Alnylam Pharmaceuticals Inc to Host Conference Call Transcript

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

Question: Eliana Merle - UBS Investment Bank - Analyst : Hey, guys, thanks so much for taking my question. Can you give us a little bit more color on how you think the month 30 all-cause mortality results compare to the stabilizers. So specifically the discussant slide showing the relative risk reduction on all-cause mortality at month 30 was 13.8%. Is that correct? We're just trying to reconcile this with a 31% all-cause mortality benefit in the overall population, 33 to 36 month time point things. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yes, thanks, Eli. Look, I think obviously, cross-study comparisons are always hazardous. First of all, these are different populations and different points in time. And I think what [Dr. Cady] was actually trying to convey there was how treatments actually have been benefiting patients and over time, and we're seeing sequentially a greater improvements in treatment outcomes. We've been in touch with Dr. Cady. I think there was actually a calculation error on the slide. So the hazard ratio that's shown is 0.69. If you just do the simple math, the relative risk reduction would be 31%. So I think there was just a typo on the slide. So it was about 31%, which is in line with the 30% to 36% reductions that we've cited in terms of relative risk reduction across all the hard outcomes in the study.

Question: Maurice Raycroft - Jefferies LLC - Analyst : Hi. Congrats on the data, and thanks for taking my question. Just wondering if you can contextualize your patient baseline data as well as the extensive background meds, HELIOS-B versus the parameters from several Phase 3s, and how this contributes the timing of full separation for HELIOS-B outcomes versus the other study?

Question: Maurice Raycroft - Jefferies LLC - Analyst : Thanks, Pushkal. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Thank you.

Question: Kostas Biliouris - BMO Capital Markets Crop - Analyst : Hello, everyone. Thanks for taking our question and congrats on the detailed data. Would you be able to break down for us the CV versus non CV deaths under the all-cause mortality. As I know, this is important for some people and sorry if it's somewhere and we missed it but I'm wondering whether you are planning to present it or you can take it down for last year. Thank you.

Question: Kostas Biliouris - BMO Capital Markets Crop - Analyst : Thanks, Joe.

Question: Gena Wang - Barclays Bank PLC - Analyst : Thank you for your one question for Dr. Solomon. And so much bigger players are important when we look at the time in this model transition, and we will continue to monitor a good baseline to back calculate the percentage of total Tier 1,704, the chips are actually beginning to hire 2,400. I know the wage costs to be able to do two things, 1.5% dependent as monotherapy in 13%. So which data point, I wanted to be turning patient and more severe.

Question: Gena Wang - Barclays Bank PLC - Analyst : Thank you, Solomon.

Question: Mike Ulz - Morgan Stanley - Analyst : Good morning. Thanks for taking the question. Maybe just more of a follow-up on the taf subgroup benefit. And maybe just to get a little bit more of context from Dr. Solomon as well and in terms of the benefit and what's meaningful in that context, what percentage of your patients would you consider putting on combo? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yeah. So look, Mike, I think I mean, first of all, it's important. Remember, we're talking about mortality and hospitalization. And so there is sort of no minimum -- no floor for that. We would want to improve those outcomes as much as possible. And what we're seeing overall, I'd just point out is a pretty substantial effect. If you just look in aggregate at what we're seeing in terms of relative risk reduction, we're talking about a 30% to 35%. If you look across a variety of the hard endpoints. So this is quite sizable. We actually put some of the absolute risk reductions run on the order of 10% to 20% which leads to actually very small numbers needed to treat if you kind of do the calculation there. So these are pretty substantial and again, not to draw too much from solid small subgroups. But in that taf subgroup, we saw 41% relative risk reduction in mortality. In patients with evidence of earlier disease, we saw 65%. And so we can look across this. But I think what you're seeing is remarkably consistent results across a broad range of patients in [Arm], but maybe Dr. Solomon you want to speak a little bit more in terms of what you consider meaningful?

Question: Mike Ulz - Morgan Stanley - Analyst : That's clearly helpful. Thank you.

Question: David Lebowitz - Citigorup Inc - Analyst : Thank you very much for taking my question. I guess two things. One, could you just comment on the nature of this sensor data in the charts and just what that exactly is? And also could you characterize that the functional data, the certainly the mortality is in the outcomes and more of a focus. But how would you characterize the functional data visibility stabilizes?

Question: David Lebowitz - Citigorup Inc - Analyst : Yep. Got it. Thank you. Dr. Solomon, wanted to add something.

