Alnylam Pharmaceuticals Q1 2025 Earnings Report

Alnylam Pharmaceuticals EPS Results

• Actual EPS: -$0.44
• Consensus EPS: -$0.37
• Beat/Miss: Missed by -$0.07
• One Year Ago EPS: -$0.16

Alnylam Pharmaceuticals Revenue Results

• Actual Revenue: $594.19 million
• Expected Revenue: $584.32 million
• Beat/Miss: Beat by +$9.87 million
• YoY Revenue Growth: +20.20%

Alnylam Pharmaceuticals Announcement Details

• Quarter: Q1 2025
• Date: 5/1/2025
• Time: Before Market Opens
• Conference Call Date: Thursday, May 1, 2025
• Conference Call Time: 8:30AM ET

Alnylam Pharmaceuticals (NASDAQ:ALNY), a biopharmaceutical company, focuses on discovering, developing, and commercializing novel therapeutics based on ribonucleic acid interference. Its marketed products include ONPATTRO (patisiran) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults; AMVUTTRA for the treatment of hATTR amyloidosis with polyneuropathy in adults; GIVLAARI for the treatment of adults with acute hepatic porphyria; and OXLUMO for the treatment of primary hyperoxaluria type 1. In addition, the company develops patisiran for the treatment of transthyretin amyloidosis, or ATTR amyloidosis, with cardiomyopathy; cemdisiran to treat complement-mediated diseases; Belcesiran for the treatment of alpha-1 liver disease; Elebsiran to treat chronic HBV infection; Zilebesiran to treat hypertension; ALN-APP to treat Alzheimer's disease and cerebral amyloid angiopathy; and ALN-HSD to treat NASH. Further, it offers Fitusiran for the treatment of hemophilia, Inclisiran to treat hypercholesterolemia, lumasiran for the treatment of advanced PH1, and vutrisiran for the treatment of ATTR amyloidosis, which is in phase 3 clinical trial. Alnylam Pharmaceuticals, Inc. has strategic collaborations with Regeneron Pharmaceuticals, Inc. to discover, develop, and commercialize RNAi therapeutics for a range of diseases by addressing therapeutic targets expressed in the eye and CNS; and Roche to develop pharmaceutical products containing zilebesiran. It also has license and collaboration agreements with Novartis AG; Vir Biotechnology, Inc.; Dicerna Pharmaceuticals, Inc.; Ionis Pharmaceuticals, Inc.; and PeptiDream, Inc. The company was founded in 2002 and is headquartered in Cambridge, Massachusetts.

Alnylam Pharmaceuticals Q1 2025 Earnings Call Transcript

Presentation

[Operator]

Good morning, ladies and gentlemen, and welcome to the Alnylam Pharmaceuticals Q1 twenty twenty five Earnings Conference Call. At this time, all lines are in a listen only mode. Following the presentation, we will conduct a question and answer session. This call is being recorded on Thursday, 05/01/2025. I would now like to turn the conference over to Alnylam.

[Operator]

Please go ahead.

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

Good morning. I'm Christine Lindenboom, Chief Corporate Communications Officer at Alnylam. With me today are Von Greenstreet, Chief Executive Officer Tova Tangular, Chief Commercial Officer Pushpul Garg, Chief Medical Officer and Jeff Bolton, Chief Financial Officer.

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

For those of

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

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. Tova 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 our upcoming milestones before we open the call to your questions. 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.

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

In addition, any forward looking statements represent our views only as of the date of this reporting 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'd

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

like to turn the call over to Yvonne. Yvonne?

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Thanks, Christine, and thank you, everyone, for joining the call today. 2025 is off to a strong start at Alnylam. In the first quarter, we made notable progress towards our goal of becoming the global TTR leader, which will play a critical role in driving sustainable growth and value creation creation this year and beyond.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Commercially, we delivered $469,000,000 in combined to net product revenues, and this represents 28% growth year over year. This is driven primarily by the robust 45% year over year growth of our US TTR franchise, which in the first quarter consisted solely of continued uptake in the hereditary polyneuropathy population. We also have several exciting portfolio advancements in the quarter, most notably the expanded indication from Vutra in ATTR cardiomyopathy with approvals in The US and Brazil. And earlier this week, we received a positive CHMP opinion in The EU. We also saw approval of the sixth Alnylam discovered RNAi therapeutic, QFIDLIA, for hemophilia a or b secured by our partners at Sanofi.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Lastly, we are we are reiterating our guidance for the year, underscoring our confidence in continued growth and a strong launch in ATTR cardiomyopathy. This also includes our goal of achieving sustainable non GAAP profitability in 2025. Now before I move on, I'd like to take just a brief moment to acknowledge the uncertainty that exists related to potential evolutions in certain policies, including tariffs, FDA personnel reorganization, and other biotech industry initiatives being discussed. While much is yet to be clarified and finalized, we've taken a comprehensive look across our business, and we believe that Alnylam is well positioned and pretty well insulated from any potential impacts associated with the key initiatives that have been announced to date. We feel that we're completely able to focus on the key tasks at hand, executing on a strong launch in ATTR cardiomyopathy and continuing to advance our robust high value pipeline.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Our achievements in early twenty twenty five underpin the three core elements of our business that we believe will drive sustainable growth and value creation for years to come. The first is TTR leadership. Tolga will provide color on our launch of Ambutra in ATTR Centimeters. But at a high level, we're very pleased with our early progress, which is focused on securing broad access, driving awareness, and supporting treatment initiation for patients in the initial few weeks since approval. The next is growth through innovation, including a pipeline with numerous multibillion dollar opportunities and an r and d engine set up to deliver sustainable innovation and value creation.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

The third element is strong financial performance with robust commercial delivery and a disciplined approach to capital allocation to enable us to sustain profitability going forward. And, of course, all of this is underpinned by a best in class team and our award winning culture. And this all represents tremendous progress against our Alnylam piece of fifth by 25 goals, and we continue to work to turn these goals into reality by the end of the year. Doing so will further establish Alnylam as a unique top tier biotech company, delivering sustainable innovation to patients for years to come. With that, let

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

me now turn the call over to Tolga for a review of our commercial performance. Tolga?

