Cytokinetics Inc (CYTK) September 9, 2026 Conference Transcript

One again to Citi's back to school biopharma conference. I'm Eric Joseph, a senior biotech analyst with Citi. And our session this afternoon is with cytokinetics. And I'm delighted to be joined by Robert Blum and several members of the cytokinetics team. Thank you all for joining us today. Rob, maybe Robert, just before, you know, hopping into Q&A, I could have you start out with some high level remarks and then we'll go from there.

So thank you. And thanks for inviting us to participate in this back-to-school event. It's our first opportunity to interact with investors in person after returning from Munich, where data from Acacia HCM were presented to a very, very large Congress hall, very, very well attended and positive reception on the part of cardiologists there attending that conference in Munich. And those results from Acacia, we believe, provide a very important milestone and catalyst for what could be additional value creation that may come our way, as that could be data incorporated into a submission for FDA and other regulatory authorities review and potential approval. and ultimately enable mycorzo to be the first cardiac myosin inhibitor approved across the full spectrum of HCM patients. Why does that matter? Because we're already demonstrating with our commercial launch of mycorzo in OHCM that it is rapidly ascending. And where we've pointed to by the end of the year, we expect to see preferential share of new prescriptions, something quite unusual for a next product launched in a category that its predecessor had already been for four years. But I do think the market is embracing Avafi Campton for the properties that we engineered into it, and the business is off to a great start with a commercial launch we're very pleased with that continues to exceed expectations. So we're NHCM to factor into the label together with OHCM. We believe that redefines the way of treatment of patients with HCM, and we're very excited about that. So I expect we'll talk a lot about AFI Campton and my CORSO, OHCM, and NHCM today. And as time permits, hopefully we can also speak about our financial picture and our outlook for the pipeline.

Great. Yeah. I hope we'll touch on all those points. But let's pick up from ESC and full presentation of the Acacia results. Actually, let's take a step back and just think about the non-obstructive HCM market. If we're looking at estimates, you know, the prevalence would seem to be roughly an even split between obstructive and non-obstructive disease if you're looking at the total HCM market. But non-obstructive disease tends to have a lower rate of diagnosis. Can you speak a little bit to sort of why that's the case and whether that has anything to do with how prominent symptomatology or how symptomatic patients often present with an HCM.

Sure. So, to my right, our colleagues, Tricia, who leads U.S. marketing, and Dan, who oversees clinical research, and maybe I'll ask them both to comment on that.

Yeah. Thanks. Can you hear me? Is this on? Okay.

Yeah. Thanks, Dan Jacoby, clinical research over here.

This is Dan Jacoby, clinical research here at cytokinetics, and I'm also a hypertrophic cardiomyopathy physician. Many years, this was a major part of my practice. I ran clinical trials. I still have a small HCM clinic. So I think I can kind of say what we're seeing is an evolution in the understanding of HCM as therapies come online and as the potential for treatment comes online. In fact, my practice, when I was practicing, I had over a thousand patients and I was more 70, 30, non-obstructive to obstructive because we didn't have an active myectomy center. I think Tricia can speak more knowledgeably to what we're seeing currently in the community, but I think we're still trying to understand the full scope of how this disease presents. It's been years of collecting data from myectomy centers and specialty centers that have prioritized the evaluation of obstructive patients. The second part of your question is really an interesting one, which is how do you know when an NACM patient is symptomatic? How do you diagnose them? Are they harder to diagnose? Where are they in the community? And what we're seeing is that physicians who take care, large numbers of cardiology patients have these patients in their practice. They're actually not that hard to diagnose, but because there's no specific treatment right now, other than just beta blockers or calcium channel blockers, they're just sitting on them. And these are not the typical patients that end up getting referred to these high volume practices. But in fact, there's a number of them. And when you talk to individual practitioners, they say, oh, I have 10 in my practice. I have 12 in my practice that I'm just sitting on. And so as we see therapy come online, that's effective. Afrocam didn't come online. That's effective for these patients. It becomes available in the commercial setting. There's going to be a shift and these practices are going to start to really look at how they diagnose and treat these patients. And I think that's going to lead potentially to a shift in them wanting to engage more with this treatment rather than refer out. So at that point, I'll hand it over to Tricia and see what your thoughts are.

Yeah, I think what Dan really hit on was the evolution that we're anticipating to happen within the marketplace and how HCM is being treated and where HCM is being treated. And we have seen over recent years, there has been a shift even in the epidemiology and the understanding of the diagnosis rates for HCM, for O and for N. I think historically, there was an assumption that there was more OHCM patients, whether that was a 60-40 or 70-30 split. But in more recent years with the recent data that we have available to us, we see that it's more of a 50-50 split. And of that 50% that is NHCM, a large proportion of those patients would be viable for a CMI treatment based on what we understand today. So a significant opportunity exists within the NHCM space. I do think we'll continue to see evolution in the space and diagnosis rates, as well as how these patients are being treated once there is a medicine that is available for NHCM.

