh into our decision along with our partner AstraZeneca to readout in 2025 which would be early, is really the blinded event rates, which are progressing on track. And of course, if we see additional information out there from other programs. we'll certainly use that information to the best [Inaudible] to make the proper decision on when to read the study out, earlier or let the study play out through to its completion. You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Brett P. Monia: Thanks, Jason.

Brett P. Monia: We're not going to comment on other companies' programs, but what I will say is this. Nothing has changed in our plans to potentially read the CARDIO-TTransform study out early, it's the same plan that we laid out last year and earlier this year as well. The key driving factor that will weigh into our decision along with our partner AstraZeneca to readout in 2025 which would be early, is really the blinded event rates, which are progressing on track. And of course, if we see additional information out there from other programs. we'll certainly use that information to the best [Inaudible] to make the proper decision on when to read the study out, earlier or let the study play out through to its completion. You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Brett P. Monia: We're not going to comment on other companies' programs, but what I will say is this.

We're not going to comment on other companies' programs, but what I.

We'll say is this.

Brett P. Monia: Nothing has changed in our plans to potentially read the CARDIO-TTransform study out early, it's the same plan that we laid out last year and earlier this year as well. The key driving factor that will weigh into our decision along with our partner AstraZeneca to readout in 2025 which would be early, is really the blinded event rates, which are progressing on track. And of course, if we see additional information out there from other programs. we'll certainly use that information to the best [Inaudible] to make the proper decision on when to read the study out, earlier or let the study play out through to its completion. You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Brett P. Monia: Nothing has changed in our plans to potentially read the CARDIO-TTransform study out early, it's the same plan that we laid out last year and earlier this year as well.

Nothing has changed in our plans to potentially read the cardio transform study out early its the same plan that we laid out last year and earlier this year as well.

Brett P. Monia: The key driving factor that will weigh into our decision along with our partner AstraZeneca to readout in 2025 which would be early, is really the blinded event rates, which are progressing on track. And of course, if we see additional information out there from other programs. we'll certainly use that information to the best [Inaudible] to make the proper decision on when to read the study out, earlier or let the study play out through to its completion. You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

The key driving factor that will.

What that will weigh into our decision along with our partner Astrazeneca to readout.

25, which would be early is really the blinded event rates.

Brett P. Monia: And of course, if we see additional information out there from other programs. we'll certainly use that information to the best [Inaudible] to make the proper decision on when to read the study out, earlier or let the study play out through to its completion. You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Which are progressing on track.

And of course, if we see additional information out there from other programs will certainly use that information to the best of our ability to make the proper decision on went through the study out earlier or let the studies play out through to its completion.

Brett P. Monia: You know Jason we really are pleased with the decision we made nearly two years ago, when we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics in the ATTR cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Jason.

We really are pleased with the decision we made.

Nearly two years ago.

When we've lengthened our study and we greatly expanded the size of the patient population to account for the changed demographics and the ATT. Our cardiomyopathy patient population. This was a very wise decision and we believe we have the optimal trial.

Brett P. Monia: This was a very wise decision and we believe we have the optimal trial designed to not only ensure for a highly successful outcome, but to provide the richest data set of any medicine that's out there today, on the market or in development. To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

Designed to not only ensure for a highly successful outcome, but to provide the richest data set.

Of any.

Any medicine, that's that's out there today on the market or in development.

Brett P. Monia: To provide the data that patients want, physicians want, payers want to drive Wainua it to as many patients around the globe as possible.

To provide the data that patients want physicians want payers want to drive.

We knew it to as many patients around the globe as possible.

Jason Gerberry: Got it okay. Thanks, guys.

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

J P. Morgan. Please go ahead.

Jessica Fye: Hey, good morning, guys, thanks for taking the question, maybe just following up on the last question. Can you talk about commercially how you expect the [Inaudible] will be used in cardiomyopathy? Both prior to 2028 [Inaudible] is still branded and then maybe also if you expect that to change at all once [Inaudible] goes generic? Thank you.

Jessica Fye: Hey, good morning, guys, thanks for taking the question, maybe just following up on the last question.

Can you talk about commercially how you expect the tcr's answers will be used in cardiomyopathy. Both prior to 2028 family. This is still branded and then maybe also if you expect that to change at all when feminists goes generic thank you.

Jessica Fye: Can you talk about commercially how you expect the [Inaudible] will be used in cardiomyopathy? Both prior to 2028 [Inaudible] is still branded and then maybe also if you expect that to change at all once [Inaudible] goes generic? Thank you.

Brett P. Monia: Thanks, Jess very it's certainly a dynamic market with several players I'd like Onaiza to jump in on this question. Yes, sure Hi, Jeff. So I think this is this is a market that's right for the clinical data for these patients we have to remind ourselves that <unk>. You might have with the patients. This is a serious disease and it's a terminal and less so with a three to six year survival rate, it's all going to pan out. <unk> data you generate and that's that's what we are really striving for and the positioning of our clinical trial and that's why we extended the trial and have duration empower that we've put in to generate the best dataset. So. We expect that silence Thursday based on their mechanism and the clinical data again with our composite endpoints showing the effect size that we anticipated showing with these first line on patients that are naive to feminists and other stabilizers and then for patients who are on <unk>. It's all going to be dependent on the clinical data that we are able to show on top of <unk>. Showing a robust cardiovascular risk reduction will really drive clinical adoption. In this space and based on the payer research that we've done. We're very confident that the physicians will bill be making the case for the use of two different classes of medications again based on that clinical data and that payers from what we've heard also in our research in the U S as well as outside of the U S quickly in person.

Brett P. Monia: Thanks, Jess very it's certainly a dynamic market with several players I'd like Onaiza to jump in on this question.

With several players I'd like amasa.

To jump in on this call on this question.

Onaiza Cadoret-Manier: Yes, sure, hi Jess. So I think this is a market that's right for the clinical data for these patients, we have to remind ourselves that cardiomyopathy patients, this is a serious disease and it's a terminal [Inaudible]. So with a three to six year survival rate it's all going to depend on the mortality data we generate, and that's what we are really striving for in the positioning of our clinical trial ,and that's why we extended the trial and have duration empower that we've put in to generate the best dataset. So we expect that [Inaudible] based on their mechanism, and the clinical data, again with our composite endpoints showing the effect size that we anticipated showing with these first line, on patients that are naive on [Inaudible] and then for patients who aren't [Inaudible] it's all going to be dependent on the clinical data that we are able to show. On top of <unk> showing a robust cardiovascular risk reduction will really drive clinical adoption in this space, and based on the payer research that we've done, we're very confident that the physicians will, they'll be making the case for the use of two different classes of medications, again based on that clinical data and that payers from what we've heard also in our research in the US, as well as outside of the US with [Inaudible]

Onaiza Cadoret-Manier: Yes, sure, hi Jess.

Onaiza Cadoret-Manier: So I think this is a market that's right for the clinical data for these patients, we have to remind ourselves that cardiomyopathy patients, this is a serious disease and it's a terminal [Inaudible]. So with a three to six year survival rate it's all going to depend on the mortality data we generate, and that's what we are really striving for in the positioning of our clinical trial ,and that's why we extended the trial and have duration empower that we've put in to generate the best dataset. So we expect that [Inaudible] based on their mechanism, and the clinical data, again with our composite endpoints showing the effect size that we anticipated showing with these first line, on patients that are naive on [Inaudible] and then for patients who aren't [Inaudible] it's all going to be dependent on the clinical data that we are able to show. On top of <unk> showing a robust cardiovascular risk reduction will really drive clinical adoption in this space, and based on the payer research that we've done, we're very confident that the physicians will, they'll be making the case for the use of two different classes of medications, again based on that clinical data and that payers from what we've heard also in our research in the US, as well as outside of the US with [Inaudible]

Yes, sure Hi, Jeff.

So I think this is this is a market that's right for the clinical data for these patients we have to remind ourselves that <unk>.

You might have with the patients.

This is a serious disease and it's a terminal and less so with a three to six year survival rate, it's all going to pan out.

Onaiza Cadoret-Manier: So with a three to six year survival rate it's all going to depend on the mortality data we generate, and that's what we are really striving for in the positioning of our clinical trial ,and that's why we extended the trial and have duration empower that we've put in to generate the best dataset. So we expect that [Inaudible] based on their mechanism, and the clinical data, again with our composite endpoints showing the effect size that we anticipated showing with these first line, on patients that are naive on [Inaudible] and then for patients who aren't [Inaudible] it's all going to be dependent on the clinical data that we are able to show. On top of <unk> showing a robust cardiovascular risk reduction will really drive clinical adoption in this space, and based on the payer research that we've done, we're very confident that the physicians will, they'll be making the case for the use of two different classes of medications, again based on that clinical data and that payers from what we've heard also in our research in the US, as well as outside of the US with [Inaudible]

<unk> data you generate and that's that's what we are really striving for and the positioning of our clinical trial and that's why we extended the trial and have duration empower that we've put in to generate the best dataset. So.

We expect that silence Thursday based on their mechanism and the clinical data again with our composite endpoints showing the effect size that we anticipated showing with these first line on patients that are naive to feminists and other stabilizers and then for patients who are on <unk>.

Onaiza Cadoret-Manier: So we expect that [Inaudible] based on their mechanism, and the clinical data, again with our composite endpoints showing the effect size that we anticipated showing with these first line, on patients that are naive on [Inaudible] and then for patients who aren't [Inaudible] it's all going to be dependent on the clinical data that we are able to show. On top of <unk> showing a robust cardiovascular risk reduction will really drive clinical adoption in this space, and based on the payer research that we've done, we're very confident that the physicians will, they'll be making the case for the use of two different classes of medications, again based on that clinical data and that payers from what we've heard also in our research in the US, as well as outside of the US with [Inaudible]

It's all going to be dependent on the clinical data that we are able to show on top of <unk>.

Onaiza Cadoret-Manier: On top of <unk> showing a robust cardiovascular risk reduction will really drive clinical adoption in this space, and based on the payer research that we've done, we're very confident that the physicians will, they'll be making the case for the use of two different classes of medications, again based on that clinical data and that payers from what we've heard also in our research in the US, as well as outside of the US with [Inaudible]

Showing a robust cardiovascular risk reduction will really drive clinical adoption.

In this space and based on the payer research that we've done.

We're very confident that the physicians will bill be making the case for the use of two different classes of medications again based on that clinical data and that payers from what we've heard also in our research in the U S as well as outside of the U S quickly in person.

Jessica Fye: Okay.

Operator: Next question please. Our next question comes from Yanan Zhu with Wells Fargo Securities. Please go ahead.

Brett P. Monia: Next question please.

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

Yanan Zhu: Thanks for taking our questions and congrats on the progress in 2023. In your view, I guess a quick follow up to of the prior questions. What is the importance of achieving benefit in the overall population versus the mono-therapy population only? And maybe in ATTR cardiomyopathy? And then a question on Angelman study readout, what would be a strong or definitive signal, given that the study is not controlled and also included several age groups, and you touched upon EEG. Could you just talk about how that endpoint will be prevented? And what is the expected natural history or placebo response? And at what level of change, change is considered meaningful? Thank you.

Yanan Zhu: Thanks for taking our questions and congrats on the progress in 2023. In your view, I guess a quick follow up to of the prior questions.

In the.

In your view I guess, a quick follow up.

Two of the prior questions what is the importance of achieving benefit in the overall population versus the mono therapy.

Yanan Zhu: What is the importance of achieving benefit in the overall population versus the mono-therapy population only? And maybe in ATTR cardiomyopathy? And then a question on Angelman study readout, what would be a strong or definitive signal, given that the study is not controlled and also included several age groups, and you touched upon EEG. Could you just talk about how that endpoint will be prevented? And what is the expected natural history or placebo response? And at what level of change, change is considered meaningful? Thank you.

Yanan Zhu: What is the importance of achieving benefit in the overall population versus the mono-therapy population only? And maybe in ATTR cardiomyopathy?

Population only.

And maybe.

Yanan Zhu: And then a question on Angelman study readout, what would be a strong or definitive signal, given that the study is not controlled and also included several age groups, and you touched upon EEG. Could you just talk about how that endpoint will be prevented? And what is the expected natural history or placebo response? And at what level of change, change is considered meaningful? Thank you.

<unk> cardiomyopathy, and then a question on <unk>.

Study readout.

What would be a strong or definitive signal.

Given that the study is not controlled and also included several age groups and you touched upon EEG.

Yanan Zhu: Could you just talk about how that endpoint will be prevented? And what is the expected natural history or placebo response? And at what level of change, change is considered meaningful? Thank you.

Could you just talk about how that endpoint will be prevented at what is the expected natural history or placebo response, and what level of change is considered meaningful. Thank you.

Maybe.

In <unk> cardiomyopathy.

And then a question on <unk>.

Sure, maybe I could ask Richard to weigh in on the importance of the overall endpoint in CARDIO_TTransform study, and also what value the subgroups of monotherapy were having. And Eugene you can jump in on the data that we think is gonna be most important for the Angelman's readout later this year. Richard. So we designed this study. Can you give us a positive readout in a combined population so our primary endpoint. On the totality of the data. Cross both populations. And we expect that that will be. That will be positive. Based on the numbers and on the duration that we put into this two years ago. We're very confident in and the readout of this study. Got it. So with regard to Angela. And again, just a reminder, we completed. At enrollment. So the multiple ascending dose study and that study was really the first in human experiment too. To describe the safety of those. <unk> as well as select the right dose and the right population for the pivotal study. It included as you mentioned it is an open label study so of course, any kind of signal will need to be. Taken very carefully. Goal of the study was to really enable us with the decision to progress into pivotal. Okay. With regard to EOG, specifically of course, there is ample natural history data that exists across various age groups. Generally speaking the AEG findings easy findings abnormalities are fairly stable and those populations. So again seeing an improvement. Or differentiation from the natural history will be meaningful. Certainly. If it correlates, especially if it correlates with clinical improvement. We will also be assessing. And I can just add to that. And then very briefly. Slightly higher level. We have a lot of experience in developing our platform for neurological diseases. As you know it's been Rosa Cal Saudi the Tau program continues to go well as anyone's program. Many other programs progressing on track. We believe we have the right platform. This is the same chemical platform as spin Rozzer Mezcal, Saudi is the rest of our pipeline, we think it's the right chemistry. For CMS. Diseases. So we're very much looking forward to the readout from our first in patient study in Haynesville means by mid year. This year.