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Thanks, Ivan, and good morning, everyone. I am particularly excited to share our commercial update on this call today. I am as encouraged as I've ever been, not only by the impact we're already having for patients affected by the conditions our medicines are indicated to treat, but also by the potential that is just beginning to unfold.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Now that our Centimeters launch is underway in The U. S. I'll review our performance in Q1 and also provide some early perspective on our ATTR Centimeters launch, which only begun in the final days of this quarter and will take shape over the quarters ahead. Our Q1 performance continues to be strong. Altogether, our portfolio delivered nearly $05,000,000,000 in combined net product revenues, representing 28% growth year over year and 4% versus Q4 twenty twenty four.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

This is tremendous growth across our portfolio several years after our initial launches. Quite simply, this means helping more patients affected by each of these devastating diseases. Before we dive into our TTR franchise and the exciting progress with our new Centimeters launch, let me briefly update you on our rare disease franchise. Our rare franchise, GIVLAARINOXLUMA, together delivered $109,000,000 in combined product sales in the first quarter, representing 8% growth compared with the first quarter of twenty twenty four. On a year over year basis, the growth in GIVLAARI patients on therapy was approximately 15% and growth in OXLUMO patients on therapy was approximately 20%.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Revenue growth for OXLUMO was less than growth in patients on therapy, primarily due to gross to net adjustments in European markets and the timing of orders in partner markets. We continue to expect full year product sales growth of approximately 15% for our rare franchise, consistent with the midpoint of our 2025 rare product sales guidance. Moving now to our TTR franchise, we continue to see strong performance in Q1. The franchise delivered $359,000,000 in global net revenues, representing a 36% increase compared with the first quarter of twenty twenty four. Importantly, this represents continued and robust growth from our base business in hereditary ATTR PN since the Centimeters indication approval came in the final days of the quarter.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

In The U. S, combined sales of ONPATTRO and ambutra in the first quarter increased by a robust 45% compared with the first quarter of twenty twenty four, continuing to drive strong growth momentum. The 45% year over year growth was primarily driven by the following: a 32% increase in demand driven by the strength of ongoing ONPATTRO patient uptake We are pleased with the growth in demand, which has been consistent over the past five quarters despite new competition entering the market at the end of twenty twenty three, which we believe is reflective of the leadership position we have established in a growing PN market over the last six years. The remaining growth in the quarter 13% is related to favorable adjustments in gross to net deductions combined with stocking dynamics as inventory in the distribution channel modestly increased in Q1. I will share additional detail on our P and N performance in The U.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

S. On the next slide. Now let me turn to our international markets for just a quick moment, where the TTR franchise grew 24% compared with the first quarter of twenty twenty four. Similar to The U. S, the year over year growth was primarily driven by increased demand for Ambutra as patient uptake remained robust.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Bottom line, our TTR based business is very strong and continues to grow. Before I provide additional color on early days of our TTR Centimeters launch, let me touch briefly on the dynamics we're seeing in The U. S. TTRP end markets. A full year after the launch of a new competitor, Ambutra remains the clear market leader in The U.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

S. Maintaining a majority of new patient starts with Ambutra capturing approximately seventy percent of new patient starts in the first quarter of twenty twenty five. This results from a strong brand value proposition coupled with continued disciplined execution by our commercial teams. What's more, as anticipated, we are finding that in categories where the majority of patients remain untreated, more treatment options mean more voices helping to raise disease awareness, ultimately accelerating category growth and increasing the number of patients on therapy. In other words, this continues to be a growth story and patients are benefiting.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

With similar dynamics anticipated across hATTR PN and ATTR Centimeters, we believe about eighty percent of the global addressable population remains untreated. This bodes well for the opportunity ahead in ATTR Centimeters. Now onto our new indication. Momentum is building fast and the team is laser focused on delivering a successful launch. On March 20, we received FDA approval for Amutra as the first and only silencer approved in The US for ATTR Centimeters.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And the only treatment indicated in The US for both the pulmonary artery manifestations of hereditary ATTR and cardiomyopathy manifestations of ATTR. Though it's still early days, we are very encouraged by what we're seeing. Our first priority out of gate was the access setup. And we're pleased to say it's progressing exactly to plan, thus enabling the second half growth story that we have described on our prior calls. Though it's of course early to quantify trends, I would like to share some examples of the very encouraging progress we're already seeing, particularly with regard to the access and health system formulary reviews that we have shared would be the early priorities and key enablers of our second half launch momentum.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Let me explain why we believe this launch is off an exceptional start with some specific examples. First, we're seeing robust patient initiations across all payer segments, Medicare fee for service, Medicare Advantage and commercial. We are continuing payer engagements and a majority of contracted lives are covered by value agreements that include the cardiomyopathy line extension. As expected, the majority of our motor patients to date pay $0 copay in ATTR Centimeters like with hATTR PM. And we continue to have widespread payer coverage exactly in line with our expectations.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Second, and this is important, about 80% of TTR volume flows through approximately 170 health systems. Our teams focused efforts enabled inclusion of Albuterol formulary in more than half of these health systems within short four weeks of label expansion. In fact, the majority of these accounts have already initiated Albuterol treatments for ATTR Centimeters patients, underscoring that with the proper setup, these accounts do indeed come online. And finally, in terms of treatment choice, we're seeing healthy demand across both prior Amutra prescribers as well as first time Amutra prescribers. And what we're hearing from prescribers is that the Almutra disruptive value proposition resonates and is enabling this early and encouraging launch momentum.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Early feedback from patients and physicians indicates clear excitement for a new mechanism of action in ATTR Centimeters that can rapidly knock down TTR. HCPs further highlighted that Amutra's clinically and statistically significant benefits in standalone all cause mortality coupled with demonstrated preservation of functional capacity and quality of life where Ambutra made significant impact on KCCQ and six minute walk distance are highly differentiating. Furthermore, physicians appreciate how quarterly HCP administered dosing gives peace of mind for verified adherence. In terms of early utilization, here too, we are very pleased by early signals. We see broad use in line with our expectations.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

