Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference Transcript

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

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And maybe before we dive into lots of fun APOLLO-B questions, high level, maybe can you frame the Alnylam pipeline and strategy and where you see the company in 3, 5 years from now?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Great. Maybe you obviously have APOLLO-B data coming out quite soon. In terms of thinking about expectations, I guess, what are you looking to see both on 6-minute walk and potentially the placebo side of things on 6-minute walk as well, as well as potentially thinking about some of the secondary end points? We know it's not powered for stat sig on some of these cardiovascular mortality or hospitalizations, but what could we potentially see in terms of trends? And what are you looking for? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2022 / 2:00PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. And there's been a lot of debate around 6-minute walk and whether this is the right end point or not. Curious your thoughts on that. But also say we have a missed primary on a 6-minute walk from APOLLO-B, maybe taking a step back from APOLLO-B and thinking about vutrisiran and HELIOS-B, how would you think about that outcome in terms of the long-term success of the ATTR franchise and thinking about the expansion to cardiomyopathy?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And in terms of the number of events, another debate that I think has become maybe more topical recently after BridgeBio is how the natural history of the disease might be changing both through the availability of tafamidis, increased diagnosis as well as potentially just the patients that are likely to be enrolled in the studies today. I guess, first, how are you thinking about the natural history and how this is evolving? And second, how are you thinking about the impact of tafamidis use on the event rates that you're potentially going to see in both APOLLO-B on a shorter basis but then longer term with HELIOS-B?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Is there any color you can give us on the statistical assumptions around tafamidis?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And if you're able to comment, I guess, what's the latest that you're seeing in the degree of tafamidis drop-ins throughout the studies as well?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And in terms of just thinking longer-term labeling, long-term commercialization relative to a potential generic tafamidis, how are you thinking about what type of effect size is needed commercially? And how is this impacted, if at all, by say, having a perhaps up to 50% of the placebo arm on tafamidis when physicians ultimately might compare the effect size across labels? How do you think about that and think about what's needed from physicians to say, hey, look, the silencers might be better or hey, look, the combination might be better. What does that look like in terms of a data generation perspective?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : How should we think about the mechanistic rationale for combination? Are there certain types of amyloid plaques or certain types of being able to reduce the amyloid burden? Help us understand mechanistically the role of stabilizers versus silencers and how to think about the added benefit?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And to the extent you can comment, I guess, are you aware of the event rates on a blinded basis, I guess, HELIOS-B and perhaps APOLLO-B trials?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Absolutely. And I guess, I mean -- the reason I ask is how should we think about things like hospitalizations in an era of COVID where people might be, say, more reluctant to go to the hospital and say, "Oh, we are not feeling so well. I don't know if I want to get COVID, if I go to the hospital." I mean if that's an end point in the trial, just I mean, from an operation perspective, how are you thinking about that?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Absolutely. And thinking from kind of a biomarker perspective, such as NT-proBNP, you mentioned sort of the technetium scan. What are some of the markers that at an early time point at 12 months we can debate what we'll see with 6-minute walk, but what are some of the other measures that you see as perhaps highly reliable on their own that we should be focused on as well?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Yes. And I guess the clinical trials generally, but yes.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : We'll stay tuned for data. It's an exciting space. Maybe beyond ATTR cardiomyopathy, what are you most excited about in the pipeline?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : I tried.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Awesome. I guess, starting with hypertension, can you tell us a little bit more about this target biology and where this fits in, in the treatment landscape for hypertension?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And how is enrollment going in the KARDIA-1 and 2 studies? And how should we think about the time frame there?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And can you tell us more about the data that you'll be looking to see from these studies? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2022 / 2:00PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Exciting. And maybe turning to ALN-APP. You mentioned this is exciting and that sort of bringing RNAi to the CNS.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : How should we think about your confidence level in the ability to deliver beyond the liver and certainly a new frontier for RNAi. And yes, your confidence in the preclinical data and what we should be looking for in the initial data?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Exiting. I certainly think that the intracellular silencing will be quite interesting in the neuro space. Maybe just from -- there's 2 questions. One, the ability to deliver to the CNS, but then also the target biology. Maybe just in terms of the delivery itself, how should we think about what we'll learn from that and how you're measuring that?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Well, we'll certainly stay tuned for the data later this year, exciting. Maybe turning to another program that I think doesn't get a lot of airtime, but OXLUMO and recurrent renal stones.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Can you help me understand sort of biology of this, obviously, approved drug, potentially could be a much broader patient population, probably similar in size to ATTR cardiomyopathy, which I know we talk a lot about. Help us understand the biology of how this could potentially work in a broader patient population? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2022 / 2:00PM, ALNY.OQ - Alnylam Pharmaceuticals Inc at UBS Global Healthcare Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And when can we expect to see that data?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And I'm sorry if this is a dumb question, but I mean the biology seems straightforward, unless maybe I'm missing something, why not start this study earlier? Are there certain questions that are maybe outstanding around the biology or study design or patient population?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Awesome. Well, before I ask about C5 and gout with a little under 4 minutes left, I want to turn it to the audience if anyone has any questions. All right. Well, maybe just in terms of gout, can you tell us a little bit about the target biology there and how we should think about the timelines from here?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : I always think it's interesting how much more time people spend on RA than gout, but I understand there's more, I guess, therapeutics there currently. Maybe in terms of when you move to Part B in gout patients, how are you thinking about the patient segmentation, whether it's before KRYSTEXXA, after and the types of patients that would be studied first?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : That's helpful. Excited to see that data. And then turning to the C5 program, broad biology in terms of the number of potential indications. I guess, how are you working in collaboration with Regeneron, thinking about the potential indication set, particularly with targeting C5 in the liver?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Awesome. Looking forward to seeing the data. It's very near term in the first half coming to a close.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Well with that, I think we're out of time, but thank you so much for joining us today. It was a great learning more all about ATTR, as well as the many things beyond ATTR.