Coming back to the full phase three data themselves, can you talk a bit about what the clinician feedback has been now since the broader clinical profile has been presented? And has it all been enthusiasm, any reservations? And what data points, I guess, are resonating most with the treating community?

Yeah, we had an opportunity to engage with a number of physicians following the full data rate out at ESI and ESC, and the receptivity is largely positive. There's a lot of excitement, a lot of recognition that prior to Acacia HCM, there were no trials that successfully demonstrated superiority. So to have the first positive NHCM trial and the hope for the first medicine that could be available for NHCM was largely communicated back to us around the anticipation to be able to treat 50% of their HCM population.

Just as we got to see more of the safety profile at ESC, I want to just pick up on the slight imbalance in heart failure events that were observed in the study. And despite them only occurring in a small minority of subjects, this may have given investors a little bit of pause. Were there any common characteristics in these patients that might have predicted for their heart failure risk or being at higher risk of heart failure? And more broadly, can you help put these SAEs in perspective? How significant are they? And, you know, how would it be managed in the real world context?

Yeah, I think I'll just go ahead and take this. So, look, we're going to be looking to bring forward, you know, more published data on this cohorts, people can better understand it. But in the interim, I think there's a couple of thoughts here. One is, and I think everybody's familiar with this, a serious adverse event, according to clinical trials, does not mean it's a serious medical event. There are criteria around what a clinical trial calls a serious event. It really can amount to a simple escalation of care that most physicians would view as routine. And that's what the majority of these were, managed by simple short course of diuretics, as Dr. Mastery, I think, pointed out during the investor conference at ESC. You asked about predisposing factors. I can't comment on whether there were predisposing factors in this population that weren't present in the patients who didn't have these SAEs. But I will tell you that among the patients who did experience this, and including the placebo patients, we commonly saw things that would tip off a physician to a potentially increased risk, an underlying history of atrial fibrillation. At advanced age, one patient was receiving an infusion of medication to help for a different disease. And so if you're receiving infusions of fluid, obviously that predisposes you to developing heart failure symptoms. And then there were a couple of patients who just seemed to have advanced disease. Maybe they weren't the most ideal patients for the study and they end up having heart transplant. So we'll get some of that data in more detail out, the overall message is that these patients, you know, probably did have many of them, some comorbidities or risk factors that you would ordinarily identify in the course of clinical practice. And the reason I point to that is because we really, we showed this data before is that these cases occurred early on in the study during titration. But when you look at the cohort from acacia, that was a placebo group that hadn't been exposed to africanthin previously that rolled over into forest and then were titrated onto africanthin. So this was new exposure to africanthin. That cohort only had two episodes of heart failure, right, in that whole cohort. So it was a much, much lower incidence of heart failure. And why is that? Well, there was physician oversight, and it's a constraint of clinical trials that there's blinded characteristics and computer-driven algorithms that drive the titration in the care. And so once you let the physician into that care pathway, where clinician judgment can be executed, the rate of heart failure goes way, way down. And physicians identify those patients. They want to push titration on more rapidly or not as rapidly, or they want to adjust diuretics on, and they don't want to adjust diuretics on. I don't have that data for you right now, but what we're seeing in the data overall is that once you introduce clinician judgment, those heart failure episodes essentially go away.

Okay. Okay. It actually, you know, once we had time to kind of dig into the data a little bit further, particularly the New England Journal publication, it struck us that the patients in Acacia seemed a little bit sicker than the population that you studied in Sequoia, H7, if we're looking at their sort of baseline disease, burden of disease, right? If you're looking at patients with a history of AFib at baseline or ICD placement. Assuming an expanded label for mycorzo, how should we be thinking about the addressable NHCM population eligible for mycorzo by their symptom severity or treatment history? I guess, is there, you know, should we think about going to market, treating a patient population that looks like what was studied in Acacia, or is it perhaps a patient cohort much broader than that?

Well, I'm going to hand it over to Tricia in a second, but I just want to comment on what you're observing. This is not unexpected. So in the, and you can look at multiple different registries and so on that will support this, but essentially if you have significant hemodynamic obstruction, you have a high gradient, that will generate symptoms even in the absence of very severe actual myocardial muscle disease, right? So you can have symptoms just from the obstruction, even if the underlying muscle is actually pretty functional with not very much diastolic dysfunction or fibrosis or whatever the case. However, if you don't have that hemodynamic obstruction, in many cases, you require more severe myocardial disease to generate symptoms. So in general, it is true that patients who have symptomatic non-obstructive disease have, I'm not going to call it more advanced, but just different or maybe slightly more severe myocardial disease than those patients who have just pure obstruction. Now, there's a tremendous overlap here. We're talking about the same disease with just a different hemodynamic structure, but it's not at all surprising that you would see that. And what that means is that the population that was enrolled in Acacia really truly does represent that population that people are seeing in their clinics who have symptomatic non-obstructive disease. One caveat to that, who has symptoms and who doesn't have symptoms is always a judgment Do you feel well today? Do you not feel well today? Some of that is highly subjective in terms of what your expectations are. And when you generate a treatment that has the potential to improve people's symptoms, they no longer are satisfied to say, it just takes me longer to walk up that hill than my husband. They want to walk up the hill at the same speed as their husband taking a walk in the evening. So now they have symptoms, whereas before they said they didn't. So it's a moving target, and I'll hand it over to Tricia for additional thoughts.

