Cytokinetics at The Citizens JMP Life Sciences Conference: Strategic Insights

On Wednesday, 07 May 2025, Cytokinetics Inc (NASDAQ:CYTK) participated in The Citizens JMP Life Sciences Conference 2025, providing a strategic overview of their current and future plans. The company highlighted their progress toward the potential approval of aficamten, a drug targeting obstructive hypertrophic cardiomyopathy (OHCM) and non-obstructive hypertrophic cardiomyopathy (NHCM). While the recent PDUFA extension has delayed some operational expenses, Cytokinetics remains optimistic about their interactions with the FDA and the differentiation of aficamten from existing treatments.

Key Takeaways

• Cytokinetics is focused on the upcoming PDUFA date for aficamten in December.
• The company is exploring expansion into general cardiology with the Maple study.
• Enrollment for the Acacia study in NHCM was completed ahead of schedule, with results expected in the first half of next year.
• The commercial team is prepared for launch, despite some operational delays.
• Positive FDA interactions have reassured investors about the potential approval of aficamten.

Operational Updates

The conference call, led by CEO Robert, emphasized the differentiation of aficamten from existing treatments like Kamsios, particularly in terms of dosing simplicity and patient tolerability. The company is also progressing with the Maple study to expand into general cardiology and the Acacia study for NHCM, with potential approval in this growing market.

• The PDUFA date for aficamten is set for December, based on the SEQUOIA study and its open-label extension, FORUST.
• The PDUFA extension has had minimal impact on launch activities, shifting some operational expenses to the following year.
• FDA interactions have been positive, with no major objections or concerns regarding the SEQUOIA results.

Clinical Trial Updates

Cytokinetics is making significant strides in their clinical trials, with several studies demonstrating promising results.

• The MAPLE HCM study is designed to compare aficamten alone to a beta-blocker, with data expected this month.
• The Acacia study for NHCM has completed enrollment ahead of schedule, with results anticipated in the first half of next year.
• REDWOOD Cohort 4 has provided positive data supporting optimism for aficamten in NHCM.
• The CK-five 86 study in heart failure with preserved ejection fraction (HFpEF) is progressing, with enrollment in the first two cohorts expected to be completed later this year.

Commercialization and Launch Strategy

Andrew, Head of Commercial Organization, outlined the company’s comprehensive launch strategy, despite the PDUFA extension.

• The launch delay has shifted operational expenses like media and sales force spend to the following year.
• The recruiting process for the sales force remains unchanged, leveraging experienced cardiovascular reps.
• A comprehensive plan is in place for supply, REMS, websites, digital presence, and Salesforce.
• The differentiation strategy emphasizes efficacy, safety, and a differentiated REMS based on clinical trial properties.

Future Outlook

Cytokinetics remains confident in their business model and the potential approval of aficamten in both OHCM and NHCM.

• The potential approval of aficamten in NHCM could eclipse the impact of the three-month delay in OHCM.
• NHCM is growing faster than OHCM, representing at least half the total market opportunity.
• The company is optimistic about the results from the Maple study, expected to expand the prescriber base into general cardiology.

Readers are encouraged to refer to the full transcript for a more detailed account of the conference call.

Full transcript - The Citizens JMP Life Sciences Conference 2025:

Jason, Host, Citizens: So I’m excited to be joined next at the Citizens Life Science Conference by Cytokinetics. Cytokinetics is a special specialty cardiology company with a focus on muscle biology. Really exciting time for the company with, Aficampton, PDUFA date. It’s just several months away now. Obviously, lots of discussion over the last week about the the PDUFA extension, so we’ll jump into that.

But Robert and team just welcome and maybe I’ll just ask you to give a couple intro introductory comments.

Robert, CEO, Cytokinetics: Thank you. Thanks to Jason. Thanks to citizens for inviting Cytokinetics to provide this update. We may be making some forward looking statements so we’ll just refer you to our recently filed 10 Q and we don’t undertake an obligation to update those statements but we are in the midst of a very exciting time as we elaborated on our earnings call yesterday. Lots going on at the company and I’m joined by Fadi who oversees R and D, Andrew who oversees our commercial organization and under, each of their supervision many work streams in support of our Vision 02/1930 starting with, our move towards a potential approval for aficamtan in patients with OHCM as we’re hoping for and expecting as could occur by the end of this year.

