Cytokinetics Inc Q1 2025 Earnings Call Transcript

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

Question: Sean McCutcheon - Raymond James - Analyst : Based on the failure of ODYSSEY and the BMS verbiage around obstructive HCM being different from nonobstructive, getting a lot of questions on what that means for ACACIA. Can you speak to how you designed ACACIA around the properties of aficamten to drive higher probability of success and how you view the importance of pushing the CMI dose higher in nonobstructive disease given you were able to get the majority of patients on that 20-milligram dose in the first nonobstructive cohort? 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 06, 2025 / 8:30PM, CYTK.OQ - Q1 2025 Cytokinetics Inc Earnings Call

Question: Salim Syed - Mizuho Securities - Analyst : So I guess I'll just ask the obvious question here on aficamten. I just want to be clear. So did the FDA initially guide you to not submit the REMS? And then what happened? Was it something internal at the FDA? Or was there something in the package that caused them to change their stance, if you want to call it that, and ask you to actually submit the REMS, if you could provide some color around that.

Question: Huidong Wang - Barclays - Analyst : This is Gena Wang actually. This is Gena Wang from Barclays. So maybe, Rob, just follow your comments. I don't know if you can comment that can you tell us whether the REMS program you submit to the FDA, was that consistent with the one you shared with the investors that the certain protocol, was that consistent when you share -- when you submit that to the FDA? And also, given this unfortunate event, but can you take advantage of it since there is only onetime extension for the PDUFA and FDA cannot extend twice, can you use the MAPLE data and try to submit the MAPLE data and try to be included in the label for the December 26 approval?

Question: Huidong Wang - Barclays - Analyst : Like the previous communication that will be like, say, the frequency will be week 2 until week 8. I'm trying to pull out the actual information that you shared in the past with investors. So just wondering, have you -- and then also minimum like the certain monitoring protocol, was that consistent with what you proposed that you think will be differentiating from Camzyos' REMS program?

Question: Paul Choi - Goldman Sachs - Analyst : Robert, earlier, you said aficamten will be differentiated, but maybe just to continue on what Fady was saying, with the recent changes to the Camzyos label, removing the -- some of the drug-drug interaction warnings as well as the extended monitoring, increasing the monitoring period to 6 months. So I guess a lot of investors are just wondering what's sort of left on the table for aficamten to be differentiated here. If you maybe slight any additional points here to help clarify that, that would be helpful.

Question: Cory Kasimov - Evercore - Analyst : My question is, did you submit a REMS as part of your EMA filing? And if not, was that brought up as part of your day 120 list of questions?

Question: Roanna Clarissa Ruiz - Leerink Partners - Analyst : So a question on the ACACIA trial. Can you talk a bit more about the pros and cons of changing the primary endpoint to a dual primary of peak VO2 in KCCQ? And I was also curious if you could share more details of the current statistical plan for ACACIA, if you're able to share with the dual primary endpoint, that would be really helpful.

Question: Akash Tewari - Jefferies - Analyst : This is actually Akash. So a couple of things. What would you have to show with the FDA in real-world data to potentially get a yearly echo requirement over time? Is that a discussion you've already had with the agency? And then just to be clear, is Cytokinetics confident that a differentiated REMS for aficamten means an educational REMS and not an ETASU one?

Question: Charles Duncan - Cantor Fitzgerald - Analyst : Congrats on the progress. I do have what I'll call a multipart question, and that is the same subject. And that is regarding MAPLE-HCM, absolutely respect the strategy with regard to the FDA. But are you thinking about the same type of strategy with regard to submitting MAPLE after the fact for the EMEA as well as in China to the NMPA? And if so, why?

Question: Tessa Romero - JPMorgan - Analyst : Did the FDA indicate at any point during these 3 meetings that you outlined before your NDA was filed that they did not think that a REMS would be necessary? And why didn't you disclose that there was no REMS submitted back when you submitted the NDA? And when exactly did the FDA request the REMS? 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 06, 2025 / 8:30PM, CYTK.OQ - Q1 2025 Cytokinetics Inc Earnings Call

Question: Tessa Romero - JPMorgan - Analyst : You did. I'm just curious why a disclosure wasn't made back when you submitted the NDA that there was no REMS that was submitted.

Question: Maxwell Skor - Morgan Stanley - Analyst : So I'll probably approach this a little bit differently or try to. But given that the Camzyos REMS was updated recently, you submitted a 120-day safety update from the FOREST trial. I'm just wondering whether the REMS you recently submitted to the FDA potentially differs from what you would have submitted with the initial filing or discussed during your pre-NDA meetings.

