Q1 2024 Alnylam Pharmaceuticals Inc Earnings Call

May 2, 2024

Engineered automated message advising your hand is raised to withdraw your question. Please press star. One again, please be advised that today's conference is being recorded I would now like to hand, the conference over to the company for their remarks. Please go ahead.

Operator: - You will then hear an automated message advising your hand is raised. To withdraw your question, please press Star 11 again. Please be advised that today's conference is being recorded, and I would now like to hand the conference over to the company for their remarks. Please go ahead.

Christine Regan Lindenboom: Good morning, I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer, Tolga Tanguler, Chief Commercial Officer, Pushkal Garg, Chief Medical Officer, and Jeff Poulton, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page of our website, investors.alnylam.com/events. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context, Tolga will provide an update on our global commercial progress, Pushkal will review pipeline updates and clinical progress, and Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions.

Christine Lindenboom: Good morning. I'm Christine Lindenboom, Senior Vice President of Investor Relations and Corporate Communications at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Medical Officer; and Jeff Poulton, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress. And Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions.

Good morning, I'm, Christine molybdenum senior Vice President of Investor Relations and corporate communications.

Christine Regan Lindenboom: With me today are Yvonne Greenstreet, Chief Executive Officer, Taylor, Chief Commercial Officer, Chris Carr, Chief Medical Officer, and Jeff Walton <unk> Chief Financial Officer.

Christine Regan Lindenboom: For those of you participating via conference call, the accompanying slides can be accessed by going to the events section of the investors page of our website, investors.alnylam.com slash events. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context, Tolga will provide an update on our global commercial progress, Pushkal will review pipeline updates and clinical progress, and Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions.

For those of you participating via conference call. The accompanying slides can be accessed by the events section of the investors page for that site and that first off.

Christine Lindenboom: During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress. And Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions.

<unk> dot com part of that.

Christine Regan Lindenboom: During today's call as outlined in slide two ivano offer introductory remarks and provide some general context total will provide an update on our global commercial progress push Goldberg, you pipeline updates and clinical progress and Jeff will review, our financials and guidance.

Christine Regan Lindenboom: A number of upcoming milestones before we open the call to your question.

Christine Regan Lindenboom: I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision under the Private Security Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to Yvonne.

Christine Lindenboom: I would like to remind you that this call will contain remarks concerning ALNYLAM's future expectations, plans, and prospects, which constitute forward-looking statements for the purposes of the Safe Harbor Provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to Yvonne. Yvonne?

Christine Regan Lindenboom: I would like to remind you that this call will contain our market comparing our balance sheet.

Christine Regan Lindenboom: Patients plans and prospects, which constitute forward looking statements for the purposes of the safe Harbor provision under the private Securities Litigation Reform Act of 995 actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including.

Christine Regan Lindenboom: And those discussed in our most recent periodic report on file with SEC. In addition, any forward looking statements represent our views only as the date of this recording and should not be relied upon as representing our views of any subsequent date.

Christine Lindenboom: In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements. With that, I'll turn the call over to Yvonne. Yvonne?

Christine Regan Lindenboom: We specifically disclaim any obligation to update such statements with that I'll turn the Colorado upon Avon.

Yvonne L. Greenstreet: Thanks, Christine, and thank you everyone for joining the call today. 2024 is off to a very strong start and shaping up to be an impactful year for Alnylam. Commercially, in the first quarter, we delivered robust product revenue growth for our four wholly-owned medicines, achieving $365 million in revenue, or 32% year-over-year growth, compared to Q1 2023. An important part of this was the continued momentum from our TTR franchise, which delivered 29% year-over-year growth versus Q1 2023. From a pipeline perspective, our ZILEBESIRAN Hypertension Program was a major highlight, with positive results presented from the KARDIA-2 Phase II study evaluating ZILEBESIRAN in combination with certain standard of care antihypertensives and the initiation of KARDIA-3. This program represents a significant opportunity to reimagine the treatment of hypertension and position Alnylam as the leader in treating cardiovascular disease. To that end, we're on the cusp of reporting top-line results from the Helios-B Phase III study of VUTRISIRAN in patients with TTR amyloidosis with cardiomyopathy. As we've highlighted previously, we have many reasons to be highly confident in a positive Helios-B outcome, including the encouraging data from the Apollo B study of VUTRISIRAN.

Yvonne Greenstreet: Thanks, Christine. And thank you, everyone, for joining the call today. 2024 is off to a very strong start and shaping up to be an impactful year for Alnylam. Commercially, in the first quarter, we delivered robust product revenue growth for our four wholly-owned medicines, achieving $365 million in revenue, or 32% year-over-year growth compared to Q1 2023. An important part of this was the continued momentum from our TTR franchise, which delivered 29% year-over-year growth versus Q1 2023. From a pipeline perspective, our zilebesiran hypertension program was a major highlight, with positive results presented from the KARDIA-2 Phase II study evaluating zilebesiran in combination with certain standard-of-care antihypertensives and the initiation of KARDIA-3. This program represents a significant opportunity to reimagine the treatment of hypertension and to position Alnylam as a leader in treating cardiovascular disease.

Colorado: Thanks, Christine and thank you everyone for joining the call today 2024 is off to a very strong start and shaping up to be an impactful year from items.

Yvonne L. Greenstreet: Commercially, in the first quarter, we delivered robust product revenue growth for our four wholly-owned medicines, achieving $365 million in revenue, or 32% year-over-year growth, compared to Q1 2023. An important part of this was the continued momentum from our TTR franchise, which delivered 29% year-over-year growth versus Q1 2023. From a pipeline perspective, our Zarbisaran Hypertension Program was a major highlight, with positive results presented from the CARDIA 2 Phase 2 study evaluating Zarbisaran in combination with certain standard of care antihypertensives and the initiation of CARDIA 3. This program represents a significant opportunity to reimagine the treatment of hypertension and position Alnylam as the leader in treating cardiovascular disease. To that end, we're on the cusp of reporting top-line results from the Helios B Phase III study of Lutriceram in patients with TTR amyloidosis with cardiomyopathy. As we've highlighted previously, we have many reasons to be highly confident in a positive HDS-B outcome, including the encouraging data from the Apollo B study of T-cells.

Speaker Change: Commercially in the first quarter, we delivered robust product revenue, Greg Roth for wholly owned medicines, achieving $365 million in revenue or 32% year over year growth compared to Q1 2020 create unimpeded.

Colorado: An important part of this was the continued momentum from our TTS franchise, which delivered 29% year over year growth versus Q1 2023.

Yvonne Greenstreet: From a pipeline perspective, our zilebesiran hypertension program was a major highlight, with positive results presented from the KARDIA-2 Phase II study evaluating zilebesiran in combination with certain standard-of-care antihypertensives and the initiation of KARDIA-3. This program represents a significant opportunity to reimagine the treatment of hypertension and to position Alnylam as a leader in treating cardiovascular disease.

Colorado: From a pipeline perspective as a booster on hypertension program was a major highlight with published the results presented from the cardiac two phase III study.

Colorado: Valuation southeast around in combination with standard of care anti hypertensive and the initiation of cardio suite.

Yvonne L. Greenstreet: This program represents a significant opportunity to reimagine the treatment of hypertension and position Alnylam as the leader in treating cardiovascular disease. To that end, we're on the cusp of reporting top-line results from the Helios B Phase III study of Lutriceram in patients with TTR amyloidosis with cardiomyopathy. As we've highlighted previously, we have many reasons to be highly confident in a positive HDS-B outcome, including the encouraging data from the Apollo B study of T-cells.

Colorado: This program represents a significant opportunity to re imagine the treatment of hypertension and competition on items as the leader in treating cardiovascular disease.

Yvonne Greenstreet: To that end, we're on the cusp of reporting top-line results from the HELIOS-B phase III study of vutrisiran in patients with TTR amyloidosis with cardiomyopathy. As we've highlighted previously, we have many reasons to be highly confident in a positive HELIOS-B outcome, including the encouraging data from the APOLLO-B study of vutrisiran. We remain on track to report top-line data from HELIOS-B in late June or early July, which, if positive, is expected to support the filing of an sNDA by the end of this year. With this progress, we continue to advance our Alnylam P5x25 goals, making Alnylam a top-tier biotech, developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases driven by a high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results.

Colorado: Does that trend we're on the cusp of reporting top line results from the Helios B phase III study of <unk> in patients with <unk> amyloidosis with cardiomyopathy.

Colorado: As we've highlighted previously we have many reasons to be highly confident in a positive previous be outcomes, including the encouraging data from the Apollo B study are pretty strong.

Yvonne L. Greenstreet: And we remain on track to report top-line data from Helios-B in late June or early July, which, if positive, is expected to support the filing of an SNDA by the end of this year. With this progress, we continue to advance our Alnylam P5x25 goals, making Alnylam a top-tier biotech, developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases, driven by a high-yielding pipeline of first- and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results. With that, let me now turn the call over to Tolga, who'll review our commercial performance. , thanks, Yvonne, and good morning, everyone. Q1 was another strong quarter for our commercial portfolio, delivering $365 million combined net product revenues as we continue our growth momentum with our rare and TTR franchises. Our overall portfolio grew by 32% in the first quarter versus the prior year as we continue to steadily increase the number of patients on our therapy. First, let me summarize our first quarter TTR results.

Colorado: And we remain on track to report top line data competed speak in late June or early July which if positive is expected to support the filing of an NDA by the end of this year.

Yvonne Greenstreet: With this progress, we continue to advance our Alnylam P5x25 goals, making Alnylam a top-tier biotech, developing and commercializing transformative medicines for patients around the world with rare and prevalent diseases driven by a high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine, all while delivering exceptional financial results. With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Colorado: With this progress we continue to advance our nylon pizza, Chris by 'twenty five goals Mickey on item, a top tier biotech developing and commercializing transformative medicines for patients around the world with Ram and prevalent diseases, driven by our high yielding pipeline of SaaS and our best in class product candidate.

Colorado: Tomorrow organic product engine, all while delivering exceptional financial results with that let me now turn the call over to Targa.

Yvonne Greenstreet: With that, let me now turn the call over to Tolga for a review of our commercial performance. Tolga?

Tolga Tanguler: Thanks, Yvonne, and good morning, everyone. Q1 was another strong quarter for our commercial portfolio, delivering $365 million combined net product revenues, as we continue our growth momentum with our rare and TTR franchises. Our overall portfolio grew by 32% in the first quarter versus the prior year, as we continue to steadily increase the number of patients on our therapies. First, let me summarize our first quarter TTR results. The TTR franchise achieved $264 million in global net product revenues, representing a 4% increase, compared with the fourth quarter of '23, and 29% growth compared with the first quarter of '23. Our U.S. combined TTR sales of ONPATTRO and AMVUTTRA increased by 3% compared with the fourth quarter of '23, and a robust 35% year-over-year, driven by continued strong AMVUTTRA uptake. The U.S.

Targa: A few of our commercial performance.

Tolga Tanguler: Thanks, Yvonne. Good morning, everyone. Q1 was another strong quarter for our commercial portfolio, delivering $365 million combined net product revenues as we continue our growth momentum with our rare and TTR franchises. Our overall portfolio grew by 32% in the first quarter versus prior year as we continue to steadily increase the number of patients on our therapies. First, let me summarize our first quarter TTR results. The TTR franchise achieved $264 million in global net product revenues, representing a 4% increase compared with the fourth quarter of 2023 and 29% growth compared with the first quarter of 2023. Our US combined TTR sales of ONPATTRO and AMVUTTRA increased by 3% compared with the fourth quarter of 2023 and a robust 35% year-over-year driven by continued strong AMVUTTRA uptake.

Colorado: <unk>.

Targa: Thanks, Ivan and good morning, everyone.

Tolga Tanguler: Q1 was another strong quarter for our commercial portfolio, delivering $365 million combined net product revenues as we continue our growth momentum with our rare and TTR franchises. Our overall portfolio grew by 32% in the first quarter versus the prior year as we continue to steadily increase the number of patients on our therapy. First, let me summarize our first quarter TTR results.

Targa: Q1 was another strong quarter for our commercial portfolio delivering $365 million combined net product revenues.

Targa: We continue our growth momentum with our rare NTT our franchises.

Speaker Change: Our overall portfolio grew by 32% in the first quarter versus prior year as you continue to steadily increase the number of patients on our therapies.

Tolga Tanguler: First, let me summarize our first quarter TTR results. The TTR franchise achieved $264 million in global net product revenues, representing a 4% increase compared with the fourth quarter of 2023 and 29% growth compared with the first quarter of 2023. Our US combined TTR sales of ONPATTRO and AMVUTTRA increased by 3% compared with the fourth quarter of 2023 and a robust 35% year-over-year driven by continued strong AMVUTTRA uptake.

Tolga Tanguler: The TTR franchise achieved $264 million in global net product revenues, representing a 4% increase compared with the fourth quarter of 2023 and 29% growth compared with the first quarter of 2020. Our U.S. combined TTR sales of Ompatra and Ambutra increased by 3% compared with the fourth quarter of 2023 and a robust 35% year-over-year, driven by continued strong Ambutra uptake. The U.S.

Speaker Change: First let me summarize our first quarter <unk> results.

Speaker Change: The TCR franchise achieved $264 million in global net product revenues.

Speaker Change: Presenting a 4% increase compared with the fourth quarter of 23, and 29% growth compared with the first quarter of 'twenty three.

Speaker Change: Our U S. Combined GTR sales of <unk> increased by 3% compared with the fourth quarter of 'twenty, three and a robust 35% year over year driven by continued strong <unk> uptake.

Tolga Tanguler: The US year-over-year growth was primarily driven by the following: a 39% increase in total demand versus Q1 2023, which was driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that switched to AMVUTTRA. Inventory dynamics decreased reported growth by approximately 4% as both ONPATTRO and AMVUTTRA inventory in the channel decreased in the quarter, another favorable sign of robust Q1 demand. Now, let me turn to our international markets, where TTR franchise growth increased by 5% compared with Q4 2023 and 23% year-over-year. The year-over-year growth was primarily driven by increased demand for AMVUTTRA as new patient adds remained robust, including launches at the end of last year in Spain, Italy, and Sweden, and continued strong ONPATTRO performance in a few markets where AMVUTTRA is not yet available.

Speaker Change: The U S year over year growth was primarily driven by the following.

Tolga Tanguler: The U.S. year-over-year growth was primarily driven by the following: 39% increase in total demand versus the first quarter of '23, which was driven by the strength of ongoing AMVUTTRA patient uptake, more than offsetting the decrease in patients on ONPATTRO that switched to AMVUTTRA. Inventory dynamics decreased reported growth by approximately 4% as both ONPATTRO and AMVUTTRA inventory in the channel decreased in the quarter, another favorable sign of robust Q1 demand. Now, let me turn to our international markets, where TTR franchise growth increased by 5% compared with the fourth quarter of '23 and 23% year-over-year. The year-over-year growth was primarily driven by increased demand for AMVUTTRA, as new patient ads remained robust, including launches at the end of last year in Spain, Italy, and Sweden, and continued strong ONPETTRO performance in a few markets where AMVUTTRA is not yet available. As a reminder, AMVUTTRA is now reimbursed in all major international markets. Demand growth in international markets was partially offset by lower pricing in certain countries, primarily in Germany, as the end of the initial six-month free pricing period for AMVUTTRA occurred in Q2 2023, as previously reported.

Tolga Tanguler: A 39% increase in total demand versus the first quarter of 2020, which was driven by the strength of ongoing amutrapation, more than offsetting the decrease in patients on Ompatra that switched to Omvutra. Inventory Dynamics, decreased reported growth by approximately 4% as both Ompatra and Amutra inventory in the channel decreased in the quarter, another favorable sign of robust Q1 demand. Now let me turn to our international markets, where TTR franchise growth increased by 5% compared with the fourth quarter of 23 and 23% year over year. The year-over-year growth was primarily driven by increased demand for Ombutra, as new patient ads remained robust, including launches at the end of last year in Spain, Italy, and Sweden, and continued strong Onpetra performance in a few markets where Almutra is not yet available. As a reminder, Alutra is now reimbursed in all major international markets. Demand growth in international markets was partially offset by lower pricing in certain countries, primarily in Germany.

Speaker Change: 39% increase in total demand versus the first quarter of 'twenty three.

Speaker Change: Which was driven by the strength of ongoing <unk> patient uptake.

Speaker Change: More than offsetting the decrease in patients on all Patrick that switch to on road truck.

Speaker Change: Inventory dynamics decreased reported growth by approximately 4% as both on Petro and I would say inventory in the channel decreased in the quarter and other favorable sign of robust Q1 demand.

Tolga Tanguler: Now, let me turn to our international markets, where TTR franchise growth increased by 5% compared with Q4 2023 and 23% year-over-year. The year-over-year growth was primarily driven by increased demand for AMVUTTRA as new patient adds remained robust, including launches at the end of last year in Spain, Italy, and Sweden, and continued strong ONPATTRO performance in a few markets where AMVUTTRA is not yet available.

Speaker Change: Now, let me turn to our international markets, where GTR franchise growth increased by 5% compared with the fourth quarter of 'twenty three.

Speaker Change: 23% year over year.

Tolga Tanguler: The year-over-year growth was primarily driven by increased demand for Ombutra, as new patient ads remained robust, including launches at the end of last year in Spain, Italy, and Sweden, and continued strong Onpetra performance in a few markets where Almutra is not yet available. As a reminder, Alutra is now reimbursed in all major international markets. Demand growth in international markets was partially offset by lower pricing in certain countries, primarily in Germany.

Speaker Change: The year over year growth was primarily driven by increased demand for on road truck as new patient adds remained robust.

Speaker Change: <unk> launches at the end of last year in Spain, Italy, and Sweden.

Speaker Change: And continued strong on Petro performance in a few markets, where I would say is not yet available.

Tolga Tanguler: As a reminder, AMVUTTRA is now reimbursed in all major international markets. Demand growth in international markets was partially offset by lower pricing in certain countries, primarily in Germany, as the end of the initial six-month free pricing period for AMVUTTRA occurred in Q2 2023, as previously reported. I would also like to provide additional color on the continued growth momentum of our TTR franchise in the US. We remain confident and very pleased with the impact we're seeing from AMVUTTRA in expanding the opportunity for our TTR franchise, as reflected by the robust 35% year-over-year growth that we achieved in Q1 2024. This is a growing category with significant unmet needs remaining. Importantly, leading market indicators remain aligned with our demand growth, galvanizing AMVUTTRA's market leadership, both in patients and healthcare providers, for the treatment of patients with hATTR amyloidosis with polyneuropathy.

Speaker Change: As a reminder.

Speaker Change: <unk> is now reimbursed in all major international markets.

Speaker Change: Demand growth in international markets was partially offset by lower pricing in certain countries.

Tolga Tanguler: As the end of the initial six-month free pricing period for AMVUTTRA occurred in Q2 2023, as previously reported. I would also like to provide additional color on the continued growth momentum of our TTR franchise in the U.S. We remain confident and very pleased with the impact we're seeing from Almutra in expanding the opportunity for our TTR franchise, as reflected by the robot's 35% year-over-year growth that we achieved in the first quarter of 2024. This is a growing category with significant unmet needs remaining. Importantly, leading market indicators remain aligned with our demand growth, galvanizing Amutra's market leadership, both in patients and healthcare providers. Here are some key highlights.

Tolga Tanguler: As the end of the initial six-month free pricing period for AMVUTTRA occurred in Q2 2023, as previously reported.

Speaker Change: Primarily in Germany.

Speaker Change: At the end of the initial six month free pricing period for ultra occurred in Q2 2023 as previously reported.

Tolga Tanguler: I would also like to provide additional color on the continued growth momentum of our TTR franchise in the U.S. We remain confident and very pleased with the impact we're seeing from AMVUTTRA in expanding the opportunity for our TTR franchise, as reflected by the robust 35% year-over-year growth that we achieved in the first quarter of 2024. This is a growing category with significant unmet needs remaining. Importantly, leading market indicators remain aligned with our demand growth, galvanizing AMVUTTRA's market leadership, both in patients and healthcare providers for the treatment of patients with HATTR Amyloidosis with polyneuropathy. Here are some key highlights: More physicians are prescribing AMVUTTRA, evidenced by the more than 50% year-over-year growth in our prescriber base. We strongly believe that HATTRPN is a condition that requires high engagement between healthcare professionals and their patients. AMVUTTRA offers the flexibility for this engagement to happen at the hospital, at an outpatient center, or for many patients at home. In alignment with our patient access philosophy, we continue to demonstrate seamless access to AMVUTTRA with more than 99% of our patients having confirmed access and approximately 70% of patients having zero out-of-pocket costs. Last, we are monitoring its use and compliance metrics, which show that more than 95% of our patients remain on therapy and comply with AMVUTTRA's quarterly dosing regimen.

Speaker Change: I would also like to provide additional color on the continued growth momentum.

Speaker Change: GTR franchise in the U S.

Tolga Tanguler: We remain confident and very pleased with the impact we're seeing from AMVUTTRA in expanding the opportunity for our TTR franchise, as reflected by the robust 35% year-over-year growth that we achieved in Q1 2024. This is a growing category with significant unmet needs remaining. Importantly, leading market indicators remain aligned with our demand growth, galvanizing AMVUTTRA's market leadership, both in patients and healthcare providers, for the treatment of patients with hATTR amyloidosis with polyneuropathy.

Speaker Change: We remain confident and very pleased with the impact we're seeing from Australia, expanding the opportunity for our TTS franchise is reflected by the robust 35% year over year growth that we achieved in the first quarter of 2024.