Question: David Lebowitz - Citigorup Inc - Analyst : Thank you. (multiple speakers)

Question: Luca Issi - RBC Capital - Analyst : Great. thanks so much for taking my question and obviously congrats on the data. Maybe Pushkal at high level. Obviously, one of the challenges here is that you Pfizer BridgeBio, obviously have run trials in different eras. And so not only the baseline characteristics are very different, but obviously, you have a much higher rate of drop in both the families as well as SGLT2. However, I think you did mention during your top-line data, do you believe you'll just be establishing who tries a first-line therapy? Can you just maybe articulate why you think docs should actually take this therapy over families or [AcryMed] for newly diagnosed patients? Any color there much appreciated. Thanks so much. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Sure, Luca. Let me start and then, Tolga, you may have something he wants to add as well. Look, I think there's a couple of points. First of all, I do think we should just step back and recognize that there's a tremendous unmet need in this disease. The majority patients are not treated. It's not that's not even diagnosed. Some don't respond and many progress on current therapy. And so there's a social need for new therapies in this progressive and ultimately fatal disease. The study we did here was in the modern era. This was a really stringent test of efficacy. I think you heard that from the podium as well today to be able to show efficacy in a modest sized study on top of rigorous and effective background therapies is actually quite remarkable. And in that context, the drug hit 10 out of 10. And now when you look in the data set itself, what you see is pretty strong results as a monotherapy on 35%, 36% reductions in mortality, which Dr. Solomon has commented on, is on the high end of what's typically seen in heart failure study. So that in and of itself is quite remarkable. Now the other thing that we see is some evidence of additive benefits on top of taf. This I think suggest two things. One, I think it suggests just again the possibility that there's additive effect, but also that the stabilizers may be leaving some efficacy on the table. The Blue Tree strength is able to fulfil. And so that I think is a pretty remarkable finding as well. And so what we also then see is benefits in terms of disease progression, which Dr. Solomons point out is really important to clinicians, they want to be able to start to feel better. They don't want to lose that function that allows them to go to the kid's ballgame or the grandkids ball game or do other activities. And so that's very important to look. Physicians and patients will have additional choices now, and we think that's a good thing given the unmet need this year. But we do think that when you look at these data in totality, they stand up quite well to what's available. And we'll make this drug suitable both for first-line use as well as for patients who may be progressing on another therapy.

Question: Luca Issi - RBC Capital - Analyst : Thank you, Tolga. 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: Gary Nachman - Raymond James & Associates Inc - Analyst : Hi. Great. And thanks for taking my questions. So how early are patients typically getting diagnosed now with ATTR-CM? And what's the likelihood you can get these patients on treatment as early as possible. That's clearly where you saw the best results in this study. And do you think physicians will think differently about how they'll use Greetri later on in more severe patients given that dynamic?

Question: Gary Nachman - Raymond James & Associates Inc - Analyst : Great.

Question: Whitney Ijem - Canaccord Genuity LLC - Analyst : Hey, guys. Thanks for taking the question. And just to follow-up on the diagnosis rate question, I guess, can you remind us or talk about kind of the existing efforts and from a screening or genetic testing perspective. And in particular, I think I'm remembering a partnership with a 23 in me. Can you -- I guess, talk about what you're seeing with that with some of the genetic screening efforts and maybe any acceleration in terms of patient identification or early screening efforts in that regard from a genetic perspective, that are planned or ongoing?

Question: Ritu Baral - TD Cowen - Analyst : Hi, everyone from the Wi-Fi black hole at the London conference center. (Laughter) Thank you for taking my question. Now that we've seen that you guys have actually hit statistical significance on the double-blind portion mortalities? How should we think about mortality claim in your labels and the potential for that? And will that be impacted at any point or could that be impacted by that little, I guess some blip that we saw in the monotherapy curves where the curves cross and then on cross sort of early on? Thanks. Pushkal Garg - Alnylam Pharmaceuticals Inc - Chief Medical Officer, Executive Vice President - Development and Medical Affairs Yeah, thanks, Ritu. Look, I am not going to prognosticate the details of the label by any stretch, but what I can say is that I agree with your general premise here, which is not only did we hit the mortality at month 42, which was the prespecified standalone endpoint. But obviously the rigor and strength of the data are only compounded by hitting mortality during the double-blind period with statistical significance. And so this study was designed for an indication of reducing mortality and hospitalization in patients with ATTR-CM. And we think it's convincingly done that. Now, as you see, we have multiple data points on mortality alone that show the rigor of the data and the strength of the data. So we feel good about that.

Question: Salveen Richter - Goldman Sachs Group Inc - Analyst : Thank you. And a question for Dr. Solomon. In the context of the data set presented at what is your view on future separation? The mortality to 18 months after accommodate consistent meaningful class action is, as you think now with the other carriers that you're going to have here. Help us understand how your treatment paradigm may change within your practice? 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: Tazeen Ahmad - BofA Securities - Analyst : Thank you.

Question: Liisa Bayko - Evercore ISI - Analyst : Hi. Thanks for taking my question. A question for Dr. Solomon. As you look at this data and sort of think of some of the other treatment options at Stamatis Docurama this may be available soon and there may be another silencer as well. Like what attributes are you going to consider when you're kind of choosing which therapy to put a patient on? And then how many -- how do you think it will ultimately break down between sort of to families fitusiran at Ramatis? And how many do you think you'd put on combination therapy? Thank you.

Question: Jessica Fye - JPMorgan Chase & Co - Analyst : Hey, guys, good morning. Thanks for taking my question. Curious if you could speak to how the 6-minute walk and KCCQ results look in the monotherapy population tap the group and with their consistency there, I think we saw this for the overall population and curious if you could shed any light on the subgroups. And then I did just have a housekeeping one, which was can you just confirm what percent of patients were on background task by the end of the trial? I think you mentioned earlier more than half, so it was about 40% at baseline. And then just where did it land at the end after all those taf? Thank you.