Brett P. Monia: Sure, maybe I could ask Richard to weigh in on the importance of the overall endpoint in CARDIO_TTransform study, and also what value the subgroups of monotherapy were having. And Eugene you can jump in on the data that we think is gonna be most important for the Angelman's readout later this year. Richard.

Brett P. Monia: Sure, maybe I could ask Richard to weigh in on the importance of the overall endpoint in CARDIO_TTransform study, and also what value the subgroups of monotherapy were having.

Video readout.

What would be a strong or definitive signal.

Endpoint.

Given that the study is not controlled and also included several age groups and you've touched upon EEG.

Cardio transform study and also with value to subgroups, the monotherapy Manhattan and Eugene you can jump in on the data that we think is gonna be most important for the Angelman readout later this year Richard.

Brett P. Monia: And Eugene you can jump in on the data that we think is gonna be most important for the Angelman's readout later this year. Richard.

Could you talk about how that endpoint will be prevented and what is the expected natural history or placebo response, and what level of change change is considered meaningful. Thank you.

So we designed this study.

Can you give us a positive readout in a combined population so our primary endpoint.

Happy to. So we designed this study to give us a positive readout in a combined population, so our primary endpoint is on the totality of the data across both populations. And we expect that that will be positive, and based on the numbers and on the duration that we put into this two years ago, we're very confident in the readout of this study. Got it. So with regard to Angela. And again, just a reminder, we completed. At enrollment. So the multiple ascending dose study and that study was really the first in human experiment too. To describe the safety of those. <unk> as well as select the right dose and the right population for the pivotal study. It included as you mentioned it is an open label study so of course, any kind of signal will need to be. Taken very carefully. Goal of the study was to really enable us with the decision to progress into pivotal. Okay. With regard to EOG, specifically of course, there is ample natural history data that exists across various age groups. Generally speaking the AEG findings easy findings abnormalities are fairly stable and those populations. So again seeing an improvement. Or differentiation from the natural history will be meaningful. Certainly. If it correlates, especially if it correlates with clinical improvement. We will also be assessing. And I can just add to that. And then very briefly. Slightly higher level. We have a lot of experience in developing our platform for neurological diseases. As you know it's been Rosa Cal Saudi the Tau program continues to go well as anyone's program. Many other programs progressing on track. We believe we have the right platform. This is the same chemical platform as spin Rozzer Mezcal, Saudi is the rest of our pipeline, we think it's the right chemistry. For CMS. Diseases. So we're very much looking forward to the readout from our first in patient study in Haynesville means by mid year. This year.

Richard Geary: Happy to. So we designed this study to give us a positive readout in a combined population, so our primary endpoint is on the totality of the data across both populations. And we expect that that will be positive, and based on the numbers and on the duration that we put into this two years ago, we're very confident in the readout of this study.

Richard Geary: Happy to. So we designed this study to give us a positive readout in a combined population, so our primary endpoint is on the totality of the data across both populations.

Brett: Sure maybe I could ask Richard to win on the importance of the overall.

On the totality of the data.

Cross both populations.

Brett: Point Cardio transform study and also with values of subgroups, the monotherapy Manhattan and Eugene you can jump in on the data that we think is gonna be most important for the angelman.

And we expect that that will be.

Richard Geary: And we expect that that will be positive, and based on the numbers and on the duration that we put into this two years ago, we're very confident in the readout of this study.

That will be positive.

Based on the numbers and on the duration that we put into this two years ago.

Brett: Readout later this year Richard.

Speaker Change: Happy to so we designed this study.

We're very confident in and the readout of this study.

Speaker Change: Can you give us a positive readout.

Eugene Schneider: So with regard to Angelman, and again it's just a reminder, we completed enrollments of the multiple ascending dose study, and that study was really the first in-human experiment to describe the safety of this product as well as select the right dose and the right population for the pivotal study. It included, as you mentioned it is an open label study, so of course any kind of signal will need to be taken very carefully, but the goal of the study was to really enable us with the decision to progress into pivotal development. With regard to EEG specifically, of course there is ample natural history data that exists across various age groups, generally speaking the EEG findings abnormalities are fairly stable and those populations, so again seeing an improvement, or differentiation from the natural history will be meaningful. Certainly, if it correlates, especially if it correlates with clinical improvement which we will also be assessing. And I can just add to that very briefly, steps at a higher level. We have a lot of experience in developing our platform for neurological diseases. As you know it's been Rosa Cal Saudi the Tau program continues to go well as anyone's program. Many other programs progressing on track. We believe we have the right platform. This is the same chemical platform as spin Rozzer Mezcal, Saudi is the rest of our pipeline, we think it's the right chemistry. For CMS. Diseases. So we're very much looking forward to the readout from our first in patient study in Haynesville means by mid year. This year.

Speaker Change: Combined population so our primary endpoint.

Got it.

So with regard to Angela.

Brett: On the totality of the data.

And again, just a reminder, we completed.

Brett: Cross both populations.

At enrollment.

Brett: And we expect that that will be.

So the multiple ascending dose study and that study was really the first in human experiment too.

Brett: That will be positive.

Brett: And based on the numbers and on the duration that we put into this two years ago.

To describe the safety of those.

Eugene Schneider: It included, as you mentioned it is an open label study, so of course any kind of signal will need to be taken very carefully, but the goal of the study was to really enable us with the decision to progress into pivotal development. With regard to EEG specifically, of course there is ample natural history data that exists across various age groups, generally speaking the EEG findings abnormalities are fairly stable and those populations, so again seeing an improvement, or differentiation from the natural history will be meaningful. Certainly, if it correlates, especially if it correlates with clinical improvement which we will also be assessing.

<unk> as well as select the right dose and the right population for the pivotal study.

Brett: We're very confident in and the readout of this study.

It included as you mentioned it is an open label study so of course, any kind of signal will need to be.

Speaker Change: Got it.

Speaker Change: So with regard to Angela.

Speaker Change: And again, just a reminder, we we.

Taken very carefully.

Goal of the study was to really enable us with the decision to progress into pivotal.

Speaker Change: We completed enrollment.

Brett: So the multiple ascending dose study and that study was really the first in human experiment too.

Eugene Schneider: With regard to EEG specifically, of course there is ample natural history data that exists across various age groups, generally speaking the EEG findings abnormalities are fairly stable and those populations, so again seeing an improvement, or differentiation from the natural history will be meaningful. Certainly, if it correlates, especially if it correlates with clinical improvement which we will also be assessing.

Okay.

With regard to EOG, specifically of course, there is ample natural history data that exists across various age groups.

Brett: To describe the safety of this product.

Brett: Product as well as select the right dose and the right population for the pivotal study at.

Generally speaking the AEG findings easy findings abnormalities are fairly stable and those populations. So again seeing an improvement.

Brett: It included as you mentioned it is an open label studies of course, any kind of signal will need to be.

Eugene Schneider: Certainly, if it correlates, especially if it correlates with clinical improvement which we will also be assessing.

Taken very carefully about the goal of that study was to really enable us with the decision to progress into pivotal development.

Or differentiation from the natural history will be meaningful.

Certainly.

If it correlates, especially if it correlates with clinical improvement.

Brett P. Monia: And I can just add to that very briefly, steps at a higher level. We have a lot of experience in developing our platform for neurological diseases, as you know it's been [Inaudible] Qalsody, the Tau program continues to go well as anyone's program, many other programs progressing on track. We believe we have the right platform, this is the same chemical platform as Spinraza, as Qalsody as the rest of our pipeline, we think it's the right chemistry for CNS diseases. So we're very much looking forward to the readout from our first in-patient study [Inaudible] by mid year this year.

Brett: With regard to EG, specifically of course, there is ample natural history data that exists across various age groups.

We will also be assessing.

And I can just add to that.

And then very briefly.

Slightly higher level.

Brett: Generally speaking the AG findings easy findings abnormalities are fairly stable in this population so again seen any improvement.

We have a lot of experience in developing our platform for neurological diseases. As you know it's been Rosa Cal Saudi the Tau program continues to go well as anyone's program. Many other programs progressing on track.

Brett: Or differentiation from the natural history will be meaningful.

Brett P. Monia: We believe we have the right platform, this is the same chemical platform as Spinraza, as Qalsody as the rest of our pipeline, we think it's the right chemistry for CNS diseases. So we're very much looking forward to the readout from our first in-patient study [Inaudible] by mid year this year.

Brett P. Monia: We believe we have the right platform, this is the same chemical platform as Spinraza, as Qalsody as the rest of our pipeline, we think it's the right chemistry for CNS diseases.

Brett: Certainly.

Brett: If it correlates, especially if it correlates with clinical improvement.

We believe we have the right platform.

This is the same chemical platform as spin Rozzer Mezcal, Saudi is the rest of our pipeline, we think it's the right chemistry.

Brett: We will also be assessing.

Speaker Change: And I can just add to that.

Speaker Change: And then very briefly a step.

For CMS.

Brett P. Monia: So we're very much looking forward to the readout from our first in-patient study [Inaudible] by mid year this year.

Speaker Change: Slightly higher level.

Diseases. So we're very much looking forward to the readout from our first in patient study in Haynesville means by mid year. This year.

Speaker Change: We have a lot of experience in developing our platform for neurological diseases. As you know it's been rising Khalsa.

Outside a Tau program continues to go well as anyone's program. Many other programs progressing on track.

Yanan Zhu: Very helpful. Thank you.

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

Our next question comes from Myles Minter with William Blair. Please go ahead.

Brett: We believe we have the right platform.

Brett: And the same chemical platform as a spin RASM as Cal Saudi is the rest of our pipeline, we think it's the right chemistry.

Myles Minter: Please go ahead, sir on for miles congrats on another great year. So a couple from us on cardio transform our patients and cardio transform that or do you think the feminists required to demonstrate some sort of disease progression to be eligible to enroll and how do you think its particular subgroup will compare to send this experienced patients and other studies from like a patient demographic. Eugene you want to take that.

Myles Minter: Please go ahead, sir on for miles congrats on another great year.

So a couple from us on cardio transform our patients and cardio transform that or do you think the feminists required to demonstrate some sort of disease progression to be eligible to enroll and how do you think its particular subgroup will compare to send this experienced patients and other studies from like a patient demographic.

Myles Minter: So a couple from us on cardio transform our patients and cardio transform that or do you think the feminists required to demonstrate some sort of disease progression to be eligible to enroll and how do you think its particular subgroup will compare to send this experienced patients and other studies from like a patient demographic.

Brett: For CNS disease.

Brett: Diseases. So we're very much looking forward to the readout from our first in patient study in Haynesville means by mid year. This year.

Speaker Change: Very helpful. Thank you.

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

Unknown: Eugene you want to take that? Sure. So the first question was related to requirement for any kind of disease progression, but certainly not the case as long as the eligibility criteria have been met. Patients are eligible to enroll whether they are on to congress or not. We. As already mentioned we remain pretty. Confident in the design of the study and all of the changes that were made quite a quite some time ago to react primarily to the changing demographics and that really addresses your second point, but demographics, but we're seeing over the last couple of years are quite different from what was seen in very early days of <unk>. Therapeutic development. So we're seeing very similar trends, but have been described recently in the literature. And then just to add to the disease progression. [noise] answer from Eugene. Remember it I think it's important to realize that. The vast majority of patients onto families are do progress in many of those patients don't get much benefit to begin with so. These patients are progressing they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease. So. There's a lot of room for improvement here and we're looking to to fill that gap with with windows.

Unknown: Eugene you want to take that?

Eugene you want to take that.

Sure. So the first question was related to requirement for any kind of disease progression, but certainly not the case as long as the eligibility criteria have been met.

Eugene Schneider: Sure, so the first question was related to requirement for any kind of disease progression, but certainly not the case as long as the eligibility criteria have been met. Patients are eligible to enroll, whether they are on hundreds or not, we, I think Brett already mentioned, we remain pretty confident in the design of the study, and all of the changes that were made quite some time ago to react primarily to the changing demographics, and that really addresses your second point. The demographics, that we're seeing over the last couple of years are quite different from what was seen in the very early days of ATTR therapeutic development. So we're seeing very similar trends that have been described recently in the literature. And then just to add to the disease progression. [noise] answer from Eugene. Remember it I think it's important to realize that. The vast majority of patients onto families are do progress in many of those patients don't get much benefit to begin with so. These patients are progressing they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease. So. There's a lot of room for improvement here and we're looking to to fill that gap with with windows.

Eugene Schneider: Sure, so the first question was related to requirement for any kind of disease progression, but certainly not the case as long as the eligibility criteria have been met.

Myles Minter: Please go ahead, sir on for miles congrats on another great year.

Myles Minter: So a couple from us on cardio transform our patients and cardio transform that Eric do you think the family that's required to demonstrate some sort of disease progression to be eligible to enroll and how do you think its particular subgroup will compare to Sam's experienced patients and other studies from like a patient demographic.

Eugene Schneider: Patients are eligible to enroll, whether they are on hundreds or not, we, I think Brett already mentioned, we remain pretty confident in the design of the study, and all of the changes that were made quite some time ago to react primarily to the changing demographics, and that really addresses your second point. The demographics, that we're seeing over the last couple of years are quite different from what was seen in the very early days of ATTR therapeutic development. So we're seeing very similar trends that have been described recently in the literature.

Patients are eligible to enroll whether they are on to congress or not.

We.

As already mentioned we remain pretty.

Confident in the design of the study and all of the changes that were made quite a quite some time ago to react primarily to the changing demographics and that really addresses your second point, but demographics, but we're seeing over the last couple of years are quite different from what was seen in very early days of <unk>.

Myles Minter: Eugene you want to take that.

Eugene: Sure. So the first question was related to requirement for any kind of disease progression, but certainly not the case as long as the eligibility criteria have been met.

Eugene Schneider: The demographics, that we're seeing over the last couple of years are quite different from what was seen in the very early days of ATTR therapeutic development. So we're seeing very similar trends that have been described recently in the literature.

