Alnylam Pharmaceuticals Inc will Discuss the HELIOS-B Topline Results Summary

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

Question: Eliana Merle - UBS Investment Bank - Analyst : Congrats on the truly phenomenal data here. I think you're going up against a pretty well established competitor into tafamidis . Can you elaborate on why you believe the [tracer] and will be a first line therapy and the new standard of care? Thanks.

Question: Eliana Merle - UBS Investment Bank - Analyst : Great, thanks.

Question: Tazeen Ahmad - Bank of America Corporation - Analyst : Hi, guys. Good morning and congrats for me as well on the high-quality data. Yvonne, I did want to maybe clarify on some of the wording in the press release as it relates to on efficacy seen with patients on background to tafamidis . Can we interpret anything from the wording there that you did see a better than expected results when combining vutrisiran with Taf. We know that the study wasn't powered to show that, but it has been a point of question and debate with the investor community? And then secondly, is there any color you can provide on the monotherapy mortality benefit as to when that benefit starts to kick in? Thanks.

Question: Kostas Biliouris - BMO Capital Markets - Analyst : Good morning, everyone. Thanks for taking our question and congrats on the huge outcome. Great day for Alnylam. Great day for the entire biotech space I would say. One question from us on the competition, given that I think now the focus will shift on the market share in ATTR cardiomyopathy. One of your competitors with a TTR stabilizer has mentioned that the bar for the monotherapy arm of AMVUTTRA on your primary composite endpoint should be 42%. And obviously cross-trial comparisons are biased, but can you discuss a little bit your thoughts around that, given that you achieved 33%, which is lower than the 42% that other companies believe is about. Thank you And huge congrats again on the out.

Question: Ritu Subhalaksmi Baral - TD Cowen - Analyst : Congratulations on the data and Happy Monday, which I don't think I've seen ever. Yvonne, can you and Pushkal elaborate a little bit on the time point of the mortality analysis. Obviously, those 36%, 35% are fantastic numbers. But can you elaborate on the rationale behind the 42 month time points? And any thoughts on why the two groups are so close IgG versus monotherapy? Thanks.

Question: David Neil Lebowitz - Citigroup Inc. - Analyst : So thank you very much for taking my question. Could you comment on the p-values for the composite endpoint, given that the monotherapy was higher than the overall, what can that tell us about the combination patients and the ITT population? Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes, Dave, I think look I think a couple of points. Again, the results here are phenomenal. I'd focus on the magnitude of effect and that they hit very stringent criteria for statistical significance. P-values, a function of a number of different parameters. It's a function of effect, size, and event rate. But most of all, it's a function of just sample size. If HB had been twice as large, the p-values would have been smaller, we still would have shown a 35% or 36% reduction in mortality. And so the purpose of the p-value is to exclude a chance finding. And I think if you look at this data set, there's absolutely zero question about the robustness of this results. We had 10 out of 10. There's no question. This was not a chance finding this drug as profound activity in this disease.

Question: David Neil Lebowitz - Citigroup Inc. - Analyst : Excellent. Congratulations and thanks for taking my questions pretty much.

Question: Maurice Thomas Raycroft - Jefferies LLC - Analyst : Hi, good morning. I'll add my congrats.Wanted to ask a question just about switching and how you're thinking about that and whether you have enough data from HELIOS-B and potentially your expanded access program to encourage switching from tafamidis to Blue Tree? And what is your latest view on what strip the switch or patients could look like? Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes. Thank you, Maury. Look again, we're super excited about this, and I think it's really time. So rethink of this how this disease is going to be treated. Just to remind everyone, this is a highly progressive disease that causes irreversible damage and it is fatal. So what we're hearing from the physicians is they want to start treatment early and start with the best available treatment. That's there really the argument for first line. Now, we also recognize that a lot of the patients that are being treated with stabilizers either don't respond or they continue to progress. We've seen this in polyneuropathy. We have seen this on our own early access program when we announced it for our own [Patiromer]. So this remarkable mortality benefit that we achieved in a contemporary setting, I think is going to be a compelling evidence for physicians once approved to have these patients that are progressing to be switched very quickly. Now post tafamidis LOE, I think we would anticipate that maybe they would be put on top of AMVUTTRA. And I think that's the concept that we would like to start thinking about when it comes to how this disease is going to be treated.

