Alnylam Pharmaceuticals Inc at Jefferies London Healthcare Conference Summary

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

Question: Maurice Raycroft - Jefferies - Analyst : That was a great intro. Let's dive into ATTR. So with AMVUTTRA, there, you filed the sNDA quickly for the cardiomyopathy opportunity in less than four months from the topline data. You should be hearing back on filing acceptance soon in early December. Has there been any notable feedback from FDA on the sNDA filing package that you can highlight today? 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 20, 2024 / 9:30AM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Jefferies London Healthcare Conference

Question: Maurice Raycroft - Jefferies - Analyst : Got it. And can you remind us what's in the NDA and whether you plan to supplement the filing with any additional data from the

Question: Maurice Raycroft - Jefferies - Analyst : Okay. So no additional supplement that you're anticipating.

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Okay. And then let's talk about the launch in cardiomyopathy. How will the patient's baseline disease profile influence prescribers choice to pick a silencer versus a stabilizer in the frontline setting? And what proportion of cardiologists you expect to be early adopters and how will that prescriber base change over time as you move from big center, multidisciplinary centers to broader base? 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 20, 2024 / 9:30AM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Jefferies London Healthcare Conference

Question: Maurice Raycroft - Jefferies - Analyst : Got it. And what were your messaging to the prescriber base be? Do you see AMVUTTRA ahead of tafamidis in de novo patients? Do you have any insight into what proportion of patients may want a daily oral versus a quarterly injectable?

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Makes a lot of sense. And I want to talk about the switching opportunity as well. And so Pfizer commented on their third-quarter conference call that they expect headwinds due to a new entrant and noted potential switching of existing patients that your recent TTR day, you noted about half of current tafamidis-treated patients, which could be about 20,000, 40,000 patients could potentially switch. What are scenarios and drivers as it relates to the rate of switching? And how you influence incentivized switching?

Question: Maurice Raycroft - Jefferies - Analyst : Okay. Do you anticipate there could be a bolus of switching at the beginning or tough to say on that?

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Okay. Well, you've talked about the cardiomyopathy treatment paradigm being a monotherapy-driven market prior to tafamidis' loss of exclusivity, which is year-end '26 in EU and then year-end '28 in the United States. But we've also heard from doctors who said they would welcome combo use, and anecdotally, it could be possible to do this depending on the strength of the prescriber's recommendation. What are you hearing from payers on this topic? And what are you hearing from doctors as it relates to the willingness to get a patient on combo?

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Yeah, that makes sense. And for AMVUTTRA sales in polyneuropathy, it has been going really well. Maybe talk about that, what you're learning from that. And I'm wondering if you can comment on the proportion of mixed phenotype patients that are currently on AMVUTTRA for the variant versus the wild-type population.

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Makes sense. And with just large academic centers that are already familiar with HCP administered drug reimbursement with a buy-and-bill approach, what about community settings? How much update do you expect there? And is there already a broad-based footprint of injection-ready clinics based on your polyneuropathy presence, or will building out that footprint for cardiomyopathy be a key part of your launch expansion efforts?

Question: Maurice Raycroft - Jefferies - Analyst : Got it. And there has been a lot of debate around Part B versus Part D and the trade-offs there. Maybe talk a little bit more about the strategy for choosing a Part B path. And one of the key things that stands out to me is that doctors are incentivized to use Part B drugs because of how they get paid. And so just wondering what your thoughts are on that and if that's an important part of the strategy and how that influences Ionis commercially as well, which really hasn't gotten that much uptake. 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 20, 2024 / 9:30AM, ALNY.OQ - Alnylam Pharmaceuticals Inc at Jefferies London Healthcare Conference

Question: Maurice Raycroft - Jefferies - Analyst : Got it. Okay. And let's shift gears briefly. You had great data at AHA with the IKARIA platform sc04, maybe talk about that. Is that something we could learn more about the strategy in February at the R&D Day?

Question: Maurice Raycroft - Jefferies - Analyst : Got it. And maybe I think we're out of time, and in closing up, you've got R&D Day planned for early next year, what updates can we expect there? And what are the key advantage should investors be focused on for Alnylam?