Eugene Schneider: The demographics, that we're seeing over the last couple of years are quite different from what was seen in the very early days of ATTR therapeutic development.

Brett: Patients are eligible to enroll whether they are on to congress or not.

Therapeutic development.

Eugene Schneider: So we're seeing very similar trends that have been described recently in the literature.

Brett: We.

So we're seeing very similar trends, but have been described recently in the literature.

Brett: As already mentioned we remained pretty.

Brett P. Monia: And then just to add to the disease progression answer from Eugene. Remember I think is important to realize that the vast majority of patients on [Inaudible] do progress, and many of those patients don't get much benefit to begin with. So these patients are progressing, they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease. So there's a lot of room for improvement here and we're looking to to fill that gap with Wainua.

Brett P. Monia: And then just to add to the disease progression answer from Eugene.

Brett: Confident in the design of the study and all of the changes that were made quite a quite some time ago to react primarily to the changing demographics and that really addresses your second point, but demographics, but we're seeing over the last couple of years are quite different from what was seen in very early days of <unk>.

And then just to add to the disease progression.

[noise] answer from Eugene.

Brett P. Monia: Remember I think is important to realize that the vast majority of patients on [Inaudible] do progress, and many of those patients don't get much benefit to begin with. So these patients are progressing, they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease. So there's a lot of room for improvement here and we're looking to to fill that gap with Wainua.

Brett P. Monia: Remember I think is important to realize that the vast majority of patients on [Inaudible] do progress, and many of those patients don't get much benefit to begin with.

Remember it I think it's important to realize that.

The vast majority of patients onto families are do progress in many of those patients don't get much benefit to begin with so.

Brett P. Monia: So these patients are progressing, they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease. So there's a lot of room for improvement here and we're looking to to fill that gap with Wainua.

Brett P. Monia: So these patients are progressing, they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease.

These patients are progressing they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease.

Brett: Sure.

Brett: Therapeutic development.

Brett: So we're seeing very similar trends, but have been described recently in the literature.

Brett P. Monia: So there's a lot of room for improvement here and we're looking to to fill that gap with Wainua.

So.

There's a lot of room for improvement here and we're looking to to fill that gap with with windows.

And then just to add to the disease progression.

Eugene: Answer from Eugene.

Eugene: Remember it I think it's important to realize that.

Myles Minter: Great. Thanks for taking the question.

Eugene: The vast majority of patients onto families are do progress in many of those patients don't get much benefit to begin with so.

Operator: Our next question comes from Debjit Chattopadhyay Javier Please, with William Blair, please go ahead.

Javier Please with William Blair. Please go ahead.

Brett: These patients are progressing they need better treatment options, either in combination or as a monotherapy to halt or reverse their disease.

Unknown: Debjit, You're with Guggenheim. [laughter], We're not hearing you.

You were Guggenheim.

Brett: So.

[laughter].

Brett: There's a lot of room for improvement here and we're looking to fill that gap with with windows.

Okay.

We're not hearing you.

Debjit Chattopadhyay: On Angelman will the data include a decision on go/no go from Biogen. And also what endpoints are most relevant to a potential Phase II trial design?

Speaker Change: Great. Thanks for taking the question.

Included decision on go assess no go.

Brett: Our next question comes from Doug <unk>.

From Biogen.

Doug: Jakob <unk>.

And also what endpoints are most relevant to a potential phase II trial design.

Doug: Please with William Blair. Please go ahead.

Thanks Debjit, I think you were cut off a little bit in the beginning but I think I got your first question. We're very much looking forward to the data readout for the Angelman program around mid year this year, and at that, Biogen as you rightly pointed out will have an option to license the program, the next step for the program is to go to Phase III development. When we share the top line data, we will also be able to lay out the next steps, whether Biogen will take the program forward or Ionis or some other scenario, so yeah all of that planning will come out at once. And then the second part of the question, whats most important do you think in the clinical endpoints for Angelman's? since. Well again. Robert If you look at natural history migrating into a face redesign sorry sure. The natural history of Evangeline patients. So it's been quite well described various. Age age groups within the population. So we're we included all of the. Standard measures of newer developments and function. In that study. Again, we will we will be data driven. And we will be looking at response in all of these age groups, but we included in the study that was the purpose of a learning study that we're conducting first. But the standard measures that are included or baileys scale. Development before specifically in Vineland. Which probably has the richest natural history. Dataset. In addition to that of course, we're looking at clinical Angela specific clinical global impression of change again, thats been well described and validated. As well as some of the. More of a surrogate measure. The measures. Activity like <unk> Sigma insurance et cetera. Thank you Jean <unk>. Thanks, Robert next question please.

Brett P. Monia: Thanks Debjit, I think you were cut off a little bit in the beginning but I think I got your first question. We're very much looking forward to the data readout for the Angelman program around mid year this year, and at that, Biogen as you rightly pointed out will have an option to license the program, the next step for the program is to go to Phase III development. When we share the top line data, we will also be able to lay out the next steps, whether Biogen will take the program forward or Ionis or some other scenario, so yeah all of that planning will come out at once. And then the second part of the question, whats most important do you think in the clinical endpoints for Angelman's?

Brett P. Monia: Thanks Debjit, I think you were cut off a little bit in the beginning but I think I got your first question.

Brett: Yes.

Speaker Change: You were Guggenheim.

We're I'm very much looking forward to the data readout for the Angelman program around mid year this year.

Brett: Yeah.

Brett P. Monia: We're very much looking forward to the data readout for the Angelman program around mid year this year, and at that, Biogen as you rightly pointed out will have an option to license the program, the next step for the program is to go to Phase III development. When we share the top line data, we will also be able to lay out the next steps, whether Biogen will take the program forward or Ionis or some other scenario, so yeah all of that planning will come out at once. And then the second part of the question, whats most important do you think in the clinical endpoints for Angelman's?

Brett: Yes.

Speaker Change: We're not hearing you.

Speaker Change: On Angelman will the data at <unk>.

And at that Biogen as you rightly pointed out.

Speaker Change: Included decision on go assess no go.

<unk>.

Brett: And Biogen.

It has an option to license the program next step for the program is to go to phase III development.

Brett: And also what endpoints are most relevant to a potential phase III trial design.

When we share the top line data.

Speaker Change: Thanks, Robert I think you cut off a little bit there in the beginning but I think I got your first question.

Brett P. Monia: When we share the top line data, we will also be able to lay out the next steps, whether Biogen will take the program forward or Ionis or some other scenario, so yeah all of that planning will come out at once. And then the second part of the question, whats most important do you think in the clinical endpoints for Angelman's?

We will also we will also be able to lay out the next steps, whether biogen will take the program forward or <unk> or some other scenario. So yeah. All of those planning will come out at once and then the second part of the question Whats. Most important do you think in the clinical endpoints for Angelman since.

Brett: We're very much looking forward to the data readout for the Angelman program around midyear this year.

Brett: And at that Biogen as you rightly pointed out.

Well again.

Brett P. Monia: And then the second part of the question, whats most important do you think in the clinical endpoints for Angelman's?

Brett:

Robert If you look at natural history migrating into a face redesign sorry sure.

Brett: <unk> has an option to license the program next step for the program is to go to phase III development.

The natural history of Evangeline patients. So it's been quite well described various.

Brett: When we share the top line data.

Unknown: since. Well again. Robert [Inaudible] migrating into a face redesign sorry sure. The natural history of Evangeline patients. So it's been quite well described various. Age age groups within the population. So we're we included all of the. Standard measures of newer developments and function. In that study. Again, we will we will be data driven. And we will be looking at response in all of these age groups, but we included in the study that was the purpose of a learning study that we're conducting first. But the standard measures that are included or baileys scale. Development before specifically in Vineland. Which probably has the richest natural history. Dataset. In addition to that of course, we're looking at clinical Angela specific clinical global impression of change again, thats been well described and validated. As well as some of the. More of a surrogate measure. The measures. Activity like <unk> Sigma insurance et cetera. Thank you Jean <unk>. Thanks, Robert next question please.

Unknown: since. Well again. Robert [Inaudible]

Unknown: since. Well again. Robert

Multiple: [Inaudible]

Unknown: migrating into a face redesign sorry sure. The natural history of Evangeline patients. So it's been quite well described various. Age age groups within the population. So we're we included all of the. Standard measures of newer developments and function. In that study. Again, we will we will be data driven. And we will be looking at response in all of these age groups, but we included in the study that was the purpose of a learning study that we're conducting first. But the standard measures that are included or baileys scale. Development before specifically in Vineland. Which probably has the richest natural history. Dataset. In addition to that of course, we're looking at clinical Angela specific clinical global impression of change again, thats been well described and validated. As well as some of the. More of a surrogate measure. The measures. Activity like <unk> Sigma insurance et cetera. Thank you Jean <unk>. Thanks, Robert next question please.

Brett P. Monia: migrating into a face redesign sorry sure.

Brett: We will also.

Brett: We will also be able to lay out the next steps, whether biogen will take the program forward or <unk> or some other scenario. So yeah all of that planning will come out at once and then the second part of the question Whats. Most important you think in the clinical endpoints for Angelman.

Age age groups within the population. So we're we included all of the.

Unknown: The natural history of Angelman patients has been quite well described, various age groups within the population, so we're, we included all of the standard measures of neuro developments and function in that study. And again, we will be data driven, and we will be looking at response in all of these age groups that we included in the study, that was the purpose of a learning study that we're conducting first. But the standard measures that are included or bayley scale of development before specifically in [Inaudible] which probably has the richest natural history dataset. In addition to that of course, we're looking at clinical Angela-specific clinical global impression of change, again thats been well described and validated, as well as some of the more of a surrogate measures of activity like [Inaudible] et cetera. Thank you Jean <unk>. Thanks, Robert next question please.

Eugene Schneider: The natural history of Angelman patients has been quite well described, various age groups within the population, so we're, we included all of the standard measures of neuro developments and function in that study. And again, we will be data driven, and we will be looking at response in all of these age groups that we included in the study, that was the purpose of a learning study that we're conducting first. But the standard measures that are included or bayley scale of development before specifically in [Inaudible] which probably has the richest natural history dataset. In addition to that of course, we're looking at clinical Angela-specific clinical global impression of change, again thats been well described and validated, as well as some of the more of a surrogate measures of activity like [Inaudible] et cetera.

Standard measures of newer developments and function.

In that study.

Again, we will we will be data driven.

Speaker Change: Well again.

And we will be looking at response in all of these age groups, but we included in the study that was the purpose of a learning study that we're conducting first.

Eugene Schneider: And again, we will be data driven, and we will be looking at response in all of these age groups that we included in the study, that was the purpose of a learning study that we're conducting first. But the standard measures that are included or bayley scale of development before specifically in [Inaudible] which probably has the richest natural history dataset. In addition to that of course, we're looking at clinical Angela-specific clinical global impression of change, again thats been well described and validated, as well as some of the more of a surrogate measures of activity like [Inaudible] et cetera.

Speaker Change: Robert If you look at natural history migrating into a phase II design sorry sure.

Speaker Change: The natural history of Angelman patients. So it's been quite well described various.

But the standard measures that are included or baileys scale.

Brett: Age age groups within the population. So we're we included all of the.

Development before specifically in Vineland.

Eugene Schneider: But the standard measures that are included or bayley scale of development before specifically in [Inaudible] which probably has the richest natural history dataset. In addition to that of course, we're looking at clinical Angela-specific clinical global impression of change, again thats been well described and validated, as well as some of the more of a surrogate measures of activity like [Inaudible] et cetera.

Eugene Schneider: But the standard measures that are included or bayley scale of development before specifically in [Inaudible] which probably has the richest natural history dataset.

Which probably has the richest natural history.

Brett: Standard measures of neuro development and function.

Richard: In that study.

Dataset.

Richard: Again, we will we will be data driven.

In addition to that of course, we're looking at clinical Angela specific clinical global impression of change again, thats been well described and validated.

Eugene Schneider: In addition to that of course, we're looking at clinical Angela-specific clinical global impression of change, again thats been well described and validated, as well as some of the more of a surrogate measures of activity like [Inaudible] et cetera.

Richard: And we will be looking at response in all of the age groups that we included in the study that was the purpose of the learning study that we're conducting first.

As well as some of the.

More of a surrogate measure.

Richard: But the standard measures that are included or baileys scalar.

The measures.

Activity like <unk> Sigma insurance et cetera.

Richard: Development before specifically in Vineland.

Thank you Jean <unk>.

Unknown: Thanks Eugene Thanks, Robert next question please.

Unknown: Thanks Eugene

Unknown: Thanks, Robert next question please.

Richard: Which probably has the richest natural history.

Thanks, Robert next question please.

Operator: Our next question comes from Michael Ulz with Morgan Stanley. Please go ahead.

Richard: Dataset.

Our next question comes from Mike <unk> with Morgan Stanley. Please go ahead.

Richard: In addition to that of course, we're looking at clinical Angela specific clinical global impression of change again, thats been well described and validate it.

Michael Ulz: Hey, guys, thanks for taking the question, maybe just one on Wainua, or just given the early launch here, I know it's early but any feedback you can provide there? And what are you hearing specifically related to your monthly at home dosing, which is pretty differentiated here? Thanks.

Michael Ulz: Hey, guys, thanks for taking the question, maybe just one on Wainua, or just given the early launch here, I know it's early but any feedback you can provide there?

Maybe just one on where new or just given the early launch here.

Richard: As well as some of the more of a surrogate.

It's early but any feedback you can provide there and what are you hearing specifically related to your monthly at home dosing, which is pretty differentiated here. Thanks.

Richard: Measures of of <unk>.

Activity like E signatures et cetera.

Michael Ulz: And what are you hearing specifically related to your monthly at home dosing, which is pretty differentiated here? Thanks.

Speaker Change: Thanks Rajiv.

Speaker Change: Thanks, Robert next question please.

Yes, Onaiza would you like to take that? Sure Hey, Mike Yeah, we're really excited to see our renew on market and available at the new treatment option for patients. So I'm just doing well. And I'm very pleased to actually see how the joint teams are executing to plan. Importantly. When you are in the launch stage, you're really seeing how things are working with the customer facing teams. The sales teams that RM teams and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills. To really ensure that the product actually gets to patient Wow. They have a very well. Well position, but the product profile as well as the self administer eye administration profile that you just mentioned and with Astrazeneca is fairly broad commercial reach and our D to T. Our expertise, but really. Opening up kind of the treatment option with win win in the marketplace.