PDUFA date December year. That’s based on a study called SEQUOIA and together with its open label extension called FORUST, we’ve seen some very significant clinically meaningful effects of aficamtan overlaid to standard of care for patients with OHCM and those effects were both on primary and secondary endpoints and Fadi can elaborate on those specifics. But we do believe that aficamtan represents some major innovations for patients with O HCM and that may hopefully be complemented by results from another study called Maple HCM that’s due to readout this month. So maple HCM and sequoia HCM together with forest HCM we believe sets the table nicely for what could be a new medicine for patients with O HCM. O HCM represents roughly half of HCM, the other half being non obstructive HCM and yesterday we announced an accelerated completion of enrollment of a study called Acacia that’s going to read out in the first half of next year in patients with NHCM.

So consider those two bookends as could be enabling of aficamtan to be a breakthrough medicine if approved for patients with HCM. Aficamten represents the first of three legs of a stool for our specialty cardiology franchise the other two being, a compound called omecamtiv mecarbil being studied in patients with heart failure and reduced ejection fraction. Another compound called CK586 heart failure with preserved ejection fraction and those three together form the cornerstone of a business that we’re building under Andrew’s supervision for what could be go to market activities in North America and Europe, for an enduring business in specialty cardiology. So we can talk about all of those matters as you may have interest.

Jason, Host, Citizens: Great. Thank you, Robert. So maybe start with the obvious point, the PDUFA extension in the background there. I think one thing that may be obvious, be lost in the midst here a little bit you’ve had a lot of interactions with FDA including through the NDA review, including the mid cycle review meeting. There doesn’t seem to be any pushbacks or major objections or major questions coming out of FDA when it comes in regards to the data that you’ve submitted and the potential for approval.

So can we just maybe start with that focus? Is that the right way to think about this that you know, the FDA isn’t pushing back or doesn’t have strong questions around the Sequoia results?

Robert, CEO, Cytokinetics: Correct, period. On top of that I’ll say we’ve engaged at very senior levels of FDA, both within the division of cardiology and Nephrology as well as the division that oversees risk mitigation and REMS. They’ve been present and active in multiple meetings. We had as we elaborated on our earnings call yesterday three meetings prior to submitting the NDA between the time we had the Sequoia results and the time we submitted the NDA and it was accepted for filing three meetings and we’ve had interactions since then both a mid cycle meeting as well as many, other interactions where FDA has asked questions, we’ve answered them, asked for analyses, we’ve provided them. There are ongoing inspections and other activities as you would expect would be aligned to what could be a regulatory process proceeding as planned, as intended, and as we hope will lead to a potential approval.

So all those things suggest that FDA is proceeding in the review as one would expect.

Jason, Host, Citizens: So look, people can go back and listen to the earnings call yesterday for all the details. I think what matters now is where we’re at today and what we’re thinking about the future. And I I I think what what hasn’t changed is that, investors were widely expecting you to have a REMS and one that had a potential to be differentiated from from Kamsios, the the first in class cardiac myosin inhibitor. I know you don’t want to give details about the REMS that you’ve proposed to FDA, so maybe I’ll ask it a different way. Can you talk a little bit about where you see the opportunity based on the Kamsios REMS today and the update where you see the opportunities to differentiate?

Robert, CEO, Cytokinetics: Maybe I’ll ask my colleagues Fadi and Andrew to speak to that because they come at it from different optics. Fadi from the standpoint of evidence generated in our clinical studies but also as was originally intended in the design of Aficamt and has been elaborated pre clinically and clinically. And then maybe Andrew from the standpoint of what we know in market research, and where the touch points are for potential distinction or differentiation.

Fadi, Head of R&D, Cytokinetics: Yeah, when we designed Afikampton one of the goals was to simplify dosing of the drug in a way that allowed people to rapidly escalate dose, achieve symptom relief in a relatively short period of time, as well as to have confidence that if they exceeded the target dose that if they lowered the dose patients would, that the effect would subside in a relatively short period of time. We demonstrated that through phase two and phase three studies, a fairly straightforward way of escalating the drug, Simple, you know, similar to any other titrated drug that people use guided by echocardiography in this case. And importantly, you know, you do exceed the threshold for ejection fraction rather than discontinue the drug and wait for it to wear off, you just merely drop the dose and continue on the lower dose that you previously tolerated. So that’s been successful in Sequoia, that strategy is successful in Forest when the physicians are actually guiding dosing and it’s essentially the same strategy we’re using in Maple and Acacia. The other things have to do with the profile of the drug as it relates to drug drug interactions.