More specifically, we're seeing Amutra use in first line. We're also seeing stabilizer progressor patients switch to Amutra. We're seeing broad utilization including an academic and community settings supported by the broad alternate site of care networks that's been established. Simply put, the mechanism of action and the well established safety and tolerability of Ambutra hit home. Our consistent data speaks volumes.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

HCP administered VERIFI adherence is real and patients are getting on therapy on Ambutra, most with zero co pay. In conclusion, the launch is off to an exceptional start. These are, of course, the early days of launch. We will continue to share more as the launch progresses, including both qualitative and quantitative launch indicators. We've provided full year guidance projecting robust 36% year over year growth in our TTR franchise revenues at the midpoint of the guidance.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

This reflects our confidence in the launch and the future potential of this franchise. Now with a few early weeks of experience since launch, we remain as confident as ever. In conclusion, we are pleased with the results in the first quarter with both our TTR and rare franchises delivering strong growth in patients on therapy as well as delivering robust year over year growth in revenues, giving us confidence in our ability to deliver substantial growth, achieve profitability, and most importantly, deliver our highly differentiated and transformative medicines to more patients in need around the world. With that, I will now turn it over to Pushkal to review our recent R and D and pipeline progress. Pushkal?

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

Thanks, Tolga, and good morning, everyone. To echo my colleagues, I'm very excited about the launch of Ambutrin and ATTR Centimeters at the end of Q1 and that we've hit the ground running to educate physicians and patients and drive awareness. And I'm delighted by the early progress that Tolga just described, which is based on great execution by our commercial and medical teams and the impressive HELIOS B results summarized here. In a population representative of today's ATTR Centimeters patients, nearly half of whom were already being treated with a stabilizer, we saw a substantial benefit in Vutra on cardiac outcomes, including a thirty five percent to thirty six percent reduction in the risk of all cause mortality alone. We saw broad benefits on a series of other important clinical parameters, such as cardiac biomarkers, echocardiographic measures and disease progression.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

These together with an encouraging safety profile and an infrequent HCP administered dosing regimen that enables a high degree of adherence support the potential for Ambutra to become a first line therapy in this disease. Based on these exceptional data, we quickly submitted filings to regulatory agencies in key geographies and we're pleased with the pace of progress thus far. We of course achieved U. S. Approval of the sNDA in March, followed shortly thereafter by approval in Brazil.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

And earlier this week, we announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending approval of vutrisiran and ATTR Centimeters. This should enable the European Commission to approve Ambutra in Europe in Q3 and possibly in Q2. So things are progressing swiftly and we look forward to launching in other important territories in the coming quarters. Now beyond those primary results that discussed a moment ago, we continue to share additional insights from the HELIOS B dataset. At ACC last month, we shared a few new analyses that further support vutrisiran's compelling profile.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

In one, we highlighted echocardiographic data, which demonstrated that treatment with Vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular and right ventricular systolic function at month eighteen compared to placebo. These indicate that is favorably impacting cardiac function, which is truly remarkable. We also shared an exploratory subgroup analysis, which demonstrated vutrisiran reduced all cause mortality and recurrent CV events across a range of baseline heart failure severity in patients with this disease. And lastly, a separate analysis confirmed that Vutrisiran significantly maintained or improved functional capacity and patient reported health status and quality of life compared to placebo over thirty months. These last two analyses were also published in the Journal of the American College of Cardiology.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

We look forward to continuing our analysis of this landmark study and educating the TTR amyloidosis community about the differentiated profile of VANVUTRA. Further to our leadership and commitment to innovation in this disease and to these patients, at R and D Day in February, we shared updated plans for pivotal studies of nucreseran, our next generation RNAi therapeutic targeting TTR with the potential for deeper knockdown and biannual dosing. TRITON Centimeters will be a randomized double blind events driven outcome study in ATTR Centimeters patients with either hereditary or wild type disease and a medical history of symptomatic heart failure, NYHA Class I through III. All patients will be allowed to be on background stabilizer therapy. Approximately 1,200 patients will be randomized and the primary endpoint will be a composite of all cause mortality and CV events.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

The primary analysis will be event driven and will occur a minimum twenty four months of the last patient enrolled. If successful, we target launching NUCRISERAN in ATTR Centimeters around 02/1930. In parallel, we have the goal of bringing NUCRISRAN to patients as quickly as possible and see an opportunity to do so in hereditary ATTR PN. Though we're not yet prepared to discuss the full details of TRITON PN, we plan to initiate the pivotal study by the end of this year and anticipate the potential to launch in this indication several years ahead of ATTR Centimeters. We look forward to sharing more details in due course.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

R and D Day also showcased a number of exciting advancements early in our pipeline that underscore the bright future for RNAi therapeutics across a broad range of diseases. Key among these updates, we disclosed two new clinical programs. ALN434 targets GRB14 for the treatment of Type two diabetes with a novel mechanism of action. It acts as

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

an insulin

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

sensitizer addressing a tremendous unmet need in diabetes where insulin resistance is a major issue. We're pleased to announce today that we've initiated the Phase one study for ALN434. The second program is 100 that targets liver derived plasminogen. And this molecule represents a potential universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. Another key highlight was our update on delivery solutions with best in class potential for adipose, muscle, heart and kidney tissue, as well as a new approach to crossing the blood brain barrier.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

As we announced at our R and D Day, our goal is to achieve delivery of RNAi therapeutics in every major tissue by 02/1930. Lastly, I'd like to congratulate our partners at Sanofi for securing FDA approval for QFYTILIA, fitusiran for hemophilia A or B with or without factor VIII or IX inhibitors. With this approval, Qufilia becomes the sixth Alnylam discovered RNAi therapeutic approved by the Food and Drug Administration. In summary, this remarkable and unique pace of innovation puts us in a great position to have a deep self sustainable pipeline that can continue to deliver meaningful impact to patients for many years to come. And with that, let me now turn it over to Jeff to review our financial results and upcoming milestones.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

Jeff?