Question: Huidong Wang - Barclays Bank PLC - Analyst : Thank you. Congrats on the great pay high. You. Congrats on the great results. I think this is a big victory for Alnylam and the patients having a, especially after all the bumpy roads with APOLLO-B regulatory path multiple in our ATTR cardiomyopathy Phase 3 trial changes in the field and this is truly a very important happy day for everyone. And so I wanted to ask about the 42 all-cause mortality question. So just wanted to know that if you look at the 30 to 36 months was the hazard ratio higher and with additional six months that help significantly regarding the all-cause mortality. And it was a hit also stacks using, say 33 to 36 month follow-up. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes, first of all, Wang , thank you for your kind words. It's been a long journey, but I couldn't be prouder of the team here. The tenacity to kind of go deal with the ups and downs and follow through on all the details and deliver study. People never lost sight of the mission here, and we're really, really excited about these results. But these are top line today data today, the magnitude of benefit, as you know, is very large, 35% to 36% reduction in all-cause mortality in heart failure is something remarkable and is of honest, until we've stated, we think this could be the new standard of care for this disease. I will share more at an upcoming meeting, but what I can say is that the overall effects with this drug manifest early and specifically with regards to mortality, separation grows over time, just as you would expect. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Huidong Wang - Barclays Bank PLC - Analyst : Okay. Thank you.

Question: Luca Issi - RBC Capital Markets - Analyst : Well, great. Thanks so much for taking my question. And really, really Congrats on the fantastic data here. Maybe just a quick one here. Given we already have spoken about many of the other subgroups, can you just talk about wild-type versus hereditary had just wondering if the benefit was seen across both or maybe it was driven a little bit more by the hereditary patients again, any call they're much appreciated. Thanks so much. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Thanks, Luke. I know we saw benefits in both populations. We'll share more on all those subgroups coming forward. But again, what you're seeing is an incredibly robust result and I think it just highlights the power of the mechanism of this disease.

Question: Paul Andrew Matteis - Stifel, Nicolaus & Company, Incorporated - Analyst : Hi, let me add my congratulations and thanks so much for taking my question. I had was just on the specific impacts on hospitalizations. Typically, there's more hospitalization events in these trials versus mortality events. And we noticed that the impact on mortality is bigger than the impacts on the composite is the right inference here that the impact on hospitalizations was less robust than the impact on death. And maybe I'm splitting hairs, but I was just kind of curious if you could kind of comment on that. The hospitalization secondary endpoint, given that the infection hospitalizations across studies in this space has been so widely variable. Thank you. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Thanks Paul. No, look, I think what I would say is, again, the primary endpoint and the second and all-cause mortality have slightly different analytic methods as we've talked about. So I wouldn't infer that from that. What we see in the primary endpoint is actually remarkable consistency on both sets of -- both components of the primary composite. They basically move in concert with each other.

Question: Mani Foroohar - Leerink Partners - Analyst : Thanks taking the question and congrats on the positive data. In comparing the data versus competitors and versus other landmark studies, can you give us some exact detail on what the data looked like at 30 months, which is sort of the appropriate apples to apples timepoint, just so we can think about competitive positioning in this market where 80% of patients remain untreated?

Question: Myles Robert Minter - William Blair & Company L.L.C. - Analyst : Congrats on the data. Really impressive to say this. My question is just on your use of our early separation. I think previously when we sold the APOLLO-B data, you made a comment that there was potential for early separation when a patisiran showed a mortality or favorable mortality as early as nine months. Just wondering whether that sort of time point is aligned still with your definition of what early separation would be on mortality or whether it's better to think of that as relatively early compared to the 18, 19 months we've seen with the PS stabilizer compounds. Thanks very much. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes, thank you, Myles. And look, I don't think I can give you any more color today. I think there's a lot of data to share. We have sharing the top line today and will and I think I'll let the comments I made stand and we'll share more at ESC.