We’re very careful about how we designed Aficamtin in that regard. We don’t expect any common clinically meaningful drug drug interactions to be an issue. The predictability I think gives confidence as you escalate that patients will have a predictable response and I think that also gives one confidence in terms of maximizing dose so that you maximize efficacy instead of treating patients potentially on suboptimal doses. So all of those things were part of how we design the molecule and then generate the clinical evidence supporting those points.

Andrew, Head of Commercial Organization, Cytokinetics: From a commercial point of view, guess ultimately it will depend on our label and the REMS final, But from a differentiation, there’s differentiation in efficacy, safety, as well as, the REMS we’ve submitted. I’m not going to get into the details of it, but just if you think of the clinical trial and the properties of aficampton in terms of speed of onset, the ability to titrate immediately, drug to drug interactions, you have to disrupt existing therapies that patients are on. When you get below an EF of 50 as Fady had described, downward dosing as compared to interruption of therapy, the ability to start at the lowest dose and then titrate up very quickly. So when we do testing, with efficacy, it always starts with efficacy, safety, REMS. We’re hearing from physicians that these products are differentiated from their point of view.

The second thing is Maple further differentiates. Maple should help us expand into general cardiology, as well as, a differentiated REMS. It won’t be all of cardiology. Right now you have about a thousand that are writing, maybe 600 that are 80% of the market. If we can get that thousand into 2,000 or 3,000, that’s meaningful.

So, thirdly, while we’re in launch mode, if if acacia reads out positively, and I have Sequoia with a launch, if maple’s positive, acacia, that’s really going to get a lot of momentum as well as kind of a halo effect. To your first comment about moving back PDUFA three months, we would have been launching, at the October by the time you’ve implemented the REMS and get supply in. So you’re launching during November holiday period, which is not the easiest time to launch. So, we would have certainly liked to have launched in September or got approved in September. If we do get approved in December, then I think we’re off to the races right away without kind of holidays and that kind of interruption from, building momentum.

Right.

Jason, Host, Citizens: So as much as three months is a long time, it’s not really a long time at all. So can you just talk Andrew about the the the work you’re doing this year and and to what extent anything has has changed? Obviously, the the sales force hires get shifted back, you know, a few months, but anything else in terms of your approach to the launch that changes because

Andrew, Head of Commercial Organization, Cytokinetics: of the PDUFA extension? Sure. So we don’t really change a lot, to be honest. I mean, think when you when you look at just OpEx, there’s things like media, sales force spend, launch meetings, etcetera, that push OpEx out to next year. So we we do have that.

But when you actually look at launch activities within, I mean, we’re very buttoned up in terms of all the things that have to happen in launch. Within twenty four hours, we were able to turn around an entirely new launch plan with supply, with REMs, with websites, with digital, with Salesforce. We’re not changing our Salesforce recruiting process or timeline because we’ve built good momentum. Again, there’s holidays in there. We have over 4,000 recruits right now for, you know, about 125 to 150 positions.

Vast majority because of all the layoffs that have occurred in pharma are cardiovascular reps over 90%, on average have more than ten years experience that translates to relationships. They know cardiology, they can get into offices, but we’re not really changing. Think it gives us a little more time to test things to integrate patient experience is really important. There’s a lot that happens on the back end, you will. It’s a complex process to integrate copay and patient assistance and free goods and medical exception and nurse navigators.

So there’s a lot of to coordinate. I think that gives us a little more time to test and make sure that kind of de risking the launch and that patient experience even more. But you know three months doesn’t really change a lot for us.

Jason, Host, Citizens: So maybe we’ve moved on to the Maple study. It’s relatively infrequent to see a a head to head study versus standard of care, at at all for drug, you know, this, you know, this early in the drug’s life cycle. So can you speak to what drove you to run that study? What gives you confidence that you’ll see a monotherapy benefit in Maple?