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Thanks, Pushkar, and good morning, everyone. I'm pleased to be presenting a summary of Alnylam's Q1 twenty twenty five financial results and discussing our full year guidance. Before turning to the details on our Q1 financial performance, I'd like to further some of Tolga's comments on the early observations of our cardiomyopathy launch. I'm extremely pleased with the commercial execution demonstrated by the U. S.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

TTR team thus far. We have guided Centimeters revenue being a second half story with the second quarter focusing on continuing to build awareness, unlocking patient access and supporting treatment initiation for patients. Given the early progress that Tolga described, I'm confident in reiterating our financial guidance, including TTR product sales, which I will discuss later. With that, let's begin with a summary of our P and L results for Q1 twenty twenty five compared with prior year. Total product revenues for the quarter were $469,000,000 or 28% growth versus last year, driven by the 36% growth in our TTR franchise, with particularly strong performance in The U.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

S. Market, Tolga described. As Tolga also noted, INVUTRO was approved for ATTR cardiomyopathy with only one week remaining in the first quarter, so did not contribute to our Q1 results. Collaboration revenue for the quarter was $99,000,000 or a 16% decrease compared to the first quarter of last year. The decrease was primarily driven by the $65,000,000 Roche milestone achieved Q1 twenty twenty four related to the first patient being dosed in the CARDIO3 study, partially offset by the $30,000,000 milestone achieved from Veer and reimbursements from our collaboration with Regeneron in Q1 twenty twenty five.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Royalty revenue for the quarter was $26,000,000 representing a 16,000,000 increase compared to last year, driven by Novartis' increased LECVIO sales. Gross margin on product sales was 85% for the quarter, which was consistent with the first quarter of twenty twenty four as the Ambucha royalty rate payable to Sanofi resets at the beginning of each calendar year. For the balance of the year, our gross margin on product sales is expected to decrease as the Ambutra average royalty rate escalates, driven by annual sales of Ambutra reaching higher royalty tiers. Our non GAAP R and D expenses were $241,000,000 or in line with prior year as increases in clinical trial expenses associated with our CARDIA-three study for zalbesiran and the myvelsiran Phase II CAA study were offset by reductions related to the wind down of the HELIOS B Phase III study. We do expect that R and D expenses will increase compared to twenty twenty four for the balance of the year as Phase III studies for both selvesiran and lucrisiran ramp up.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Our non GAAP SG and A expenses increased 12% in the first quarter compared to the same period last year, primarily driven by increased investments in support of Ambutra for the cardiomyopathy launch. Our non GAAP operating profit for the quarter was $75,000,000 representing a $73,000,000 improvement compared to last year, driven by the strength of our top line growth combined with more moderate growth in operating expenses. Finally, we ended the quarter with cash, cash equivalents and marketable securities of $2,600,000,000 compared to $2,700,000,000 at the end of twenty twenty four. Now turning to our guidance, where as I previously mentioned, we are reiterating our 2025 guidance as presented during our last earnings call and as summarized on our guidance slide. Additionally, I'd like to provide two additional points of perspective.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Our guidance continues to assume foreign exchange rates as of 12/31/2024, which are noted in the footnote of our guidance slide. As you are aware, the U. S. Dollar has weakened considerably in recent weeks. If the current FX rates continue through the remainder of the year, we expect currency upside relative to our current product sales guidance of approximately $50,000,000 We will reevaluate our full year guidance for FX in Q2.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Secondly, I'd like to make some brief remarks on the potential impact of recently announced tariffs as well as pharma tariffs that are currently being contemplated. As it relates to the tariffs that are now in place, we do not see a material impact on our business and believe we can absorb any resulting cost increases within our existing 2025 financial guidance. As it relates to the pharma tariffs that are being considered, there is obviously still uncertainty as we await the drafting of the final rules. However, we are comfortable sharing some high level perspective that reflects our positioning as a company. Our commercial supply chain is global in nature, but the majority of our products are manufactured through third party contract manufacturing organizations in The U.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

S. Additionally, our intellectual property is also primarily based in The U. S. We think both of these factors position us well in terms of limiting exposure to potential future pharma tariffs. We will provide further updates as we get more clarity on tariff policy.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

Let me now turn from financials and discuss some key goals and upcoming twenty twenty five milestones. We intend to initiate the TRITON Centimeters Phase III study of nucreseren and ATTR Centimeters in the first half of twenty twenty five. TRITONPN is expected to initiate by the end of twenty twenty five. We expect additional approvals of VANBUTRA and ATTR cardiomyopathy in Japan in Q2 and the European Union in Q3. Plan to report data from the CARDIA-three Phase II trial of vizalbesiran in the second half of the year.

[Jeff Poulton, Chief Financial Officer at Alnylam Pharmaceuticals]

These results will help inform the final design for the Phase III CVOT of vizalbesiran, which we also expect to initiate in the second half of twenty twenty five. Let me now turn it back to Christine to coordinate our Q and A session. Christine?

[Christine Lindenboom, Chief Corporate Communications Officer at Alnylam Pharmaceuticals]

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.