Tolga Tanguler: This is a growing category with significant unmet needs remaining. Importantly, leading market indicators remain aligned with our demand growth, galvanizing Amutra's market leadership, both in patients and healthcare providers. Here are some key highlights.

Speaker Change: This is a growing category with significant unmet needs remaining.

Speaker Change: Importantly, leading market indicators remain aligned with our demand growth galvanizing I wont say its market leadership, both in patient and health care providers for the treatment of patients with <unk> amyloidosis with Polyneuropathy.

Tolga Tanguler: Here are some key highlights. More physicians are prescribing AMVUTTRA, evidenced by the more than 50% year-over-year growth in our prescriber base. We strongly believe hATTR-PN is a condition that requires high engagement between healthcare professionals and their patients. AMVUTTRA offers the flexibility for this engagement to happen at the hospital, at an outpatient center, or for many patients at home. In alignment with our patient access philosophy, we continue to demonstrate seamless access to AMVUTTRA, with more than 99% of our patients having confirmed access and approximately 70% of patients having zero out-of-pocket costs. Last, we are monitoring adherence and compliance metrics, which show that more than 95% of our patients remain on therapy and comply with AMVUTTRA's quarterly dosing regimen.

Speaker Change: Here are some key highlights.

Tolga Tanguler: More physicians are prescribing Amutra, evidenced by the more than 50% year-over-year growth in our prescriber bill. We strongly believe that HATTRPN is a condition that requires high engagement between healthcare professionals and their patients. Amutra offers the flexibility for this engagement to happen at the hospital, at an outpatient center, or, for many patients, at home. In alignment with our patient access philosophy, we continue to demonstrate seamless access to Al Mutrah with more than 99% of our patients having confirmed access and approximately 70% of patients having zero out-of-pocket calls. Last, we are monitoring its use and compliance, which shows that more than 95% of our patients remain on therapy and comply with our MUTRA's quarterly dosing regimen.

Speaker Change: More physicians are prescribing on whatsapp, evidenced by the more than 50% year over year growth in our prescriber base.

Speaker Change: We strongly believe <unk>.

Speaker Change: <unk> is a condition that requires high engagement between healthcare professionals and their patients.

Speaker Change: <unk> offers the flexibility afforded to engagement to happen at the <unk>.

Speaker Change: Hospital, as an outpatient center or for many patients at home.

Tolga Tanguler: In alignment with our patient access philosophy, we continue to demonstrate seamless access to AMVUTTRA, with more than 99% of our patients having confirmed access and approximately 70% of patients having zero out-of-pocket costs. Last, we are monitoring adherence and compliance metrics, which show that more than 95% of our patients remain on therapy and comply with AMVUTTRA's quarterly dosing regimen.

Speaker Change: In alignment with our patient access philosophy, we continue to demonstrate seamless access to on what's wrong with more than 99% of our patients having confirmed active and approximately 70% of patients having zero out of pocket costs.

Speaker Change: Last we are monitoring is serious and compliance metrics, which show that more than 95% of <unk> patients remain on therapy and comply with <unk> quarterly dosing regimen.

Tolga Tanguler: As we have previously communicated, we believe that approximately 80% of the 25,000 to 30,000 patients with HATTR polyneuropathy globally are undiagnosed or are untreated, which represents a significant opportunity to find and treat more patients. Given that HATTR polyneuropathy is also rapidly progressing, we believe patients and physicians stand to benefit most from a therapy that rapidly knocks down the disease-causing protein with unparalleled speed, depth, and duration. AMVUTTRA offers these benefits in a single quarterly dose and has the ability to reverse the polyneuropathy manifestations of HARTTR amyloidosis, combined with a favorable access track record and well-established safety profile. With this foundation, we are in a position of strength, as we embark on a branded patient awareness campaign to raise patient awareness of the disease, and the benefits of AMVUTTRA, and its unique rapid knockdown profile. Shifting to our rare franchise and the performance of GIVLAARI and OXLUMO, our global rare franchise delivered $101 million in combined global net product revenue during the first quarter, representing a solid 9% increase compared with the fourth quarter of 2023, and an impressive 40% growth compared with the first quarter of 2023.

Tolga Tanguler: As we have previously communicated, we believe approximately 80% of the 25,000 to 30,000 patients with hATTR polyneuropathy globally are undiagnosed or untreated, which represents a significant opportunity to find and treat more patients. Given that hATTR polyneuropathy is also a rapidly progressing disease, we believe patients and physicians stand to benefit most from a therapy that rapidly knocks down the disease-causing protein with unparalleled speed, depth, and duration. AMVUTTRA offers these benefits in a single quarterly dose and has the ability to reverse the polyneuropathy manifestations of hATTR amyloidosis, combined with a favorable access track record and well-established safety profile. With this foundation, we are in a position of strength as we embark on a branded patient awareness campaign to raise patient awareness of the disease and the benefits of AMVUTTRA and its unique rapid knockdown profile.

Speaker Change: As we have previously communicated we believe that approximately 80% of the 25% to 30000 patients with <unk> polyneuropathy globally are undiagnosed or untreated.

Speaker Change: Which represents a significant opportunity to find and treat more patients.

Speaker Change: Given that <unk> Polyneuropathy is also rapidly progressing disease.

Speaker Change: We believe patients and physicians.

Speaker Change: <unk> to benefit most from a therapy that rapidly knocks down the disease, causing protein with unparalleled speed depth and duration.

Tolga Tanguler: AMVUTTRA offers these benefits in a single quarterly dose and has the ability to reverse the polyneuropathy manifestations of hATTR amyloidosis, combined with a favorable access track record and well-established safety profile. With this foundation, we are in a position of strength as we embark on a branded patient awareness campaign to raise patient awareness of the disease and the benefits of AMVUTTRA and its unique rapid knockdown profile.

Speaker Change: Also offers these benefits in a single quarterly dose and has the ability to reverse polyneuropathy manifestations of Hei GTR amyloidosis combined with a favorable access track record and well established safety profile.

Tolga Tanguler: With this foundation, we are in a position of strength as we embark on a branded patient awareness campaign to raise patient awareness of the disease and the benefits of Amutra and its unique rapid knockdown profile. Shifting to our rare franchise and the performance of Givlar and OpsLuma, our global rare franchise delivered $101 million in combined global net product revenue during the first quarter, representing a solid 9% increase compared with the fourth quarter of 2023 and an impressive 40% growth compared with the first quarter of 2023.

Speaker Change: With this foundation, we are in a position of strength as we embarked on a branded patient awareness campaign.

Speaker Change: <unk> patient awareness of the disease and the benefits of <unk> and its unique rapid knockdown profile.

Tolga Tanguler: Shifting to our rare franchise and the performance of GIVLAARI, OXLUMO, our global rare franchise delivered $101 million in combined global net product revenue during Q1, representing a solid 9% increase compared with Q4 2023 and an impressive 40% growth compared with Q1 2023. For GIVLAARI, revenues increased by 21% in Q1 compared to the same period last year, with the following regional dynamics: a 28% increase in the US, primarily driven by growth in new patients on therapy, with modest additional upside from favorable gross-to-net changes. 10% growth in the rest of the world, primarily driven by demand growth, which was partially offset by an increase in gross-to-net deductions year-over-year.

Speaker Change: Okay.

Speaker Change: Shifting to our rare franchise and the performance of <unk> silver.

Speaker Change: Our global rare franchise delivered $101 million in combined global net product revenue during the first quarter.

Speaker Change: Representing a solid 9% increase compared with the fourth quarter of 2023, and an impressive 40% growth compared with the first quarter of 2023.

Tolga Tanguler: For GIVLAARI, revenues increased by 21% in Q1 compared to the same period last year, with the following regional dynamics: a 28% increase in the US, primarily driven by growth in new patients on therapy, with modest additional upside from favorable gross-to-net changes. 10% growth in the rest of the world, primarily driven by demand growth, which was partially offset by an increase in gross-to-net deductions year-over-year.

Tolga Tanguler: For GIVLAARI, revenues increased by 21% in Q1 compared to the same period last year, with the following regional dynamics: A 28% increase in the US, primarily driven by growth in new patients on therapy, with modest additional upside from favorable gross to net changes. 10% growth in the rest of the world, primarily driven by demand growth, which was partially offset by an increase in gross net deductions year-over-year. For OXLUMO, we delivered a robust 77% increase in revenues year-over-year, which was driven by the following regional dynamics: A 47% increase in the U.S., primarily driven by demand growth with additional favorability from lower gross-to-net deductions. A robust 94% growth from rest of world markets driven by increased demand, a favorable growth to net adjustment, and the timing of orders in partner markets. Given the nature and magnitude of the rest of the world's Q1 growth to net and partner market timing benefits, we anticipate that we will see a reduction in global sales for OXLUMO in Q2. In conclusion, we are very pleased with our continuous growth momentum, delivering a robust 32% revenue growth versus the prior year that positions us well to reach our 2024 Net Product Revenue Guidance. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress.

Speaker Change: Forgive Laurie revenues increased by 21% in Q1 compared to the same period last year.

Speaker Change: With the following regional dynamics at.

Speaker Change: At 28% increase in the U S, primarily driven by growth in new patients on therapy with modest additional upside from favorable gross to net changes.

Speaker Change: 10% growth in rest of the world, primarily driven by demand growth, which was partially offset by an increase in gross to net deductions year over year.

Tolga Tanguler: For OXLUMO, we delivered a robust 77% increase in revenues year-over-year, which was driven by the following regional dynamics: a 47% increase in the US, primarily driven by demand growth with additional favorability from lower gross-to-net deductions; a robust 94% growth from the rest of the world markets, driven by increased demand, a favorable gross-to-net adjustment, and the timing of orders in partner markets. Given the nature and magnitude of the rest of the world's Q1 gross-to-net and partner market timing benefits, we anticipate that we will see a reduction in global sales for OXLUMO in Q2. In conclusion, we are very pleased with our continued growth momentum, delivering a robust 32% revenue growth versus prior year that positions us well to reach our 2024 net product revenue guidance. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

Speaker Change: For <unk>, we delivered a robust 77% increase in revenues year over year, which was driven by the following regional dynamics.

Tolga Tanguler: A 47% increase in the U.S., primarily driven by demand growth with additional favorability from lower gross-to-net deductions. A robust 94% growth from rest of world markets driven by increased demand, a favorable growth to net adjustment, and the timing of orders in partner markets. Given the nature and magnitude of the rest of the world's Q1 growth to net and partner market timing benefits. We anticipate that we will see a reduction in global sales for Oxnovor in Q2.

Speaker Change: At 47% increase in the U S, primarily driven by demand growth with additional favorability from lower gross to net deductions.

Speaker Change: A robust 90, 494% growth from rest of world markets, driven by increased demand a favorable gross to net adjustment and the timing of orders and partner markets.

Tolga Tanguler: Given the nature and magnitude of the rest of the world's Q1 gross-to-net and partner market timing benefits, we anticipate that we will see a reduction in global sales for OXLUMO in Q2. In conclusion, we are very pleased with our continued growth momentum, delivering a robust 32% revenue growth versus prior year that positions us well to reach our 2024 net product revenue guidance. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline progress. Pushkal?

Speaker Change: Given the nature and magnitude of the rest of World Q1, gross to net and partner market timing benefits. We anticipate that we will see a reduction in global sales for <unk> in Q2.

Tolga Tanguler: In conclusion, we are very pleased with our continuous growth momentum, delivering a robust 32% revenue growth versus the prior year that positions us well to reach our 2024 Net Product Revenue Guidelines. With that, I will now turn it over to Pushkal to review our recent R&D and pipeline program.

Speaker Change: In conclusion, we are very pleased with our continued growth momentum delivering a robust 32% revenue growth versus prior year that positions us well to reach our 2024 net product revenue guidance.

Speaker Change: With that I will now turn it over to push call to review, our recent R&D and pipeline progress.

Pushkal Garg: Thanks, Tolga. Good morning, everyone. Let's begin with our TTR franchise, where we eagerly await top-line results from Helios-B. Our outcome study is designed to expand the label for AMVUTTRA to include the treatment of patients with hereditary and wild-type HTTR amyloidosis with cardiomyopathy. As you are aware, on our Q4 earnings call in February, we announced enhancements to the Helios-B Statistical Plan to optimize the study for success and to best support a strong and competitive label. These changes were informed by insights from Apollo-B data and emerging data from the field. With these optimizations, we remain focused on clinical outcomes of death and hospitalization, which are critical to all stakeholders. But now, trying to evaluate these outcomes in the overall population, as well as in the monotherapy population, which is where we believe AMVUTTRA will have the largest treatment effect and will best demonstrate the drug's true impact. We also streamlined the secondary endpoint structure to focus on those clinical measures that we believe will best highlight AMVUTTRA's potentially differentiated profile and its benefits on stabilization of this progressive disease.

Speaker Change: Pascal.

Pushkal Garg: Thanks, Tolga. And good morning, everyone. Let's begin with our TTR franchise, where we eagerly await top-line results from HELIOS-B, our outcome study designed to expand the label for AMVUTTRA to include the treatment of patients with hereditary and wild-type ATTR amyloidosis with cardiomyopathy. As you're aware, on our Q4 earnings call in February, we announced enhancements to the HELIOS-B statistical plan to optimize the study for success and to best support a strong and competitive label. These changes were informed by insights from the APOLLO-B data and emerging data from the field.

Pascal: Thanks, Tom and good morning, everyone, let's begin with our TCR franchise, where we eagerly await topline results from Helios B outcome.

Pushkal Garg: Let's begin with our TTR franchise, where we eagerly await top-line results from Helios. Our outcome study is designed to expand the label for Ambutra to include the treatment of patients with hereditary and wild-type ATTR amyloidosis with cardiomyopathy. As you know, on our Q4 earnings call in February, we announced enhancements to the Heliospeed Statistical Plan to optimize the study for success and to best support These changes were informed by insights from Apollo B data and emerging data from the field. With these optimizations, we remain focused on clinical outcomes of death and hospitalization, which are critical to all stakeholders. But now we are trying to evaluate these outcomes in the overall population, as well as in the monotherapy population, which is where we believe Ambutra will have the largest treatment effect and will best demonstrate the drug's true impact. We also streamlined the secondary endpoint structure to focus on those clinical measures that we believe will best highlight Invutra's potentially differentiated profile and its benefits in stabilizing this progressive disease.

Pascal: Outcome study designed to expand the label Fran Butera to include the treatment of patients with hereditary and wild type <unk> amyloidosis with cardiomyopathy.

Pushkal Garg: As you're aware, on our Q4 earnings call in February, we announced enhancements to the HELIOS-B statistical plan to optimize the study for success and to best support a strong and competitive label. These changes were informed by insights from the APOLLO-B data and emerging data from the field.

Pascal: As you are aware on our Q4 earnings call in February we announced enhancements to the Helios B Statistical plan to optimize the study for success and to best support a strong and competitive label.

Pascal: Changes were informed by insights from the Apollo data and emerging data from the field.

Pushkal Garg: With these optimizations, we remain focused on clinical outcomes of death and hospitalization, which are critical to all stakeholders. But now we are trying to evaluate these outcomes in the overall population, as well as in the monotherapy population, which is where we believe Ambutra will have the largest treatment effect and will best demonstrate the drug's true impact. We also streamlined the secondary endpoint structure to focus on those clinical measures that we believe will best highlight Invutra's potentially differentiated profile and its benefits in stabilizing this progressive disease.

Pushkal Garg: With these optimizations, we've remained focused on clinical outcomes of death and hospitalization, which are critical to all stakeholders, but now plan to evaluate these outcomes in the overall population as well as the monotherapy population, which is where we believe AMVUTTRA will have the largest treatment effect and will best demonstrate the drug's true impact. We also streamlined the secondary endpoint structure to focus on those clinical measures that we believe will best highlight AMVUTTRA's potentially differentiated profile and its benefits on stabilization of this progressive disease. We enhanced the overall statistical powering of the study by incorporating up to an additional three months of event collection at the tail end of the study period, the most critical period, and firmly establishing HELIOS-B as the longest placebo-controlled study conducted to date in ATTR-CM. We remain on track to report top-line results in late June or early July.

Pascal: With these optimizations, we remain focused on clinical outcomes in death and hospitalization.

Pascal: Critical to all stakeholders, but now thanks to evaluate these outcomes in the overall population as well as the monotherapy population, which is where we believe <unk> will have the largest treatment effect and will best demonstrate the drugs to impact.

Pascal: We also streamlined the secondary endpoint structure to focus on those clinical measures that we believe will best highlight and Lucas potentially differentiated profile and its benefits on stabilization of this progressive disease.

Pushkal Garg: And we enhanced the overall statistical powering of the study by incorporating up to an additional three months of event collection at the tail end of the study period, the most critical period and firmly establishing Helios-B as the longest placebo-controlled study conducted to date in ATTRCM. We remain on track to report top-line results in late June or early July. At that time, we plan to provide P-values on the primary and secondary endpoints, as well as key details regarding safety. We also expect to provide some high-level information on subgroups, including patients on baseline to families. Full results are expected to be presented at a Scientific Congress soon thereafter. And assuming positive results from Helios-B, we expect to submit a supplemental NDA to the FDA in late 2024. Turning now to ZILEBESIRAN, our investigational RNAi therapeutic being evaluated as a treatment for hypertension. We made some very exciting progress in the first quarter on this program.

Pushkal Garg: We enhanced the overall statistical powering of the study by incorporating up to an additional three months of event collection at the tail end of the study period, the most critical period, and firmly establishing HELIOS-B as the longest placebo-controlled study conducted to date in ATTR-CM. We remain on track to report top-line results in late June or early July.

Pascal: And we enhanced the overall statistical powering of the study by incorporating up to an additional three months of event collection at the tail end of the study period.

Pascal: It's critical period and firmly establishing Helios b is the longest placebo controlled study conducted to date in <unk>.

Pascal: We remain on track to report topline results in late June or early July at that time, we plan to provide P values on the primary and secondary endpoints as well as key details regarding safety.

Pushkal Garg: At that time, we plan to provide p-values on the primary and secondary endpoints, as well as key details regarding safety. We also expect to provide some high-level information on subgroups, including patients on baseline tafamidis. Full results are expected to be presented at a scientific congress soon thereafter. Assuming positive results from HELIOS-B, we expect to submit a supplemental NDA to the FDA in late 2024. Turning now to zilebesiran, our investigational RNAi therapeutic being evaluated as a treatment for hypertension. We made some very exciting progress in Q1 on this program. Hypertension is a global health crisis and the leading addressable cause of cardiovascular morbidity and mortality around the world. Unfortunately, despite available therapies, up to 80% of patients have uncontrolled disease.

Pascal: We also expect to provide some high level information on subgroups, including patients on baseline to families.

Pushkal Garg: Including Patients on Baseline to Families. Full results are expected to be presented at a Scientific Congress soon thereafter, and assuming positive results from Helios B, we expect to submit a supplemental NDA to the FDA in late 2024. Turning now to zalbiceram, our investigational RNAi therapeutic being evaluated as a treatment for hypertension, we made some very exciting progress in the first quarter on this program.

Pascal: Full results are expected to be presented at a scientific Congress soon thereafter.

Pascal: And assuming positive results from Helios B, we expect to submit a supplemental NDA to the FDA in late 2024.

Pushkal Garg: Turning now to zilebesiran, our investigational RNAi therapeutic being evaluated as a treatment for hypertension. We made some very exciting progress in Q1 on this program. Hypertension is a global health crisis and the leading addressable cause of cardiovascular morbidity and mortality around the world. Unfortunately, despite available therapies, up to 80% of patients have uncontrolled disease.

Pascal: Turning now to Dolby surround our investigational <unk> therapeutic being evaluated as a treatment for hypertension. We made some very exciting progress in the first quarter on this program hypertension is a global health crisis, and the leading addressable cause of cardiovascular morbidity and mortality around the world.

Pushkal Garg: Hypertension is a global health crisis and the leading addressable cause of cardiovascular morbidity and mortality around the world. Unfortunately, despite available therapies, up to 80% of patients have uncontrolled disease. And beyond poor control, there are a number of other aspects of hypertension management that contribute to increased cardiovascular risk, namely poor medication adherence, variability in blood pressure, and lack of night time dipping. We believe that ZILEBESIRAN has the potential to address all of these unmet needs and improve cardiovascular outcomes by providing tonic control of blood pressure. At the ACC conference a few weeks ago, we presented the full results from the positive KARDIA-2 Phase II Study that evaluated the efficacy and safety of a single, subcutaneous dose of ZILEBESIRAN when added to one of three standard of care antihypertension, a THIAZIDE-like diuretic, INDAPAMIDE, a calcium channel blocker, AMLODIPINE, or any intensive receptor blocker, OLMESARTAN. The study achieved its primary endpoint, demonstrating clinically and statistically significant placebo-adjusted reductions of up to 12.1 mm of Mercury in 24-hour mean systolic blood pressure at month 3, as measured by ambulatory blood pressure monitoring when ZILEBESIRAN was added to one of the three background medications.

Pascal: Fortunately despite available therapies up to <unk>.

Pascal: 80% of patients have uncontrolled disease and beyond poor control. There are a number of other aspects of hypertension management that contribute to increased cardiovascular risk.