Robert, CEO, Cytokinetics: So I’ll start and then maybe ask Fadi to elaborate but we’ve taken to describing this hopefully as would be an unfair fight. We’ll find out soon enough but we designed MAPLE already knowing that in SEQUOIA patients on or not on beta blockers similarly saw effects that were clinically relevant in terms of increases in exercise stamina and as they then rolled into the open label extension, their cardiologists were increasingly comfortable taking them off of standard of care beta blockers. So then we designed what would otherwise be more likely a phase four study comparing aficamtan alone to beta blocker on an endpoint where beta blockers don’t really have any evidence to support its use. So maybe with that I’ll turn to Fadi.

Fadi, Head of R&D, Cytokinetics: Yeah, I think as Robert said in the open label extension there was an opportunity to withdraw background therapy. So importantly when people did that, we essentially saw the efficacy didn’t change, which implies that background therapy wasn’t really doing very much. There’s a lot of evidence that beta blockers reduce exercise performance. They have a lot of side effects, not well tolerated in some people. But they’re very entrenched as a standard of care in this disease and they’re obviously generic and widely available.

So we felt that for Aficamtan and the mechanism which is potentially disease modifying, in order to elevate it into the standard of care as opposed to being the drug of last resort, we needed to generate evidence against, direct evidence against, a beta blocker like metoprolol. So we designed and conducted MAPLE and it won’t only provide comparative data with regards to exercise and symptoms, but it will also look at what happens to cardiac function structure. So what are the relative differences between gradient reductions or between the regression of cardiac hypertrophy which is a disease modifying effect. And we hope to show that fundamentally a mechanism that addresses the root cause of disease is disease modifying beta blockers or not and then further distinguish them and ultimately change the standard of care.

Jason, Host, Citizens: Great and then just very quickly how should we think about defining success here? What kind of magnitude of benefit do need to see?

Fadi, Head of R&D, Cytokinetics: You know I think it’s more complicated than that because it’s both just efficacy but also safety and tolerability. So we’d like to see the trial’s power to see a two point zero increase, a pretty sizable difference in terms of peak VO2 because a small difference probably isn’t going to win the day. Probably it would still be positive down to about 1.5 or so, maybe even a little bit less. So that’s kind of the range we think is meaningful. But the other aspect is also going to be safety.

How many patients discontinue the drug? We know that with apikemptin almost nobody discontinues the drug. And so how does that compare to beta blockers? How does the relative tolerability compare? And all those things.

Jason, Host, Citizens: Great. Another important announcement last night, Robert, as you mentioned was Acacia HCM and completing enrollment almost six months ahead of schedule. Can you just speak to what you think drove such a rapid enrollment into that study?

Robert, CEO, Cytokinetics: Yeah, before I do, and I’ll ask Fadi, I think this is a big deal. I think the fact that we were able to bring in Acacia in terms of rapid enrollment and even over enroll it a bit is a big deal for the fact that within about a year we should see results for, aficamtan in NHCM. From a current value standpoint I think that eclipses what may be the effect of a three month delay of OHCM especially in light of the fact that aficamtan, if positive in Acacia and approved in NHCM, may be, the first cardiac myosin inhibitor to get that approval in a population that’s growing faster, NHCM growing faster than OHCM and representing at least half the total market opportunity. So I think that’s considerable new development here that hopefully drives investor interest as well. And maybe to answer your question, I’ll turn to Fadi to elaborate.

Fadi, Head of R&D, Cytokinetics: Well, you know what drove enrollment I think is the investigators having a lot of enthusiasm for the mechanism of action and collaboration with our clinical team that works very closely with them. They together identified sites that had patients whose investigators were invested in the mechanism of action. Generally trials increase enrollment when investigators perceive some potential benefit to their patients. So we hope that that’s reflective of this. We saw really enrollment take off broadly, globally, in what was during a holiday period, you know, generally at the end of last year when things tend to slow down.

So it caught us a little bit by surprise and it was sustained throughout the last quarter of twenty four and into the first quarter of twenty five and as I explained yesterday it enabled us to revise how we analyze the study and I think give us greater power to hit on now two endpoints.