[Operator]

Thank you. Ladies and gentlemen, we will now begin the question and answer session. The first question comes from Tazeen Ahmad at Bank of America. Please go ahead.

[Tazeen Ahmad, Analyst at Bank of America]

Hi, guys. Thanks for taking my question. I'm sorry if I missed this on the prepared remarks, but, I just wanted to get a little bit of, additional color of the, initial patients that are starting treatment. Who are the prescriber base? Are they people that have already had previous experience with Ambutra, or are you seeing a mix of doctors that are also completely new to the drug?

[Tazeen Ahmad, Analyst at Bank of America]

Thanks.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Yeah. That's a great question and one for Toga. But I think what's really encouraging, you know, about about the launch in cardiomyopathy is that really kind of all the indicators are flashing green, and we're really seeing, you know, broad and balanced use across all aspects. But, Tolga, perhaps you can speak specifically to the, you know, prescriber base.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. I mean, the the way we see this is a really good broad uptake. We see, cardiologists that have been familiar with the product, but we're also seeing a pretty good uptake in terms of those cardiologists that have not tried Amvutra. So that's really encouraging. But the most encouraging part is that what I highlighted, our number one priority, which was out the gate to set up and enable second health momentum by actually setting up these institutions to be formulary ready.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And within a short four weeks, we've been able to get into formulary of half of those accounts. And that to me is really opening up an incredible opportunity for us.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Thanks, Azim. Next question.

[Operator]

Thank you. The next question comes from Gena Wang at Barclays. Please go ahead.

[Gena Wang, MD - Biotech Equity Research at Barclays]

Thank you. So I think we saw first full quarter revenue from, I think, dollars 79,000,000 for tafatidis and the $37,000,000 for Atruby in ATTR cardiomyopathy. So which one do you think it's a good benchmark for InVutra first quarter revenue? And also my quick calculation for your ATTR franchise, this quarter versus the last quarter, of roughly $17,000,000 quarter over quarter growth. Any revenue was contributed from ATTR cardiomyopathy revenue?

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Well, I think that's really for you. It was actually quite hard to hear you, Gina, but I'll try I think there

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

was one question around how we think about benchmarks for the c m c m launch.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. Happy to take that, Gina. Look, first and foremost, we've already laid out our year end guidance. So that's really important to demonstrate and that the mid year point of the midpoint of the total growth is going to be about 36%.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

That's obviously our goal is to meet and hopefully exceed that year end guidance. Now in respect to the first quarter results of those two stabilizers, I think it's really important to highlight the category is growing. If you take out the IRA impact of tafamidis, both products have grown. In fact, I think tafamidis had led that growth. So that's a clear good early sign of how this category remains untapped in terms of growth.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

So, I mean, that's great, Touk. I mean, look, we we really are excited to be in a class of our own in this market with a sort of orthogonal mechanism and a differentiated profile. Gina, I'll just come back to you. I'm I'm not sure, you know, I heard all of your question.

[Gena Wang, MD - Biotech Equity Research at Barclays]

Sorry. Yeah. So I think that yeah. Sure. Can you hear me better now?

[Gena Wang, MD - Biotech Equity Research at Barclays]

Okay. So yes, the second question is regarding this quarter number, quarter over quarter growth when we look at the ATTR franchise, it's about $17,000,000 Just wondering any revenue contribution from you know, the ATTR cardiomyopathy.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

No. No. I actually made those points in our prepared remarks. It's it's all it's all TTR polyneuropathy. And, you know, I think that this speaks to, again, the the the profile of Vambutra that we have in polyneuropathy and the quality of commercial execution.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

I'm I'm really delighted actually by the strength of our polyneuropathy business with terrific growth. Tava, do you wanna add anything? Thank you, Gina. Next question.

[Operator]

Thank you. Next question comes from Greg Harrison at Scotiabank. Please go ahead.

[Teraesa Vitelli, Equity Research Associate at Scotiobank]

Hi, everyone. Good morning. This is Theresa Vitale on for Greg Harrison. Congrats on all of the progress this quarter, and thanks for taking our question. Curious to hear how you're leveraging your commercial expertise and maybe what additional strategic efforts are you making on the commercial front to be competitive in capturing tafamidis professors?

[Teraesa Vitelli, Equity Research Associate at Scotiobank]

Thanks.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

It's a great question, Toug. I think it goes straight to you.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. I mean, first and foremost, as Ivan indicated, we come with an entirely new mechanism of action that clearly sets us apart in terms of any stabilizers that are out there, given that we work on upstream and that rapid knockdown clearly actually manifested itself with HELIOS B results where half the patients were both on placebo as well as on the study arm, were actually already on a stabilizer. And the results are obviously quite compelling. But frankly, when you think about the disease itself, that it's a rapidly progressing fatal disease, physicians are first and foremost interested in treating the disease early and actually treating with the best possible option they have. In that case, we believe actually Avutra provides a real clear first line option.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Now in terms of those physicians who are considering a switch, we're already seeing that in our broad patient uptake, and we believe that's going to continue to be the case given that half the patients in the most recently published ACC study that shows that patients do progress on stabilizers. So we believe actually we're going to remain a very important option for those patients are progressing on any stabilizer.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Thank you, Sorka. Next question.

[Operator]

Thank you. Next question comes from Ellie Merle at UBS. Please go ahead.

[Eliana Merle, Analyst at UBS Group]

Hey guys, thanks for taking the question and congrats on the early launch progress. Just in terms of ANSUTRAS, I guess, do you expect or what are you seeing in terms of the use of the first injection free versus those going straight to paid drug? Maybe assuming that more would go straight to paid drug considering your comments on the formulary access? And then just a follow-up on your commentary on formulary access. I guess since you're already on formulary and more than half of these 170 priority centers, Are you seeing any change to the price, used for polyneuropathy from these centers?