Question: Leonid Timashev - RBC Capital Markets - Analyst : I forgot to give you guys a break from the REMS discussion. I was just curious on nHCM. Obviously, with only one drug potentially going to be approved in the near term, yours, I guess, how are you thinking about what that means for potential uptake of aficamten in nHCM if it's approved? I mean, would you expect more patient warehousing and therefore, more rapid launch? Or would you have preferred someone building out that market? And then I guess on EU versus U.S., and you've talked about 50% of patients ultimately coming from nHCM. Is that dynamic just for the U.S. or both internationally as well?

Question: David Lebowitz - Citi - Analyst : Could you characterize the nature of the market opportunity presented by MAPLE, given that while beta blockers might not necessarily be the most effective, they are cheap and they're prescribed by a wider array of doctors?

Question: Mayank Mamtani - B. Riley Securities - Analyst : Two quick process questions really. Could you touch on your confidence level in this newly submitted REMS to be accepted as is? And what sort of communication we can receive from you in this follow-up to the June late-cycle meeting that is coming up? And just high level, like do you sense independent physician feedback, say, in form of an Adcom is something that could be valuable here for the agency and the community, particularly since you'd have the MAPLE-HCM data by then to talk to that clear API differentiation?

Question: Mayank Mamtani - B. Riley Securities - Analyst : I mean you'd have some more data to be shared in a public forum about the drug's profile, especially the treatment initiation phase with the echo monitoring. So, can the agency benefit from having that independent physician feedback in a forum like what's the thought?

Question: Srikripa Devarakonda - Truist - Analyst : Robert, sorry to belabor the REMS point, but I just want to make sure I understood it correctly. You said you did not receive any guidance from FDA to submit REMS, whereas mavacamten, they did receive guidance. But you also said that during these meetings, the 3 meetings that you talked about, they give feedback in response to questions. So, based on what you're saying, is it fair to assume that you asked the FDA if you should submit the REMS? And then, based on the feedback, you concluded that it was fair not to submit the REMS program.

Question: James Condulis - Stifel - Analyst : And sorry for one more question on the REMS here. And so it sounds like ask from the FDA kind of came after the mid-cycle review. I guess, is that right? I'm just wondering if there's any color on sort of that mid-cycle review that you can give in terms of discussion around the need for the REMS or lack of that? And just kind of curious if there's any color you can provide.

Question: Jason Zemansky - Bank of America - Analyst : I apologize, I do want to return to the REMS. Just given everything that's happened, I know you are reluctant to discuss what FDA has said, but focusing in on the Cytokinetics side of things, given that the REMS has been such a focal point and it was a big matter in mavacamten's review, why not just include the REMS initially and then work around it? It seems like this was a risk hindsight being 2020 that was sort of always out there.

Question: Leland Gershell - Oppenheimer - Analyst : I'm actually going to ask a non-REMS question. Robert, I just want to ask in terms of any real-world studies that you may be performing after presumptive aficamten approval of the 24-week SEQUOIA data, will you be looking to collect real-world data that may further flesh out or delineate the benefit to septal reduction surgery for patients who are treated?

Question: Leland Gershell - Oppenheimer - Analyst : Yes, that's right.

Question: Jason Butler - Citizens JM - Analyst : Just wanted to switch gears here at the end and ask a question about CK-586 in the AMBER study. Just I guess, 2 parts. One, can you give us color on how you plan to disclose data from the first 2 cohorts. But I guess more importantly, how should we think about these first 2 doses in terms of being effective doses or when we would expect to see something that's optimally effective out of the study?

Question: John Gionco - Needham & Co. - Analyst : This is John on for Serge. Just want to underscore the expectations now between both the U.S. and EU with the amendment to ACACIA. Are regulators aligned on what would be considered approvable based on which, if not both endpoints, the trial needs to satisfy? Or is there any disparity on whether KCCQ or pVO2 are looked at in a different light between the 2 agencies? 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 06, 2025 / 8:30PM, CYTK.OQ - Q1 2025 Cytokinetics Inc Earnings Call

Question: Yasmeen Rahimi - Piper Sandler - Analyst : I guess what we're trying to figure out is like with all these different varieties of questions around the REMS, is it just a procedural mishap that it wasn't -- they should have asked you to submit it and they didn't and you guys didn't submit it, you wanted to follow with their instruction. Or is there more to read into it? Like I think that's what it comes down to. Like is it just a procedural mishap and now it's in place, it's fine? Or is there more to make sense out of this them coming back and asking. So really, I'm struggling to figure that part out. I understand the sequence of events that occurred, and I think all your remarks were very, very helpful. maybe help us understand which one it is because the stock is trading in a way that makes it thing it's not just procedural, there's more to it. So it would be wonderful if you could comment to the extent you can.