Brett P. Monia: Yes, Onaiza would you like to take that?

<unk> would you like to take that.

Onaiza Cadoret-Manier: Sure, Hey Mike. Yeah we're really excited to see a Wainua in market and available as the new treatment option for patients, so launch is doing well, and I'm very pleased to actually see how the joint teams are executing to plan. Importantly [Inaudible] when you're in the launch stage you're really seeing how things are working with the customer-facing teams. The sales teams, the FRM teams, and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills to really ensure that the product actually gets to patients as well. Yeah we're very well positioned with the product profile, as well as the self administration profile that you just mentioned, and with Astrazeneca's really broad commercial reach and our deep TTR expertise, we're really opening up kind of the treatment option within the marketplace.

Onaiza Cadoret-Manier: Sure, Hey Mike.

Sure Hey, Mike Yeah, we're really excited to see our renew on market and available at the new treatment option for patients. So I'm just doing well.

Speaker Change: Our next question comes from Mike <unk> with Morgan Stanley. Please go ahead.

Onaiza Cadoret-Manier: Yeah we're really excited to see a Wainua in market and available as the new treatment option for patients, so launch is doing well, and I'm very pleased to actually see how the joint teams are executing to plan. Importantly [Inaudible] when you're in the launch stage you're really seeing how things are working with the customer-facing teams. The sales teams, the FRM teams, and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills to really ensure that the product actually gets to patients as well. Yeah we're very well positioned with the product profile, as well as the self administration profile that you just mentioned, and with Astrazeneca's really broad commercial reach and our deep TTR expertise, we're really opening up kind of the treatment option within the marketplace.

Mike: Hey, guys. Thanks for taking the question.

Speaker Change: Maybe just one on new or just given the early launch here.

And I'm very pleased to actually see how the joint teams are executing to plan.

Speaker Change: It's early but any feedback you can provide there and what are you hearing specifically related to your monthly at home dosing, which is pretty differentiated here. Thanks.

Importantly.

Onaiza Cadoret-Manier: Importantly [Inaudible] when you're in the launch stage you're really seeing how things are working with the customer-facing teams. The sales teams, the FRM teams, and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills to really ensure that the product actually gets to patients as well. Yeah we're very well positioned with the product profile, as well as the self administration profile that you just mentioned, and with Astrazeneca's really broad commercial reach and our deep TTR expertise, we're really opening up kind of the treatment option within the marketplace.

Onaiza Cadoret-Manier: Importantly [Inaudible] when you're in the launch stage you're really seeing how things are working with the customer-facing teams.

When you are in the launch stage, you're really seeing how things are working with the customer facing teams. The sales teams that RM teams and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills.

Onaiza Cadoret-Manier: The sales teams, the FRM teams, and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills to really ensure that the product actually gets to patients as well. Yeah we're very well positioned with the product profile, as well as the self administration profile that you just mentioned, and with Astrazeneca's really broad commercial reach and our deep TTR expertise, we're really opening up kind of the treatment option within the marketplace.

Speaker Change: Yes.

Speaker Change: <unk> would you like to take that.

Speaker Change: Sure Hey, Mike Yeah, we're really excited to see renew on market and available at the new treatment option for patients.

To really ensure that the product actually gets to patient Wow.

They have a very well.

Speaker Change: I'm just doing well.

Mike: And I'm very pleased to actually see how the joint teams are executing to plan.

Onaiza Cadoret-Manier: Yeah we're very well positioned with the product profile, as well as the self administration profile that you just mentioned, and with Astrazeneca's really broad commercial reach and our deep TTR expertise, we're really opening up kind of the treatment option within the marketplace.

Well position, but the product profile as well as the self administer eye administration profile that you just mentioned and with Astrazeneca is fairly broad commercial reach and our D to T. Our expertise, but really.

Richard: Importantly.

When youre in a launch stage, you're really seeing how things are working with the customer facing teams. The sales teams that RM teams and the irony is 10 teams are working very collaboratively together and really leveraging each other's unique skills.

Opening up kind of the treatment option with win win in the marketplace.

Michael Ulz: Great. Thank you.

Operator: Our next question comes from Salveen Richter with Goldman Sachs. Please go ahead.

Richard: To really ensure that the product actually gets to patient Wow.

Richard: You have a very well.

Salveen Richter: Thank you for taking our question, this is Tammy on for Salveen. Can you just speak to your expectations here for the upcoming Phase II GA data? In particular, how are you thinking about efficacy and maybe speed of onset relative to drugs that are administered in CI? Thank you.

Salveen Richter: Thank you for taking our question, this is Tammy on for Salveen. Can you just speak to your expectations here for the upcoming Phase II GA data?

Richard: Well positioned with the product profile as well as the self administer eye administration profile that you just mentioned and with Astrazeneca is fairly broad commercial reach an RFP T T our expertise, but really.

Can you just speak to your expectations here for the upcoming phase III data in particular, how are you thinking about efficacy and maybe speed of onset relative to drugs that are administered in Ci. Thank you.

Salveen Richter: In particular, how are you thinking about efficacy and maybe speed of onset relative to drugs that are administered in CI? Thank you.

Richard: Opening up kind of the treatment option with win win in the marketplace.

Brett P. Monia: So that's data that we're expecting in the second half of the year, our primary efficacy endpoint is geographic atrophy lesions size. We have two dose levels in the study, it's a study that involves nearly 300 patients randomized or placebo group in two dose levels, monthly administration systemically, obviously subcutaneously. We think this is a big advantage versus intravitreal drugs, we're going to be able to avoid the side effects that tend to hinder intravitreal administration, as well as the inconvenience of intravitreal administration. It's also a very novel mechanism from the alternative complement pathway targeting factor B, we think holds great promise, Roche is certainly excited about it. We're operationalized in this study and we're very much looking forward to the data readout at the end of the year, but we think this is a this is highly differentiated from anything that is out there for GA and all we need is the data, we're waiting on that.

Brett P. Monia: So that's data that we're expecting in the second half of the year, our primary efficacy endpoint is geographic atrophy lesions size.

So that's data that we're expecting in the second half of the year. Our primary efficacy endpoint is geographic atrophy lesion size.

Great. Thank you.

Richard: Our next question comes from <unk> Richter with Goldman Sachs. Please go ahead.

Brett P. Monia: We have two dose levels in the study, it's a study that involves nearly 300 patients randomized or placebo group in two dose levels, monthly administration systemically, obviously subcutaneously. We think this is a big advantage versus intravitreal drugs, we're going to be able to avoid the side effects that tend to hinder intravitreal administration, as well as the inconvenience of intravitreal administration. It's also a very novel mechanism from the alternative complement pathway targeting factor B, we think holds great promise, Roche is certainly excited about it. We're operationalized in this study and we're very much looking forward to the data readout at the end of the year, but we think this is a this is highly differentiated from anything that is out there for GA and all we need is the data, we're waiting on that.

We have two dose levels in the study. It's a study that involves nearly 300 patients randomized to placebo group in two dose levels monthly administration.

Richard: Thank you for taking our question. This is Tommy on for Sullivan.

Tommy: Can you just speak to your expectations here for the upcoming phase III data in particular, how are you thinking about efficacy and maybe speed of onset relative to drugs that are administered in Ci. Thank you.

Systemically, obviously subcutaneously, we think that's a big advantage versus interim vitriol drugs were going to be able to.

Brett P. Monia: We think this is a big advantage versus intravitreal drugs, we're going to be able to avoid the side effects that tend to hinder intravitreal administration, as well as the inconvenience of intravitreal administration. It's also a very novel mechanism from the alternative complement pathway targeting factor B, we think holds great promise, Roche is certainly excited about it. We're operationalized in this study and we're very much looking forward to the data readout at the end of the year, but we think this is a this is highly differentiated from anything that is out there for GA and all we need is the data, we're waiting on that.

Richard: Okay.

Avoid the side effects that.

Richard: So that's data that we're expecting in the second half of the year. Our primary efficacy endpoint is geographic atrophy lesion size.

Sensor hinder intraventricular administration as well as the.

Brett P. Monia: It's also a very novel mechanism from the alternative complement pathway targeting factor B, we think holds great promise, Roche is certainly excited about it. We're operationalized in this study and we're very much looking forward to the data readout at the end of the year, but we think this is a this is highly differentiated from anything that is out there for GA and all we need is the data, we're waiting on that.

Brett P. Monia: It's also a very novel mechanism from the alternative complement pathway targeting factor B, we think holds great promise, Roche is certainly excited about it.

The inconvenience of Intraventricular administration.

Richard: We have two dose levels in the study. It's a study that involves nearly 300 patients randomized with the placebo group and two dose levels monthly administration.

It's also a very novel mechanism.

In the alternative complement pathway.

Brett P. Monia: We're operationalized in this study and we're very much looking forward to the data readout at the end of the year, but we think this is a this is highly differentiated from anything that is out there for GA and all we need is the data, we're waiting on that.

Targeting factor B.

Think holds great promise a roche is certainly excited about it were operationalized. This study and we're very much looking forward to the data readout.

Richard: Systemically, obviously subcutaneously, we think that's a big advantage versus <unk> drugs, we're going to be able to.

End of the year, but we think this is a this is highly differentiated from anything at all.

Richard: Avoid the side effects that.

That is out there for <unk> and and all we need is the data or waiting on that.

Richard: Sensor hinder intraventricular administration as well as the.

Richard: The inconvenience of Intraventricular administration.

Richard: It's also a very novel mechanism.

Richard: In the alternative complement pathway.

Operator: Our next question comes from Luca Issi with RBC. Please go ahead.

Richard: Targeting factor D.

Richard: Think holds great promise Roche is certainly excited about it were operationalized. This study and we're very much looking forward to the data readout.

Luca Issi: Oh, great, thanks, so much for taking my questions, congrats on all the progress, maybe just quick one on ATTR cardiomyopathy. I think [Inaudible] it's pretty definitive that shares will not pay for the combo of two branded drugs like defenders and stabilizers, one would you agree with that? And two, if you don't, what's the magnitude of the benefit that you need to show on top of the [Inaudible] to really convince the payers that they can pay for two branded drugs? In other words, what's the hazard ratio you are hoping to see in that [Inaudible] sub-group? Again any color there much appreciate it. And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there? And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Luca Issi: Oh, great, thanks, so much for taking my questions, congrats on all the progress, maybe just quick one on ATTR cardiomyopathy.

Richard: End of the year, but we think this is a this is highly differentiated from anything yet.

Luca Issi: I think [Inaudible] it's pretty definitive that shares will not pay for the combo of two branded drugs like defenders and stabilizers, one would you agree with that? And two, if you don't, what's the magnitude of the benefit that you need to show on top of the [Inaudible] to really convince the payers that they can pay for two branded drugs? In other words, what's the hazard ratio you are hoping to see in that [Inaudible] sub-group? Again any color there much appreciate it. And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there? And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Luca Issi: I think [Inaudible] it's pretty definitive that shares will not pay for the combo of two branded drugs like defenders and stabilizers, one would you agree with that?

It's pretty definitive that shares will not pay for the combo of two branded drugs like the families and establishes US one we agree with that and two if you don't whats the magnitude of the benefit that you need to show on top of the Sams to really convince the payers that they can pay for two branded drugs.

Richard: That is out there for <unk> and <unk>.

Richard: And what we need is the data and we're waiting on that.

Luca Issi: And two, if you don't, what's the magnitude of the benefit that you need to show on top of the [Inaudible] to really convince the payers that they can pay for two branded drugs? In other words, what's the hazard ratio you are hoping to see in that [Inaudible] sub-group? Again any color there much appreciate it. And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there? And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Luca Issi: And two, if you don't, what's the magnitude of the benefit that you need to show on top of the [Inaudible] to really convince the payers that they can pay for two branded drugs?

Richard: Our next.

Richard: <unk> comes from Luca <unk> with RBC. Please go ahead.

Luca Issi: In other words, what's the hazard ratio you are hoping to see in that [Inaudible] sub-group? Again any color there much appreciate it. And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there? And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Luca Issi: In other words, what's the hazard ratio you are hoping to see in that [Inaudible] sub-group? Again any color there much appreciate it.

In other words, what's the hazard ratio you are hoping to see in that path a subgroup again any color there much appreciate it.

Luca: Oh, great. Thanks, so much for taking my question Congrats on all the progress.

Luca: Kwan Ccr's cardiomyopathy.

Luca Issi: And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there? And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Luca Issi: And then second maybe on [Inaudible] could you just talk about that data readout for ALS, I think is coming in mid 2024, What are you hoping to see there?

Maybe on the taxes could you just talk about that data every Dallas for AOS I think is coming in mid 200 <unk>. What are you hoping to see there and may be related can you potentially get approved for this indication just the NFL.

Speaker Change: It's pretty definitive that payers will not pay for the combo of two branded drugs like the families and establish <unk>.

Speaker Change: We agree with that.

Luca Issi: And may be related, can you potentially get approved for this indication just at NFL similar to 12%? or do you ultimately need to show a functional benefit given this is sporadic and not on ALS? . Again any color there much appreciate it, thanks so much.

Speaker Change: If you don't whats the magnitude of the benefit that you need to show on top of the Sams to really convince the payers that they can pay for two branded drugs.

NFL similar to 12% or do you ultimately need to show a functional benefit given this is sporadic.

Luca Issi: Again any color there much appreciate it, thanks so much.

Richard: So what's the hazard ratio you are hoping to see in that path a subgroup again any color there much appreciate it.

Again any color there much appreciate it thanks so much.