Pushkal Garg: And beyond poor control, there are a number of other aspects of hypertension management that contribute to increased cardiovascular risk, namely poor medication adherence, variability in blood pressure, and lack of nighttime dipping. We believe that zilebesiran has the potential to address all of these unmet needs and improve cardiovascular outcomes by providing tonic control of blood pressure. At the ACC conference a few weeks ago, we presented the full results from the positive KARDIA-2 Phase II study that evaluated the efficacy and safety of a single subcutaneous dose of zilebesiran when added to one of three standard-of-care antihypertensives: a thiazide-like diuretic, indapamide, a calcium channel blocker, amlodipine, or an angiotensin receptor blocker, olmesartan.

Pascal: <unk> medication adherence variability in blood pressure and lack of nighttime debate, we believe that there'll be a strain has the potential to address all of these unmet needs and improve cardiovascular outcomes by providing tonic control of blood pressure.

Pushkal Garg: At the ACC conference a few weeks ago, we presented the full results from the positive KARDIA-2 Phase II study that evaluated the efficacy and safety of a single subcutaneous dose of zilebesiran when added to one of three standard-of-care antihypertensives: a thiazide-like diuretic, indapamide, a calcium channel blocker, amlodipine, or an angiotensin receptor blocker, olmesartan.

Pushkal Garg: At the ACC conference a few weeks ago, we presented the full results from the POSITIVE Cardio II Phase 2 Study that evaluated the efficacy and safety of the Cardio II Phase 2 study, of a single subcutaneous dose of zalbicerin when added to one of three standard of care antihypertension. Thiazide Light Diuretic, Dapamide, a Calcium Channel Blocker, Amlodipine, Ornangiotensin Receptor Blocker, Omasar Tensin, The study achieved its primary endpoint, demonstrating clinically and statistically significant placebo-adjusted reductions of up to 12.1 mmHg in 24-hour mean systolic blood pressure at month 3, as measured by ambulatory blood pressure monitoring when Zalvisran was added to one of the three background medications.

Pascal: At the ACC conference a few weeks ago, we presented the full results from the positive cardiac <unk> phase II study that evaluated the efficacy and safety of a single subcutaneous dose of zombie thriller when added to one of three standard of care anti hypertensive.

Pascal: I'd like diabetic <unk> calcium channel blocker and loaded <unk>, an angiotensin receptor blocker almost SAR 10.

Pushkal Garg: The study also achieved the key secondary endpoint, demonstrating clinically significant additive reductions in office systolic blood pressure in month three across all three independent cohorts. Finally, ZILEBESIRAN demonstrated an encouraging safety and tolerability profile when added to standard of care antihypertensives. We are very excited by these results, showing additive efficacy and good tolerability on top of two agents with orthogonal mechanisms and on top of an ARB, which also works in the RAS pathway, which supports continued development. To that point, we recently initiated the KARDIA-3 Phase II study, which will evaluate ZILEBESIRAN on top of two or more agents in patients who are at high cardiovascular risk. As this slide shows, we and our partners at Roche have robust plans to bring ZILEBESIRAN forward as an agent that can reshape the treatment of cardiovascular disease. This includes our intention, after KARDIA-3, to run a cardiovascular outcomes trial where we can demonstrate the benefits of tonic blood pressure control in patients at high CV risk by showing reductions in cardiovascular morbidity and mortality. Wrapping up with the pipeline, our extra-hepatic efforts in the CNS continued to progress this quarter as well. As we announced on our Q4 earnings call, we received FDA clearance to initiate the multiple-dose portion of the Phase I study of MIVALCERAN, formerly known as ALN-APP, in early-onset Alzheimer's disease, and remain on track to initiate a Phase II study in cerebral amyloid angiopathy early this year. So, in sum, we've made great progress in advancing our pipeline and platform, with much more to come.

Pushkal Garg: The study achieved its primary endpoint demonstrating clinically and statistically significant placebo-adjusted reductions of up to 12.1 mmHg in 24-hour mean systolic blood pressure at month 3, as measured by ambulatory blood pressure monitoring when zilebesiran was added to one of the 3 background medications. The study also achieved the key secondary endpoint demonstrating clinically significant additive reductions in office systolic blood pressure at month 3 across all 3 independent cohorts. Finally, zilebesiran demonstrated an encouraging safety and tolerability profile when added to standard-of-care antihypertensives. We are very excited by these results, showing additive efficacy and good tolerability on top of 2 agents with orthogonal mechanisms and on top of an ARB, which also works in the RAAS pathway, which support continued development.

Pascal: The study achieved its primary endpoint, demonstrating clinically and statistically significant placebo adjusted reductions of up to $12. One millimeters of Mercury in 24 hour mean systolic blood pressure at month, three as measured by ambulatory blood pressure monitoring when <unk> was added to one of the three background medications.

Pascal: The study also achieved the key secondary endpoint demonstrating clinically significant additive reductions in office systolic blood pressure at <unk> across all three independent cohorts.

Pushkal Garg: Finally, zilebesiran demonstrated an encouraging safety and tolerability profile when added to standard-of-care antihypertensives. We are very excited by these results, showing additive efficacy and good tolerability on top of 2 agents with orthogonal mechanisms and on top of an ARB, which also works in the RAAS pathway, which support continued development.

Pascal: Finally, <unk> has demonstrated an encouraging safety and tolerability profile when added to standard of care anti hypertensive <unk>.

Pascal: We are very excited by these results showing additive efficacy and good tolerability on top of two agents with orthogonal mechanisms and on top of an arb, which also works in the Ras pathway, which support continued development.

Pushkal Garg: To that point, we recently initiated the Cardio 3 Phase 2 study, which will evaluate Valbutrin on top of two or more agents in patients who are at high cardiovascular risk. As this slide shows, we and our partners at Roche have robust plans to bring Zalbisram forward as an agent that can reshape the treatment of cardiovascular disease. This includes our intention, after Cardio 3, to run a cardiovascular outcomes trial where we can demonstrate the benefits of tonic blood pressure control in patients at high CV risk by showing reductions in cardiovascular morbidity and mortality. Wrapping up with the pipeline, our extra-hepatic efforts in the CNS continued to progress this quarter as well. As we announced on our Q4 earnings call, we received FDA clearance to initiate the multiple-dose portion of the Phase I study of Mivalceran, formerly known as ALN-APP, in early-onset Alzheimer's, and remain on track to initiate a phase 2 study in cerebral amyloid angiopathy early this year. So, in sum, we've made great progress in advancing our pipeline and platform, with much more to come.

Pushkal Garg: To that point, we recently initiated the KARDIA-3 Phase II study, which will evaluate zilebesiran on top of two or more agents in patients who are at high cardiovascular risk. As this slide shows, we and our partners at Roche have robust plans to bring zilebesiran forward as an agent that can reshape the treatment of cardiovascular disease. This includes our intention, after KARDIA-3, to run a cardiovascular outcomes trial, where we can demonstrate the benefits of tonic blood pressure control in patients at high CV risk by showing reductions in cardiovascular morbidity and mortality. Wrapping up with the pipeline, our extrahepatic efforts in the CNS continue to progress this quarter as well.

Pascal: To that point, we recently initiated the cardiac III phase III study, which will evaluate <unk> on top of two or more agents in patients who are at high cardiovascular risk.

Pascal: As this slide shows we and our partners at Roche have robust plans to bring Dolby surround forward as an agent that can reshape the treatment of cardiovascular disease.

Pushkal Garg: This includes our intention, after KARDIA-3, to run a cardiovascular outcomes trial, where we can demonstrate the benefits of tonic blood pressure control in patients at high CV risk by showing reductions in cardiovascular morbidity and mortality. Wrapping up with the pipeline, our extrahepatic efforts in the CNS continue to progress this quarter as well.

Pascal: It includes our intention after cardiac III to win a cardiovascular outcomes trial.

Pascal: Where we can demonstrate the benefits of chronic blood pressure control in patients at high CV risk.

Pascal: Showing reductions in cardiovascular morbidity and mortality.

Pushkal Garg: Wrapping up with the pipeline, our extra-hepatic efforts in the CNS continued to progress this quarter as well. As we announced on our Q4 earnings call, we received FDA clearance to initiate the multiple-dose portion of the Phase I study of Mivalceran, formerly known as ALN-APP, in early-onset Alzheimer's, and remain on track to initiate a phase 2 study in cerebral amyloid angiopathy early this year. So, in sum, we've made great progress in advancing our pipeline and platform, with much more to come.

Pascal: Wrapping up with the pipeline our extra hepatic efforts in the CNS continued to progress this quarter as well as we announced on our Q4 earnings call. We received FDA clearance to initiate the multiple dose portion of the phase one study of <unk>, formerly known as <unk> in early onset Alzheimer's disease.

Pushkal Garg: As we announced on our Q4 earnings call, we received FDA clearance to initiate the multiple-dose portion of the phase I study of mivelsiran, formerly known as ALN-APP, in early-onset Alzheimer's disease, and remain on track to initiate a phase II study in cerebral amyloid angiopathy early this year. So in sum, we've made great progress in advancing our pipeline and platform, with much more to come. As a reminder, we plan to file proprietary INDs for nine programs by the end of 2025. Again, targets in the liver, CNS, muscle, and adipose. If we include partnered programs, we anticipate 15 new INDs by the end of 2025, representing a doubling of our clinical pipeline by the end of next year.

Pascal: And remain on track to initiate a phase II study and cerebral amyloid angiopathy early this year.

Pushkal Garg: So, in sum, we've made great progress in advancing our pipeline and platform, with much more to come. As a reminder, we plan to follow proprietary INDs for nine programs by the end of 2025 against targets in the liver, CNS, muscle, and adipose. If we include partnered programs, we anticipate 15 new INDs by the end of 2025, representing an endowment of our clinical pipeline by the end of next year. This remarkable and unique pace of innovation puts us in a great position to have a robust, self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, I now turn it over to Jeff to review our financial results and upcoming milestones. Jeff.

Pascal: So in sum, we've made great progress in advancing our pipeline and platform with much more to come.

Pushkal Garg: As a reminder, we plan to follow proprietary INDs for nine programs by the end of 2025 against targets in the liver, CNS, muscle, and adipose. If we include partnered programs, we anticipate 15 new INDs by the end of 2025, representing an endowment of our clinical pipeline by the end of next year. This remarkable and unique pace of innovation puts us in a great position to have a robust, self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, I now turn it over to Jeff to review our financial results and upcoming milestones. Jeff.

Pushkal Garg: As a reminder, we plan to file proprietary INDs for nine programs by the end of 2025. Again, targets in the liver, CNS, muscle, and adipose. If we include partnered programs, we anticipate 15 new INDs by the end of 2025, representing a doubling of our clinical pipeline by the end of next year.

Pascal: As a reminder, we plan to file a proprietary IND for nine programs by the end of 2025 again.

Pascal: <unk> targets, the liver CNS muscle and adipose. If we include partnered programs, we anticipate <unk> by the end of 2025, representing a doubling of our clinical pipeline by the end of next year.

Pushkal Garg: This remarkable and unique pace of innovation puts us in a great position to have a robust, self-sustainable pipeline that can deliver meaningful impact to patients across multiple disease areas. With that, let me now turn it over to Jeff to review our financial results and upcoming milestones. Jeff?

Pascal: This remarkable and unique pace of innovation puts us in a great position to have a robust self sustainable pipeline that can deliver a meaningful impact to patients across multiple disease areas.

Pascal: With that let me now turn it over to Jeff to review, our financial results and upcoming milestones Jeff.

Jeff Poulton: Thanks, Pushkal and good morning, everyone. I'm pleased to be presenting a summary of Alnylam's Q1 2024 financial results and discussing our full year guidance. Starting with a summary of our P&L results for Q1 2024 compared with Q1 2023. Total product revenues for the quarter were $365 million, or 32% growth versus the first quarter of 2023. Both our TTR and RARE Fright franchises reported strong growth of 29% and 40% respectively, primarily driven by strong demand, as Tolga previously highlighted. Net revenue from collaborations for the quarter was $119 million, or a 225% increase compared to the first quarter of 2023. The increase was primarily due to revenue recognized under our collaboration and license agreement with Roche, including $65 million of milestone revenue associated with the initiation of the ZILEBESIRAN KARDIA-3 clinical trial and an increase in revenue recognized under our collaboration agreement with Regeneron. Royalty revenue for the quarter was $11 million, or a 63% increase compared to the first quarter of 2023. The increase was driven by higher left veal sales compared to the same period in 2023. Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2023. We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on AMVUTTRA, as AMVUTTRA growth continues at a brisk pace. Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in ZILEBESIRAN, our Helios-B trial, and our preclinical pipeline. Non-GAAP SG&A expenses increased 15% in the first quarter compared to the same period in 2023, lower than our 32% growth in product sales, as we continue to deliver operating leverage on our journey to achieving profitability.

Jeff Poulton: Thanks, Pushkal, and good morning, everyone. I'm pleased to be presenting a summary of ALNYLAM's Q1 2024 financial results and discussing our full-year guidance. Starting with a summary of our P&L results for Q1 2024 compared with Q1 2023. Total product revenues for the quarter were $365 million, or 32% growth versus the first quarter of 2023, with both our TTR and rare franchises reporting strong growth of 29% and 40%, respectively, primarily driven by strong demand, as Tolga previously highlighted. Net revenue from collaborations for the quarter was $119 million, or a 225% increase compared to the first quarter of 2023. The increase was primarily due to revenue recognized under our collaboration and license agreement with Roche, including $65 million of milestone revenue associated with initiation of the zilebesiran KARDIA-3 clinical trial and an increase in revenue recognized under our collaboration agreement with Regeneron.

Pascal: Jeff.

Jeff Poulton: Thanks, Carl and good morning, everyone I am pleased to be presenting a summary about the items Q1, 2024 financial results and discussing our full year guidance.

Jeff Poulton: Starting with a summary of our P&L results for Q1, 2024, compared with Q1 2023.

Jeff: Total product revenues for the quarter were $365 million or 32% growth versus the first quarter of 2023.

Jeff: Our GTR in rare bright franchises reporting strong growth of 29% and 40% respectively.

Jeff: Primarily driven by strong demand as told them previously highlighted.

Jeff Poulton: Net revenue from collaborations for the quarter was $119 million, or a 225% increase compared to the first quarter of 2023. The increase was primarily due to revenue recognized under our Collaboration and License Agreement with Roche, including $65 million of milestone revenue associated with the initiation of the Zabisiran Cardia III clinical trial and an increase in revenue recognized under our Collaboration Agreement with Regeneron. Royalty revenue for the quarter was $11 million, or a 63% increase compared to the first quarter of 2023. The increase was driven by higher left veal sales compared to the same period in 2023. Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2023. We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on Imbutra, as Imbutra growth continues at a brisk pace. Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in Zalbisiran, our Helios B trial, and our preclinical pipeline. Non-GAAP SG&A expenses increased 15% in the first quarter compared to the same period in 2023, lower than our 32% growth in product sales.

Jeff: Net revenue from collaborations for the quarter was $119 million or 225% increase compared to the first quarter of 2023.

Jeff: The increase was primarily due to revenue recognized under our collaboration and license agreement with Roche.

Jeff: <unk> $65 million of milestone revenue associated with the initiation of this I'll be surround cardiac III clinical trial.

Jeff: And an increase in revenue recognized under our collaboration agreement with Regeneron.

Jeff Poulton: Royalty revenue for the quarter was $11 million, or a 63% increase compared to the first quarter of 2023. The increase was driven by higher Leqvio sales compared to the same period in 2023. Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2023. We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on AMVUTTRA as AMVUTTRA growth continues at a brisk pace. Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in zilebesiran, our HELIOS-B trial, and our preclinical pipeline.

Jeff: Royalty revenue for the quarter was $11 million or 63% increase compared to the first quarter of 2023 <unk>.

Jeff: The increase was driven by higher light vehicle sales compared to the same period in 2023.

Jeff Poulton: Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2023. We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on Imbutra, as Imbutra growth continues at a brisk pace. Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in Zalbisiran, our Helios B trial, and our preclinical pipeline. Non-GAAP SG&A expenses increased 15% in the first quarter compared to the same period in 2023, lower than our 32% growth in product sales.

Jeff: Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of 2023.

Jeff Poulton: We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on AMVUTTRA as AMVUTTRA growth continues at a brisk pace. Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in zilebesiran, our HELIOS-B trial, and our preclinical pipeline.

Jeff: We expect our gross margin on product sales will be lower for the balance of 2024, driven by higher royalties paid on in vitro is kombucha growth continues at a brisk pace.

Jeff: Our non-GAAP R&D expenses increased 13% in the first quarter compared to the same period in 2023, primarily driven by increased investments in Dolby surround our Helios B trial.

Jeff: Our preclinical pipeline.

Jeff Poulton: Our non-GAAP SG&A expenses increased 15% in the first quarter compared to the same period in 2023, lower than our 32% growth in product sales as we continue to deliver operating leverage on our journey to achieving profitability. The source of SG&A expense growth was primarily related to TTR marketing investments to help drive polyneuropathy patient-finding efforts, as well as increased investment in preparation for a potential launch in cardiomyopathy next year. Our non-GAAP operating gain for the quarter was $2 million, representing more than a $100 million improvement compared with Q1 2023, primarily driven by strong top-line results both in product sales as well as revenue from collaborations, as previously highlighted. Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion, in line with the $2.4 billion we reported at the end of 2023.

Jeff: Our non-GAAP SG&A expenses increased 15% in the first quarter compared to the same period in 2023 lower than our <unk> 30, 32% growth in product sales as we continue to deliver operating leverage on our journey to achieving profitability.

Jeff Poulton: As we continue to deliver operating leverage on our journey to achieving profitability. The source of SG&A expense growth was primarily related to TTR marketing investments to help drive polyneuropathy patient finding efforts, as well as increased investment in preparation for a potential launch in cardiomyopathy next year. Our non-GAAP operating gain for the quarter was $2 million, representing more than a $100 million improvement compared with Q1 2023, primarily driven by strong top-line results both in products with sales as well as revenue from collaborations, as previously highlighted. Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion, in line with the $2.4 billion we reported at the end of 2023. I continue to believe our current cash balance will be sufficient to bridge us to a self-sustainable financial profile. Now, I'd like to turn to our financial guidance for 2024. Today we are reiterating our 2024 guidance as presented during our earnings call in February. We anticipate combined net product revenues for our four wholly-owned commercial products will be between $1.4 and $1.5 billion, corresponding to a 13% to 21% growth rate at January 31st FX rates. Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance. We will, of course, carefully review our progress in Q2 to determine if any changes to our guidance are warranted. The Collaboration and Royalty Revenue Guidance Range is $325 to $425 million. And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1.675 and $1.775 billion, the midpoint of which reflects 9% growth compared with 2023.

Jeff Poulton: As we continue to deliver operating leverage on our journey to achieving profitability.

Jeff Poulton: The source of SG&A expense growth was primarily related to TTR marketing investments to help drive polyneuropathy patient finding efforts, as well as increased investment in preparation for a potential launch in cardiomyopathy next year. Our non-GAAP operating gain for the quarter was $2 million, representing more than a $100 million improvement compared with Q1 2023, primarily driven by strong top-line results both in products with sales as well as revenue from collaborations, as previously highlighted. Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion, in line with the $2.4 billion we reported at the end of 2023. I continue to believe our current cash balance will be sufficient to bridge us to a self-sustainable financial profile. Now, I'd like to turn to our financial guidance for 2024. Today we are reiterating our 2024 guidance, as presented during our earnings call in February. We anticipate combined net product revenues for our four wholly-owned commercial products will be between $1.4 and $1.5 billion, corresponding to a 13% to 21% growth rate at January 31st FX rates. Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance. We will, of course, carefully review our progress in Q2 to determine if any changes to our guidance are warranted. The Collaboration and Royalty Revenue Guidance Range is $325 to $425 million. And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1.675 and $1.775 billion, the midpoint of which reflects 9% growth compared with 2023.

Jeff: The source of SG&A expense growth was primarily related to GTR marketing investments to help drive polyneuropathy patient finding efforts as well as increased investment in preparation for a potential launch in cardiomyopathy next year.

Jeff Poulton: Our non-GAAP operating gain for the quarter was $2 million, representing more than a $100 million improvement compared with Q1 2023, primarily driven by strong top-line results both in product sales as well as revenue from collaborations, as previously highlighted. Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion, in line with the $2.4 billion we reported at the end of 2023.

Jeff: Our non-GAAP operating gain for the quarter was $2 million, representing more than a $100 million improvement compared with Q1 2023, primarily driven by strong top line results both in product sales as well as revenue from collaborations as previously highlighted.

Jeff Poulton: Finally, we ended the quarter with cash, cash equivalents, and marketable securities of $2.4 billion, in line with the $2.4 billion we reported at the end of 2023. I continue to believe our current cash balance will be sufficient to bridge us to a self-sustainable financial profile. Now, I'd like to turn to our financial guidance for 2024. Today we are reiterating our 2024 guidance as presented during our earnings call in February. We anticipate combined net product revenues for our four wholly-owned commercial products will be between $1.4 and $1.5 billion, corresponding to a 13% to 21% growth rate at January 31st FX rates. Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance. We will, of course, carefully review our progress in Q2 to determine if any changes to our guidance are warranted. The Collaboration and Royalty Revenue Guidance Range is $325 to $425 million. And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1.675 and $1.775 billion, the midpoint of which reflects 9% growth compared with 2023.

Jeff: Finally, we ended the quarter with cash cash equivalents in marketable securities of $2 4 billion in line with the $2 4 billion, we reported at the end of 2023.

