Alnylam Pharmaceuticals Inc Q3 2024 Earnings Call Summary

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

Question: Ellie Merle - UBS - Analyst : Hey, guys. Thanks for taking the question. Just in terms of your earlier-stage pipeline, can you elaborate a bit on some of the work that you've done to improve the ability to deliver RNAi to adipose tissue and muscle? And how are you thinking about what makes the most sense as initial targets or diseases in these tissues? And any specific advantages to your approach versus other modalities? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 31, 2024 / 12:30PM, ALNY.OQ - Q3 2024 Alnylam Pharmaceuticals Inc Earnings Call Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes. Thanks, Ellie. As Jeff highlighted, we've talked about, we are very excited about the emerging profile of RNAi therapeutics, right? What we're seeing is that these therapies appear to be well tolerated, and we can get sustained knockdown of a disease-causing protein that allows for infrequent administration. And we're guided by human genetics in terms of the diseases that we pursue, which can allow us to validate both efficacy and safety using population genetics as well as preclinical work. So adipose and muscle are two of the areas that we've highlighted in our 225 strategy as new tissues to pursue. We highlighted a little bit at R&D Day earlier in the year, some of the approaches that we're taking, and we remain on track to progress those. We actually are - we'll be talking about an R&D Day early next year, and we'll give the specific timing of that. And that's probably the best time for us to give a more substantive update on those programs. But we're making good progress. And for competitive reasons, we're probably not going to say a lot more at this point.

Question: Gena Wang - Barclays - Analyst : Thank you for taking my questions. I wanted to ask one question regarding the ALN-HTT02. It seems like very impressive data in nonhuman primates. I believe this is one of very few showing actual knocking down in nonhuman primate brains instead of most of others showing rodent brain. So I know everyone is using 50% as a benchmark. Is that something you are looking for? What else you will be looking for regarding the Phase 1 data? Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yeah. Thanks, Gena. I'm glad you highlighted the Huntington's program because it's one that we're particularly excited about. This now represents our third CNS program that we're moving into the clinic. And what we're seeing here is that many of the insights that we learned from our APP program in terms of being able to have sustained knockdown of a disease-causing gene and appears to be well tolerated in preclinical studies is very encouraging. So we believe we will have something that will allow sustained knockdown as well as hopefully be well tolerated in the clinic as we've seen with our APP program to date. The nonclinical findings were actually quite benign in the preclinical studies that we saw, as we highlighted in the slide, it was well tolerated both in rodent and nonhuman primate species. And then the targeting approach we're taking is quite unique. We're going after an upstream portion of the gene, which includes the exon 1 fragment. And there's been an emerging amount of data in the literature that suggests that beyond targeting the full-length mutant protein that targeting the exon 1 fragment may also help in progression of this otherwise very, very rapidly progressive and fatal disease. So we think we may have an opportunity for unique efficacy with this molecule. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 31, 2024 / 12:30PM, ALNY.OQ - Q3 2024 Alnylam Pharmaceuticals Inc Earnings Call So we're moving forward in our single ascending dose study. These are in patients with symptomatic disease. We'll be looking at safety and tolerability, PK, PD, we'll be looking at changes in mutant Huntington's level - mutant Huntington levels. And we'll also have in that, as we go forward, clinical and imaging and biomarker measures, measures such as NfL, et cetera, that can be very useful in looking at progression in this disease. The study is in active start-up mode in the UK Canada. And then in the United States, we also have a green light to proceed. I'll note that we do have a dose cap in the United States. And so we still have a green light to proceed in all three territories, and we're moving forward. So I'm very excited that we'll be able to do that. And we'll work with the FDA going forward if and when we need to sort of lift that dose cap. It may give us enough coverage as it is to cover the doses that we're interested in, but we'll work with the FDA in terms of lifting that dose cap over time. And so we're very excited about this program.

Question: David Lebowitz - Citi - Analyst : Thank you very much for taking my question. In terms of polyneuropathy at this point in time, how would you say the impact of a second silencer has been on the market and your overall trajectory? And additionally, I know that plenty of your prescribers for polyneuropathy are cardiologists. Have you noticed an inflection in the number of questions coming regarding the ATTR cardiomyopathy data?

Question: Paul Matteis - Stifel - Analyst : Hi. Great. Thanks so much. I wanted to ask one more follow-up question just on recent prescribing dynamics in TTR in light of the HELIOS-B data. And Tolga, I totally understand where you're coming from, right, that you guys promote solely in polyneuropathy. But just as it relates to a cardiologist if they want to prescribe AMVUTTRA right now, what are the prior auth requirements that you see? Do they need to have a neurologist offer corroboration of a polyneuropathy diagnosis? Like are there kind of significant impediments in place that really can find this drug to that true mixed phenotype population at this point before getting an expanded label? Thank you.

Question: Ritu Baral - TD Cowen - Analyst : Hi, guys. Thanks for taking the question. I wanted to ask just how Tolga and maybe, Jeff, how you are thinking about payer discussions now even ahead of potential label expansion. What are the levers, what are the topics that you're discussing? And how are you viewing the potential for volume-based discounts upon potential label expansion and increasing number of patients on AMVUTTRA?

Question: Ritu Baral - TD Cowen - Analyst : Got it. And let me ask very quick follow-up, guys, just on Paul's question. It's a follow-up to Paul's. So I'm going to squeeze this in. How is there how is the cardiologists and neurologists understanding of compressive neuropathies factor into Paul's question?

Question: Ritu Baral - TD Cowen - Analyst : Carpal tunnel spinal stenosis. Yeah, in that.

Question: Jessica Fye - JPMorgan - Analyst : Hey, guys. Good morning. Thanks for taking my question. I got another one on TTR. Is there anything that you're going to be watching for in the acoramidis label with their PDUFA coming up? And I guess, stepping back, do you see any of the potential label scenarios for that product as relevant to your expectations for your own launch in TTR cardiomyopathy? Thank you.

Question: Gary Nachman - Raymond James - Analyst : Thanks. Good morning. So as we anticipate the launches of vutri and ATTR-CM next year in both the US and then the EU, how should we think about spending levels in SG&A relative to this year for all the commercial activities you'll be doing, just order of magnitude? And then remind us of the infrastructure you have in Europe and how you think of the CM opportunity there relative to the US in terms of both accessing patients and also pricing? Thanks.

Question: Kostas Biliouris - BMO Capital - Analyst : Good morning, everyone. Thanks for and outside of your pipeline, acknowledging that your pipeline is large and very robust and can drive growth. I'm wondering whether you can comment on potential BD activities that could potentially support even additional growth in addition to your internal efforts? Thank you.

Question: Tazeen Ahmad - Bank of America - Analyst : Great. Thank you for squeezing me in. Maybe this last one is for Tolga going back to the launch. In terms of expectations, for the early part of any rare disease launch, I think companies talk about the time it's going to take from the time the script is written to the time that the script is dispensed to the patient. But since this is going to be the second indication for your product, do you expect those traditional sometimes conservative time lines as to extended time period, at least initially to hold true here? Or do you expect that to already have been smoothed out from your PN launch? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 31, 2024 / 12:30PM, ALNY.OQ - Q3 2024 Alnylam Pharmaceuticals Inc Earnings Call