Brett P. Monia: Thanks Luca, theres a lot of questions in there, let's let's try to unpack those, we're not gonna be sharing hazard ratio data, but maybe first, set it up. I'd like Onaiza to touch on the payer question for combination usage in TTR cardiomyopathy, as well as what data she thinks would convince payers to pay. Hum. Yes Luca. So. I think you have to actually convinced the clinicians here the clinician to view this as a very serious disease. No its terminal. If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers. Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos. Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah. And as far as the question <unk>. So this is a as I recall, a three month trial. Targeting <unk> two. Obviously this is a first in patient study, we're looking at safety and Tolerability. Biomarker. Knockdown. Target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as our affiliate light chain. We're not projecting just to be a registrational trial. The next step if the study is positive. Would be to go to phase III and certainly shall Saudi has has set the precedent that if a treatment for an AOS indication shows statistically significant reductions in north in the rideshare train chain with strong trends in clinical efficacy as well. Could that could be a basis for approval. So certainly that's in the cards. But that would require a phase III phase III study.

Brett P. Monia: Thanks Luca, theres a lot of questions in there, let's let's try to unpack those, we're not gonna be sharing hazard ratio data, but maybe first, set it up.

Richard: Maybe on the taxes can you talk about that data every Dallas Safra, unless I think just coming in mid 200 <unk>. What are you hoping to see there and may be related can you potentially get approved for this indication Josh.

I'd like to touch on the.

The payer question.

Brett P. Monia: I'd like Onaiza to touch on the payer question for combination usage in TTR cardiomyopathy, as well as what data she thinks would convince payers to pay.

For combination usage in <unk> cardiomyopathy, as well as what data.

Richard: Similar to 12% or do you ultimately need to show a functional benefit given this is sporadic ALS.

She thinks would convince payers.

To pay.

Hum.

Onaiza Cadoret-Manier: Yes Luca. So, I think you have to actually convinced the clinicians here, the clinicians view this as a very serious disease, it's terminal if you're showing a clinically meaningful importance terms of improvement in cardiovascular risk reduction over [Inaudible], they're going to make the case with payers. The important thing to think about here is also there are two different classes of medications right, from a payer reimbursement perspective. They have a stabilizer class and assignments of class and usually those classes in terms of how payers reimburse are viewed mechanistically different as well, which allows for reimbursement in that particular class as well. So again based on kind of both the work that we've done in understanding how payers view this, as well as what clinicians will need, we think the combination will actually get approved. Yeah. And as far as the question <unk>. So this is a as I recall, a three month trial. Targeting <unk> two. Obviously this is a first in patient study, we're looking at safety and Tolerability. Biomarker. Knockdown. Target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as our affiliate light chain. We're not projecting just to be a registrational trial. The next step if the study is positive. Would be to go to phase III and certainly shall Saudi has has set the precedent that if a treatment for an AOS indication shows statistically significant reductions in north in the rideshare train chain with strong trends in clinical efficacy as well. Could that could be a basis for approval. So certainly that's in the cards. But that would require a phase III phase III study.

Onaiza Cadoret-Manier: Hum. Yes Luca. So. I think you have to actually convinced the clinicians here the clinician to view this as a very serious disease. No its terminal. If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers. Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos. Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

Onaiza Cadoret-Manier: Hum. Yes Luca.

Speaker Change: Again any color there much appreciate it thanks so much.

Onaiza Cadoret-Manier: So. I think you have to actually convinced the clinicians here the clinician to view this as a very serious disease. No its terminal. If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers. Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos. Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

Onaiza Cadoret-Manier: So. I think you have to actually convinced the clinicians here the clinician to view this as a very serious disease. No its terminal.

Yes Luca.

So.

Speaker Change: Thanks, Luke and Theres a lot of questions in there, let's let's try to unpack those we're not gonna be sharing hazard ratio data, but maybe first set it up.

I think you have to actually convinced the clinicians here the clinician to view this as a very serious disease.

Onaiza Cadoret-Manier: If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers. Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos. Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

Onaiza Cadoret-Manier: If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers.

No its terminal.

Richard: I'd like to touch on the.

If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers.

Richard:

Richard: The payer question.

Richard: For combination usage in <unk> cardiomyopathy, as well as what data.

Onaiza Cadoret-Manier: Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos. Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

Richard: She thinks would convince payers.

Think about here is also there are two different classic medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually those clos.

Richard: To pay.

Richard: Hum.

Speaker Change: Yes Luca.

Speaker Change: So.

Speaker Change: I think you have to actually convinced the clinicians here the clinician can view this as a very serious disease.

Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement.

Onaiza Cadoret-Manier: Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement. That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

Onaiza Cadoret-Manier: Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement.

Speaker Change: Its terminal.

Speaker Change: If you're showing a clinically meaningful input in terms of improvement in cardiovascular risk reduction over to candidates, they're going to make the case with payers.

Onaiza Cadoret-Manier: That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect. Yeah.

That particular class as well so again based on kind of both the work that we've done in understanding how payers view this as well as what clinicians will need we think the combination will actually got it perfect.

Richard: Think about here is also there are two different classes of medications right from a payer reimbursement perspective to have a stabilizer class and assignments of class and usually does.

Yeah.

And as far as the question <unk>. So this is a as I recall, a three month trial.

Onaiza Cadoret-Manier: And as far as the ALS question [Inaudible] this is a, as I recall, three month trial targeting [Inaudible] to, obviously this is a first in patient study, we're looking at safety and Tolerability. Biomarker knockdown target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as [Inaudible] chain. We're not projecting just to be a registrational trial, the next step, if the study is positive, would be to go to Phase III and certainly Tegsadi has has set the precedent that if a treatment for an ALS indication shows statistically significant reductions in [Inaudible] chain with strong trends in clinical efficacy as well that could be a basis for approval. So certainly that's in the cards, but that would require a Phase III study.

Richard: Terms of how Payors reimburse our view mechanistically different as well which allows for reimbursement.

Targeting <unk> two.

Obviously this is a first in patient study, we're looking at safety and Tolerability.

Onaiza Cadoret-Manier: Biomarker knockdown target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as [Inaudible] chain. We're not projecting just to be a registrational trial, the next step, if the study is positive, would be to go to Phase III and certainly Tegsadi has has set the precedent that if a treatment for an ALS indication shows statistically significant reductions in [Inaudible] chain with strong trends in clinical efficacy as well that could be a basis for approval. So certainly that's in the cards, but that would require a Phase III study.

Onaiza Cadoret-Manier: Biomarker knockdown target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as [Inaudible] chain.

Biomarker.

Knockdown.

Target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as our affiliate light chain.

Richard: Yeah.

Richard: And as far as the ALS question <unk>. So this is a as I call. It three months trial.

Onaiza Cadoret-Manier: We're not projecting just to be a registrational trial, the next step, if the study is positive, would be to go to Phase III and certainly Tegsadi has has set the precedent that if a treatment for an ALS indication shows statistically significant reductions in [Inaudible] chain with strong trends in clinical efficacy as well that could be a basis for approval. So certainly that's in the cards, but that would require a Phase III study.

We're not projecting just to be a registrational trial.

The next step if the study is positive.

Richard: Targeting <unk> two.

Would be to go to phase III and certainly shall Saudi has has set the precedent that if a treatment for an AOS indication shows statistically significant reductions in north in the rideshare train chain with strong trends in clinical efficacy as well.

Richard:

Richard: Obviously this is a first in patient study, we're looking at safety and Tolerability.

Richard: Biomarker.

Richard: Knockdown.

Richard: Target, but also the efficacy that we'll be looking at is both the ALS functional rating scale as well as nor a film in light chain.

Could that could be a basis for approval. So certainly that's in the cards.

Richard: We're not projecting this to be a registrational trial.

Onaiza Cadoret-Manier: So certainly that's in the cards, but that would require a Phase III study.

Richard: The next step if the study is positive.

But that would require a phase III phase III study.

Richard: Would be to go to phase III and certainly shall Saudi has has set the precedent that if a treatment for an AOS indication shows statistically significant reductions in north from a rideshare train chain with strong trends in clinical efficacy as well.

Luca Issi: Super helpful. Thanks, so much.

Operator: Our next question comes from David Lebowitz with Citi. Please go ahead.

David N. Lebowitz: Thank you very much for taking my question. Given that the the impetus is to really push to be in the frontline for the treatment of cardio myopathy, how does a primary endpoint that includes Tafamidisactually play into that? Is there a necessity to actually have defined monotherapy data to make it more comparable in effect for physicians to make a decision on what is a frontline treatment?

Given that the the impetus is to really push to be in the frontline for the treatment of cardio myopathy.

Richard: Could that could be a basis for approvals is certainly that's in the cards.

How does a primary endpoint that includes the fabulous.

Richard: But that would require a phase III phase III study.

Actually play into that is there a necessity to actually have a.

David N. Lebowitz: Is there a necessity to actually have defined monotherapy data to make it more comparable in effect for physicians to make a decision on what is a frontline treatment?

Speaker Change: Super helpful. Thanks, so much.

Defined monotherapy data to make it more comparable in effect for physicians to make a decision on what is a frontline treatment.

Our next question comes from David Lebowitz with Citi. Please go ahead.

David N. Lebowitz: Thank you very much for taking my question.

Well I'll start there and then maybe on <unk> you could talk about a little bit of what she physicians. We're looking forward to the prescribed on top of a stabilizer for example, so. David as you know our primary endpoint is the total patient population, which includes a reasonably. A reasonably balanced population subpopulation of patients onto families as well as in monotherapy, we hit the primary endpoint, which we believe we are well powered to do based on the upsizing the study and the lengthening of the study that we did two years ago. That would include both patient populations right. And patients with families patients without families we're seeing. CV risk reduction of X. Italic hospitalizations et cetera, and we think that that will bear very well as Lou or subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as. Our purpose to candidates. Have all of that data as well as we're gonna have imaging data. And technician pyrophosphate data. That's also going to speak to. The these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. And Asia would you like to weigh in on some of this. Yeah sure I mean, I think you've covered it I mean, it's just a reminder, David that you know we have a really. Terry large clinical study here is to double the size of any other. Cardiomyopathy trial physicians view. This is a landmark study it's going to generate data that's again as Brad said pre. Pre specified secondary key secondary sub groups, which will give us the data and the. Overall total population, but also the patients who are naive. Q, a stabilizer and then patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing and as a result being able to communicate. The effect size in the cardiovascular risk reduction in both of those different populations I also think. Again, where we're getting data on mild and moderate and more severe GTR and being able to again generate data differently. So very disease will also be very informative to physicians in this year. Their severe should <unk> trade at what point should I treat and those will be again very informative data sets that along with the MRI data that Brett said.

Brett P. Monia: Well I'll start there and then maybe Onaiza could talk about a little bit of what she believes physicians would be looking forward to the prescribe on top of a stabilizer for example. So David as you know our primary endpoint is the total patient population, which includes a reasonably balanced population, subpopulation of patients on Tafamidis as well as in monotherapy, we hit the primary endpoint, which we believe we are well powered to do based on the upsizing study and the lengthening of the study that we did two years ago. That would include both patient populations right, in patients with Tafamidis, in patients without Tafamidis we're seeing a CV risk reduction of X mortality, hospitalizations etcetera, and we think that that will bear very well. As will our subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as on Tafamidis, so we're going to have all that data, as well as we're gonna have imaging data, MRI, technician pyrophosphate data. That's also going to speak to these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. Onaiza, would you like to weigh in on some of this? Yeah sure I mean, I think you've covered it I mean, it's just a reminder, David that you know we have a really. Terry large clinical study here is to double the size of any other. Cardiomyopathy trial physicians view. This is a landmark study it's going to generate data that's again as Brad said pre. Pre specified secondary key secondary sub groups, which will give us the data and the. Overall total population, but also the patients who are naive. Q, a stabilizer and then patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing and as a result being able to communicate. The effect size in the cardiovascular risk reduction in both of those different populations I also think. Again, where we're getting data on mild and moderate and more severe GTR and being able to again generate data differently. So very disease will also be very informative to physicians in this year.

David N. Lebowitz: Given that the the impetus is to really push to be in the frontline for the treatment of cardio myopathy.

David N. Lebowitz: How does a primary endpoint that includes the fabulous.

David as you know our primary endpoint is the total patient population, which includes a reasonably.

Brett P. Monia: So David as you know our primary endpoint is the total patient population, which includes a reasonably balanced population, subpopulation of patients on Tafamidis as well as in monotherapy, we hit the primary endpoint, which we believe we are well powered to do based on the upsizing study and the lengthening of the study that we did two years ago. That would include both patient populations right, in patients with Tafamidis, in patients without Tafamidis we're seeing a CV risk reduction of X mortality, hospitalizations etcetera, and we think that that will bear very well. As will our subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as on Tafamidis, so we're going to have all that data, as well as we're gonna have imaging data, MRI, technician pyrophosphate data. That's also going to speak to these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. Onaiza, would you like to weigh in on some of this?

David N. Lebowitz: Actually play into that is there a necessity to actually have.

A reasonably balanced population subpopulation of patients onto families as well as in monotherapy, we hit the primary endpoint, which we believe we are well powered to do based on the upsizing the study and the lengthening of the study that we did two years ago.

David N. Lebowitz: Defined monotherapy data to make it more comparable in effect for physicians to make a decision on what is a.

Richard: <unk> frontline treatment.

Speaker Change: Well I'll start there and then maybe on <unk> you could talk about a little bit of what she places physicians. We're looking forward to prescribed on top of a stabilizer for example, so.

That would include both patient populations right.

And patients with families patients without families we're seeing.

Brett P. Monia: That would include both patient populations right, in patients with Tafamidis, in patients without Tafamidis we're seeing a CV risk reduction of X mortality, hospitalizations etcetera, and we think that that will bear very well. As will our subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as on Tafamidis, so we're going to have all that data, as well as we're gonna have imaging data, MRI, technician pyrophosphate data. That's also going to speak to these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. Onaiza, would you like to weigh in on some of this?

CV risk reduction of X.

Richard: David as you know our primary endpoint is the total patient population, which includes a.

Italic hospitalizations et cetera, and we think that that will bear very well as Lou or subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as.

Richard: A reasonably balanced population subpopulation of patients onto families as well as in monotherapy, we hit the primary endpoint, which we believe we are well powered to do based on the upsizing the study and the lengthening of the study that we did two years ago.

Brett P. Monia: As will our subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as on Tafamidis, so we're going to have all that data, as well as we're gonna have imaging data, MRI, technician pyrophosphate data. That's also going to speak to these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. Onaiza, would you like to weigh in on some of this?