[Eliana Merle, Analyst at UBS Group]

And just your latest expectation on how this pricing will play out between polyneuropathy versus cardiomyopathy? Thanks.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

So two questions. I think one about our Quick Start program and the second around formulary and Yeah,

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

I mean, maybe I'll take the second question first. We have a single price and we don't see any price difference between our both of our indications, which are both rare conditions. Now in terms of our I think you're referring to our Quick Start program. Look, I mean, if you take a step back, we have a plethora of services that is actually developed by our in house patient support program, helping patients to actually navigate a very complex US healthcare system. And frankly, if you look at our track record, our conversion rates when patient comes into those patient outcomes is actually very fast and is very effective and patients stay on on monotherapy.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Now that program itself includes a quick start program. And we had it frankly for that program for years. And so far we're seeing a very limited use of this quick start program as we had seen in polyneuropathy. And what we're really pleased is frankly, those patients that are coming into the program across a different payer mix are getting on therapy, whether it's through Medicare fee for service, Medicare Advantage, as well as in commercial. And I must also add, as we anticipated, most of those patients are paying zero co pay as we had seen in polyneuropathy as well.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Very important. We're getting good patient access.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Next question?

[Operator]

Next question comes from Gary Nachman at Raymond James. Please go ahead.

[Gary Nachman, Managing Director - Equity Research at Raymond James Financial]

Great. Thanks for taking the question, and congrats on the progress. So with the TrueBee in the early launch phase and getting some traction, is that creating a headwind for Ambutra's launch in Centimeters? Or is it helping create more noise for the entire category? So what's the early read on physician receptivity to a new silencer versus a new stabilizer out there?

[Gary Nachman, Managing Director - Equity Research at Raymond James Financial]

And then just maybe specifically on the reimbursement side, how are the dynamics playing out as a Part b drug, versus the stabilizers that are Part d drugs? Thank you very much.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Yeah. No. Those are those are two great questions. I think, you know, you know, Tolga has, you know, made the point that we really are in a category And, you know, what we're just seeing is actually continued evidence of a large growing and and frankly unsatisfied market.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

And I think, you know, we're very excited to be able to participate in this market with the recent launch of and which we're in cardiomyopathy. I think the second question was around the part part b, part d dynamics and how that plays through.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

So look, I mean,

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

I think a good example of how we've been managing part d, part b dynamics, frankly, is what we've already demonstrated in polyneuropathy. We just shared with you in this past quarter, after one year of launch as a Part B product, we've actually been able to achieve seventy percent of all new patients and continue to grow actually in an accelerated phase base from a larger base of business. Now in terms of what we're seeing in this new line extension we have, we're seeing no headwinds. And thankfully, with the value based agreements we have, and we're seeing this uptick across all payer mixes. So there are no signals that we can iterate right now that would suggest otherwise.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And in terms of differentiation and whether we're actually seeing any headwinds, look, what really sets us apart is the strength of our data. It's complete, consistent and cohesive. We're presenting the full picture with scientific rigor. And in contrast, we're seeing some in this space selectively highlighting data points with creative interpretations. And we already see and believe investors and physicians alike value the clarity and integrity of a comprehensive dataset, and that's exactly what we're delivering.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

And, yes, and, you know, it's what we've been doing for the past several years as we focused on meeting the needs of patients. Next next question.

[Operator]

Next question from Jessica Tsai at JPMorgan. Please go ahead.

[Jessica Fye, Managing Director & Equity Research Analyst - Biotechnology at JP Morgan]

Hey, guys. Good morning. Thanks for taking my questions. You mentioned providing additional launch indicators with 2Q results. Can you just touch on what those will be?

[Jessica Fye, Managing Director & Equity Research Analyst - Biotechnology at JP Morgan]

And then of those 70 priority health systems, I think you mentioned more than half already have Ambutra on formulary. Can you just speak to your goal of where you want that number to stand maybe next quarter and by year end? Thank you.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Yeah. That's huge.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. Yeah. Look.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

I mean, I think we've been very consistent about how we're describing in the way we're updating the investors. And in this case, our goal, frankly, was to complete the inclusion and formulary by year end. As you can see, we're taking our progress has been faster, and we're very pleased with that. So it's absolutely by, you know, year end, we wanna be able to get there so that we have access. What's most encouraging, frankly, about the the most recent development is a big majority of these accounts not only included in the formulary, but those accounts that have included the formulary already actually initiating patients on therapy.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And that's incredibly encouraging. Now in terms of our Q2 data, I think the biggest update is going to be revenue uptake and the pull through and how we're actually seeing that. And obviously, we're committed to providing additional color in terms of the broad patient uptake and what that really looks like and prescriber update and so forth.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

That's great. Yeah. We're looking forward to sharing much more to our next earnings call. Next question?

[Operator]

Next question from Ritu Baral at TD Cowen. Please go ahead.

[Ritu Baral, MD & Senior Biotechnology Analyst at TD Cowen]

Good morning, guys. Thanks. You mentioned that you're seeing first line use already. Tolga, can you speak a little to the type of patient or profile of patient that is making up that first line use? And then I have a clarification on formulary inclusion.

[Ritu Baral, MD & Senior Biotechnology Analyst at TD Cowen]

When you have formulary inclusion, is that where any prior authorization requirements sort of get set for use in the health system, as well? And and if so, how should we be thinking about what you're seeing for prior auths in formulary inclusion?