Jeff Poulton: We continue to believe our current cash balance will be sufficient to bridge us to a self-sustainable financial profile. Now I'd like to turn to our financial guidance for 2024. Today, we are reiterating our 2024 guidance as presented during our earnings call in February. We anticipate combined net product revenues for our four wholly-owned commercial products will be between $1.4 and 1.5 billion, corresponding to a 13% to 21% growth rate at 31 January FX rates. Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance. We will, of course, carefully review our progress at Q2 to determine if any changes to our guidance are warranted. Our collaboration and royalty revenue guidance range is $325 to 425 million.

Jeff: We continue to believe our current cash balance will be sufficient to bridge us to a self sustainable financial profile.

Speaker Change: Now I'd like to turn to our financial guidance for 2024.

Jeff Poulton: Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance. We will, of course, carefully review our progress in Q2 to determine if any changes to our guidance are warranted. The Collaboration and Royalty Revenue Guidance Range is $325 to $425 million. And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1.675 and $1.775 billion, the midpoint of which reflects 9% growth compared with 2023.

Jeff: Today, we are reiterating our 2024 guidance as presented during <unk>.

Jeff: Our earnings call in February.

Jeff: We anticipate combined net product revenues for our four wholly owned commercial products will be between one four and $1 5 billion corresponding to a 13% to 21% growth rate at January 31, FX rates Q.

Jeff: Q1 was a strong start to the year, giving us confidence in our ability to meet or exceed our product sales guidance.

Jeff: We will of course carefully review our progress in Q2 to determine if any changes to our guidance are warranted.

Jeff: Our collaboration and royalty revenue guidance range is $325 million to $425 million.

Jeff Poulton: And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1.675 and $1.775 billion, the midpoint of which reflects 9% growth compared with 2023. Let me now turn from financials and discuss some key goals and upcoming milestones slated for early and mid-2024. We expect three trial initiations in early 2024, including a phase II study for mivelsiran in patients with cerebral amyloid angiopathy, Part B of the phase I study of ALN-KHK and Type 2 diabetes, and a phase I study of ALN-B-CAT and hepatocellular carcinoma. As has been highlighted, we remain on track to report top-line results from the HELIOS-B study of vutrisiran in late June or early July. Given how important the readout is, we plan to enter a quiet period beginning 13 May in advance of those results.

Jeff: And lastly, our guidance for combined non-GAAP R&D and SG&A expenses remains a range between $1 675, and $1 775 billion, the midpoint of which reflects 9% growth compared with 2023.

Jeff Poulton: Let me now turn from financials and discuss some key goals and upcoming milestones slated for early and mid 2024. We expect three trial initiations in early 2024, including a Phase II study for [inaudible] in patients with cerebral amyloid angiopathy, part B of the Phase I study of ALN-KHK and Type 2 diabetes, and a Phase I study of ALN-BCAT in hepatocellular carcinoma. As has been highlighted, we remain on track to report top-line results from the Helios-B study of VITRISIRAN in late June or early July. Given how important the readout is, we plan to enter a quiet period beginning May 13th, in advance of those results. I may now turn it back to Christine to coordinate our Q&A session. Thank you, Jeff. Operator, we will now open the call.

Jeff Poulton: Let me now turn from financials and discuss some key goals and upcoming milestones slated for early and mid 2024. We expect three trial initiations in early 2024, including a Phase II study for MIVELSIRAN in patients with cerebral amyloid angiopathy, part B of the Phase I study of ALN-KHK and Type 2 diabetes, and a Phase I study of ALN-BCAT in hepatocellular carcinoma. As has been highlighted, we remain on track to report top-line results from the Helios-B study of VITRISIRAN in late June or early July. Given how important the readout is, we plan to enter a quiet period beginning May 13th, in advance of those results. I may now turn it back to Christine to coordinate our Q&A session.

Jeff: Let me now turn to financials and discuss some key goals and upcoming milestones slated for early in mid 2024.

Jeff Poulton: We expect three trial initiations in early 2024, including a phase II study for mivelsiran in patients with cerebral amyloid angiopathy, Part B of the phase I study of ALN-KHK and Type 2 diabetes, and a phase I study of ALN-B-CAT and hepatocellular carcinoma. As has been highlighted, we remain on track to report top-line results from the HELIOS-B study of vutrisiran in late June or early July. Given how important the readout is, we plan to enter a quiet period beginning 13 May in advance of those results.

Jeff: We expect three trial initiations in early 2024, including the Phase III study for <unk>.

Jeff: And patients with cerebral amyloid angiopathy.

Jeff: Part B of the phase one study of <unk> in type two diabetes.

Jeff: In our phase one study of <unk> and <unk>.

Jeff: <unk> cellular carcinoma.

Jeff: And has and has been highlighted we remain on track to report topline results from the Helios B study of <unk> in late June or early July.

Christine Regan Lindenboom: We remain on track to report top-line results from the Helios B study of Lutriceran in late June or early July. Given how important the readout is, we plan to enter a quiet period beginning May 13, May 13, in advance of those results. Christine. Thank you, Jeff. Operator, we will now open the call.

Jeff: Given how important the readout is we plan to enter our quiet period, beginning May 13 may 13 in advance of those results.

Jeff Poulton: Let me now turn it back to Christine to coordinate our Q&A session. Christine?

Christine Regan Lindenboom: Thank you, Jeff. Operator, we will now open the call for your questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions. Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Our first question comes from the line of David Lebowitz, The City. You may go ahead.

Jeff: I'll now turn it back to Christine to coordinate our Q&A session Christine.

Christine Lindenboom: Thank you, Jeff. Operator, we will now open the call for your questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

Christine Regan Lindenboom: Thank you Jeff Operator, we will now open the call to your question. It does tell them if you'd like to ask you to limit yourself to one question each and then get back in the queue. If you have additional questions.

Operator: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press Star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press Star 11 again. Please stand by while we pile the Q&A roster. Our first question comes from the line of David Lebowitz from Citi. You may go ahead.

Operator: Thank you. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of David Liebowitz, Citi. You may go ahead.

Operator: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you'll need to press star one on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Our first question comes from the line of David Lebowitz, The City. You may go ahead.

Speaker Change: Thank you at this time, we will conduct a question and answer session. As a reminder to ask question you will need to press star one on your telephone and wait for your name to be announced.

Speaker Change: To withdraw your question. Please press star one again, please standby, while we can tie all the Q&A roster.

Christine Regan Lindenboom: Our first question comes from the line of David Leibowitz with Citi. You May go ahead.

David N. Lebowitz: Thank you very much for taking my question. I'm curious, there's been some talk recently about what is considered to be the relevant improvement over the control arm, certainly on the monotherapy side, to make it easier to compare one drug versus another. And numbers have been batted about 30% relative improvement versus 42% relative improvement. I'm just curious - I know that information won't come in the top line release, but what are your thoughts on that discussion? And how do you think we should think about it?

David Lebowitz: Thank you very much for taking my question. I'm curious. There's been some talk recently about what is considered to be the relevant improvement over the control arm, certainly on the monotherapy side, to make it easier to compare one drug versus another. And numbers have been bandied about, about 30% relative improvement versus 42% relative improvement. I'm just curious. I know that information won't come in the top-line release, but what are your thoughts on that discussion, and how do you think we should think about it?

David N. Lebowitz: Alright, Thank you very much for taking my question.

David N. Lebowitz: I'm curious.

David N. Lebowitz: There has been some talk recently about what you consider to be the relevant improvement over the control arm certainly on the monotherapy side that make it easier to.

David N. Lebowitz: To compare one drug versus another.

<unk> numbers have been bandied about about 30% relative improvement versus 42% relative improvement.

David N. Lebowitz: Just curious I know does that information won't come in the topline released but what are your thoughts on that discussion.

David N. Lebowitz: We should think about it.

Yvonne L. Greenstreet: Thanks, Dave, for the question. You know, just as a reminder, Helios-B is an outcome study, and that's really what we need to deliver from the study. And it's quite clear, you know, in discussions with regulators, payers, and physicians, that if we're able to show a benefit in outcomes, this will be an important medicine. Clearly, we made some changes to the statistical plan, which we shared in some detail on our last call, and we're happy to reprise, you know, the rationale behind that. But, you know, at this point in time, I think the best way to look at this is delivering outcomes in this study will be, you know, the important results. And we also expect to see some other aspects of differentiation if we consider the results that we got out of Helios-B with respect to stabilization of diseases. So, I think if we're able to deliver all this, we believe that we'll have a differentiated profile that will be an important contribution to managing the disease in these patients. Pushkal, is there anything you want to add?

Yvonne Greenstreet: Thanks, Dave, for the question. Just as a reminder, HELIOS-B is an outcome study, and that's really what we need to deliver from the study. It's quite clear in discussions with regulators, payers, and physicians that if we're able to show a benefit on outcomes, this will be an important medicine. Clearly, we made some changes to the statistical plan, which we shared in some detail on our last call, and we're happy to reprise the rationale behind that. At this point in time, I think the best way to look at this is delivering outcomes in the study will be the important results. We also expect to see some other aspects of differentiation if we consider the results that we got out of HELIOS-B with respect to stabilization of disease.

David N. Lebowitz: Okay.

Speaker Change: Thanks, Dave for the question.

Yvonne L. Greenstreet: Just as a reminder.

Yvonne L. Greenstreet: <unk> is an outcome study and Thats really what we need to deliver from the study and its quite clear.

David N. Lebowitz: And discussions with regulators payers and physicians that if we're able to show a benefit on outcomes.

Yvonne L. Greenstreet: This will be an important medicine.

Yvonne Greenstreet: Clearly, we made some changes to the statistical plan, which we shared in some detail on our last call, and we're happy to reprise the rationale behind that. At this point in time, I think the best way to look at this is delivering outcomes in the study will be the important results. We also expect to see some other aspects of differentiation if we consider the results that we got out of HELIOS-B with respect to stabilization of disease.

Yvonne L. Greenstreet: <unk>.

David N. Lebowitz: Clearly we made some changes.

Yvonne L. Greenstreet: The statistical plan, which we shared in some detail on our last call and were happy to reprise the rationale behind that.

Yvonne L. Greenstreet: But, you know, at this point in time, I think the best way to look at this is that delivering outcomes in this study will be, you know, the important results. And we also expect to see some other aspects of differentiation if we consider the results that we got out of Helios B with respect to stabilization of diseases. So I think if we're able to deliver all this, we believe that we'll have a differentiated profile that will... that will be an important contribution to managing the disease in these patients. Pushkal, is there anything you want to add?

Yvonne L. Greenstreet: But at this point in time I think the best way to look at this is des.

Pushkal Garg: Delivering outcomes in this study will be.

Pushkal Garg: The important results and we also expect to see some other aspects of differentiation.

Pushkal Garg: If we.

Pushkal Garg: Considered the results for the quarter PSB with respect to stabilization of disease, and so I think if we're able to deliver all of this we believe that will have a differentiated profile that will.

Yvonne Greenstreet: I think if we're able to deliver all this, we believe that we'll have a differentiated profile that will be an important contribution to managing the disease of these patients. Pushkal, is there anything you want to add?

Pushkal Garg: That will that will be an important contribution.

Pushkal Garg: Managing the disease in these patients, but Scott anything you want to add.

Pushkal Garg: Yeah, I mean, I agree with everything you said, Yvonne. Dave, maybe just a couple other points. I mean, again, when it comes to clinical outcomes such as death and hospitalization, any change is considered clinically significant. And I think it's important to, again, go back to the unmet need in this disease. This is a steadily progressive disease where month on month patients continue to decline. They experience hospitalizations, worsening quality of life, worsening physical function, and ultimately, unfortunately, succumb to this disease. And whether you're on a once-a-day stabilizer or a twice-a-day stabilizer, you know, patients - the clinical trial data suggests that patients unfortunately continue to decline. And an orthogonal class of medicines could be helpful here. So, we're encouraged by the Apollo-B data. We're looking to demonstrate outcomes, and we think that clinicians will be looking at the magnitude of effect, as well as when separation occurs, as well as whether there's evidence of disease stabilization, which is really important, looking at the totality of the data. So, we're looking forward to reporting the results in late June and early July.

Jeff Poulton: Yeah. I mean, I agree with everything you said, Yvonne. Dave, maybe just a couple other points. I mean, again, when it comes to clinical outcomes such as death and hospitalization, any change is considered clinically significant. And I think it's important to, again, go back to the unmet need in this disease. This is a steadily progressive disease where month-on-month, patients continue to decline. They experienced hospitalizations, worsening quality of life, worsening physical function, and ultimately, unfortunately, succumbed to this disease. And whether you're on a once-a-day stabilizer or a twice-a-day stabilizer, the clinical trial data suggests that patients, unfortunately, continue to decline. And the orthogonal class of medicines could be helpful here. So we're encouraged by the APOLLO-B data. We're looking to demonstrate outcomes.

Pushkal Garg: Yeah. I mean, I agree with everything you said, Yvonne. Dave, maybe just a couple other points. I mean, again, when it comes to clinical outcomes such as death and hospitalization, any change is considered clinically significant. And I think it's important to, again, go back to the unmet need in this disease. This is a steadily progressive disease where month-on-month, patients continue to decline.

Pushkal Garg: Yes, I agree with everything you said it bottom Dave maybe just a couple of other points I mean again when it comes to clinical outcomes, such as death and hospitalization any change is considered clinically significant.

Pushkal Garg: And I think it's important to again go back to the unmet need in this disease. This is a.

Pushkal Garg: Steadily progressive disease, where month on month.

Pushkal Garg: They experienced hospitalizations, worsening quality of life, worsening physical function, and ultimately, unfortunately, succumbed to this disease. And whether you're on a once-a-day stabilizer or a twice-a-day stabilizer, the clinical trial data suggests that patients, unfortunately, continue to decline. And the orthogonal class of medicines could be helpful here. So we're encouraged by the APOLLO-B data. We're looking to demonstrate outcomes.

Pushkal Garg: Patients continued to decline.

Pushkal Garg: They experienced hospitalizations of worsening quality of life and physical function and ultimately unfortunately.

Pushkal Garg: Come to this disease and whether youre on a once a day stabilizer a twice a day stabilizer.

Pushkal Garg: Patients the data the clinical trial data suggest that patients. Unfortunately continued to decline and orthogonal class of medicines.

Pushkal Garg: So we're encouraged by the Apollo B data. We're looking to demonstrate outcomes, and we think that clinicians will be looking at the magnitude of effect, as well as when separation occurs, as well as whether there's evidence of disease stabilization, which is really important, looking at the totality of the data. So we're looking forward to reporting the results in late June and early July.

Speaker Change: It could be helpful. Here. So we're encouraged by the Apollo data, we're looking to demonstrate outcomes and we think that clinicians will be looking at the magnitude of effect as well as when separation occurs as well as whether as evidence of disease stabilization, which is really important looking at the totality of the data. So we're looking forward to report the results in late June early July.

Jeff Poulton: We think that clinicians will be looking at the magnitude of effect as well as when separation occurs, as well as whether there's evidence of disease stabilization, which is really important, looking at the totality of the data. So we're looking forward to report the results in late June and early July.

Pushkal Garg: We think that clinicians will be looking at the magnitude of effect as well as when separation occurs, as well as whether there's evidence of disease stabilization, which is really important, looking at the totality of the data. So we're looking forward to report the results in late June and early July.

Operator: All right, Pushkal, thank you very much for taking my question. One moment for our next question.

Yvonne L. Greenstreet: Thanks, Pushkal,

David Lebowitz: Thanks, Pushkal. Thank you very much for taking my question.

Speaker Change: Thanks Crystal. Thank you very much for taking my question.

David N. Lebowitz: Thank you very much for taking my question. One moment for our next question.

David N. Lebowitz: Thank you very much for taking my question.

Operator: One moment for our next question. Our next question comes from the line of Paul Matteis with Stifel. You may go ahead.

Speaker Change: One moment for our next question.

Operator: One moment for our next question. Our next question comes from the line of Paul Matteis with Stifle. You may go ahead.

Operator: Our next question comes from the line by Paul Matteis with Stifle. You may go ahead.

Operator: Our next question comes from the line of Tom <unk> with Stifel. You May go ahead.

Paul Matteis: Thanks so much for taking my question. I wanted to ask just about what Alnylam may look like organizationally in a scenario where Helios-B works versus one where it fails. Jeff, if Helios-B succeeds, do you expect to be changing guidance as it relates to spending and ramping up infrastructure ahead of the cardiomyopathy launch? And then, conversely, if Helios-B doesn't work, as you guys talk about nine INDs by the end of 2025, or 15 if you include partner programs, do you feel like that still stands? Do you think Alnylam is still going to have the balance sheet to execute on that? Or are you going to have to prioritize within the R&D pipeline? Thank you.

Jeff Poulton: Thanks so much for taking my question. I wanted to ask just about what ALNYLAM may look like organizationally in a scenario where HELIOS-B works versus one where it fails. Jeff, if HELIOS-B succeeds, do you expect to be changing guidance as it relates to spending and ramping up infrastructure ahead of the cardiomyopathy launch? And then conversely, if HELIOS-B doesn't work, as you guys talk about 9 INDs by the end of 2025 or 15 if you include partnered programs, do you feel like that still stands? Do you think ALNYLAM is still going to have the balance sheet to execute upon that, or are you going to have to prioritize within the R&D pipeline? Thank you.

Paul Matteis: Thanks so much for taking my question. I wanted to ask just about what ALNYLAM may look like organizationally in a scenario where HELIOS-B works versus one where it fails. Jeff, if HELIOS-B succeeds, do you expect to be changing guidance as it relates to spending and ramping up infrastructure ahead of the cardiomyopathy launch?

Paul Matteis: Thanks, So much for taking my question I wanted to ask.

Paul Matteis: Just about what all myeloma may look like organizationally in a scenario of Helios B works versus one where it fails.

Paul Matteis: <unk> succeeds.

Paul Matteis: Do you expect to be changing guidance as it relates to spending and ramping up infrastructure ahead of the cardiomyopathy launch and then Conversely, if helios B doesn't work as you guys talk about nine IND by the end of 2025 or 15. If you include partner programs do you feel like that still stands do you think all myeloma is still going to have the balance sheet to execute upon.

Paul Matteis: And then conversely, if HELIOS-B doesn't work, as you guys talk about 9 INDs by the end of 2025 or 15 if you include partnered programs, do you feel like that still stands? Do you think ALNYLAM is still going to have the balance sheet to execute upon that, or are you going to have to prioritize within the R&D pipeline? Thank you.

Paul Matteis: Or are you going to have to prioritize within the R&D pipeline. Thank you.

Jeff Poulton: Yeah, hi, Paul. Thanks for the question. Let me start with the first one, which I think was around our guidance for this year and whether or not that would need to change on the spending side, if we had a positive Helios-B result. The answer is no, the guidance reflects what we think we need for the year with a positive Helios-B result. So, I don't anticipate that we will be raising the guidance, we think we have plenty of opportunity to invest behind the opportunity to drive success. I think the other questions were around, you know, how might things evolve if we were in the unlikely scenario of a failed Helios-B. Certainly, we would need to look at prioritization across the business in that scenario. And we're doing the work on that, if we're in that scenario - again, we think that's unlikely - but we would be prepared to talk to the market about the prioritization decisions that we would make in that outcome. I also think it's important just to reflect.

Jeff Poulton: Yeah. Hi, Paul. Thanks for the question. Let me start with the first one, which I think was around our guidance this year and whether or not that would need to change on the spending side if we have a positive HELIOS-B result. The answer is no. The guidance reflects what we think we need for the year with a positive HELIOS-B result. So I don't anticipate that we would be raising the guidance. We think we have plenty of opportunity to invest behind the opportunity to drive success. I think the other questions were around how might things evolve if we were in the unlikely scenario of a failed HELIOS-B. Certainly, we would need to look at prioritization across the business in that scenario. And we're doing the work on that.

Speaker Change: Yes, Hi, Paul.

Speaker Change: Thanks for the question, let me start with the first one which I think was around our guidance this year and whether or not that would need to change on the spending side. If we have a positive Helios B result, the answer is no. The guidance reflects what we think we need for the year.

Speaker Change: With a positive Helios b results. So I don't anticipate that we would be raising the guidance. We think we have.

Jeff Poulton: We think we have plenty of opportunity to invest behind the opportunity to drive success. I think the other questions were around how might things evolve if we were in the unlikely scenario of a failed HELIOS-B. Certainly, we would need to look at prioritization across the business in that scenario. And we're doing the work on that. If we're in that scenario, again, we think that's unlikely, but we would be prepared to talk to the market about the prioritization decisions that we would make in that outcome.

Jeff Poulton: Plenty of opportunity to invest behind the opportunity to drive success.

Jeff Poulton: The guidance reflects what we think we need for the year with a positive Helios B result. So I don't anticipate that we will be raising the guidance. We think we have plenty of opportunity to invest behind the opportunity to drive success. I think the other questions were around, you know, how might things evolve if we were in the unlikely scenario of a failed Helios B. Certainly, we would need to look at prioritization across the business in that scenario. And we're doing the work on that. If we're in that scenario, again, we think that's unlikely, but we would be prepared to talk to the market about the prioritization decisions that we would make in that outcome. I also think it's important just to reflect.

Speaker Change: I think the other questions were around.

Jeff Poulton: How might things evolve if we were in the unlikely scenario.

Jeff Poulton: Failed Helios b.

Jeff Poulton: Certainly we would need to look at.

Jeff Poulton: Prioritization across the business in that scenario.

Jeff Poulton: And we're doing the work on that. If we're in that scenario, again, we think that's unlikely, but we would be prepared to talk to the market about the prioritization decisions that we would make in that outcome. I also think it's important just to reflect.

Jeff Poulton: If we're in that scenario, again, we think that's unlikely, but we would be prepared to talk to the market about the prioritization decisions that we would make in that outcome.