Our purpose to candidates.

Have all of that data as well as we're gonna have imaging data.

Richard: That would include both patient populations right.

And technician pyrophosphate data.

That's also going to speak to.

Richard: In patients with families patients without families we're seeing.

Brett P. Monia: That's also going to speak to these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy. Onaiza, would you like to weigh in on some of this?

The these different subpopulations, which we think will be extremely valuable when we bring it to the market for GTR cardiomyopathy.

CV risk reduction of X.

Richard: Mortality hospitalizations et cetera, and we think that that will bear very well as low or subgroup analysis, which is a key secondary stratified subgroup, which is both monotherapy as well as.

And Asia would you like to weigh in on some of this.

Onaiza Cadoret-Manier: Yeah sure, I mean I think you've covered it, I mean it's just a reminder David that you know we have a really very large clinical study here, is double the size of any other Cardiomyopathy trial. Physicians view this as a landmark study, it's going to generate data that's, again as Brett said, pre-specified, secondary, key secondary sub-groups, which will give us the data in the overall total population, but also the patients who are naive to a stabilizer and the patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing, and as a result being able to communicate the effect size in the cardiovascular risk reduction in both of those different populations. I also think, again, we're getting data on mild and moderate and more severe GTR and being able to again generate data and different to every disease will also be very informative to physicians in this year. If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said. So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Yeah sure I mean, I think you've covered it I mean, it's just a reminder, David that you know we have a really.

Richard: On purpose to candidates.

Richard: You have all that data as well as we're gonna have imaging data.

Terry large clinical study here is to double the size of any other.

Richard: And technician pyrophosphate data.

Richard: That's also going to speak to.

Onaiza Cadoret-Manier: Physicians view this as a landmark study, it's going to generate data that's, again as Brett said, pre-specified, secondary, key secondary sub-groups, which will give us the data in the overall total population, but also the patients who are naive to a stabilizer and the patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing, and as a result being able to communicate the effect size in the cardiovascular risk reduction in both of those different populations. I also think, again, we're getting data on mild and moderate and more severe GTR and being able to again generate data and different to every disease will also be very informative to physicians in this year. If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said. So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Cardiomyopathy trial physicians view. This is a landmark study it's going to generate data that's again as Brad said pre.

Richard: The these different subpopulations, which we think will be extremely valuable when we bring when you went to the market for GTR cardiomyopathy.

Pre specified secondary key secondary sub groups, which will give us the data and the.

Richard: And Asia would you like to weigh in on some of this.

Overall total population, but also the patients who are naive.

Asia: Yeah sure I mean, I think you covered it I mean, it's just a reminder, David that you know we have a really.

Q, a stabilizer and then patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing and as a result being able to communicate.

Onaiza Cadoret-Manier: So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing, and as a result being able to communicate the effect size in the cardiovascular risk reduction in both of those different populations. I also think, again, we're getting data on mild and moderate and more severe GTR and being able to again generate data and different to every disease will also be very informative to physicians in this year. If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said. So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Speaker Change: Terry large clinical study here to double the size of any other.

Speaker Change: Cardiomyopathy trial physicians view. This is a landmark study it's going to generate data. That's again as Brad said Prespecified secondary key secondary separates which will give us the data.

The effect size in the cardiovascular risk reduction in both of those different populations I also think.

Onaiza Cadoret-Manier: I also think, again, we're getting data on mild and moderate and more severe GTR and being able to again generate data and different to every disease will also be very informative to physicians in this year. If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said. So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Richard: Overall total population, but also the patients who are naive.

Again, where we're getting data on mild and moderate and more severe GTR and being able to again generate data differently. So very disease will also be very informative to physicians in this year.

Richard: Q, a stabilizer and then patients on top of the stabilizer. So from a promotional perspective, you can see that our sales representatives will be able to bring in both sets of data depending on the position and type of patient that they're seeing and as a result be able to communicate.

Their severe should <unk> trade at what point should I treat and those will be again very informative data sets that along with the MRI data that Brett said. So again landmark studies lots of data to go to market with that and we're really excited about the trial design that we have. Put into place and are looking for and waiting for data.

Onaiza Cadoret-Manier: If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said. So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Onaiza Cadoret-Manier: If there's severe should treat? At what point should I treat? and those will be again very informative data sets along with the MRI data set that Brett said.

Their severe should <unk> trade at what point should I treat and those will be again very informative data sets that along with the MRI data that Brett said.

Richard: The effect size in the cardiovascular risk reduction in both of those different populations.

So again landmark studies lots of data to go to market with that and we're really excited about the trial design that we have.

Onaiza Cadoret-Manier: So again landmark studies, lots of data to go to market with, and we're really excited about the trial design that we have put into place, and are looking for and waiting for data.

Richard: So think again, where we're getting data on mild and moderate and more severe GTR and being able to again generate data differently. So very disease will also be very informative to physicians and this year. If there's severe should <unk> trade at what point should I treat and those will be again very informative datasets that.

Put into place and are looking for and waiting for data.

David N. Lebowitz: Thanks for taking my questions.

Operator: Thanks, David Our next question comes from Joseph Stringer with Needham <unk> Company. Please go ahead.

Brett P. Monia: Thanks, David

Operator: Our next question comes from Joseph Stringer with Needham & Company. Please go ahead.

Along with MRI data that Brett said.

Joseph Stringer: Hi, Thanks for taking our questions, a couple on HAE and Donidalorsen. Can you just remind us what will be included in the data submission package for the NDA? Will the switch data be included in that? And then looking ahead to the data presentation this year on the on the Phase III OASIS trial, just let me frame expectations based on your market research. What metrics from prophylactic HAE therapy resonates most with patients, physicians and Payers?

Joseph Stringer: Hi, Thanks for taking our questions, a couple on HAE and Donidalorsen. Can you just remind us what will be included in the data submission package for the NDA?

Richard: So again landmark study lots of data to go to market with them Theyre.

Hey, Ian Danita Lorson can you just remind us what will be included in the.

Richard: Really excited about the trial design that we have.

Data submission package for the NDA will switch data would be included in that and then looking ahead to the date.

Richard: Put into place and are looking for and waiting for data.

Joseph Stringer: Will the switch data be included in that? And then looking ahead to the data presentation this year on the on the Phase III OASIS trial, just let me frame expectations based on your market research. What metrics from prophylactic HAE therapy resonates most with patients, physicians and Payers?

Speaker Change: Thanks for taking my questions.

Data presentation this year on the on the <unk>.

Speaker Change: Thanks, David Our next question comes from Joseph Stringer with Needham <unk> Company. Please go ahead.

Phase III.

Oasis trial.

Frame expectations based on your market research what metrics from.

Prophylactic agent therapy resonates most with.

Joseph Stringer: What metrics from prophylactic HAE therapy resonates most with patients, physicians and Payers?

Joseph Stringer: Hi, Thanks for taking our questions.

Joseph Stringer: <unk>.

Patients physicians and Payors.

Joseph Stringer: Okay, Ian Donnie Dolores and can you just remind us what will be included in the.

Richard Geary: Richard we can talk about the data submission and presentation, maybe you could talk a little bit about the what resonates with our drivers. Yeah sure so in the NDA. The switch data will definitely be included. So we will have oasis plus and the switch data as well as the registration study and importantly, the phase II study has been. Included and guided by FDA as a confirmatory study for us so it could also be. Implemented and we think the label would be strengthened by having all of the data the totality of data. So thats the NDA I think I caught everything and then as. As far as what resonates with patients I would say, it's really control. Whether they feel controlled by a prophylactic and of course. Tolerability. And we think that the once monthly and every two months. Painless small volume auto injector really makes a difference. As I always like to carry that forward.

Brett P. Monia: Richard you can talk about the data submission and presentation, maybe you could talk a little bit about the what resonates with our drivers.

Beth: Data submission package for the NDA well, let me switch data would be included in that and then looking ahead to the.

Yeah sure so in the NDA.

Beth: Data presentation this year.

Richard Geary: Yeah sure. So in the NDA the switch data will definitely be included, so we'll have oasis plus and the switch data as well as the registration study and importantly, the Phase II study has been included and guided by FDA as a confirmatory study for us, so it could also be implemented and we think the label would be strengthened by having all of the data, the totality of data. So thats the NDA, I think I caught everything, and then as far as what resonates with patients, I would say it's really control. Whether they feel controlled by a prophylactic, and of course tolerability, and we think that the once monthly and every two months of painless, small volume auto injector really makes a difference. As I always like to carry that forward.

Richard Geary: Yeah sure.

Beth: Ms III.

Richard Geary: So in the NDA the switch data will definitely be included, so we'll have oasis plus and the switch data as well as the registration study and importantly, the Phase II study has been included and guided by FDA as a confirmatory study for us, so it could also be implemented and we think the label would be strengthened by having all of the data, the totality of data. So thats the NDA, I think I caught everything, and then as far as what resonates with patients, I would say it's really control. Whether they feel controlled by a prophylactic, and of course tolerability, and we think that the once monthly and every two months of painless, small volume auto injector really makes a difference.

The switch data will definitely be included.

Beth: Oasis trial, just maybe frame expectations.

Beth: Patients based on your market research what metrics from.

So we will have oasis plus and the switch data as well as the registration study and importantly, the phase II study has been.

Beth: Prophylactic agent therapy resonates, most with patients physicians and Payors.

Beth: Richard we can talk about the data submission and presentation, maybe you could talk a little bit about the what resonates with prescribers.

Included and guided by FDA as a confirmatory study for us so it could also be.

Richard: Yeah sure so in the NDA.

Implemented and we think the label would be strengthened by having all of the data the totality of data.

The switch data will definitely be included.

Beth: So we will have oasis plus and the switch data as well as the registration study and importantly, the phase III study has been.

So thats the NDA I think I caught everything and then as.

Richard Geary: So thats the NDA, I think I caught everything, and then as far as what resonates with patients, I would say it's really control. Whether they feel controlled by a prophylactic, and of course tolerability, and we think that the once monthly and every two months of painless, small volume auto injector really makes a difference.

Richard Geary: So thats the NDA, I think I caught everything, and then as far as what resonates with patients, I would say it's really control.

As far as what resonates with patients I would say, it's really control.

Beth: Included and guided by FDA as a confirmatory study for us so it could also be.

Whether they feel controlled by a prophylactic and of course.

Richard Geary: Whether they feel controlled by a prophylactic, and of course tolerability, and we think that the once monthly and every two months of painless, small volume auto injector really makes a difference.

Tolerability.

And we think that the once monthly and every two months.

Beth: Implemented and we think the label would be strengthened by having all of the data the totality of data.

Painless small volume auto injector really makes a difference.

Richard Geary: Onaiza would you like to carry that forward? Sure. Thanks Richard. Yeah, I think the market research on this has been really consistent we've been looking at this market for a while ever since you know we started the phase II phase III. Thank God, you're the patients are really looking for that efficacy and tolerability and convenience in a single and a single drive and they just don't have that right now and that is the biggest unmet need and we do believe that the down at the lowest and data will actually provide that along with our positive topline results from the study. Hitting on a multitude of different efficacy parameters safety Tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here. And then complementary to that will be the switch data that you already asked about and matured addressed as well as the early data, which will continue to show the durability of the south so. I'm very excited. And look forward to sharing the data later on in the medical need. And when we presented our plans our plans to present payer. Joey later this year. We will include the not only the phase III data, but also the phase II open label extension data. Well as a really really good robust presentation on the switch study. Never seen there so stay tuned.

Brett P. Monia: Onaiza would you like to carry that forward?

Beth: So thats the NDA.

As I always like to carry that forward.

Richard Geary: Sure, thanks Richard. Yeah, I think the market research on this has been really consistent, we've been looking at this market for a while ever since you know we started the phase III. I think that here the patients are really looking for that efficacy and tolerability and convenience in a single drive, and they just don't have that right now, and that is the biggest unmet need. And we do believe that the Donidalorsen data will actually provide that, along with our positive top-line results from the OASIS study, hitting on a multitude of different efficacy parameters, safety, tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here. And then complementary to that will be the switch data that you already asked about and Richard addressed as well as the [Inaudible] data, which will continue to show the durability of [Inaudible] So I'm very excited and look forward to sharing the data later on in the medical need. And when we presented our plans our plans to present payer. Joey later this year. We will include the not only the phase III data, but also the phase II open label extension data. Well as a really really good robust presentation on the switch study. Never seen there so stay tuned.

I caught everything and then.

Sure. Thanks Richard. Yeah, I think the market research on this has been really consistent we've been looking at this market for a while ever since you know we started the phase II phase III. Thank God, you're the patients are really looking for that efficacy and tolerability and convenience in a single and a single drive and they just don't have that right now and that is the biggest unmet need and we do believe that the down at the lowest and data will actually provide that along with our positive topline results from the study. Hitting on a multitude of different efficacy parameters safety Tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here. And then complementary to that will be the switch data that you already asked about and matured addressed as well as the early data, which will continue to show the durability of the south so. I'm very excited. And look forward to sharing the data later on in the medical need. And when we presented our plans our plans to present payer. Joey later this year. We will include the not only the phase III data, but also the phase II open label extension data. Well as a really really good robust presentation on the switch study. Never seen there so stay tuned.

As far as what resonates with patients I would say, it's really control.

Yeah, I think the market research on this has been really consistent we've been looking at this market for a while ever since you know we started the phase II phase III.

Beth: Whether they feel controlled by a prophylactic kind of course.

Richard Geary: I think that here the patients are really looking for that efficacy and tolerability and convenience in a single drive, and they just don't have that right now, and that is the biggest unmet need. And we do believe that the Donidalorsen data will actually provide that, along with our positive top-line results from the OASIS study, hitting on a multitude of different efficacy parameters, safety, tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here. And then complementary to that will be the switch data that you already asked about and Richard addressed as well as the [Inaudible] data, which will continue to show the durability of [Inaudible] So I'm very excited and look forward to sharing the data later on in the medical [Inaudible].

<unk> Tolerability.

Thank God, you're the patients are really looking for that efficacy and tolerability and convenience in a single and a single drive and they just don't have that right now and that is the biggest unmet need and we do believe that the down at the lowest and data will actually provide that along with our positive topline results from the study.

