Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference Summary

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

Question: Eliana Merle - UBS - Analyst : <_ALACRA_META_ABSTRACT>Maybe just to start off, you've mentioned that we're approaching a large inflection point for the company. Maybe to start off, can you provide a summary of some of the highlights from this past year, but then also going forward, what we should be focused on? Jeffrey Poulton - Alnylam Pharmaceuticals Inc - Chief Financial Officer, Executive Vice President Absolutely. I'll kick this off. So we reported our Q3 results at the end of October. We had a very strong quarter from a product sales perspective. Overall growth in the portfolio was 34%, and that was the third quarter this year that we've had year-over-year growth of north of 30% in both franchises, both the TTR business as well as the ultra-rare business are growing north of 30% year to date. That performance actually allowed us at the Q2 results to upgrade our guidance for the year on product sales by about 11%. So it has been a good year commercially, and I'm sure we'll talk more about some of the dynamics in the TTR marketplace, where we've got new competition for the first time this year. And then moving to the big event for the year, obviously, was the HELIOS-B readout. We had top line readout at the end of June, and then we presented the full results at ESC and had a simultaneous presentation in The New England Journal of Medicine. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 4:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference Data was terrific obviously from our perspective. We hit on all 10 endpoints stat sig in the study, and we're now -- and we've gotten very good feedback, I would say, from the marketplace in the KOL community on that data. And we're now moving through the regulatory process. So we announced, I think it was at our TTR Investor Day, that we had filed in the US in early October. We've also completed submissions in Europe, and we announced this week in Japan as well. On the US side, we'll use a priority review voucher. So that means six months from the date of filing is when we would expect an FDA action date. So that would put the approval and launch some early next year, if you go from six months from early October. Let's see. I think we also held a TTR Investor Day in New York in October, and we really talked about the opportunity that we see ahead in the cardiomyopathy part of the market, some of the dynamics in the market that are allowing it to grow at a pretty rapid pace, a lot of unmet need. And we talked about why we think we're well positioned for leadership there longer term. As it relates to the pipeline, a couple of things going on in the pipeline. One is, of course, our hypertension program. We are -- we have initiated a Phase 2 study called KARDIA-3 that's looking at zilebesiran in combination with multiple standard-of-care medicines. We expect that study to read out next year, and that will really be informative for a CVOT that will follow. We've also made a lot of progress in the pipeline in CNS, our ALN-APP program. We've provided some initial data in the multi-dose portion of that study where knockdown and safety still look good. We've also initiated a Phase 2 study in CNA CAA with mivelsiran. And we've also recently announced that we've initiated a Phase 1 study in Huntington's, which I'm sure Sandeep will have some comments on later. I think the things to look for towards the end of the year and early next year that people are interested in the pipeline. ALN-APP, we have the potential to initiate a study, a Phase 2 study in Alzheimer's at or around the end of the year. And then I think that the big thing that people are focused on in the pipeline is TTRSc04 and what the Phase 3 design will look like. And we've commented that we expect to provide data on that in the first quarter of next year. So those are, whistle stop, two of the highlights, I would say, for the year so far.

Question: Eliana Merle - UBS - Analyst : Makes sense. Maybe before we dive into some of the pipeline programs starting with TTR. So the cardiomyopathy launch next year is going to be watched very, very closely and helpful Investor Day on the TTR commercial landscape. But maybe I just want to dive into a little bit sort of your views of the frontline market and how you view uptake in, say, naive patients versus switches. I think you made some interesting commentary around seeing sort of a lot of uptake in naive patients. Maybe just as we think of the cadence of the launch next year, where do you see sort of this initial uptake between the naive and switches? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 4:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Merle - UBS - Analyst : Absolutely. It's a very compelling data. And another topic of conversation, and this is something that we've certainly heard from physicians. I find that sometimes I get a different answer from physicians on if I say, well, what medicine would you want to be on versus what are you going to prescribe where reimbursement is a huge factor? I know there's a lot of conversations around BD and understanding that. But yeah, what drives your confidence and -- REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 4:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Merle - UBS - Analyst : Absolutely, it makes sense. And just from a coverage perspective, like logistically, how does this take place? You already have the coverage in polyneuropathy, do you then automatically get coverage in cardio --

Question: Eliana Merle - UBS - Analyst : Any color you can share from recent conversations with the payers?

Question: Eliana Merle - UBS - Analyst : Understood. And another topic of conversation is how to think about the market long term, particularly when tafamidis goes generic. I mean, theoretically, this could be a very good thing or a very bad thing depending on how the payers treat it. What's your perspective?

Question: Eliana Merle - UBS - Analyst : Interesting. Could you tell us a little bit more about that? Maybe just the different potential strategies that you could take with Sc04.

Question: Eliana Merle - UBS - Analyst :

Question: Eliana Merle - UBS - Analyst : Understood. Okay. And another question that you perhaps might decline to answer. But we're all trying to think about how to model the cadence of uptake in cardiomyopathy next year. How are you thinking about that?

Question: Eliana Merle - UBS - Analyst : Great. Well, we'll definitely come back to some of the modeling and thinking about breakeven. But first, I just want to touch a little bit more on the pipeline. So Sandeep, you mentioned a handful of programs. Maybe just in some of the earlier stage pipeline, Huntington's, Alzheimer's, what are you most excited about? And talk us through some of the milestones we can expect there.

Question: Eliana Merle - UBS - Analyst : Very exciting. In terms of the Huntington's program, you recently started a Phase 1 study. Can you tell us a bit more about what you're looking to see from this study, what would be good data, and when can we maybe see this data?

Question: Eliana Merle - UBS - Analyst : Great. Yeah, absolutely. And then when it comes to the Alzheimer's and CAA programs, I mean, we've seen target engagement as we've seen with all of your programs, you're successfully able to reach the protein. But maybe how should we think about the timing for when we could see clinical data and understand the effects on cognition?

Question: Eliana Merle - UBS - Analyst : Got it. SP1 And it seems like you do have a growing pipeline. But from a BD perspective, can you tell us a little bit more about your philosophy from here? Are there areas that you think that, for instance, we've seen a lot of development in the RNA editing space. Are there any sort of technologies that you feel like would complement the Alnylam platform?

Question: Eliana Merle - UBS - Analyst : Absolutely, that makes sense. And maybe just when it comes to thinking about profitability you're doubling your pipeline, major launch in cardiomyopathy. How do we think about the outlook from here? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 4:45PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Merle - UBS - Analyst : Great. And as we think about the cardiomyopathy sort of sales force and the build-up there, just the US as well as ex-US, sort of where are you in this build-up already?

Question: Eliana Merle - UBS - Analyst : Okay. Great. And then ex-US, how are you thinking maybe about the commercial opportunity there for in cardiomyopathy relative to the US as well as the investment.

Question: Eliana Merle - UBS - Analyst : Okay. Great. And one thing we didn't touch on as it relates to TTR are the mixed phenotype patients. And I mean, we've heard a wide range of estimates of what proportion? How does this play into some of the prescribing behavior?

Question: Eliana Merle - UBS - Analyst : Great. Well, I think we'll end it there. But Jeff, Sandeep, thank you so much for the time and the insight.