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. I'm I'm I'm we too high. I'm grateful for your question. Let me take this last one first, meaning the type of formulary and and whether that will require actually prior auth. So we're talking about two types of access here.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

One is the the access where, you know, you're you're dealing with the payers. That's the Medicare before service, Medicare advantage, as well as commercial. They're actually all products are are go through a medical exception process, and and it's usually essentially, if you're a part d product, the prior authorization is is in almost all sorts of circumstances that is required. What makes us unique is in Medicare fee for service. There are no prior auth request.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

The second part, which I was alluding to, is the 70 health care systems. And these systems is just a question of the organization saying, we're actually going to be buying this product because now it's actually included with this new indication. That requires no prior authorization. So I just wanted to make that very clear. Now in terms of the type of patients that we see in the first line, You know what's really exciting about this is when doctors believe actually Amutra and understand Amutra's profile that is clearly differentiated as a rapid nocturne agent, they don't actually make a lot of differences in terms of what patients they want to put in.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

What they see is if the patient is progressing on a stabilizer, they immediately put that patient on Ambutra. If they see a new patient, whether that's early onset or actually they're already progressive, they immediately put that patient on the first line. So it's not so much about the type of patient, but it's also whether the doctor have clearly understood the compelling data set that we get to present with HELIOS P and additional real world evidence.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Carter.

[Ritu Baral, MD & Senior Biotechnology Analyst at TD Cowen]

Thank you.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Next question?

[Operator]

Next question from Salveen Richter at Goldman Sachs. Please go ahead.

[Tommie Reerink, Biotech Equity Research Associate at Goldman Sachs]

Hi, this is Tommy on for Salveen. Thank you for taking our question. We just want to confirm some of the metrics that he gave out. So 170 health systems over half on formularies and over 75 initiated, one per system, around 65 patients give or take. Is that accurate to think about?

[Tommie Reerink, Biotech Equity Research Associate at Goldman Sachs]

And just a follow-up, we're wondering if you're seeing some more standardized guidelines for identifying stabilizer progressors among HCPs now that we have new options. Thank you.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Togo, why don't you take the first question and then I think Pushkar will take take the second.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. I mean, just

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

to be clear, we clearly laid those out on the slide, which essentially says eighty percent of the TTR treatments are initiated through these 170 US healthcare systems. These are some regional networks, maybe local networks as well as national networks. Once those institutions include a product because it's a buy and build product in their formulary, that means actually that institution can acquire and can initiate therapy. And what we're alluding to is of those 170 within three to four weeks, those systems are already set up as online. Now, majority of those systems are already initiating treatments in the setting.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

That's what we're referring to. I don't know if that captures I think that's covered the question.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Maybe we get on

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

to the second question, Poscolffi.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

Yeah. Tony, in terms of the stabilizer progressors, maybe just a couple of points on this because it does come up not infrequently. Doctors are well trained cardiologists to evaluate patients with heart failure and whether they're doing well or not well on therapy. That's why you've seen over the years many studies that have said, hey, how are patients doing on stabilizers? And they report thirty percent to fifty percent of patients do progress on those therapies.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

And so that's, I think that's where that's coming from. And so I think they're well trained. I think if you look for example at ESC heart failure guidelines that were set up for ATTR Centimeters, they show that doctors look at factors like clinical symptoms. Are they hospitalized? What's their walking ability?

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

What's their shortness of breath? What's happening on imaging like echocardiograms for example? What's happening with critical biomarkers like NT proBNP and troponin? And so I think doctors are well attuned to looking at those factors and examining them. I think once again, really heartening to us about the profile of Ambutra is that on actually every one of those parameters, we see a benefit in terms of delaying or favorably impacting disease progression.

[Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs at Alnylam Pharmaceuticals]

I think that's a core aspect of this disease. As I mentioned, we just published data showing that actually there's actually improvements in aspects of cardiac function with this drug, which indicates the potential for a disease modifying profile. So that's what's compelling about this. I think there will be more guidelines, etcetera, around this. But I think really what we're seeing is that doctors know how to recognize heart failure in heart patients who aren't doing well and then reaching for the best therapy for their patients.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Great. Thanks, Pascal. Next question.

[Operator]

Next question from Kostas Belouris at BMO Capital Markets. Please go ahead.

[Kostas Biliouris, Director - Equity Research at BMO Capital Markets]

Thanks for taking our question and congrats on the progress. One question from us on Ambutra. I'll try to push my luck here a little bit for some more granularity. BridgeBio recently mentioned that they saw an impact from Ambutra launch on the number of Atrobi script, And this impact was particularly from switch patients. So that said, I wonder whether you see the majority of the early Ambutra uptake coming from switch patients or new patients.

[Kostas Biliouris, Director - Equity Research at BMO Capital Markets]

Any quantitative or directional color there would be very helpful. Thank you.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

I'll take that question. Hi, Costas. Look, I think the way we best describe given that still early days is broad. What I'm really, really excited is again, we're taking all kinds of patients, including definitely first line patients as well as switch patients. And look, those physicians that choose to switch, they also start new patients on Ambutra.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And that's definitely an early trend that we start seeing. By the way, before we move on, I also want to take a quick moment since I know the team is always listening in to call out their phenomenal work, what they've done. Honestly, what I witnessed leading up to this launch and in these early days has been nothing short of world class. Our customer facing and patient support teams are really firing on all cylinders, bringing the exceptional profile of Ambutra to a patient community that's long waited for a breakthrough medicine. And the early momentum cost us, as I shared, is strong and all signs point to us being right on track to deliver something truly impactful.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Silke, thanks for those perspectives. Next question, please.

[Operator]

Next question from Luca Ezzi at RBC Capital Markets. Please go ahead.

[Luca Issi, Senior Biotechnology Analyst at RBC Capital Markets]

Great. Thanks so much for taking my question. Congrats on the progress. Maybe, Talga, a quick one here on access. At least based on our checks, it sounds like step edits are likely going to be implemented for commercial patients but are much, much less likely on the Medicare fee for service patients.