Beth: And we think that the once monthly and every two months.

Beth: Painless small volume auto injector really makes a difference.

Richard Geary: And we do believe that the Donidalorsen data will actually provide that, along with our positive top-line results from the OASIS study, hitting on a multitude of different efficacy parameters, safety, tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here. And then complementary to that will be the switch data that you already asked about and Richard addressed as well as the [Inaudible] data, which will continue to show the durability of [Inaudible] So I'm very excited and look forward to sharing the data later on in the medical [Inaudible].

Speaker Change: I'd just like to carry that forward.

Sure. Thanks Richard.

Beth: Hey.

Speaker Change: Yeah, I think the market research on this has been really consistent we've been looking at this market for a while ever since.

Hitting on a multitude of different efficacy parameters safety Tolerability and self administered door volume injection, either every four or eight weeks, we can actually really change the treatment paradigm here.

Speaker Change: <unk> started the phase II phase III.

Speaker Change: I think that the patients are really looking for that efficacy and tolerability and convenience in a single and a single drive and they just don't have that right now and that is the biggest unmet need and we do believe that down at the lowest and data will actually provide that with a positive top line results from the study.

Richard Geary: And then complementary to that will be the switch data that you already asked about and Richard addressed as well as the [Inaudible] data, which will continue to show the durability of [Inaudible] So I'm very excited and look forward to sharing the data later on in the medical [Inaudible].

And then complementary to that will be the switch data that you already asked about and matured addressed as well as the early data, which will continue to show the durability of the south so.

Richard Geary: So I'm very excited and look forward to sharing the data later on in the medical [Inaudible].

I'm very excited.

And look forward to sharing the data later on in the medical need.

Richard Geary: And when we presented our plans our [Inaudible] Joey later this year, we will include the not only the Phase III data, but also the Phase II open label extension data, as well as a really really good robust presentation on the switch study, on everything that we're seeing there, so stay tuned.

Beth: <unk>.

Beth: Hitting on a multitude of different efficacy parameters safety Tolerability and self administered dose volume injection either every four or eight weeks, we can actually really change the treatment paradigm here.

And when we presented our plans our plans to present payer. Joey later this year. We will include the not only the phase III data, but also the phase II open label extension data.

Beth: And then complementary to that will be the switch data that you already asked about and Richard addressed as well as the early data, which will continue to show the durability of the south so.

Well as a really really good robust presentation on the switch study.

Never seen there so stay tuned.

Joseph Stringer: Great great. Thanks, so much for taking our questions.

Operator: Our next question comes from Kostas Biliouris with BMO capital markets. Please go ahead.

Speaker Change: I'm very excited.

And look forward to sharing the data later on in the medical need.

Speaker Change: And when we presented our plans our plans to present payer. Joey later this year. We will include the not only the phase III data, but also the phase II open label extension data.

Kostas Biliouris: Thanks for taking our question, a two part question from us on CARDIO-TTransform. Can you remind us how long is the minimum follow up for each patient in the study? And what would be the maximum follow up that you will have there in some patients? And the second part, how important do you think is the [Inaudible] that occurred between 30 and 36 months in this population? Thank you.

Kostas Biliouris: Thanks for taking our question, a two part question from us on CARDIO-TTransform. Can you remind us how long is the minimum follow up for each patient in the study?

Part question from Us on kind of your thoughts Paul can you remind us how long is the minimum follow up.

Beth: Well as a really really good robust presentation on the switch study.

For each patient in the study and what would be the maximum follow up that.

Kostas Biliouris: And what would be the maximum follow up that you will have there in some patients? And the second part, how important do you think is the [Inaudible] that occurred between 30 and 36 months in this population? Thank you.

Speaker Change: Never seen there so stay tuned.

You will have that in some patients and the second part how important do you think they're not that of events that occurred between 30 and 36 months in this population. Thank you.

Speaker Change: Great great. Thanks, so much for taking our questions.

Speaker Change: Our next question comes from Joseph <unk> with BMO capital markets. Please go ahead.

Thanks for taking our question.

So, this is a highly competitive space Kostas, we're not sharing follow up data but we expect when we read out the study of course we don't know, we're going to be reading out the study early or later anyway. But we're not sharing expectations on what percentage of patients would be on treatment for what length of time at this point, we will look forward to doing that when the study reads out. As far as number of events over over a few months, I mean Eugene, it's pretty negligible isn't it? Yeah, I would think so. In comparison as a proportion of the total. Yeah, Hi, I'm observing. Difficult to say exactly what that is but it's. Your question was related to just a couple of months, so I'm not I'm not sure what we have. Really good answer. It's probably very minimal we think we have the right trial design trial duration. And the size of the study costs. This. I'll take a few months is really going to matter that much. And we're very pleased that we made the decision we made several years ago to upsize our study.

Brett P. Monia: So, this is a highly competitive space Kostas, we're not sharing follow up data but we expect when we read out the study of course we don't know, we're going to be reading out the study early or later anyway. But we're not sharing expectations on what percentage of patients would be on treatment for what length of time at this point, we will look forward to doing that when the study reads out. As far as number of events over over a few months, I mean Eugene, it's pretty negligible isn't it?

Joseph Stringer: Two part question from us on that.

So.

Speaker Change: The attach falling can you remind us how long is the minimum follow up.

This is a highly competitive space cost as we're not sharing follow up data what we expect when we read out. The study of course, we don't know we're going to be reading out the study early or later anyway.

Beth: For each patient in the study and what would be the maximum follow up to that.

Beth: You will have that in some patients and the second part how important do you think is the number of events that occurred between Hep B and 36 months in this population. Thank you.

Brett P. Monia: But we're not sharing expectations on what percentage of patients would be on treatment for what length of time at this point, we will look forward to doing that when the study reads out. As far as number of events over over a few months, I mean Eugene, it's pretty negligible isn't it?

But we're not sharing.

Expectations for.

John.

What percentage of patients would be on treatment for them.

Length of time at this point, we will look forward to doing that when the study reads out.

Brett P. Monia: As far as number of events over over a few months, I mean Eugene, it's pretty negligible isn't it?

Beth: Okay.

As far as number of events over over a few months I mean Eugene.

Beth: So.

Beth: This is a highly competitive space cost as we're not sharing follow up data what we expect when we read out. The study of course, we don't know we're going to be reading out the study early or later anyway.

Pretty negligible isn't it.

Yeah, I would think so, in comparison, as a proportion of the total eye of observation it's difficult to say exactly what that is, but it's, your question was related to just a couple of months, so I'm not I'm not sure that we have really good answer. But it's probably very minimal. we think we have the right trial design trial duration. And the size of the study costs. This. I'll take a few months is really going to matter that much. And we're very pleased that we made the decision we made several years ago to upsize our study.

Eugene Schneider: Yeah, I would think so, in comparison, as a proportion of the total eye of observation it's difficult to say exactly what that is, but it's, your question was related to just a couple of months, so I'm not I'm not sure that we have really good answer. But it's probably very minimal.

Yeah, I would think so.

In comparison as a proportion of the total.

Yeah, Hi, I'm observing.

Difficult to say exactly what that is but it's.

Beth: But we're not sharing.

Beth: Expectations for.

Your question was related to just a couple of months, so I'm not I'm not sure what we have.

Beth: What percentage of patients would be on treatment for.

Eugene Schneider: But it's probably very minimal.

Really good answer.

Beth: Length of time at this point, we will look forward to doing that when the study reads out.

It's probably very minimal we think we have the right trial design trial duration.

Brett P. Monia: Yeah we think we have the right trial design, trial duration and the size of the study costs is we don't few months is really going to matter that much. And we're very pleased that we made the decision we made several years ago to upsize our study.

Brett P. Monia: Yeah we think we have the right trial design, trial duration and the size of the study costs is we don't few months is really going to matter that much.

Beth: As far as number of events over over a few months I mean Eugene.

And the size of the study costs. This.

Speaker Change: It's pretty negligible isn't it.

Speaker Change: Yeah.

I'll take a few months is really going to matter that much.

Brett P. Monia: And we're very pleased that we made the decision we made several years ago to upsize our study.

Beth: So.

Beth: Saracens as a proportion of the total.

And we're very pleased that we made the decision we made several years ago to upsize our study.

Beth: Of observation.

Beth: It's difficult to say exactly.

Kostas Biliouris: Very helpful. Thank you.

Beth: It is but it's.

Operator: Our next question comes from Yaron Werber with Cowen. Please go ahead.

Beth: Your question was related to just a couple of months.

Speaker Change: Not sure we have really good answers.

Yaron Benjamin Werber: Great, I got a couple of questions when you guys expanded, essentially doubled the study of CRDIO-TTransform, if I remember correctly I think one of the reasons was to also go and enroll in areas with Tafamidis wasn't necessarily available just remind us if thats correct? And if that's so, do you have a sense, are you able to enroll New York Heart I and II? A lot of those patients in any sense, what the overall dTafamidis dropping is going to be? and then just quickly on OASIS, can you give us any color on how the Phase II stacks relative to the Phase II in efficacy? Thank you.

Speaker Change: It's probably very minimal.

A questions when when you close them expanded essentially doubled the study of <unk>.

Speaker Change: We think we have the right trial design trial duration.

Cardio transform.

Beth: And the size of the study cost as we.

If I remember correctly I think one of the reasons was to also go and enrolled in areas with the feminist wasn't necessarily.

Beth: We don't think a few months is really in a matter that much.

Beth: And we're very pleased that we made the decision we made several years ago to upsize our study.

Available just remind us if thats correct.

Yaron Benjamin Werber: And if that's so, do you have a sense, are you able to enroll New York Heart I and II? A lot of those patients in any sense, what the overall Tafamidis dropping is going to be? And then just quickly on OASIS, can you give us any color on how the Phase II stacks relative to the Phase II in efficacy? Thank you.

If that's so do you have a sense are you able to enroll New York Heart, one and two a lot of those patients in any sense, what the overall defamatory dropping is going to be and then just quickly on oasis can you give us any color on how the face silver stacks relative to the phase II efficacy. Thank you.

Speaker Change: Very helpful. Thank you.

Speaker Change: Our next question comes from Yaron Werber with Cowen. Please go ahead.

Beth: Great.

Yaron Benjamin Werber: And then just quickly on OASIS, can you give us any color on how the Phase II stacks relative to the Phase II in efficacy? Thank you.

Yaron Benjamin Werber: Couple of questions when when you expanded essentially doubled the study of.

Yaron Benjamin Werber: Cardio transform if I remember correctly I think one of the reasons for US to also go in enrollment areas with a feminist wasn't necessarily.

Brett P. Monia: Thank you Aaron, so you remember correctly. The sites that we opened up initially in the CARDIO-TTransform study were largely US sites right? And as you know in the US there's a lot of Tafadimis usage. So we actually slowed down, stop enrollment at one point, a couple of years ago in the US except for sites that had the hereditary patients, that they were able to continue to bring in because we got a good percentage of those patients in the study too. And we emphasized we prioritized sites outside the US or anywhere really, if we could find sites in the US too that were [Inaudible] and available that worked, we have a good balance between patients that are naive on stabilizers, as well as on [Inaudible] We're also pleased with NHY class the proportion we haven in classes is I, II and III, I'm looking at Eugene he's nodding his head yes with that. we're not going to do comparisons VRM. <unk>. Our phase III and phase II data, we're going to look forward to sharing that data at. At a conference as I mentioned earlier around mid year. This year. So. Tuned for that. Yeah. And then maybe we have time for one more question.

Brett P. Monia: Thank you Aaron, so you remember correctly.

Thank you Aaron so.

Brett P. Monia: The sites that we opened up initially in the CARDIO-TTransform study were largely US sites right? And as you know in the US there's a lot of Tafadimis usage. So we actually slowed down, stop enrollment at one point, a couple of years ago in the US except for sites that had the hereditary patients, that they were able to continue to bring in because we got a good percentage of those patients in the study too. And we emphasized we prioritized sites outside the US or anywhere really, if we could find sites in the US too that were [Inaudible] and available that worked, we have a good balance between patients that are naive on stabilizers, as well as on [Inaudible] We're also pleased with NHY class the proportion we haven in classes is I, II and III, I'm looking at Eugene he's nodding his head yes with that.

Brett P. Monia: The sites that we opened up initially in the CARDIO-TTransform study were largely US sites right? And as you know in the US there's a lot of Tafadimis usage.

Speaker Change: Available just remind us if that's correct.

Ah you're you remember correctly.

Beth: If that's so do you have a sense are you able to enroll New York Heart, one and two a lot of those patients and any sense of what the overall defamatory dropping is going to be and then just quickly on oasis can you give us any color on how the phase three stacks relative to the phase II efficacy. Thank you.

Are the sites that we opened up initially in the cardio transform study were largely U S sites right.

Brett P. Monia: So we actually slowed down, stop enrollment at one point, a couple of years ago in the US except for sites that had the hereditary patients, that they were able to continue to bring in because we got a good percentage of those patients in the study too. And we emphasized we prioritized sites outside the US or anywhere really, if we could find sites in the US too that were [Inaudible] and available that worked, we have a good balance between patients that are naive on stabilizers, as well as on [Inaudible] We're also pleased with NHY class the proportion we haven in classes is I, II and III, I'm looking at Eugene he's nodding his head yes with that.

And as you know in the U S. There's a lot of the feminists usage so.

So we actually slowed down stop enrollment at one point.

A couple of years ago.

In the U S except for sites that had the hereditary.

Speaker Change: Thanks Darren.

Ah patients.

Speaker Change: So.

Patients that they were able to continue to bring in because we got a good percentage of those patients in the study too and we emphasize we prioritize sites outside the U S.

Beth: Ah you're you remember correctly.

Brett P. Monia: And we emphasized we prioritized sites outside the US or anywhere really, if we could find sites in the US too that were [Inaudible] and available that worked, we have a good balance between patients that are naive on stabilizers, as well as on [Inaudible] We're also pleased with NHY class the proportion we haven in classes is I, II and III, I'm looking at Eugene he's nodding his head yes with that.

Beth: Are the sites that we opened up initially in the cardio transform study were largely U S sites right.