Jeff Poulton: And we're doing the work on that.

Jeff Poulton: If we're in that scenario again, we think that's unlikely, but we would be prepared to talk to the market about.

Yvonne L. Greenstreet: I also think it's important just to reflect on the magnitude of opportunity that we have in front of us as a company. I mean, Pushkal, you know, touched on the richness of our pipeline, currently 15 programs in the clinic. We're looking at doubling that number by 2025. So, as we look out at the opportunity set in front of us at Alnylam, we couldn't be more excited about being able to move forward the programs that we have. So, we're, you know, obviously looking forward to a positive outcome from EVSB and then really continuing to drive the pipeline that's in front of us. Thank you. One moment.

Jeff Poulton: The prioritization decisions that we would make in that outcome. I also think it's important just to reflect on the magnitude of opportunity that we have in front of us as a company.

Jeff Poulton: I also think it's important just to reflect on the magnitude of opportunity that we have in front of us as a company. I mean, Pushkal, you know, touched on the richness of our pipeline, currently 15 programs in the clinic. We're looking at doubling that number by 2025. So as we look out at the opportunity set in front of us at Alnylam, we couldn't be more excited about being able to move forward the programs that we have. So we're, you know, obviously looking forward to a positive outcome from EVSB and then really continuing to drive the pipeline that's in front of us. Thank you. One moment.

Yvonne Greenstreet: I also think it's important just to reflect on the magnitude of opportunity that we have in front of us as a company. I mean, Pushkal touched on the richness of our pipeline. Currently, 15 programs in the clinic. We're looking at doubling that number by 2025. So as we look out at the opportunity set in front of us at Alnylam, we couldn't be more excited about being able to move forward the programs that we have. So we're obviously looking forward to a positive outcome from HELIOS-B and then really continuing to drive the pipeline that's in front of us.

Jeff Poulton: Touched on the richness of our pipeline currently 15 programs in the clinic and we're looking at doubling that number by 2025. So as we look out at the opportunity set in front of us It online and we couldnt be more excited about being able to move forward the programs.

Jeff Poulton: We have.

Jeff Poulton: Obviously looking forward to a positive outcome from TSB, and then really continuing to drive the pipeline that's in front of us.

Jeff Poulton: Thank you.

Paul Matteis: Thank you.

Speaker Change: Thank you.

Operator: One moment for our next question. Our next question comes from Maury Raycroft with Jefferies. You may move ahead.

Speaker Change: One moment for our next question.

Yvonne L. Greenstreet: Thank you. One moment.

Paul Matteis: Thank you.

Operator: One moment for our next question. Our next question comes from Maury Raycroft with Jeffreys. You may move ahead.

Jeff Poulton: Our next question comes from Maury Raycroft with Jefferies. You May move ahead.

Maury Raycroft: Hi, thanks for taking my question. In both Attribute and Attract studies, the slope of the KM curve for events gets steeper in the last few months of those studies. And I think it was mentioned in the prepared remarks that that's a critical time for Helios-B. Should we expect a similar trajectory for the placebo arm in the last few additional months for Helios-B that you added to the stats plan? And would that widen the delta? And can you talk a little bit more about what your expectations are for the events during that time of the study?

Jeff Poulton: Hi. Thanks for taking my question. In both ATTRibute and ATTR-ACT studies, the slope of the KM curve for events gets steeper in the last few months of those studies. I think it was mentioned in the prepared remarks that that's a critical time for HELIOS-B. Should we expect a similar trajectory for the placebo arm in the last few additional months for HELIOS-B that you added to the stats plan, and would that widen the delta? Can you talk a little bit more about what your expectations are for the events during that time of the study?

Maury Raycroft: Hi. Thanks for taking my question. In both ATTRibute and ATTR-ACT studies, the slope of the KM curve for events gets steeper in the last few months of those studies. I think it was mentioned in the prepared remarks that that's a critical time for HELIOS-B. Should we expect a similar trajectory for the placebo arm in the last few additional months for HELIOS-B that you added to the stats plan, and would that widen the delta? Can you talk a little bit more about what your expectations are for the events during that time of the study?

Maury Raycroft: Hi, Thanks for taking my question.

Maury Raycroft: In both attribute and attracts studies the slope of the km curve for events get steeper in the last few months of those studies and I think it was mentioned in the prepared remarks that that's a critical time for us.

Maury Raycroft: Helios B should we expect a trajectory for the placebo arm in the last few additional months opera Helios B.

Maury Raycroft: Added to the stats plan and without widened the Delta can you talk a little bit more about what your expectations are for the events during that time.

Yvonne L. Greenstreet: Yeah, no, that's a question. And clearly, you know, I think the critical period of the study, as you say, is at the end of the study and in this disease, where patients continue to progress. So, you know, we do expect that that's a period where we'll see most events. Pushkal, anything else you want to add?

Maury Raycroft: Of the study.

Yvonne Greenstreet: Yeah. No, that's a great question. And clearly, I think the critical period of a study, as you say, is at the end of the study in this disease where patients continue to progress. So we do expect that that's the period where we'll see most events. Pushkal, anything else you want to add?

Speaker Change: Yes, no that's a.

Yvonne L. Greenstreet: Great Great question, and clearly I think the critic.

Yvonne L. Greenstreet: Critical period of the study as you said at the end of the study in this disease, where patients continues to progress. So we do expect that that's the period, where we will see most events.

Pushkal Garg: Pushkal, anything else you want to add? Well, there's nothing to add, Yvonne.

Pushkal, anything else you want to add?

Pushkal Garg: Well, there's nothing to add, Yvonne. You covered it.

Pushkal Garg: I was going to add to that, but I think you covered it already.

Jeff Poulton: I don't think there's anything to add, Yvonne. I think you covered it.

Pushkal Garg: I don't think there's anything to add, Yvonne. I think you covered it.

Yvonne L. Greenstreet: Anything else.

Speaker Change: Has anything to add about any covenant.

Operator: Okay, okay, thanks for taking my question. One moment for our next question.

Maury Raycroft: Okay, okay, thanks for taking my question.

Jeff Poulton: Okay. Okay. Thanks for taking my question.

Maury Raycroft: Okay. Okay. Thanks for taking my question.

Speaker Change: Okay. Okay. Thanks for taking my question.

Operator: One moment for our next question. Our next question comes from Gary Nachman with Raymond James. You may proceed.

Operator: One moment for our next question.

Operator: One moment for our next question. And our next question comes from Gary Nachman with Raymond James. You may proceed.

Operator: And our next question comes from Gary Nachman with Raymond James. Please proceed.

Operator: And our next question comes from Gary Gary Nachman with Raymond James You May proceed.

Pushkal Garg: Thanks. Good morning. So in ATTR-CM, are you still just thinking of Vutri as primarily a monotherapy drug as tafamidis continues to grow as standard of care in ATTR-CM? If the combo data with TAF are positive enough and show enough of a benefit over TAF alone, would you reconsider that thinking? And what are you doing now to prepare for the launch in CM? Just some details there would be helpful. Thank you.

Gary Nachman: Thanks. Good morning. So in ATTR-CM, are you still just thinking of Vutri as primarily a monotherapy drug as tafamidis continues to grow as standard of care in ATTR-CM? If the combo data with TAF are positive enough and show enough of a benefit over TAF alone, would you reconsider that thinking? And what are you doing now to prepare for the launch in CM? Just some details there would be helpful. Thank you.

Operator: Okay.

Gary Nachman: Thanks. Good morning. So in <unk> are you still just thinking of victory is primarily a monotherapy drug as <unk> continues to grow as standard of care and ATP RCN. If the combo data with caps are positive and show enough of a benefit over a task alone would you reconsider.

Gary Nachman: That thinking.

Gary Nachman: And what are you doing now to prepare for the launch in CF just some details there would be helpful. Thank you.

Gary Nachman: Thanks, good morning. So, in ATTRCM, are you still just thinking of vutri as primarily a monotherapy drug as [inaudible] continues to grow as standard of care and TTRCM, if the combo data with [inaudible] are positive enough and show enough of a benefit over [inaudible] alone, would you reconsider that thinking? And what are you doing to prepare for the launch, in CM? Just some details here would be helpful. Thank you. Yeah, no, some really good questions there. So Tolga, maybe you want to talk about how we're looking at the cardiomyopathy market and, you know, how we're preparing for launch. I mean, clearly, we are playing to win in this space. We're very excited about the opportunity to get into this very rapidly growing category.

Gary Nachman: Thanks, good morning. So, in ATTRCM, are you still just thinking of vutri as primarily a monotherapy drug as TAFAMIDIS continues to grow as standard of care and TTRCM, if the combo data with TAF are positive enough and show enough of a benefit over TAF alone, would you reconsider that thinking? And what are you doing to prepare for the launch, in CM? Just some details here would be helpful. Thank you.

Yvonne Greenstreet: Yeah. No, some really good questions there. So Tolga, maybe you want to talk about how we're looking at the cardiomyopathy market and how we're preparing for launch. I mean, clearly, we're playing to win in this space. We're very excited about the opportunity of getting into this very rapidly growing category. Tolga?

Gary Nachman: Yes, there are some really good questions that the toga, maybe you want to talk about how we're looking at.

Yvonne L. Greenstreet: Cardiomyopathy market.

Yvonne L. Greenstreet: How are we preparing for launch I mean, clearly we're playing we're playing to win in this space. We're very excited about the opportunity of getting into this very rapidly.

Yvonne L. Greenstreet: Yeah, no, some really good questions there. So Tolga, maybe you want to talk about how we're looking at the cardiomyopathy market and, you know, how we're preparing for launch. I mean, clearly, we are playing to win in this space. We're very excited about the opportunity to get into this very rapidly growing category. Tolga?

Tolga Tanguler: Tolga?

Tolga Tanguler: Growing category silica, yes. Thank you that's exactly right. We're really here to play to win and look at the end of the day, we need to look at the fundamentals of this category. There are 80 patients 80% of the patients remain on diagnose. This is a rapidly progressing disease with irreversible damages and.

Jeff Poulton: Yeah. No, thank you. That's exactly right. We're really here to play to win. And look, at the end of the day, we need to look at the fundamentals of this category. There are 80% of the patients remain undiagnosed. This is a rapidly progressing disease with irreversible damages. And frankly, patients and physicians are both looking at quickly being able to deal with the disease as quickly as possible. So if you look at the pharmacodynamics of what AMVUTTRA has to offer and how we impact the disease-causing protein at the upstream and rapidly knocking down that toxic protein, that is going to be a key clear differentiator. At the end of the day, we know that AMVUTTRA provides speed, depth, and duration as early as the first dose. And this is what physicians are really looking for.

Tolga Tanguler: Yeah. No, thank you. That's exactly right. We're really here to play to win. And look, at the end of the day, we need to look at the fundamentals of this category. There are 80% of the patients remain undiagnosed. This is a rapidly progressing disease with irreversible damages. And frankly, patients and physicians are both looking at quickly being able to deal with the disease as quickly as possible.

Tolga Tanguler: Thank you. That's exactly right. We're really here to play to win. And look, at the end of the day, we need to look at the fundamentals of this category. 80% of the patients remain undiagnosed. This is a rapidly and progressing disease with irreversible damages. And frankly, patients and physicians are both looking at quick ways to deal with the disease as quickly as possible. So, if you look at the pharmacodynamics of what AMVUTTRA has to offer and how we impact the disease-causing protein at the upstream and rapidly knock down that toxic protein, that is going to be a key clear differentiator. At the end of the day, we know that AMVUTTRA provides speed, depth, and duration as early as the first dose. And this is what physicians are really looking for. It is true, and it's great to see that TAFAMIDIS is making great progress, but it's not just the standard of care, it's the only treatment in this category.

Tolga Tanguler: We're really here to play to win. And look, at the end of the day, we need to look at the fundamentals of this category. 80% of the patients remain undiagnosed. This is a rapidly progressing disease with irreversible damages. And frankly, patients and physicians are both looking for ways to deal with the disease as quickly as possible. So if you look at the pharmacodynamics of what Amutra has to offer and how we impact the disease-causing protein at the upstream and rapidly knock down that toxic protein, that is going to be a key clear differentiator. At the end of the day, we know that Amutra provides speed, depth, and duration as early as the first dose. And this is what physicians are really looking for. It is true, and it's great to see that Tefamidis is making great progress, but it's not just the standard of care. It's the only treatment in this category.

Tolga Tanguler: And frankly patients and physicians are both looking at quickly be able to deal with the disease as quickly as possible. So if you look at the.

Tolga Tanguler: So if you look at the pharmacodynamics of what AMVUTTRA has to offer and how we impact the disease-causing protein at the upstream and rapidly knocking down that toxic protein, that is going to be a key clear differentiator. At the end of the day, we know that AMVUTTRA provides speed, depth, and duration as early as the first dose. And this is what physicians are really looking for.

Tolga Tanguler: The pharmacodynamics of what <unk> has to offer and how we impact the disease, causing protein at the upstream and rapidly knocking down the toxic protein that is going to be a key clear differentiator.

Tolga Tanguler: At the end of the day, we know that <unk> provides speed depth and duration as early as the first dose and this is what physicians are really looking for it is true and it's great to see the parameters is making great progress, but it's not just the standard of care. It's the only cure in this category. So one needs to remember that and I think Dave.

Tolga Tanguler: And this is what physicians are really looking for. It is true, and it's great to see that Tefamidis is making great progress, but it's not just the standard of care. It's the only treatment in this category.

Jeff Poulton: It is true, and it's great to see that tafamidis is making great progress, but it's not just the standard of care. It's the only care in this category. So one needs to remember that. And I think Dave just reiterated the fact that the LOE in the US in particular is going to remain until the end of 2028, which really means mainly because of the access pressures, but also, again, the way this product is going to be positioned and obviously, depending on the data, we need to demonstrate. We believe we're going to be able to actually be the first-line agent. And after all, there are going to be, as Pushkal indicated, a substantial number of patients who are being treated that are continuing to progress. And we believe physicians and patients are looking for an alternative.

Tolga Tanguler: It is true, and it's great to see that tafamidis is making great progress, but it's not just the standard of care. It's the only care in this category. So one needs to remember that. And I think Dave just reiterated the fact that the LOE in the US in particular is going to remain until the end of 2028, which really means mainly because of the access pressures, but also, again, the way this product is going to be positioned and obviously, depending on the data, we need to demonstrate.

Tolga Tanguler: So, one needs to remember that. And I think they've just reiterated the fact that the LOE in the U.S., in particular, is going to remain until the end of 2028, which really means - mainly because of the access pressures, but also again, the way this product is going to be positioned, and obviously, pending on the data, we need to demonstrate - we believe we're going to be able to actually be the first line agent. And after all, there are going to be, as Pushkar indicated, a substantial number of patients who are being treated, that are continuing to progress. And we believe physicians and patients are looking for an alternative. And in that case, we believe it's going to be a very important option in the arsenal of the physicians in this difficult disease.

Tolga Tanguler: <unk>.

Tolga Tanguler: <unk> reiterated the fact that the low <unk> in the U S. In particular is going to remain on until the end of 2028, which really means.

Tolga Tanguler: Mainly because of the access pressures, but also again the way this product is going to be position and obviously pending on the data we need to demonstrate we believe we're going to be able to actually be the first line agents and after all there are going to be as a pushcart indicated a substantial number of patients.

Tolga Tanguler: We believe we're going to be able to actually be the first-line agent. And after all, there are going to be, as Pushkal indicated, a substantial number of patients who are being treated that are continuing to progress. And we believe physicians and patients are looking for an alternative.In that case, we believe it's going to be a very important option in the armamentarium of the physicians in this difficult disease.

Tolga Tanguler: And after all, there are going to be, as Pushkar indicated, a substantial number of patients who are being treated that are continuing to progress. And we believe physicians and patients are looking for an alternative. And in that case, we believe it's going to be a very important option in the arsenal of the physicians in this difficult disease.

Tolga Tanguler: Who are being treated.

Tolga Tanguler: There are continued to progress and we believe that physicians and patients are looking for an alternative and in that case, we believe it's going to be a very important option.

Jeff Poulton: In that case, we believe it's going to be a very important option in the armamentarium of the physicians in this difficult disease.

Tolga Tanguler: In the armamentarium of physicians in this difficult disease, that's absolutely spot on.

Yvonne L. Greenstreet: That's absolutely spot on, Tolga, and I think it's just instructive when you reflect on our expanded access group, where, you know, within a matter of, you know, a very short space of time, we maxed out on the program. I think that, again, is just an illustration of the level of unmet medical need in this space and the fact that, you know, patients continue to progress on TAFAMIDIS and are looking for alternative therapies. - Next question.

Yvonne Greenstreet: That's absolutely spot on, Tolga. And I think it's just instructive when you reflect on our expanded access program where within a matter of a very short space of time, we maxed out on the program. I think that, again, is just an illustration of the level of unmet medical need in this space and the fact that patients continue to progress on tafamidis and are looking for alternative therapies. Next question.

Yvonne L. Greenstreet: It's a constructive when you reflect on our expanded access program.

Yvonne L. Greenstreet: Within a matter of.

Yvonne L. Greenstreet: Very short space of time.

Yvonne L. Greenstreet: We maxed out on the program I think that again, it's just an illustration of the.

Yvonne L. Greenstreet: The level of unmet medical need is just based on the fact that.

Yvonne L. Greenstreet: Patients continue to progress on the Fabulous and they're looking for alternative therapies.

Speaker Change: Next question.

Operator: A moment for our next question. Our next question comes from the line of Tazeen Ahmad with B of A securities. You may proceed.

Operator: One moment for our next question. Our next question comes from the line of Tazeen Ahmad with B of A Securities. You may proceed.

Speaker Change: One moment for our next question.

Tazeen Ahmad: Our next question comes from the line of <unk> Ahmad with B of a securities you May proceed.

Tazeen Ahmad: Hi, good morning. Thanks for taking my questions - or question. I appreciate all the color you've been giving about expectations for what to show on the top line. But in terms of trying to drill into the detail on mortality specifically, you know, fully understanding there's a lot of undermet need, even with what's available right now, how important is it going to be to know when the mortality benefit kicks in for vutri? So, I think for TAFAMID it is that benefit in the Pfizer study started around month 18. Is it going to be important to have a number at the end that hovers around that month 18? Or, potentially, could it be better than that? Thanks.

Tazeen Ahmad: Hi. Good morning. Thanks for taking my question. I appreciate all the color you've been giving about expectations for what to show at the top line. But in terms of trying to drill into the detail on mortality specifically, fully understanding there's a lot of unmet need even with what's available right now, how important is it going to be to know when the mortality benefit kicks in for Vutri? So I think for tafamidis, that benefit in the Pfizer study started around month 18. Is it going to be important to have a number at the end that hovers around that month 18, or potentially, could it be better than that? Thanks.

Tazeen Ahmad: Hi, good morning, Thanks for taking my question.

Speaker Change: Question I have.

Tazeen Ahmad: Appreciate all the color you've been giving about expectations for outlet to show at the top line, but in terms of trying to drill into the detail on mortality specifically <unk>.

Tazeen Ahmad: Really understanding there's a lot of under met need even with what's available right now.

Tazeen Ahmad: Is it going to be to know when the mortality benefit kicks in for <unk>. So I think Brexit damn it is that that benefit in the Pfizer study started around month 18.

Tazeen Ahmad: So I think for tafamidis, that benefit in the Pfizer study started around month 18. Is it going to be important to have a number at the end that hovers around that month 18, or potentially, could it be better than that? Thanks.

Tazeen Ahmad: Is it going to be important to have.

Tazeen Ahmad: At the end of that hovers around that Monday tuner potentially could it be better than that thanks.

Pushkal Garg: Pushkal, I have one for you. Yeah, thanks, Tazeen. Look, I think what we've seen in terms of mortality separation, if I call both for tefamidus and the acaramidus data that are under review, is around month 18 is when we start to see the mortality separation. You know, look, we're encouraged by what we saw coming out of the original Apollo data and then the Apollo B data where we seem to see evidence, again, in underpowered studies of separation on mortality occurring earlier, roughly month nine or so.

Yvonne L. Greenstreet: Pushkal, I have one for you.

Yvonne Greenstreet: Pushkal, you have some for you.

Pushkal Garg: Yeah, thanks, Tazeen. Look, I think what we've seen in terms of mortality separation, if I call both for TAFAMIDIS and the ACORAMIDIS data that are under review, is around month 18 is when we start to see the mortality separation. You know, look, we're encouraged by what we saw coming out of the original Apollo data and then the Apollo-B data where we seem to see evidence, again, in underpowered studies of separation on mortality occurring earlier, roughly month 9 or so. So, we'll have to see in Helios-B if we're able to recapitulate those results in this larger, powered study. You know, again, I think it's going to be important to look at the totality of all the data that come out. Obviously, that will be one parameter. What is the mortality difference? When is it emerging? What about hospitalizations? And then, again, what's happening in terms of disease stabilization? So, we think all of those are going to be important parameters. But look, the early data that we've seen from Apollo, and particularly Apollo-B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect in potentially earlier separation.

Jeff Poulton: Yeah. Thanks, Tazeen. Look, I think what we've seen in terms of mortality separation, if I call both for tafamidis and the acoramidis data that are under review, is around month 18 is when you start to see the mortality separation. Look, we're encouraged by what we saw coming out of actually the original APOLLO data and then the APOLLO-B data where we seem to see evidence, again, in underpowered studies of separation on mortality occurring earlier, roughly month nine or so. So we'll have to see in HELIOS-B if we're able to recapitulate those results in this larger powered study. Again, I think it's going to be important to look at the totality of all the data that come out. Obviously, that will be one parameter. What is the mortality difference? When is it emerging? What about hospitalizations?