Jason, Host, Citizens: And Robert you mentioned that if the study is positive, aficamtin could be the first approved CMI for non obstructive HCM. We saw a few weeks ago negative results for mavacamten in the same indication of the OHDSI study. What gives you the confidence still that aficamten is going to work in non obstructive HCM? Yeah, we were disappointed to see the results of ODiSI as we hoped for mavacamten that would represent a win in NHCM.

Robert, CEO, Cytokinetics: What gives us confidence in light of that? We look at our REDWOOD Cohort four data as we’re encouraging of moving from phase two to phase three as supportive of our optimism. Moreover, the size of that study, the duration of that study, we believe reads well augurs positively for what we should expect in phase three, especially in light of the fact that we’re taking the same dosing regimen into, phase three that has already shown positive effects in, Sequoia and Forest as well as in Redwood and, we’re going into centers that already have experience with Aficamden. We’re not increasing the number of centers beyond what already we believe should be seasoned in their use of a cardiac myosin inhibitor in a population such as this. There are other things that we think in the design and conduct of Acacia give us reasons to be optimistic and I’ll ask Fadi if he wants to add anything else.

Fadi, Head of R&D, Cytokinetics: Yeah, think phase two experience we had was really quite positive and we treated 40 patients in an open label fashion in part to ensure that we could best understand how to dose the drug. You know in NHCM you don’t have the same guardrail as to when to stop dosing as you do in OHCM with the gradients. We found the aficamtin was well tolerated up to the highest dose, fifteen milligrams. About eighty five percent of the patients got there. Symptom improvements that were generally much larger than you’d expect from placebo, biomarker response, echo, improvements in terms of diastolic function.

So all of those things in isolation bode well for testing the drug in Phase III and enabling the design of the Phase III trial which took advantage of that. So we were able to implement the same dosing scheme in Phase III with fairly good confidence it’s well tolerated. We were able to refine the entry criteria a bit to look to maximize, if you will, a treatment effect. And then we were again very careful about sites that we selected, places we went to, people we engaged with that were real HCM experts, and we have our own HCM experts at the company that validated literally every patient as they entered the trial.

Robert, CEO, Cytokinetics: The other thing to note is there’s approximately 40 patients from REDWOOD Cohort four roll into Forrest and the open label extension and that enables us a real time assessment of how they’re doing on an ongoing basis in Forrest and they continue to thrive.

Jason, Host, Citizens: I just want to squeeze in one more here as we think about the broader opportunity

Jason, Host, Citizens: set and that’s on CK-five 86 in heart failure with preserved ejection fraction. So you you also updated last night that you’ll be completing enrollment in the first, two cohorts, later this year. As we think about, you know, the context of the Acacia data, you know, roughly twelve months from now, how should we think about the read through to HFPAF and our confidence there?

Robert, CEO, Cytokinetics: Well this is the beauty of the business model that we set about building quite some time ago, But each of these programs and studies reads and informs on validation for the next and yes, what we’re learning in NHCM we think has direct relevance to this mechanism in HFpEF albeit a subset of patients of HFpEF and Fadi can speak to that.

Fadi, Head of R&D, Cytokinetics: Well, you know, think some of the audience know heart failure with preserved ejection fraction is a pretty heterogeneous condition. Some of it is due to obesity and has been addressed very nicely by some of

Robert, CEO, Cytokinetics: the

Fadi, Head of R&D, Cytokinetics: GLP-1s. But before the obesity epidemic twenty, twenty five years ago, HFpEF was really marked by people that had normal body weights, normal habitus, hypercontractile cardiac function, and symptoms of heart failure, which is why it was such a puzzling disease. The heart looks like it’s working well when you look at it, but they have all the symptoms of heart failure. And so in many ways they mimic what an NHCM patient looks like. A heart that looks like it’s hyperdynamic, no other real medical issues.

So we’ve designed a study that focuses on population of high ejection fraction, elevated biomarkers, symptoms of heart failure, and other metrics that help us hopefully recreate that NHCM patient model in this adjacent population and see if we are directionally similar with five eighty six.

Jason, Host, Citizens: Fantastic. Well Robert, Fadi, Andrew, really appreciate you being with us this morning and exciting few months ahead as usual with Cytokinetics. Thank you.

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