Alnylam Pharmaceuticals Inc Q2 2023 Earnings Call Transcript

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

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : For HELIOS-B, can you elaborate on your rationale for using Anderson-Gill as a statistical method versus the (inaudible) pairwise analysis that was used in the [stabilizer] Phase III such as the recent BridgeBio data? And then second, just in terms of the event rate, how are you thinking about the proportion of cardiovascular hospitalizations that will come from the urgent heart failure visit component and the importance of including the urgent heart failure as part of this endpoint definition? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 03, 2023 / 12:30PM, ALNY.OQ - Q2 2023 Alnylam Pharmaceuticals Inc Earnings Call

Question: Myles Robert Minter - William Blair & Company L.L.C., Research Division - Analyst : HTT. Pushkal P. Garg - Alnylam Pharmaceuticals, Inc. - Chief Medical Officer and Executive VP of Development & Medical Affairs Yes. So thanks, Sarah, for the question. I think, look, as I said in the remarks and as you've heard from us in a couple of recent calls, I think what we've seen in the CNS space with ALN-APP has been really, we think, groundbreaking. It really opens up a whole new vista where we can take RNAi therapeutics to affect a wide variety of neurodegenerative diseases and beyond in the CNS. Now when you look at what we see there? We see with the levels of up to 84%, 90% lowering of soluble APP alkaline beta, that really signifies that we're getting deep brain penetration. That's always a big question as you're trying to think about additional targets that you can pursue can you get into the deeper brain structures. And that level of knockdown signifies that. And then you have durability where we're seeing knockdown preclinically, that's now translating clinically and comparable to what we saw in the liver. And we think these drugs can be dosed 6 months a year or every 6 months or even less frequently. And so that's exciting. And then the third and most critically, frankly, is the fact that so far the solubility -- safety and tolerability is really encouraging as well. And so this really opens up for us the opportunity to pursue multiple targets with our colleagues at Regeneron, who we've been working on in terms of this groundbreaking science. And so to your point, HTT is another molecule that we recently announced as a development candidate. We're doing preclinical work now, IND-enabling work, to bring that into the clinic. We haven't formally announced the time line for that. But you can imagine that we're pursuing that rapidly. Our colleagues at Regeneron are advancing a molecule against -- for ALS. Again, (inaudible) also in preclinical development right now. And we have additional targets behind that, that we're going to bring forward.