Pushkal Garg: Yeah. Thanks, Tazeen. Look, I think what we've seen in terms of mortality separation, if I call both for tafamidis and the acoramidis data that are under review, is around month 18 is when you start to see the mortality separation. Look, we're encouraged by what we saw coming out of actually the original APOLLO data and then the APOLLO-B data where we seem to see evidence, again, in underpowered studies of separation on mortality occurring earlier, roughly month nine or so.

Speaker Change: Please go ahead.

Pushkal Garg: Yes. Thanks, <unk> look I think I think what we've seen in terms of mortality separation that break the call both for <unk> and the <unk> data that are under review is around month 18 is when you start to see the mortality separation look we're encouraged by what we saw coming out of actually the original Apollo data and then the Apollo data.

Pushkal Garg: Where we seem to see evidenced again, an underpowered studies of separation on mortality occurring earlier roughly month nine or so so we'll have to see in Helios b, if we're able to recapitulate those results in this larger powered study.

Pushkal Garg: So we'll have to see in Helios B if we're able to recapitulate those results in this larger, powered study. You know, again, I think it's going to be important to look at the totality of all the data that come out. Obviously, that will be one parameter. What is the mortality difference? When is it emerging? What about hospitalizations? And then, again, what's happening in terms of disease stabilization? So we think all of those are going to be important parameters. But look, the early data that we've seen from Apollo and particularly Apollo B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect in potentially earlier separation.

Pushkal Garg: So we'll have to see in HELIOS-B if we're able to recapitulate those results in this larger powered study. Again, I think it's going to be important to look at the totality of all the data that come out. Obviously, that will be one parameter. What is the mortality difference? When is it emerging? What about hospitalizations?

Pushkal Garg: Again, I think it's going to be important to look at the totality of all the data that come out obviously that will be one parameter what is the mortality difference when it's an emerging what about hospitalizations and then again, what's happening in terms of disease stabilization.

Pushkal Garg: What about hospitalizations? And then, again, what's happening in terms of disease stabilization? So we think all of those are going to be important parameters. But look, the early data that we've seen from Apollo and particularly Apollo B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect in potentially earlier separation. Thanks, Pushkal. Next question.

What about hospitalizations? And then, again, what's happening in terms of disease stabilization? So we think all of those are going to be important parameters. But look, the early data that we've seen from Apollo and particularly Apollo B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect in potentially earlier separation.

Jeff Poulton: And then again, what's happening in terms of disease stabilization? So we think all of those are going to be important parameters. But look, the early data that we've seen from APOLLO and particularly APOLLO-B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect and potentially earlier separation.

Pushkal Garg: And then again, what's happening in terms of disease stabilization? So we think all of those are going to be important parameters. But look, the early data that we've seen from APOLLO and particularly APOLLO-B, which is in the same patient population, gives us a lot of confidence that we should be able to see a substantial effect and potentially earlier separation.

Pushkal Garg: So we think all of those are going to be important parameters, but look the early data that we've seen from Apollo and particularly Apollo B, which is in the same patient population.

Pushkal Garg: It gives us a lot of confidence that we should be able to see a substantial effect and potentially earlier separation.

Yvonne Greenstreet: Thanks, Pushkal. Next question.

Pushkal Garg: Crystal.

Yvonne L. Greenstreet: Thanks, Pushkal. Next question.

Pushkal Garg: Next question.

Operator: One moment for our next question. Our next question comes from line of Ritu Baral with T.D. Cohen. You may proceed.

Operator: One moment for our next question. Our next question comes from the line number two, Boris with TD Cowen. You may proceed.

Speaker Change: One moment for our next question.

Operator: Okay.

Baral: Our next question comes from the line of her to borrow with TD Cowen you May proceed.

Ritu Baral: Good morning, guys. Thanks for taking the question. I want to thank you for the detail that you’ve given on the top line release, but I wanted to just dig a little further if I could. Pushkal, and Yvonne, when you mentioned that you would give us some more details on subpopulation. Will you be able to give us sort of drivers of potential composite benefit of the TAF subpopulation or the composite - I’m sorry, combined subpopulation as well just given the conversation – investor conversation and focus on hospitalizations, driving previous data sets where we get sort of a tell on what the major drivers are. And then just a very quick follow-up on data release. You drop proBNP and echo parameters to exploratory endpoints, and those are ones that at least our KOLs actually deeply, deeply value. We were wondering if those would be released with first medical presentation. Thank you.

Ritu Baral: Good morning, guys. Thanks for taking the question. I want to thank you for the detail that you've given on the top line release, but I wanted to just dig a little further if I could. Pushkal and Yvonne, when you mentioned that you would give us some more details on subpopulation, will you be able to give us sort of drivers of potential composite benefit of the TAF subpopulation or the composite, I'm sorry, combined subpopulation as well, just given the investor conversation and focus on hospitalizations driving previous data sets? Will we get sort of a tell on what the major drivers are? And then just a very quick follow-up on data release. You drop proBNP and echo parameters to exploratory endpoints, and those are ones that at least our KOLs actually deeply, deeply value. We were wondering if those would be released with first medical presentation.

Baral: Good morning, guys. Thanks for taking the question.

Operator: I want to thank you for the detail that you've given on the top line release, but I wanted to just dig a little further if I could.

Operator: Lets call anyone when you when you mentioned that you would give us some more details on subpopulation.

Operator: Will you be able to give us sort of drivers of potential composite benefit of the Tau sub population or the composite I'm, sorry, combined sub population as well.

Operator: Just given the conversation investor conversation and focus on hospitalizations dragging previous datasets, where we get sort of a tail on what the major drivers are and then just a very quick follow up on data release.

Operator: Will we get sort of a tell on what the major drivers are? And then just a very quick follow-up on data release. You drop the pro BMP and echo parameters to exploratory endpoints, and those are ones that at least our KOLs actually deeply, deeply value. We were wondering if those would be released with the first medical pre-release.

Ritu Baral: Will we get sort of a tell on what the major drivers are? And then just a very quick follow-up on data release. You drop proBNP and echo parameters to exploratory endpoints, and those are ones that at least our KOLs actually deeply, deeply value. We were wondering if those would be released with first medical presentation. Thank you.

Operator: Dropped pro BNP and echo parameters to exploratory endpoints and those are ones that at least our kols actually deeply deeply value. We were wondering if those would be released with first medical presentation.

Yvonne L. Greenstreet: Yes, Ritu I mean, I think that’s a – yes, it’s a good question. And I think we’ve been quite clear about how we’re going to be handling the release. I mean, clearly we’re going to show kind of p values for the primary endpoints and key secondary endpoints. So, we’re going to provide some information on safety, obviously, that’s an important consideration. And we’ve said we will give some information with respect to subgroups. I know he’s particularly interested in the TAFAMIDIS subgroup, but I think that’s where we stand at this point in time. We’re kind of obviously looking forward to being able to share the top line results. We’re still on track for end of June, early July. And then, of course, we will present fulsome data at a proximal medical congress. So, stay tuned. We will be providing some additional color over and above P-values for the primary and secondary endpoints, but that’s probably all we can say at this point in time. Your second question?

Ritu Baral: Thank you.

Yvonne Greenstreet: Yeah, over to you. I mean, I think that's a good question. And I think we've been quite clear about how we're going to be handling the release. I mean, clearly, we're going to show kind of p-values for the primary endpoints and key secondary endpoints. So we're going to provide some information on safety. Obviously, that's an important consideration. And we've said we will give some information with respect to subgroups. I know everyone's particularly interested in the tafamidis subgroup, but I think that's where we stand at this point in time. We're kind of obviously looking forward to being able to share the top line results. We're still on track for end of June, early July. And then, of course, we'll present fulsome data at a prominent medical congress. So stay tuned.

Speaker Change: Yes, Richard.

Ritu Baral: Yes.

Ritu Baral: It's a good question and I think I think we've been quite clear about how we're going to be handling the release I mean, clearly we're going to show kind of P values for the primary endpoint.

Ritu Baral: Key secondary endpoints, so we're going to provide some information on safety, obviously thats an important consideration and then we said we will give some.

Yvonne Greenstreet: Obviously, that's an important consideration. And we've said we will give some information with respect to subgroups. I know everyone's particularly interested in the tafamidis subgroup, but I think that's where we stand at this point in time. We're kind of obviously looking forward to being able to share the top line results. We're still on track for end of June, early July. And then, of course, we'll present fulsome data at a prominent medical congress. So stay tuned.

Ritu Baral: Information with respect the subgroups lineup was particularly interested in the <unk> subgroup.

Ritu Baral: I think that that's where we stand at this point in time, we had kind of.

Yvonne L. Greenstreet: But, you know, I think that's where we stand at this point in time; we're kind of obviously looking forward to being able to share the top line results. We're still on track for, you know, the end of June or early July. And then, of course, you know, we'll present fulsome data at a, you know, proximal medical congress. So stay tuned. You know, we will be providing some additional color over and above the key values for the primary and secondary endpoints. But that's probably all we can say at this point in time. Your second question. I think, Ritu, you were just talking about the NT PRO BNP and ECHO data.

But, you know, I think that's where we stand at this point in time; we're kind of obviously looking forward to being able to share the top line results. We're still on track for, you know, the end of June or early July. And then, of course, you know, we'll present fulsome data at a, you know, proximal medical congress. So stay tuned. You know, we will be providing some additional color over and above the key values for the primary and secondary endpoints. But that's probably all we can say at this point in time. Your second question.

Yvonne L. Greenstreet: Looking forward to.

Yvonne L. Greenstreet: Being able to SaaS the topline results with FID on track for.

Yvonne L. Greenstreet: In the end of June at each of the eye and then of course.

Yvonne L. Greenstreet: We will present full data at a proximal medical Congress so stay tuned.

Yvonne Greenstreet: We will be providing some additional color over and above p-values for the primary and secondary endpoints, but that's probably all we can say at this point in time. Your second question?

Yvonne L. Greenstreet: We will be providing some additional color over and above.

Yvonne L. Greenstreet: <unk> for the primary and secondary endpoints, but that's probably all we can say.

Yvonne L. Greenstreet: At this point in time.

It was on the - I think, Ritu, you were just talking about the NT PRO BNP and ECHO data.

Ritu Baral: It was on the -

Yvonne L. Greenstreet: Your second question.

Jeff Poulton: I think, over to you. You were just talking about the NT-proBNP and the echo data. Look, I think we haven't mapped out exactly what will be the top line presentation. Obviously, it will be limited in terms of what we can, we want to make sure that we, and we'll work with the investigators to make sure that there's a fulsome presentation. But you can imagine with a data set like this that there'll be a number of presentations to speak to the various aspects of the data. And certainly, yeah, BNP, echo, etc., over to you, are important parameters that we'll be reporting on.

Pushkal Garg: I think, over to you. You were just talking about the NT-proBNP and the echo data. Look, I think we haven't mapped out exactly what will be the top line presentation. Obviously, it will be limited in terms of what we can, we want to make sure that we, and we'll work with the investigators to make sure that there's a fulsome presentation.

Pushkal Garg: You were just [inaudible] the NT-proBNP and the echo data. Look, I think, we haven’t mapped out exactly what will be in the top line presentation. Obviously, we’ll be limited in terms of what we can, we want to make sure that we and we’ll work with the investigators to make sure that there’s a fulsome presentation. But you can imagine with a data set like this that there’ll be a number of presentations to speak to the various aspects of the data. And certainly BNP, echo, et cetera, or two are important parameters that we’ll be reporting on.

Speaker Change: Richard you were just about the anti <unk> Echo data look I think we haven't mapped out exactly what will be the topline presentation, obviously will be limited in terms of what we can and want to make sure that we will.

Pushkal Garg: Look, I think, you know, we haven't mapped out exactly what the top line presentation will be. Obviously, it will be limited in terms of what we can do, but we want to make sure that we, you know, and we'll work with the investigators to make sure that there's a fulsome presentation. But you can imagine with a data set like this, that there'll be a number of presentations speaking to the various aspects of the data. And certainly, yeah, BNP, ECHO, et cetera, Ritu, are important parameters that we'll be reporting on. Absolutely, Pascal.

Look, I think, you know, we haven't mapped out exactly what the top line presentation will be. Obviously, it will be limited in terms of what we can do, but we want to make sure that we, you know, and we'll work with the investigators to make sure that there's a fulsome presentation. But you can imagine with a data set like this, that there'll be a number of presentations speaking to the various aspects of the data. And certainly, yeah, BNP, ECHO, et cetera, Ritu, are important parameters that we'll be reporting on.

Pushkal Garg: The work with the investigators to make sure that Theres, a fulsome presentation, but you can imagine with a data set like this that there'll be a number of presentations to speak to the various aspects of the data and certainly BNP echo et cetera are important parameters that maybe reporting on absolutely.

Pushkal Garg: But you can imagine with a data set like this that there'll be a number of presentations to speak to the various aspects of the data. And certainly, yeah, BNP, echo, etc., over to you, are important parameters that we'll be reporting on.

Yvonne L. Greenstreet: Absolutely, Pushkal. I mean, we’re clearly very interested in those parameters, but you kind of have to prioritize how many secondary endpoints you have with respect to managing alpha. And clearly, we’re pretty confident about what we’re going to be able to demonstrate with those additional endpoints. But they’re going to be endpoints that we’ll be able to share. But we really wanted to prioritize the very clinically relevant secondary endpoints. And we’ve discussed what those are with respect to disease progression, mortality, as well as a six-minute walk test in KCCQ.

Yvonne L. Greenstreet: I mean, you know, we're clearly very interested in those parameters, but you kind of have to prioritize how many secondary endpoints you have with respect to managing alpha. And, you know, clearly, we're pretty confident about what we're going to be able to demonstrate for those additional endpoints. But, you know, they're going to be endpoints that we'll be able to share. But we really wanted to prioritize, you know, the very clinically relevant secondary endpoints. And we discussed what those are with respect to disease progression, mortality, as well as six-minute walks off in KCCQ. Great, thank you. Thanks. One moment.

I mean, you know, we're clearly very interested in those parameters, but you kind of have to prioritize how many secondary endpoints you have with respect to managing alpha. And, you know, clearly, we're pretty confident about what we're going to be able to demonstrate for those additional endpoints. But, you know, they're going to be endpoints that we'll be able to share. But we really wanted to prioritize, you know, the very clinically relevant secondary endpoints. And we discussed what those are with respect to disease progression, mortality, as well as six-minute walks off in KCCQ.

Yvonne Greenstreet: I mean, absolutely, Pushkal. I mean, we're clearly very interested in those parameters, but you kind of have to prioritize how many secondary endpoints you have with respect to managing alpha. And clearly, we're pretty confident about what we're going to be able to demonstrate with those additional endpoints. But they're going to be endpoints that we'll be able to share. But we really wanted to prioritize the very clinically relevant secondary endpoints. And we've discussed what those are with respect to disease progression, mortality, as well as 6-minute walk tests in case you seek you.

Yvonne L. Greenstreet: We're clearly very interested in those practice, but you kind of have surprised by.

Yvonne L. Greenstreet: How many secondary endpoints you have with respect to managing alpha.

Yvonne L. Greenstreet: Clearly, where we are pretty confident about what we're going to be able to demonstrate that those additional.

Yvonne Greenstreet: But they're going to be endpoints that we'll be able to share. But we really wanted to prioritize the very clinically relevant secondary endpoints. And we've discussed what those are with respect to disease progression, mortality, as well as 6-minute walk tests in case you seek you.

Yvonne L. Greenstreet: Endpoints.

Yvonne L. Greenstreet: They're going to be endpoints that we'll be able to SaaS.

Yvonne L. Greenstreet: But we really wanted to prioritize the.

Yvonne L. Greenstreet: The very clinically relevant.

Yvonne L. Greenstreet: Secondary endpoints.

Yvonne L. Greenstreet: With respect to disease progression mortality as well as a six minute walk in cases in Q.

Ritu Baral: Great. Thank you.

Great, thank you. Thanks. One moment.

Ritu Baral: Great, thank you.

Yvonne Greenstreet: Thanks. Yeah.

Operator: One moment for our next question. And our next question is from Jessica Fye with JP Morgan. You may proceed.

Speaker Change: Great. Thank you.

Operator: One moment for our next question, and our next question is from Jessica Fye with J.P. Morgan. You may proceed. Hey guys, good morning.

One moment for our next question, and our next question is from Jessica Fye with J.P. Morgan. You may proceed.

Operator: One moment for our next question. Our next question is from Jessica Fye with JP Morgan. You may proceed.

Yvonne L. Greenstreet: Yes.

Speaker Change: One moment for our next question.

Operator: And our next question is from Jessica Fye with Jpmorgan you May proceed.

Jessica Fye: Hey, guys. Good morning. Thanks for taking my question. For HELIOS-B, when you talk about when you talk about any impact on outcomes being clinically meaningful, on the one hand, I completely hear you. These are outcomes. But then again, when we ask physicians about this, they usually have a magnitude or a threshold in mind that's not just any benefit. So I'm curious how to kind of reconcile that, or maybe you could just elaborate there.

Jessica Fye: Hey, guys. Good morning, Thanks for taking my question.

Jessica Fye: Helios B when you talk about.

Jessica Fye: And when you talk about any impact on outcomes being clinically meaningful on the one hand I completely hear you. This their outcomes, but then again when we ask physicians about this they usually have a magnitude or a threshold in mind thats not just any benefit so I'm curious how to kind of reconcile that or maybe you could just elaborate there.

Jessica Fye: Hey, guys. Good morning. Thanks for taking my question. For Helios-B, when you talk about any impact on outcomes being clinically meaningful. On the one hand, I completely hear you their outcomes. But then again, when we ask physicians about this, they usually have a magnitude or a threshold in mind that’s not just any benefit. So, I’m curious how to kind of reconcile that. Or maybe you could just elaborate there?

Pushkal Garg: Yes. Look, Jessica, I think, I don’t know that I can give you a lot more information other than to say, just have to, again, remember what the unmet need in this disease is that there are patients who currently, a large number of patients, as Tolga has outlined, many of them are undiagnosed and untreated, who have a steadily progressive disease that leads to irreversible damage, and ultimately patients pass away. And so what I think, and as evidenced by, as Yvonne highlighted, our EAP experience after Apollo-B, and that was in the setting without any outcomes benefit being demonstrated in IV drug. We rapidly enrolled a population of patients, many of whom were progressing on TAFAMIDIS, which was the only available therapy to them. So, it highlights the unmet need. So, we think that when we come forward with hopefully a positive Helios-B, showing an outcomes benefit, a mortality and hospitalization, along with these other differentiating factors that we’ve talked about, and an orthogonal mechanism that rapidly knocks down the disease causing protein of this disease, that we think that that’s going to address the key unmet needs for these patients. So, we’re looking forward to that and we’ll let the data speak for themselves. Thank you.

Pushkal Garg: Yeah. Look, Jessica, I think I don't know that I can give you a lot more information other than to say you just have to, again, remember what the unmet need in this disease is, that there are patients who currently a large number of patients, as Tolga has outlined, many of them are undiagnosed and untreated, who have a steadily progressive disease that leads to irreversible damage. And ultimately, patients pass away. And so what I think and as evidenced by, as Yvonne highlighted, our EAP experience after APOLLO-B, and that was in the setting without any outcomes benefit being demonstrated and IV drug, we rapidly rolled a population of patients, many of whom were progressing on tafamidis, which was the only available therapy to them. So it highlights the unmet need.

Jessica Fye: Yeah look Jessica I think.

Jessica Fye: I don't know that I can give you a lot more information other than to say is that again remember what the unmet need in this disease is that there are patients who currently.

Jessica Fye: A large number of patients as Targa has outlined many of them are on diagnosed and untreated.

Jessica Fye: Who have a steadily progressive disease.

Jessica Fye: That leads to irreversible damage and ultimately patients pass away.

Pushkal Garg: And so what I think and as evidenced by, as Yvonne highlighted, our EAP experience after APOLLO-B, and that was in the setting without any outcomes benefit being demonstrated and IV drug, we rapidly rolled a population of patients, many of whom were progressing on tafamidis, which was the only available therapy to them. So it highlights the unmet need.

Jessica Fye: And so what I think and as evidenced by <unk>.

Jessica Fye: So it highlights the unmet need. So we think that when we come forward with, hopefully, a positive Helios B, showing an outcomes benefit, mortality, and hospitalization, along with these other differentiating factors that we've talked about, and an orthogonal mechanism that rapidly knocks down the disease-causing protein of this disease, we think that that's going to address the key unmet needs for these patients. So we're looking forward to that, and we'll let the data speak for themselves.

Jessica Fye: <unk> highlighted.

Jessica Fye: Our EAP experience after Apollo B and that was in the setting without any outcomes benefit being demonstrated an IV drug we rapidly enrolled a population of patients. Many of them were progressing on to <unk>, which was the only available therapy to them. So it highlights the unmet need so we think that when we come forward with hopefully a positive helios b showing an outcomes benefit.

Pushkal Garg: So we think that when we come forward with hopefully a positive HELIOS-B showing an outcomes benefit, a mortality, and hospitalization, along with these other differentiating factors that we've talked about and an orthogonal mechanism that rapidly knocks down the disease-causing protein of this disease, that we think that that's going to address the key unmet needs for these patients. So we're looking forward to that. And we'll let the data speak for themselves.