Or anywhere really if we could find sites in the U S to the famous wasn't available networks, we have a good balance between Ah patients that are naive.

Beth: And as you know in the U S. There's a lot of the feminist usage so.

Beth: So we actually slowed down stop enrollment at one point.

Stabilizer as well as on.

Beth: A couple of years ago.

Beth: In the U S except for sites that had the hereditary.

We're also pleased with NH why any class the proportion we havent classes, one two and three I'm looking at your leisure.

Brett P. Monia: We're also pleased with NHY class the proportion we haven in classes is I, II and III, I'm looking at Eugene he's nodding his head yes with that.

Beth: Ah patients that they were able to continue to bring in because we got a good percentage of those patients in the study too and we emphasize we prioritize sites outside the U S.

Nodding his head yes.

Yeah.

Yes, we're not going to do comparisons VRM.

Eugene Schneider: Yeah we're not going to do comparisons on Phase III and Phase II data, we're going to look forward to sharing that data at a conference, as I mentioned earlier around mid year this year so stay tuned to that. And then maybe we have time for one more question.

Beth: Or anywhere really if we can find sites in the U S to that where parents wasn't available networks. We have a good balance between Ah patients that are naive.

<unk>.

Our phase III and phase II data, we're going to look forward to sharing that data at.

At a conference as I mentioned earlier around mid year.

Beth: Stabilizer as well as on.

This year.

So.

Beth: We're also pleased with NH why any class the proportion we havent classes, one two and three I'm looking at your niche.

Tuned for that.

Eugene Schneider: And then maybe we have time for one more question.

Yeah.

And then maybe we have time for one more question.

Operator: Our final question comes from Allison Bratzel with Piper Sandler. Please go ahead.

Beth: Yes.

Beth: With that.

Beth:

Speaker Change: Yes, we're not going to do comparisons Yaron.

Allison Bratzel: Hey, Thanks for fitting me in and taking my question, so just another one on Donidolarsen. Just on that switching study, can you remind us of the washout or [Inaudible] protocol prior of patients starting on Donidolarsen? And just how well does that represents a feasible real world switching strategy for patients currently on injectable or oral prophylaxis? And then just separately, from your conversations with the field, how oes Q8 week versus monthly dosing changed patients and physicians view of the drugs convenience profile? Thank you.

Allison Bratzel: Hey, Thanks for fitting me in and taking my question, so just another one on Donidolarsen.

Beth: Phase III and phase two data.

Beth: Are going to look forward to sharing that data at <unk>.

<unk> just switching study can you remind us of the washout are weaning protocol tired of patients starting on <unk> and just how well does that.

Allison Bratzel: Just on that switching study, can you remind us of the washout or [Inaudible] protocol prior of patients starting on Donidolarsen? And just how well does that represents a feasible real world switching strategy for patients currently on injectable or oral prophylaxis? And then just separately, from your conversations with the field, how oes Q8 week versus monthly dosing changed patients and physicians view of the drugs convenience profile? Thank you.

Allison Bratzel: Just on that switching study, can you remind us of the washout or [Inaudible] protocol prior of patients starting on Donidolarsen?

At a conference as I mentioned earlier around mid year.

Beth: This year.

Beth: So.

Stay tuned for that.

Beth: Yes.

Allison Bratzel: And just how well does that represents a feasible real world switching strategy for patients currently on injectable or oral prophylaxis? And then just separately, from your conversations with the field, how oes Q8 week versus monthly dosing changed patients and physicians view of the drugs convenience profile? Thank you.

Allison Bratzel: And just how well does that represents a feasible real world switching strategy for patients currently on injectable or oral prophylaxis?

Represent a feasible real world switching strategy for patients currently on injectable or oral prophylaxis.

Speaker Change: And then maybe we have time for one more question.

Speaker Change: Our final question comes from Allison <unk> with Piper Sandler. Please go ahead.

Then just separately from.

Allison Bratzel: And then just separately, from your conversations with the field, how oes Q8 week versus monthly dosing changed patients and physicians view of the drugs convenience profile? Thank you.

Allison: Hey, Thanks for fitting me in and taking taking my question. So just another one on <unk>. Just switching study can you remind us of the washout, meaning protocol prior to patients starting on <unk> and just how well does that.

From your conversations with the field.

Does Q eight week versus monthly dosing it changed.

Patients and physicians view of the trucks convenience profile. Thank you.

Yes, maybe I'll ask Onaiza to take that second one on Q4, Q8 week dosing, but Eugene, I don't think of this as a washout right, these patients are not being washed out, they would be at risk for attacks if they were being washed out. It's really just understand, just knowing what the half life of the drug is, how long it lasts, and we bring that, we wean them off of a prophylactic treatment and we win them onto Donidalorsen, which has a fast onset of action to begin with, and thereby we can win them off without putting them into any harm's way if you will. So there's not really a washout it's a [Inaudible] half life is different for oral versus injectable, so we'll publish all of that data in detail, the point of that study was really to provide some specifics around how these patients can be [Inaudible] And we're pleased that really we haven't had any gaps and protection I mean pay these patients are getting on very well as we transition them onto done divorce and so very. Very much looking forward to that. Our presentation. On Asia, what do you think about every four weeks and every eight week dosing from a competitive or a patient preference standpoint. Yeah, Allison I think here the physicians are saying listen. We wanted to in order to kind of for a prophylactic to really prevent the breakthrough attacks is for the patient to be compliant and they see a lot of switching off currently. Current therapies, where they're migrating to a less frequent dose, but then they start having attacks and they go back to a more frequent desk and they go back to less frequent guests. So they see that cycle and what they really want is the compliance and with the efficacy as well. So we really do think that this gives them another treatment paradigm shifts where you can. It started out at four week and potentially have patients who are stable and not having any attacks go through the eight week and keep them there for a long period of time, so the compliance drive the efficacy of the product.

Brett P. Monia: Yes, maybe I'll ask Onaiza to take that second one on Q4, Q8 week dosing, but Eugene, I don't think of this as a washout right, these patients are not being washed out, they would be at risk for attacks if they were being washed out. It's really just understand, just knowing what the half life of the drug is, how long it lasts, and we bring that, we wean them off of a prophylactic treatment and we win them onto Donidalorsen, which has a fast onset of action to begin with, and thereby we can win them off without putting them into any harm's way if you will. So there's not really a washout it's a [Inaudible] half life is different for oral versus injectable, so we'll publish all of that data in detail, the point of that study was really to provide some specifics around how these patients can be [Inaudible]

Beth: Representing a feasible real world switching strategy for patients currently on injectable or oral prophylaxis and then just separately.

I don't think of this as a washout right. These patients are not being washed out they would be at risk for the tax if they were being washed out it's really just understand just knowing what the half life of the drug is how long it lasts and we bring them, we wean them off of a prophylactic treatment and we win them onto dominant worsened, which has a fast onset of.

From your conversations with the field.

Brett P. Monia: It's really just understand, just knowing what the half life of the drug is, how long it lasts, and we bring that, we wean them off of a prophylactic treatment and we win them onto Donidalorsen, which has a fast onset of action to begin with, and thereby we can win them off without putting them into any harm's way if you will. So there's not really a washout it's a [Inaudible] half life is different for oral versus injectable, so we'll publish all of that data in detail, the point of that study was really to provide some specifics around how these patients can be [Inaudible]

Beth: Does Q eight week versus monthly dosing change.

Beth: Patients and physicians view of the trucks convenience profile. Thank you.

Action to begin with.

And thereby we can win them off without putting them into dania harm's way.

Speaker Change: Yes, maybe I'll ask <unk> to take that second one on Q4, Q eight week dosing, but Eugene.

If you will so there's not really a washout.

And that will be different for each prophylactic different for different prophylaxis with different categories plasma half life is different for oral versus injectable. So we'll publish all of that data in detail at the point of that study was really to provide some specific specifics around how these patients can be tricky.

Brett P. Monia: So there's not really a washout it's a [Inaudible] half life is different for oral versus injectable, so we'll publish all of that data in detail, the point of that study was really to provide some specifics around how these patients can be [Inaudible]

Unknown: And we're pleased that really we haven't had any gaps in protection, I mean pay these patients are getting on very well as we transition them onto Donidalorsen, so very much looking forward to that presentation. Onaiza what do you think about every four weeks and every eight week dosing from a competitive or a patient preference standpoint? Yeah, Allison I think here the physicians are saying listen. We wanted to in order to kind of for a prophylactic to really prevent the breakthrough attacks is for the patient to be compliant and they see a lot of switching off currently. Current therapies, where they're migrating to a less frequent dose, but then they start having attacks and they go back to a more frequent desk and they go back to less frequent guests. So they see that cycle and what they really want is the compliance and with the efficacy as well. So we really do think that this gives them another treatment paradigm shifts where you can. It started out at four week and potentially have patients who are stable and not having any attacks go through the eight week and keep them there for a long period of time, so the compliance drive the efficacy of the product.

And we're pleased that really we haven't had any gaps and protection I mean pay these patients are getting on very well as we transition them onto done divorce and so very.

Beth: Action to begin with.

Beth: And thereby we can win them off without putting them into harm's way.

Beth: If you will so there's not really a washout.

Beth: And that will be different for each prophylactic different for different prophylaxis.

Very much looking forward to that.

Unknown: Onaiza what do you think about every four weeks and every eight week dosing from a competitive or a patient preference standpoint?

Our presentation.

On Asia, what do you think about every four weeks and every eight week dosing from a competitive or a patient preference standpoint.

Beth: <unk> plasma half life is different for oral versus injectable. So we'll publish all of that data in detail at the point of that study was really to provide some specific specifics around how these patients could be transition. We're pleased that really we haven't had any gaps and protection I mean pay these patients are getting on very well.

Onaiza Cadoret-Manier: Yeah, Allison I think here the physicians are saying listen, we want in order to kind of, for a prophylactic to really prevent the breakthrough attacks is for the patient to be compliant, and they see a lot of switching off. Currently, current therapies where they're migrating to a less frequent dose, but then they start having attacks and they go back to a more frequent dose and they go back to less frequent guests. So they see that cycle and what they really want is the compliance, and with the efficacy as well, so we really do think that this gives them another treatment paradigm shifts where you can start on the 4 week and potentially have patients who are stable and not having any attacks, go through the eight week and keep them there for a long period of time. So the compliance drives the efficacy of the product.

Yeah, Allison I think here the physicians are saying listen.

We wanted to in order to kind of for a prophylactic to really prevent the breakthrough attacks is for the patient to be compliant and they see a lot of switching off currently.

Onaiza Cadoret-Manier: Currently, current therapies where they're migrating to a less frequent dose, but then they start having attacks and they go back to a more frequent dose and they go back to less frequent guests. So they see that cycle and what they really want is the compliance, and with the efficacy as well, so we really do think that this gives them another treatment paradigm shifts where you can start on the 4 week and potentially have patients who are stable and not having any attacks, go through the eight week and keep them there for a long period of time. So the compliance drives the efficacy of the product.

As we transition them onto done divorce and so.

Speaker Change: I'm very much looking forward to that that our presentation.

Current therapies, where they're migrating to a less frequent dose, but then they start having attacks and they go back to a more frequent desk and they go back to less frequent guests. So they see that cycle and what they really want is the compliance and with the efficacy as well. So we really do think that this gives them another treatment paradigm shifts where you can.

Speaker Change: On Asia, what do you think about every four weeks and every eight week dosing from a competitive or a patient.

Onaiza Cadoret-Manier: So they see that cycle and what they really want is the compliance, and with the efficacy as well. So we really do think that this gives them another treatment paradigm shifts where you can start on the 4 week and potentially have patients who are stable and not having any attacks, go through the eight week and keep them there for a long period of time. So the compliance drives the efficacy of the product.

Onaiza Cadoret-Manier: So they see that cycle and what they really want is the compliance, and with the efficacy as well.

Beth: Preference standpoint.

Yeah, Allison I think here the physicians are saying listen.

Onaiza Cadoret-Manier: So we really do think that this gives them another treatment paradigm shifts where you can start on the 4 week and potentially have patients who are stable and not having any attacks, go through the eight week and keep them there for a long period of time. So the compliance drives the efficacy of the product.

Speaker Change: We wanted to in order to kind of for a prophylactic to really prevent the breakthrough attacks is for the patient to be compliant and they see a lot of switching off currently with the current therapy, where they're migrating to a less frequent dose, but then they start having attacks and they got back to a more frequent desk and they go back to less frequent dose so.

It started out at four week and potentially have patients who are stable and not having any attacks go through the eight week and keep them there for a long period of time, so the compliance drive the efficacy of the product.

Onaiza Cadoret-Manier: So the compliance drives the efficacy of the product.

Okay.

Brett P. Monia: Well, thanks, Allison, thanks Onaiza, thanks everybody for participating for joining us on our call today. We really are excited about the great progress we've already made this year and everything ahead of us, it's really shaping up to be a. Really remarkable exciting 2024,

Brett P. Monia: Well, thanks, Allison, thanks Onaiza, thanks everybody for participating for joining us on our call today.

Beth: They see that cycle and what they really want is the compliance and with the efficacy as well. So we really do think that this gives them another treatment paradigm shifts where you can yes.

Brett P. Monia: We really are excited about the great progress we've already made this year and everything ahead of us, it's really shaping up to be a. Really remarkable exciting 2024,

Beth: Let's start on a four week and potentially have patients who are stable and not having any attacks go through the eight week and keep them there for a long period of time, so the compliance drives the efficacy of the product.

Really remarkable exciting 2024, and we're looking forward to sharing updates along the way until then have a great day everybody. Thanks.

Really remarkable exciting 2024,

Brett P. Monia: And we're looking forward to sharing updates along the way, until then have a great day everybody. Thanks.

Operator: Goodbye.

Brent: Okay.

Brent: Thanks, Alison Thanks, Vanessa thanks, everybody for participating for joining us on our call. Today, we really are excited about the great progress. We've already made this year and everything ahead of us, it's really shaping up to be.

Brent: Really remarkable exciting 2024, and we're looking forward to sharing updates along the way until then have a great day everybody. Thanks.

Brent: Goodbye.

Q4 2023 Ionis Pharmaceuticals Inc Earnings Call

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