Alnylam Pharmaceuticals Inc at Needham Virtual Healthcare Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Joseph Stringer - Needham & Company - Analyst : Great. Well, I guess we'll start high level here. A lot going on lately, but can you give us your high-level thoughts on the recent tariffs and Alnylam's exposure here? How big of an impact does this have on your business?

Question: Joseph Stringer - Needham & Company - Analyst : Got it. And what's your take on some of the recent developments and layoffs within HHS and FDA and what specifically -- what impact do you think it could have on some of your programs? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. APRIL 08, 2025 / 3:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Needham Virtual Healthcare Conference

Question: Joseph Stringer - Needham & Company - Analyst : Got it. That fair enough and helpful insight. 2025 revenue guidance for Alnylam, but specifically I want to focus on the TTR front, [$1.6 million to $1.725 million] just in TTR sales. So I guess one of the key areas that if you execute very well, could drive revenue to the high end of that guidance or potentially in the best case even exceed it.

Question: Joseph Stringer - Needham & Company - Analyst : Yeah, and still sticking with polyneuropathy where we get into cardiomyopathy, you mentioned the strong growth, just referencing your 4Q numbers, $343 million, you mentioned it grew 35% year-over-year. From -- you're seeing strong growth both in the US and rest of world. So it's impressive given your drug was proven in 2018, and there's been a recent launch of a competitor in the space. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. APRIL 08, 2025 / 3:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Needham Virtual Healthcare Conference So what's been driving the overall growth in the polyneuropathy market here? And any metrics you can share around that? And I guess, as a follow-up to that, what gives you the confidence that you can maintain that majority share?

Question: Joseph Stringer - Needham & Company - Analyst : Got it. And last one on polyneuropathy, just given the metrics that you mentioned and the strong growth, market is increasing here. How big of an opportunity is polyneuropathy alone, just any quantitative metrics that you can provide there?

Question: Joseph Stringer - Needham & Company - Analyst : Great. Well, the recent approval to cardiomyopathy AMVUTTRA, I want to touch on the price there. You had announced that you're maintaining the current annual price of around $477,000 per year on average. But you decreased this price over time, as more patients get on the drug. So I guess, that said, what are the potential risks in taking this approach given that the oral stabilizer are priced much lower around $240,000 to $270,000 per year?

Question: Joseph Stringer - Needham & Company - Analyst : Got it. How big do you think the total cardiomyopathy market is, just given what we know about (technical difficulty) 2024 was $5.5 billion, which historically, you kind of use that as a proxy for the cardiomyopathy market and some of the commentary from Pfizer around perhaps the drugs only 20% penetrated of the market. So collectively, what are your thoughts on how big market could be?

Question: Joseph Stringer - Needham & Company - Analyst : And big picture, how do you see the cardiomyopathy market playing out given the competitive dynamics? I mean, obviously, two oral stabilizers on market. A third silencers is in Phase III development. What percentage of TTR patients would you anticipate would be on in the buckets of

Question: Joseph Stringer - Needham & Company - Analyst : What percentage of total patients are on AMVUTTRA are currently on value-based agreements, how do you see this changing following the cardiomyopathy approval?

Question: Joseph Stringer - Needham & Company - Analyst : Got it. Makes sense. In terms of the patients on [polyneuropathy] and AMVUTTRA, what's the relative split in terms of community setting versus centers of excellence or, I guess, more general noncommunity setting? And with the larger cardiomyopathy indication coming online, how do you see the split evolving?

Question: Joseph Stringer - Needham & Company - Analyst : You kind of touched on this before, but in terms of monotherapy versus combo therapy use in -- combo meaning silencer plus stabilizer, what percentage of patients currently on AMVUTTRA are on combo therapy? And how do you think this will change with the cardiomyopathy approval? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. APRIL 08, 2025 / 3:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Needham Virtual Healthcare Conference

Question: Joseph Stringer - Needham & Company - Analyst : Great. Yeah, you mentioned the tafamidis LOE late 2028. How do you think this will impact AMVUTTRA use? Where do you anticipate that it would increase slow or stay about the same? I guess could make theoretical arguments for both side. But what are your thoughts on that?

Question: Joseph Stringer - Needham & Company - Analyst : Okay. Great. Nucresiran, your next-gen TTR therapy, you guys have talked about the advantages here, totally owned, more continued dosing, potentially better efficacy. Of course, better economics to Alnylam. So I guess the question is, in terms of the positioning of this drug, what's the goal here? Would it be that ultimately, all patients on [ONPATTRO] and AMVUTTRA would eventually transition to this drug? And I know we're a long ways away from data, but how realistic would that be in a real-world setting of that switching dynamic?

Question: Joseph Stringer - Needham & Company - Analyst : One more Nucresiran, obviously, Alnylam markets ONPATTRO and AMVUTTRA but Sanofi has a significant economic interest in the revenue stream. So I guess, in the scenario where Nucresiran is ultimately proved in TTR, how could you see this commercialization dynamic play out?

Question: Joseph Stringer - Needham & Company - Analyst : Great. Fair enough. But Alnylam, they have an expansive pipeline. We don't have time to cover everything, but I guess if you had to pick one outside of your marketed therapies, which one are you most excited about? And you think could be a meaningful value driver for shareholders and why?

Question: Joseph Stringer - Needham & Company - Analyst : Great. Very helpful, Sandeep. And last question from us, it's a financial question. So sustainable non-GAAP profitability was a big goal for Alnylam, and it looks like you're on track to hit that in 2025. So I guess what's the next financial goal here? And we start to think more about operating margins, deployment of capital, what's the right balance between investment in the pipeline and maximizing profitability?

Question: Joseph Stringer - Needham & Company - Analyst : John and Sandeep, thanks so much for the excellent discussion. It was very informative.