Jessica Fye: Our mortality and hospitalization along with these other differentiating factors that we've talked about in an orthogonal mechanism that rapidly knock down the disease, causing protein of this disease that we think that thats going to address the key unmet needs for these patients. So we're looking forward to that.

Jessica Fye: And we'll let the data speak for themselves.

Jessica Fye: Thank you.

Jessica Fye: Okay.

Jessica Fye: Thank you.

Speaker Change: Thank you.

Operator: One moment for our next question. Our next question comes from the line of Kostas Biliouris with BMO Capital Markets. You may proceed.

Operator: One moment for our next question. Our next question comes from the line of Costas Biliouris with BMO Capital Markets. You may proceed.

Speaker Change: Our next question.

Kostas Biliouris: Our next question comes from the line of cost just Flores with BMO capital markets. You May proceed.

Kostas Biliouris: Good morning, everyone. Thanks for taking our question and congrats on the progress. A question from us on Helios-B, just for a change. How important do you think is the ratio between hospitalization events and deaths as a metric, especially when we compare different drugs? Do you look at this ratio as an important metric, or you just look at those two types of events together as a composite? Thank you.

Konstantinos Biliouris: Good morning, everyone. Thanks for taking our question, and congrats on the progress. A question from us on HELIOS-B just for a change. How important do you think is the ratio between hospitalization events and deaths as a metric, especially when we compare different drugs? Do you look at this ratio as an important metric, or you just look at those two types of events together as a composite? Thank you.

Kostas Biliouris: Good morning, everyone. Thanks for taking our question, and congrats on the progress. A question from us on HELIOS-B just for a change. How important do you think is the ratio between hospitalization events and deaths as a metric, especially when we compare different drugs? Do you look at this ratio as an important metric, or you just look at those two types of events together as a composite? Thank you.

Kostas Biliouris: Good morning, guys. Thanks for taking our question and congrats on the progress question from us on failures be desktop page.

Kostas Biliouris: How important do you think is the ratio between hospitalization events and deaths are domestic especially when we compare different drugs do you look at this.

Kostas Biliouris: <unk> is an important metric or do you just look at those two types of events to get that as a composites. Thank you.

Yvonne L. Greenstreet: Thanks for the question, Kostas. Pushkal, this is one to you.

Yvonne Greenstreet: Thanks for the question, Costas. Pushkal, this is on to you.

Speaker Change: Thanks for the question.

Pushkal Garg: Yes, no, I think it’s an interesting question, Kostas. I think, in general, we look at them together and we don’t make a huge, huge distinction here. I mean, I think part of the reason that composite endpoints like this were created was because hospitalizations tend to correlate very strongly with mortality events. And so, these are both clinically meaningful outcomes. And so, we would expect that they will both go directly in the same direction. That’s what we’ve seen with other drugs. That’s what we’ve seen throughout the cardiovascular disease area with lots of drugs and lots of different diseases, disease classes. So, I would expect them to go in similar directions, Kostas, and I think the main thing is seeing a benefit, hopefully in both of those that trend in the right direction.

Pushkal Garg: Okay.

Pushkal Garg: Yeah. No, I think it's an interesting question, Costas. I think in general, we look at them together, and we don't make a huge, huge distinction here. I mean, I think part of the reason this composite endpoints like this were created was because hospitalizations tend to correlate very strongly with mortality events. And these are both clinically meaningful outcomes. And so we would expect that they will both go directly in the same direction. That's what we've seen with other drugs. That's what we've seen throughout the cardiovascular disease area with lots of drugs and lots of different diseases, disease classes. So we would expect them to go in similar directions, Costas. And I think the main thing is seeing a benefit, hopefully, in both of those, the trend in the right direction.

Pushkal Garg: Yes, no I think it's an interesting question cuts I think in general we look at them together and we don't make a huge distinction here I mean I think.

Pushkal Garg: Part of the reason the composite endpoints like this were created was because.

Pushkal Garg: Hospitalizations tend to correlate very strongly with mortality events and so and these are both clinically meaningful outcomes and so we would expect that they will both go directionally in the same direction and that's what we've seen with other drug that's what we've seen throughout the cardiovascular.

Pushkal Garg: That's what we've seen with other drugs. That's what we've seen throughout the cardiovascular disease area with lots of drugs and lots of different diseases, disease classes. So we would expect them to go in similar directions, Costas. And I think the main thing is seeing a benefit, hopefully, in both of those, the trend in the right direction.

Pushkal Garg: That's what we've seen with other drugs. That's what we've seen throughout the cardiovascular, you know, disease area with lots of drugs and lots of different diseases, disease classes. So I would expect them to go in similar directions, Kostas, and I think the main thing is seeing a benefit, hopefully, in both of those. The trend in the right direction.

Pushkal Garg: In a disease area with lots of drugs in lots of different diseases disease classes. So.

Pushkal Garg: We would expect them to go in similar directions cost us and I think the main thing is seeing a benefit hopefully both of those the trend in the right direction.

Operator: Thank you. Very helpful. One moment for our next question.

Kostas Biliouris: Thank you. Very helpful.

Konstantinos Biliouris: Thank you. Very helpful.

Kostas Biliouris: Thank you. Very helpful.

Speaker Change: Thank you very helpful.

Operator: One moment for our next question. Our next question comes from the line of Ellie Merle with UBS. You may proceed.

Operator: One moment for our next question.

Operator: One moment for our next question. And our next question comes from the line of Ellie Merle with UBS. You may proceed.

Operator: And our next question comes from the line of Ellie Merle with UBS. You may proceed.

Operator: And our next question comes from the line of Ellie Merle with UBS you May proceed.

Jessica Fye: Hi. Thanks for taking the question. In ATTR, what proportion of patients do you think are mixed phenotype in the real world? And how is this being defined both by doctors and by payers? And do you see silencers as more likely to gain a larger share in this population versus stabilizers longer term when we look to the cardiomyopathy expansion? Thanks.

Ellie Merle: Hi. Thanks for taking the question. In ATTR, what proportion of patients do you think are mixed phenotype in the real world? And how is this being defined both by doctors and by payers? And do you see silencers as more likely to gain a larger share in this population versus stabilizers longer term when we look to the cardiomyopathy expansion? Thanks.

Ellie Merle: Hi, Thanks for taking the question.

Ellie Merle: The PBR what proportion of the patients do you think are mixed phenotype in the real world.

Ellie Merle: How it is being defined by doctors and payers and do you see out there with more likely to gain a larger share of this population versus stabilizers.

Ellie Merle: Longer term when we look to the cardiomyopathy.

Operator: Thanks.

Ellie Merle: Hi. Thanks for taking the question. In ATTR, what proportion of patients do you think are mixed phenotype in the real world? And how is this being defined both by doctors and by payers? And do you see silencers as more likely to gain a larger share in this population versus stabilizers longer term, when we look to the cardiomyopathy expansion? Thanks. I think Pushkal will win first and then Tolga will follow up. Yeah.

Ellie Merle: Hi. Thanks for taking the question. In ATTR, what proportion of patients do you think are mixed phenotype in the real world? And how is this being defined both by doctors and by payers? And do you see silencers as more likely to gain a larger share in this population versus stabilizers longer term, when we look to the cardiomyopathy expansion? Thanks.

Yvonne Greenstreet: I think Pushkal first, and then Tolga will follow up with a quick perspective.

Ellie Merle: I think first you'll pass then telco a follow up.

Pushkal Garg: Yeah. Ellie, I think you raised a very important question, and I think we've oftentimes, people have sort of classified these as two very distinct diseases, polyneuropathy and cardiomyopathy, when in fact, it's the same protein. When it's misfolded, it's causing both manifestations of the disease. And we've seen, for example, that in the hereditary population, when we looked in APOLLO and HELIOS-A, that more than half of those patients had concomitant cardiomyopathy. And conversely, studies that have been done in cardiomyopathy patients suggest that a significant proportion of those patients may have polyneuropathy manifestations. So there are reports ranging from 15% to 30% or more of patients with wild-type ATTR or V122i, for example, which might have a primary cardiomyopathy manifestation, have concomitant polyneuropathy.

Ellie Merle: Lee I think you raised a very important question and I think we've oftentimes people have sort of classified these as two very distinct diseases, polyneuropathy and cardiomyopathy when in fact.

Ellie Merle: At the same protein when it's misfolded, it's causing both manifestations of the disease and I would you know.

Ellie Merle: We have seen for example that in the hereditary population when you looked into pollo and Helios a bit more than half of those patients had concomitant cardiomyopathy and Conversely studies that have been done in cardiomyopathy patients.

Pushkal Garg: And conversely, studies that have been done in cardiomyopathy patients suggest that a significant proportion of those patients may have polyneuropathy manifestations. So there are reports ranging from 15% to 30% or more of patients with wild-type ATTR or V122i, for example, which might have a primary cardiomyopathy manifestation, have concomitant polyneuropathy.

Ellie Merle: Suggest that a significant proportion of those patients may have polyneuropathy manifestation. So there are reports ranging from <unk>.

Ellie Merle: 15% to 30% or more of patients with wild type ATR or <unk> for example.

Yvonne L. Greenstreet: I think Pushkal first, and then Tolga will follow up.

Ellie Merle: Which might have a primary cardiomyopathy manifestation have concomitant polyneuropathy.

Pushkal Garg: And certainly, you know, we've seen that with the silencer class of drugs, particularly with, you know, patia serrana and ambutra, that the magnitude of effect in polyneuropathy is really quite unsurpassed in terms of its clinical profile. And so it'll be interesting to see, and Tolga can probably comment more about this, you know, how clinicians will make decisions when they have patients who have multiple manifestations of this disease when they, hopefully, have multiple classes of therapies available. Yeah, no, I mean, just add some.

Pushkal Garg: Yes. Ellie, I think you raised a very important question, and I think we’ve oftentimes people have sort of classified these as two very distinctive diseases, polyneuropathy and cardiomyopathy, when in fact, it’s the same protein, when it’s misfolded, that’s causing both manifestations of the disease. And I would – we’ve seen, for example, that in the hereditary population, when we looked in Apollo and Helios-A, that more than half of those patients had concomitant cardiomyopathy. And conversely, studies that have been done in cardiomyopathy patients suggest that a significant proportion of those patients may have polyneuropathy manifestations. So, there are reports ranging from 15% to 30% or more of patients with wild type ATTR or V122I, for example, which might have a primary cardiomyopathy manifestation, have concomitant polyneuropathy. And certainly we’ve seen that with the silencer class of drugs, particularly with patisiran and AMVUTTRA, that the magnitude of effect in polyneuropathy is really quite unsurpassed in terms of its clinical profile. And so, it’ll be interesting to see, and Tolga can probably comment more about this, how clinicians will make decisions when they have patients who have multiple manifestations of this disease, when they hopefully have multiple classes of therapies available.

Pushkal Garg: Certainly, we've seen that with the silencer class of drugs, particularly with patisiran and AMVUTTRA, the magnitude of effect in polyneuropathy is really quite unsurpassed in terms of its clinical profile. It'll be interesting to see, and Tolga can probably comment more about this, how clinicians will make decisions when they have patients who have multiple manifestations of this disease when they hopefully have multiple classes of therapies available to them.

Ellie Merle: And certainly.

Pushkal Garg: We've seen that with the silencer class of drugs, particularly with <unk>.

Speaker Change: <unk> that the magnitude of effect in Polyneuropathy is really quite unsurpassed in terms of its clinical profile.

Pushkal Garg: And so it'll be interesting to see in Togo can probably comment more about this.

Pushkal Garg: How clinicians will make decisions when they have patients who have multiple manifestations of this disease when they hopefully have multiple classes of therapies available.

Tolga Tanguler: Yes, no, I mean, just to add one quick point on that is, if you look at the clinical practice of how physicians actually diagnose and treat this disease, it starts with the suspicion, and the suspicion usually doesn’t necessarily start whether you have cardiac manifestation of diseases or the polyneuropathy manifestations of this disease. Eventually, based on the data we have obviously both with ONPATTRO and AMVUTTRA, physicians are absolutely looking for neuropathic manifestations to make sure that they can treat this as effectively as possible. And the disease is treated always through multidisciplinary centers. So, at the end of the day, physicians don’t just look at the patients with whether they have CM, PN or mixed genotype. They go through how to best understand the disease and then through a multidisciplinary approach, try to treat the disease in the best possible way and based on the indications of the products.

Tolga Tanguler: Yeah, no, I mean, just to add one quick point on that is, if you look at the clinical practice of how physicians actually diagnose and treat this disease, it starts with suspicion. And the suspicion usually doesn't necessarily start whether you have cardiac manifestations of the disease or the polyneuropathy manifestations of this disease. Eventually, based on the data we have, obviously, both with Ompatra and Amutra, physicians are absolutely looking for, you know, neuropathic manifestations to make sure that they can treat this as effectively as possible. And the disease is always treated through multidisciplinary centers. So at the end of the day, physicians don't just look at the patients and see whether they have CM, PN, or mixed phenotype. They go through how to best understand the disease and then, through a multidisciplinary approach, try to treat the disease in the best possible way and based on the indications of the product.

Yvonne Greenstreet: Yeah, no. I mean, just to add one quick point on that is, if you look at the clinical practice of how physicians actually diagnose and treat this disease, it starts with the suspicion. The suspicion usually doesn't necessarily start whether you have cardiac manifestation of diseases or the polyneuropathy manifestations of this disease. Eventually, based on the data we have, obviously, both with ONPATTRO and AMVUTTRA, physicians are absolutely looking for neuropathic manifestations to make sure that they can treat this as effectively as possible. The disease is treated always through multidisciplinary centers. So at the end of the day, physicians don't just look at the patients with whether they have CM, PN, or mixed phenotype.

Tolga Tanguler: Yeah, no. I mean, just to add one quick point on that is, if you look at the clinical practice of how physicians actually diagnose and treat this disease, it starts with the suspicion. The suspicion usually doesn't necessarily start whether you have cardiac manifestation of diseases or the polyneuropathy manifestations of this disease.

Tolga Tanguler: Yes, no I mean, just add one quick point on that is if you look at the clinical practice of how physicians actually diagnose and treat this disease. It starts with the suspicion and the suspicion usually doesn't necessarily start whether you have cardiac manifestations of diseases or the polyneuropathy manifestations of this disease.

Tolga Tanguler: Eventually, based on the data we have, obviously, both with ONPATTRO and AMVUTTRA, physicians are absolutely looking for neuropathic manifestations to make sure that they can treat this as effectively as possible. The disease is treated always through multidisciplinary centers. So at the end of the day, physicians don't just look at the patients with whether they have CM, PN, or mixed phenotype.

Tolga Tanguler: I actually.

Tolga Tanguler: Based on the data we have obviously, both with <unk> and <unk> physicians are absolutely looking for.

Tolga Tanguler: Neuropathic manifestations to make sure that they can treat this as effectively as possible.

Tolga Tanguler: And the disease is always treated through multidisciplinary centers. So at the end of the day, physicians don't just look at the patients and see whether they have CM, PN, or mixed phenotype. They go through how to best understand the disease and then, through a multidisciplinary approach, try to treat the disease in the best possible way and based on the indications of the product.

Tolga Tanguler: And the disease is treated always through multidisciplinary centers. So so at the end of the day physicians don't just look at the patients with whether they have <unk> or mixed phenotype. They go through how to best understand the disease and then.

Yvonne Greenstreet: They go through how to best understand the disease and then, through a multidisciplinary approach, try to treat the disease in the best possible way and based on the indications of the products. Thanks, Tolga. Next question.

Tolga Tanguler: They go through how to best understand the disease and then, through a multidisciplinary approach, try to treat the disease in the best possible way and based on the indications of the products. Thanks, Tolga. Next question.

Tolga Tanguler: Through a multidisciplinary approach try to treat the disease and the best best possible way and based on the indications of the products.

Yvonne L. Greenstreet: Thanks, Tolga. Next question.

Speaker Change: Thanks Tucker.

Tolga Tanguler: Next question.

Operator: One moment for our next question. Our next question comes from the line of Gena Wang with Barclays. You may proceed. Thank you. Sorry. I will ask another AMVUTTRA question. So, regarding the subgroup, the top line you will share? Will you share, are the subgroup information, both primary and secondary endpoint, and also in the scenario that HELIOS-B is positive, will you also at some point lower a AMVUTTRA price to be competitive compared to say, tafamidis and other tools [ph]?

Operator: One moment for our next question. Our next question comes from the line of Gena Wang with Barclays. You may proceed.

Operator: One moment for our next question. Our next question comes from the line of Gina Wang with Barclays. You may proceed.

Speaker Change: In a moment for our next question.

Gena Wang: Thank you. Sorry. I will ask another AMVUTTRA question. So, regarding the subgroup, the top line you will share? Will you share the subgroup information, both primary and secondary endpoint, and also in the scenario that Helios-B is positive, will you also at some point lower a AMVUTTRA price to be competitive compared to say, TAFAMIDIS and other drugs?

Operator: Our next question comes from the line of Gena Wang with Barclays. You May proceed.

Huidong Wang: Thank you. Sorry, I will ask another AMVUTTRA question. So, regarding the subgroup, the top line you will share, will you share the subgroup information, both primary and secondary endpoint? And also, in the scenario that HELIOS-B is positive, will you also, at some point, lower AMVUTTRA price to be competitive compared to, say, tafamidis and other drugs?

Gena Wang: Thank you. Sorry, I will ask another AMVUTTRA question. So, regarding the subgroup, the top line you will share, will you share the subgroup information, both primary and secondary endpoint? And also, in the scenario that HELIOS-B is positive, will you also, at some point, lower AMVUTTRA price to be competitive compared to, say, tafamidis and other drugs?

Gena Wang: Thank you sorry, I will ask you.

Gena Wang: Future question.

Gena Wang: So regarding the subgroup. The topline you were sure we you sure at the subgroup information both primary and secondary endpoint.

Gena Wang: And also in the scenario that Helios B is positive will you also at some point lower and future price to be competitive compared to say pick that Emerson talks.

Yvonne L. Greenstreet: I’ll just take the pricing question. I mean, I think it’s really too early for us to talk about kind of specific kind of pricing approaches here, just to remind you. And Tolga touched on this in his introductory remarks. I mean, we will obviously bear in mind our patient access principles, and we’ll be making sure that we have considerations around access and affordability to make sure that patients are going to be able to benefit from what we hope will be a medicine with a very robust profile. Pushkal, do you want to take the question on?

Yvonne Greenstreet: So I'll just take the pricing question. I mean, I think it's really too early for us to talk about kind of specific kind of pricing approaches here. Just to remind you, and Tolga touched on this in his introductory remarks, I mean, we will obviously bear in mind our patient access principles and will be making sure that we have considerations around access and affordability to make sure that patients are going to be able to benefit from what we hope will be a medicine with a very robust profile. Pushkal, do you want to take the question on?

Gena Wang: So I'll just take the pricing question I mean, I think it's really too early for us.

Pushkal Garg: Can you talk about kind of specific kind of pricing approaches here just a reminder, on silica touched on.

Gena Wang: Introductory remarks, I mean, we will obviously bear in mind, our patient access principles, who will be making sure that.

Pushkal Garg: You have considerations around access and affordability to make sure that patients are going to be able to benefit from.

Gena Wang: What we hope will be.

Gena Wang: Medicine with a very robust protocol.

Yvonne L. Greenstreet: Yeah, I mean, Gena, I don't know that there's a lot more that I can add in terms of the remarks I made, and then Yvonne has reiterated in terms of the top line. We plan, again, to speak to the primary endpoint, which is now in the two populations, the secondary endpoints across those populations, safety, and we'll make some commentary on subgroups. But it's hard to give you anything more than that today. That's that's that's our plan. [inaudible] Next question.

Pushkal Garg: Yes, I mean, Gena, I don’t know that there’s a lot more that I can add in terms of the remarks that I made and then Yvonne has reiterated in terms of the top line. We plan again to speak to the, primary endpoint, which is now in the two populations, the secondaries across those populations, safety. And we’ll make some commentary around subgroups, but it’s hard to give you anything more than that today. That’s our plan.

Pushkal Garg: Yeah. I mean, Gina, I don't know that there's a lot more that I can add in terms of the remarks that I made. And then Yvonne has reiterated in terms of the top line. We plan, again, to speak to the primary endpoint, which is now in the two populations, the secondaries across those populations, safety, and we'll make some commentary around subgroups. But it's hard to give you anything more than that today. That's our plan.

Pushkal Garg: Chris do you want to take the question on <unk> I don't know that Theres a lot more than I can add in terms of loop remarks, I made and then Ivan as reiterated in terms of the topline we plan again to speak to the the primary endpoint, which is now in the two populations the secondaries across those population safety and we'll make some commentary.

Yvonne L. Greenstreet: Round subgroups.

Yvonne L. Greenstreet: But it's hard to give you anything more than that today that strips out that's our plan.

Yvonne Greenstreet: Thanks, Pushkal. Next question.

Yvonne L. Greenstreet: Thanks.

Speaker Change: Okay next question.

Operator: One moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. You may proceed.

Speaker Change: Our next question.

[inaudible] Next question.

Gena Wang: All right, thanks, Pushkal.

Yvonne L. Greenstreet: Next question.

Operator: One moment for our next question. Our next question comes on the line from Salveen Richter with Goldman Sachs. You may proceed. Thanks.

Operator: One moment for our next question. Our next question comes from the line of Salveen Richter with Goldman Sachs. You may proceed.

Yvonne L. Greenstreet: Our next question comes from line of Salvino, Victor with Goldman Sachs. You May proceed.