[Luca Issi, Senior Biotechnology Analyst at RBC Capital Markets]

One, is that a fair characterization? And two, if so, how should we think about the Medicare Advantage patients,

[Luca Issi, Senior Biotechnology Analyst at RBC Capital Markets]

the one kind of

[Luca Issi, Senior Biotechnology Analyst at RBC Capital Markets]

in between the two buckets? Are they conceptually closer to commercial patients where step edits are likely, or are they closer to fee for service patients where step edits are less likely? Any thoughts there, much appreciated.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yes, know, I appreciate the question. Look, first and foremost, what we've already seen is a very nice broad uptake on all payer mix. So we're really not seeing any headwinds in terms of any restrictions on the product. Now, when it comes to fee for service, since surely there won't be any limitations. So definitely half of the Medicare patients will be able to have access very seamlessly and we're seeing that with zero co pay, I must say, in most of the patients.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

In terms of commercial and Medicare Advantage, we're not seeing any step edits so far. And we obviously have established a great infrastructure through our value based agreements that enables us to be able to actually demonstrate clinical value. And that clinical value provides us that similar advantage. Now if there were to be any step edits, we certainly have the tools to be able to address that if that were to be the case. But look, we have seen it in polyneuropathy.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

We're now seeing in Centimeters. We have the patients getting on treatment in a very quick short amount of time and staying on treatment. Thanks to again the product profile and the support that we provide.

[Operator]

Next question from Paul Matias at Almirall. Please go ahead.

[Paul Matteis, Managing Director, Head of Therapeutics Research at Stifel Financial Corp]

Thanks. Paul from Stifel. Appreciate you taking the time. As it relates to uptake so far, Tolga, when we had dinner five weeks ago, you talked about how there are certain physicians who they actually can use the drug without going through a P and C committee. Any metrics there?

[Paul Matteis, Managing Director, Head of Therapeutics Research at Stifel Financial Corp]

Like, what percent of the prescriber base is that, and what have you seen from that population? And then as it relates to Medicare fee for service patients, given the ease of access, is this the kind of thing where over time you think a patient who has who's insured who's covered by Medicare fee for service could actually get drug, the first dose of drug the same day that it's prescribed? Thank you.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. I mean, maybe I'll take care of your last question first. Look, at the end of the day, this is a healthcare professionally administered product, which requires actually injection, buy and bill, and that requires some level of coordination. So it will never be a one day administration, but it's certainly very quick given the kind of support that we provide. And we obviously track those patients.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

What's also very encouraging is whether you're a fee for service advantage or commercial patients, these patients come in through a start form where we don't actually see any distinction based on their insurance coverage. We are neutral the payer mix. And despite that, those patients start getting on therapy. And the main reason is, and I really want to underline this, whether it's Stepedate or prior auth, this is a rare and a very, very severe disease that rapidly progressing. And because of this, we see really great coverage of this category as a whole.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

And given what we have to offer and based on the value based agreements that we've established, we believe actually we have the ability to have the appropriate patients put on therapy as the physician requires.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Thanks, Silgan. So I think we've got time for one last question.

[Operator]

Next question from Mike Ulz at Morgan Stanley. Please go ahead.

[Michael Ulz, Analyst at Morgan Stanley]

Good morning. Thanks for taking the question. Maybe just another one in cardiomyopathy. Wonder if you can talk about the rate of diagnosis and maybe if you've noticed the shift since the beginning of the year now that there's two additional products on the market. And then maybe just secondly, with about twenty percent of patients currently diagnosed, what do you think that could look like at the end of the year?

[Michael Ulz, Analyst at Morgan Stanley]

Thanks.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Two great questions.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

Yeah. No. Thank you. Look, I think we actually have empirical evidence now.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

What you see in polyneuropathy from fifty percent growth rate to sixty percent just with another product in polyneuropathy already accelerated that and we remain the market leader. Now when you look at actually the Q1 results of both stabilizers, actually in The U. S, the stabilizer has grown the fastest ever in the quarter. I think that's somewhat also supported by IRA changes as well. But we see this category growth only accelerating.

[Tolga Tanguler, Executive VP & Chief Commercial Officer at Alnylam Pharmaceuticals]

We used to provide analogies with multiple sclerosis and other products. Now we see it in our own category. So there's definitely evidence of that. Now in terms of how large the category and how much diagnosis rate is going to go up, it's going to be very difficult for us to predict that now. But I think we will all see and I'm sure all voices in this category is gonna help accelerate that in the future.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Good. Okay. Well, look. Thank you everyone for joining us on the call. As you can hear, 2025 is off to a great start at Alnylam, and we look forward to providing with further updates as the year progresses.

[Yvonne Greenstreet, Chief Executive Officer at Alnylam Pharmaceuticals]

Thanks, everybody.

[Operator]

And gentlemen, this concludes your conference call for today. We thank you for participating and we ask that you please disconnect your lines.

Participants

Executives

• Christine Lindenboom, Chief Corporate Communications Officer
• Yvonne Greenstreet, Chief Executive Officer
• Tolga Tanguler, Executive VP & Chief Commercial Officer
• Pushkal Garg, Chief Medical Officer and Executive VP of Development & Medical Affairs
• Jeff Poulton, Chief Financial Officer

Analysts

• Tazeen Ahmad, Analyst at Bank of America
• Gena Wang, MD - Biotech Equity Research at Barclays
• Teraesa Vitelli, Equity Research Associate at Scotiobank
• Eliana Merle, Analyst at UBS Group
• Gary Nachman, Managing Director - Equity Research at Raymond James Financial
• Jessica Fye, Managing Director & Equity Research Analyst - Biotechnology at JP Morgan
• Ritu Baral, MD & Senior Biotechnology Analyst at TD Cowen
• Tommie Reerink, Biotech Equity Research Associate at Goldman Sachs
• Kostas Biliouris, Director - Equity Research at BMO Capital Markets
• Luca Issi, Senior Biotechnology Analyst at RBC Capital Markets
• Paul Matteis, Managing Director, Head of Therapeutics Research at Stifel Financial Corp
• Michael Ulz, Analyst at Morgan Stanley