Salveen Richter: Thanks for taking our question. This is Tommy Ohm for Salveen. So beyond the top line and regarding data analyses presented on the forward, would you include detailed analyses on AMVUTTRA's impact in patients who were defined as fast progressors given the unmet need in this population and just to see how AMVUTTRA could benefit these patients? Thank you.

Salveen Richter: Thanks for taking a question with Tommy and Calvin beyond the top line and then regarding data analyses presented on the FRE would you include detailed analyses on Brexit impact in patients who were defined as <unk> progresses, given the unmet need in this population.

Salveen Richter: <unk> benefiting patients. Thank you.

Tommy Yan: Thanks for taking our question. This is Tommy Yan for Salveen. So, beyond the top line, and regarding data analyses presented on the forward, would you include detailed analysis on AMVUTTRA impact in patients who were defined as past progressors given the unmet need in this population and just to see how AMVUTTRA could benefit these patients? Thank you.

Tolga Tanguler: Yes, Tommy, I think what you’re asking about is actually deeper cuts of the data, and certainly this is going to be a very rich and large data set. So, you can imagine that we’ll be looking at this in a lot of different ways. But again, I think, I guess the primary thing I would focus on is the fact that we will have a pretty robust data set, both with the drug treated as a monotherapy and in patients who came in on TAFAMIDIS. And I think you have to ask yourself, why would someone who’s on a drug decide to enroll in a three plus year clinical trial? And that really indicates that they are obviously not satisfied with how they’re feeling or functioning at that moment in time. And so, I think our combination group, where we do have a sizable portion of patients, and we’ll be able to report on that, will help address part of your question.

Pushkal Garg: Yeah, Tommy, I think what you're asking about is actually deeper cuts of the data. And certainly, this is going to be a very rich and large data set. So you can imagine that we'll be looking at this in a lot of different ways. But again, I think I guess the primary thing I would focus on is the fact that we will have a pretty robust data set, both with the drug treated as a monotherapy and in patients who came in on tafamidis. And I think you have to ask yourself, why would someone who's on a drug decide to enroll in a three-plus-year clinical trial? And that really indicates that they are obviously not satisfied with how they're feeling or functioning at that moment in time.

Pushkal Garg: Okay.

Salveen Richter: Yes, Tommy I think.

Operator: I think what you are asking about is actually deeper cuts of the data and certainly this is going to be a very rich and large data set. So you can imagine that we'll be looking at this in a lot of different ways, but again I think I guess the primary thing I would focus on is the fact that we will have a pretty robust dataset, both with the drug treated as amount.

Operator: Therapy and in patients who came in on <unk> and I think you have to ask yourself why would someone who's on a drug decided to enroll in a three plus year clinical trial.

Pushkal Garg: And I think you have to ask yourself, why would someone who's on a drug decide to enroll in a three-plus-year clinical trial? And that really indicates that they are obviously not satisfied with how they're feeling or functioning at that moment in time.And so I think our combination group, where we do have a sizable portion of patients and we'll be able to report on that, will help address part of your question.

Operator: And I think you have to ask yourself, why would someone who's on a drug, who's on tefamidin, decide to enroll in a three plus year clinical trial? And that really indicates that they will know they are obviously not satisfied with how they're feeling or functioning at that moment in time, and so you know, I think our combination group, where we do have a sizable portion of patients and we'll be able to report on that, will help address part of your question. One moment for our next question.

And I think you have to ask yourself, why would someone who's on a drug, who's on tefamidin, decide to enroll in a three plus year clinical trial? And that really indicates that they will know they are obviously not satisfied with how they're feeling or functioning at that moment in time, and so you know, I think our combination group, where we do have a sizable portion of patients and we'll be able to report on that, will help address part of your question.

Operator: And that really indicates that they will they are obviously not satisfied with the.

Operator: Sure.

Operator: So feeling a functioning at that moment in time in there and so I think our combination group, where we do have a sizable portion of patients that we'll be able to report on that will will help address part of your question.

Pushkal Garg: And so I think our combination group, where we do have a sizable portion of patients and we'll be able to report on that, will help address part of your question.

Operator: Okay.

Operator: One moment for our next question. Thank you. Our next question comes from the line of Mike Yee with Morgan Stanley. You may proceed.

Speaker Change: One moment.

Operator: Yes.

Operator: Okay.

Operator: One moment for our next question. Our next question comes from the line of Mike Ulz with Morgan Stanley. You may proceed. Good morning. Thanks for taking the question. Maybe just a follow-up on the launch preparation question. Just curious what you guys have sort of done so far in preparing for a potential launch, and then what are the sort of remaining steps that will be triggered by positive data from HELIOS-B?

Operator: One moment for our next question. Our next question comes from the line of Mike Ulz with Morgan Stanley. You may proceed.

Operator: Thank you. Our next question comes on the line from Mike Ulz with Morgan Stanley. You may proceed.

Operator: Okay.

Michael Eric Ulz: Thank you. Our next question comes from the line of Mike <unk> with Morgan Stanley You May proceed.

Mike Ulz: Good morning. Thanks for taking the question. Maybe just a follow-up on the launch preparation question. Just curious what you guys have sort of done so far in preparing for a potential launch, and then what are the sort of remaining steps that will be triggered by positive data from Helios-B?

Michael Eric Ulz: Good morning, Thanks for taking the question, maybe just a follow up on the launch preparation question.

Michael Eric Ulz: Just curious what you guys are sort of done so far and preparing for potential launch.

Michael Eric Ulz: And then what are the sort of remaining steps.

Michael Eric Ulz: That will be triggered by a positive data from Helios B, Greg Greg I think Greg because I'm going to pass on Paragon I, just one quick one.

Yvonne L. Greenstreet: That’s a great question. I’m going to pass it on to Tolga. And I just want to kind of, underscore how pleased I am, actually, with the commercial footprint that we built. And I think, if you look at our performance with respect to AMVUTTRA in patients with polyneuropathy I think we’re really demonstrating strong growth momentum here, and I’m just really pleased with how the commercial organization is focusing on meeting the needs of patients in this indication, I have no doubt that we’ll do the same, assuming a possibility of Helios-B and being able to launch into the cardiomyopathy indication. But Tolga, you may have some specific comments about how we’re thinking about launching into what I think is going to be actually one of the most exciting categories.

Yvonne Greenstreet: That's a great question. I'm going to pass it on to Tolga. I just want to kind of underscore how pleased I am actually with the commercial footprint that we built. I think if you look at our performance with respect to AMVUTTRA in patients with polyneuropathy, I think we're really demonstrating strong growth momentum here. I'm just really pleased with how the commercial organization is focusing on meeting the needs of patients. In this indication, I have no doubt that we'll do the same, assuming a positive HELIOS-B and being able to launch into the cardiomyopathy indication. But Tolga, you may have some specific comments about how we're thinking about launching into what I think is going to be actually one of the most exciting categories.

Yvonne L. Greenstreet: Underscore how pleased IMAX slate.

Yvonne L. Greenstreet: The commercial footprint that we built in I think.

Yvonne L. Greenstreet: No.

Yvonne L. Greenstreet: If you look at our performance.

Yvonne L. Greenstreet: With respect.

Speaker Change: I'm good.

Yvonne L. Greenstreet: And patients with Polyneuropathy I think I think I think we are really demonstrating strong growth momentum here and I'm just really pleased with how the commercial organization is focusing on meeting the needs of patients in this indication I have no doubt that will be the same.

Yvonne Greenstreet: I'm just really pleased with how the commercial organization is focusing on meeting the needs of patients. In this indication, I have no doubt that we'll do the same, assuming a positive HELIOS-B and being able to launch into the cardiomyopathy indication. But Tolga, you may have some specific comments about how we're thinking about launching into what I think is going to be actually one of the most exciting categories.

Yvonne L. Greenstreet: And I'm really pleased with how, you know, the commercial organization is focusing on meeting the needs of patients. In this indication, I have no doubt that we'll do the same, assuming a positive HESV and being able to launch into the cardiomyopathy indication. But Tolga, you may have some specific comments about how we're thinking about launching into what I think is going to be one of the most exciting categories.

Tolga Tanguler: Assuming a positive ESP and being able to launch into the cardiomyopathy indication, but telco you may have some specific comments about how we're thinking about launching answer what I think is going to be actually one of the most exciting categories.

Tolga Tanguler: You took a little bit of wind away Yvonne, because I was just going to highlight the fact that despite competition, the growth of our TTR franchise now in the U.S. is 35% year-over-year, which is quite important, and I think is an important indicator of the growth momentum that we built. Look, we have a great brand, great data in polyneuropathy, which clearly demonstrated 90% market share in Europe and Japan, where we actually do compete with TAFAMIDIS and the same indication. And now in the U.S., we’re essentially established a very important stronghold in centers that actually treat both cardiomyopathy and polyneuropathy. We obviously strictly promote our polyneuropathy indication, but the asset, the product, is now known both by cardiologists, who also tend to diagnose this disease, as well as neurologists. Therefore, we’re really well positioned to launch pending the Helios-B outcome results, which is going to be obviously very critical. And as Yvonne indicated, we’re going to play to win. We have a great footprint, a well informed and trained organization, not just in the customer facing side, but also patient facing side. And we also are very cognizant that this opportunity is going to be tenfold of the opportunity that we currently have. Therefore, we’re going to make the right appropriate adjustments and make sure that we are clearly differentiated and more importantly, set ourselves so that the product is affordable and accessible to the patients.

Pushkal Garg: You took a little bit of wind away, Yvonne, because I was just going to highlight the fact that despite competition, the growth of our TTR franchise now in the US is 35% year-over-year, which is quite important and I think is an important indicator of the growth momentum that we've built. Look, we have a great brand, great data in polyneuropathy, which clearly demonstrated 90% market share in Europe and Japan where we actually do compete with tafamidis in the same indication. And now in the US, we're essentially established a very important stronghold in centers that actually treat both cardiomyopathy and polyneuropathy. We obviously strictly promote our polyneuropathy indication. But the asset, the product is now known both by cardiologists who also tend to diagnose this disease as well as neurologists.

Tolga Tanguler: You took a little bit of wind away, Yvonne, because I was just going to highlight the fact that despite competition, the growth of our TTR franchise now in the US is 35% year-over-year, which is quite important and I think is an important indicator of the growth momentum that we've built. Look, we have a great brand, great data in polyneuropathy, which clearly demonstrated 90% market share in Europe and Japan where we actually do compete with tafamidis in the same indication.

Yvonne L. Greenstreet: Sure.

Yvonne L. Greenstreet: Yes.

Tolga Tanguler: Took a little by wind away bond because I was just going to highlight the fact that despite competition the growth of our ctr franchise in the U S is 35% year over year, which is quite important and I think is an important indicator of the growth momentum that we've built we have a great brand.

Tolga Tanguler: Great.

Tolga Tanguler: Data in Polyneuropathy, which clearly demonstrated.

Tolga Tanguler: 90% market share in Europe, and Japan, where we actually do compete with Fabulous in the same indication and now in the U S where.

Tolga Tanguler: And now in the US, we're essentially established a very important stronghold in centers that actually treat both cardiomyopathy and polyneuropathy. We obviously strictly promote our polyneuropathy indication. But the asset, the product is now known both by cardiologists who also tend to diagnose this disease as well as neurologists.

Tolga Tanguler: Essentially established a very important stronghold in centers that actually treat both cardiomyopathy and polyneuropathy. We obviously strictly promotes are pull neuropathy indication, but it's.

Tolga Tanguler: The asset the product is now known by both by Cardiologists, who also tend to diagnose this disease as well as neurologists, therefore, we're really well positioned.

Tolga Tanguler: Therefore, we're really well positioned to launch the pending Helios P outcome results, which is going to be obviously very critical, and as Yvonne indicated, we're going to play to win. We have a great footprint, a well-informed and trained organization, not just on the customer-facing side, but also on the patient-facing side, and we also are very cognizant that this opportunity is going to be tenfold of Therefore, we're going to make the appropriate adjustments and make sure that we are clearly differentiated, and, more importantly, you know, set ourselves so that the product is affordable and accessible to the consumer.

Pushkal Garg: Therefore, we're really well positioned to launch, pending the HELIOS-B outcome results, which is going to be obviously very critical. And as Yvonne indicated, we're going to play to win. We have a great footprint, a well-informed and trained organization, not just in the customer-facing side, but also patient-facing side. And we also are very cognizant that this opportunity is going to be tenfold of the opportunity that we currently have. Therefore, we're going to make the right appropriate adjustments and make sure that we are clearly differentiated and, more importantly, set ourselves so that the product is affordable and accessible to the patients.

Tolga Tanguler: Therefore, we're really well positioned to launch, pending the HELIOS-B outcome results, which is going to be obviously very critical. And as Yvonne indicated, we're going to play to win. We have a great footprint, a well-informed and trained organization, not just in the customer-facing side, but also patient-facing side. And we also are very cognizant that this opportunity is going to be tenfold of the opportunity that we currently have.

Tolga Tanguler: To launch the pending the Helios B outcome results, which is going to be obviously very critical.

Tolga Tanguler: And as Ivan indicated we're going to play to win.

Tolga Tanguler: Have.

Tolga Tanguler: A great footprint a well.

Tolga Tanguler: Formed in trained organs.

Tolga Tanguler: Organization not just in the customer facing side, but also patient facing side and we also are very cognizant that this opportunity is going to be 10 fold of the opportunity that we currently have therefore, we're going to make the right appropriate adjustments.

Tolga Tanguler: Therefore, we're going to make the right appropriate adjustments and make sure that we are clearly differentiated and, more importantly, set ourselves so that the product is affordable and accessible to the patients.

Tolga Tanguler: And make sure that we are clearly differentiated and more importantly.

Tolga Tanguler: Set ourselves so that the product is affordable and accessible to the patients.

Yvonne Greenstreet: Thanks, Tolga. I think I've got a, sorry, Yvonne. I think we're taking one more question. That's my understanding.

Speaker Change: Thanks Toga.

Yvonne L. Greenstreet: I think, I think, I think we've got a... I think we've got... I think we're taking one more question. That's my understanding.

Yvonne L. Greenstreet: Thanks, Tolga. I think we’ve got - [inaudible] - Sorry, I think - [inaudible].

Tolga Tanguler: I think I think we're going to.

Yvonne L. Greenstreet: Sorry.

Yvonne L. Greenstreet: Sure.

Yvonne L. Greenstreet: And we're taking one more question that's my understanding.

Operator: We’re taking one more question. That’s my understanding. And our last question comes from the line of Whitney Ijem with CG. You may move ahead. Hey guys, thanks for taking the question. And I’m just going to throw one non-HELIOS-B question in there, because there will be catalysts after that. So can you help remind us, I guess, for Part B of the ALN-APP study, what we should expect to see later this year, particularly around any biomarker or imaging data?

Operator: We’re taking one more question. That’s my understanding. And our last question comes from the line of Whitney Ijem with CG. You may move ahead.

Operator: And our last question comes from the line of Whitney Isham, with CG. You may move ahead.

Operator: Our last question comes from the line of Whitney Isom with William Blair. You may move ahead.

Whitney G. Ijem: Hey guys, thanks for taking the question. And I’m just going to throw one non-Helios-B question in there, because there will be catalysts after that. So, can you help remind us, I guess, for Part B of the ALN-APP study, what we should expect to see later this year, particularly around any biomarker or imaging data?

Yvonne L. Greenstreet: And our last question comes from the line of Whitney <unk> with <unk> you May move ahead.

Christine Lindenboom: Hey, guys. Thanks for taking the question. I'm just going to throw one non-HELIOS-B question in there because there will be catalysts after that. So can you help remind us, I guess, for part B of the ALN-APP study, what we should expect to see later this year, particularly around any biomarker or imaging data?

Whitney Ijem: Hey, guys. Thanks for taking the question. I'm just going to throw one non-HELIOS-B question in there because there will be catalysts after that. So can you help remind us, I guess, for part B of the ALN-APP study, what we should expect to see later this year, particularly around any biomarker or imaging data?

Whitney Isham: Hey, guys. Thanks for taking the question and I am just going to throw one non Helios b question in there because there will be catalysts to after that so can you help remind us I guess for part B of the alien ABP study, what we should expect to see later this year, particularly around any biomarker imaging data.

Pushkal Garg: Yes. Thanks, Whitney, for your question about APP. It’s a program that we’re incredibly excited about. The data that we shared last year really suggested that we can have pretty profound impacts on the protein, on amyloid precursor protein, as well as the downstream isoforms of AB40 and AB42 that are involved in both Alzheimer’s disease and CAA. We have the Part B that’s ongoing and we hopefully will show ongoing data with regards to knockdown safety as well as imaging and biomarker data. So, look for that as something we’re also going to be initiating our CAA studies soon. We’re very excited about the opportunity that’s the second leading cause of hemorrhagic stroke major - with really no available treatments for these patients.

Pushkal Garg: Yeah. Thanks, Whitney, for your question about APP. It's a program that we're incredibly excited about. The data that we shared last year really suggested that we can have pretty profound impacts on the protein, on amyloid precursor protein, as well as the downstream isoforms of AB40 and 42 that are involved in both Alzheimer's disease and CAA. We have the part B that's ongoing, and we hopefully will show ongoing data with regards to knockdown safety as well as imaging and biomarker data. So look for that as something. We're also going to be initiating our CAA studies soon. We're very excited about the opportunity. That's the second leading cause of hemorrhagic stroke, major with really no available treatments for these patients. And we think that lowering APP could be beneficial in that disease. We'll be kicking off a phase 2 shortly.

Whitney Isham: Yes, Thanks Whitney for your question about APB, It's a program that we're incredibly excited about it.

Whitney Isham: The data that we shared last year really suggests that we can have pretty profound impacts on the protein amyloid precursor protein as well as the downstream.

Whitney Isham: Isoforms of ABB, 40% and 42 that are involved in both.

Pushkal Garg: We have the part B that's ongoing, and we hopefully will show ongoing data with regards to knockdown safety as well as imaging and biomarker data. So look for that as something. We're also going to be initiating our CAA studies soon. We're very excited about the opportunity. That's the second leading cause of hemorrhagic stroke, major with really no available treatments for these patients. And we think that lowering APP could be beneficial in that disease. We'll be kicking off a phase 2 shortly.

Whitney Isham: Alzheimer's disease and CIA.

Whitney Isham: We have the part B, that's ongoing and we are now.

Pushkal Garg: So, you know, look for that as something we're also going to be initiating our CAA studies soon. We're very excited about the opportunity. That's the second leading cause of hemorrhagic stroke, major, you know, with really no available treatments for these patients.

Whitney Isham: We will show ongoing data with regards to knockdown safety as well as.

Pushkal Garg: Imaging and biomarker data so look for that.

Pushkal Garg: Something we're also going to be initiating our study soon we're very excited about the opportunity that is the second leading cause of hemorrhagic stroke.

Pushkal Garg: Major with really no available treatments for these patients and we think that lowering <unk> could be beneficial in that disease will be kicking off the phase II shortly and we've also announced that we plan to kick off a Alzheimer's disease study at or around year end of this year. So this is a really exciting program and then it allows US then with our colleagues at Regeneron to move forward a number of <unk>.

Pushkal Garg: And we've also announced that we plan to kick off an Alzheimer's disease study at or around year-end of this year. So this is a really exciting program. And then it allows us then, with our colleagues at Regeneron, to move forward a number of other programs in the CNS space. So thanks for your question. Lots of excitement there.

Pushkal Garg: And we think that lowering APP could be beneficial in that disease. We’ll be kicking off a Phase II shortly, and we’ve also announced that we plan to kick off a Alzheimer’s disease study at or around year end of this year. So, this is a really exciting program. And then, it allows us then with our colleagues at Regeneron to move forward a number of other programs in the CNS space. So, thanks for your question. Lots of excitement there.

Pushkal Garg: Their programs in the CNS space.

Pushkal Garg: So thanks for your question lots of excitement there.

Christine Regan Lindenboom: Great. Thank you Pushkal, and thank you everyone for joining us on the call. We’re really proud of our strong start to 2024. We’ve delivered robust commercial growth and exciting pipeline progress and we look forward to executing on the remainder of our 2024 goals. Our path to becoming a top tier biotech company. So, thanks everyone and have a great day.

Yvonne Greenstreet: Great. Thank you, Pushkal. And thank you, everyone, for joining us on the call. We're really proud of our strong start to 2024. We've delivered robust commercial growth and exciting pipeline progress. And we look forward to executing on the remainder of our 2024 goals on our path to becoming a top-tier biotech company. So thanks, everyone, and have a great day.

Pushkal Garg: Great.

Speaker Change: Thank you for Scotland.

Pushkal Garg: Thank you everyone for joining us on the call.

Pushkal Garg: We're really proud of our strong start to 2024, we delivered robust commercial growth and exciting pipeline progress.

Pushkal Garg: We look forward to executing on the remainder of our 2024 goals.

Pushkal Garg: Path to becoming a top tier biotech company.

Speaker Change: Thanks, everyone and have a great day.

Operator: Thank you, everyone, for your participation in today's conference. This does conclude the program.

Operator: Thank you everyone for your participation in today’s conference. This does conclude and you may now disconnect.

Speaker Change: Thank you everyone for your participation in today's conference. This does goodbye and you may now disconnect.

Christine Lindenboom: Goodbye.

Operator: And you may now disconnect.

Operator: Okay.

Operator: [music].

Q1 2024 Alnylam Pharmaceuticals Inc Earnings Call

Request a DemoDemo

ALNY

Alnylam Pharmaceuticals

Earnings