Yeah, and I think from a commercial perspective, how we will communicate the viable patient will be largely dependent on how our label and our indication is written. If you think about OHCM, it's not specified to a certain NYHA class. It says symptomatic patients. So to that point, if we would assume a mirrored indication, we would speak to the symptomatic NHCM patients, which is a large proportion of those diagnosed NHCM for the patient population with all the points that Dan made considered as well.

Okay. Maybe you can talk us through some of the commercial preparations that are underway ahead of a potential expanded approval for non-obstructive disease. I know it's a very forward-looking question, given that the S&DA hasn't been filed yet, but maybe you can sort of speak to, you know, what commercial prep is we should be thinking about in the lead-up to a potential expansion launch there.

So maybe I'll start and ask Tricia also to comment. I will emphasize that when we made decisions many years ago to build a commercial business, it was with the expectation that for the work we were doing in research and development, we were going to build a franchise in areas where they would be addressing concentrated markets and where sales and marketing infrastructure would return a high yield on investment. And when we made a commitment to go to market for AfiCampton, it was with the expectation that there was high overlap in terms of that customer base across OHCM and NHCM, not to mention between HCM and heart failure, where our pipeline is directed. And when we built that commercial organization, the sales team leaders, the medical affairs colleagues, and ultimately the field personnel, both medical and sales, it was with a view that OHCM would beget NHCM and we would be right-sized for the opportunities across all of HCM. and frankly, for that matter, in large part, heart failure, at least that which is the more severe form. So none of this should come as a surprise to our investors who have been following cytokinetics along the way. With that, I'll ask Tricia maybe to comment more specifically about the transition from OHCM to NHCM.

Yeah, so with the positification results now in hand, we are doing our full due diligence to ensure that we are maximizing the opportunity with the hopeful future expansion into NHCM. We know that we have the chance to potentially be the first and only available treatment for the entirety of the HCM ecosystem. So we want to ensure that we're maximizing that through what we're doing today and building out the strategy, building out the messaging, ensuring that we're understanding where the NHCM patients are today in their journey of treatment so that we're appropriately reaching them. So there's a significant amount of work going on from a commercial perspective to ensure that we are ready at the earliest possible date to launch into the marketplace for both ON and HCM, but also ensuring that the appropriate education is happening around the understanding of NHCM, the symptom presentation that patients are coming in, the understanding of any differences from a pathophysiology perspective.

So there's a lot of education work that also has to happen that we didn't necessarily have to undertake I think it's still a reasonable question to ask whether you know going into a potential expanded with the approval of an expanded indication, whether the rems program would need an update, or whether additional rems training would be needed to support expansion to not obstructive HCM not assuming that it's required, but if it were um would that pot would that process be more streamlined than the one you're currently

navigating for in support of uh obstructive today with my corzo so i'll take that with regard to streamlining um the current rems uh for afi campton my corzo in ohcm has potential to be streamlined as we generate more and more real-world evidence. So already we have our eyes set on how that might occur over time, as could be relaxing or even ultimately removing of a REMS. However, to your question about NHCM, our assumption, base case assumption, is that if approved, Haffey-Champton will be approved with a REMS covering OHCM and NHCM. So really we're talking about a single REMS and we're not aware of any precedent for there being two different REMS for two different indications for the same drug. So we're assuming base case one REMS, but for where the dosing instructions, whether they be in training or whether they be in label, will address what may be nuances between OHCM and NHCM. The good news is with both OHCM and NHCM, the pivotal clinical trials employed the same up titration doses, 5, 10, 15, and 20. But how you get there may ultimately speak to what you look to monitor and what you keep an eye out for. That's the purpose of labeling more than REMS.

And we would hope that as we engage FDA, we might see language pertaining to um monitoring and guidance to dosing reflected in label do you have um okay i just wonder whether you kind of have uh flexibility to depart a little bit from the uh titration protocol as set forth in the acacia study when it comes to the recommended uh escalation or relative to the language that may end up in a label when it speaks to recommended dosing?

Yes. So the label for OHCM speaks to how gradient reduction informs up titration and echo monitoring along the way. It was up titrated differently in acacia and different between that clinical trial and the open-label extension that follows. So maybe I'll ask Dan to remind everyone how we uptitrated in acacia versus how uptitration is occurring in forest.

Yeah, sure, Robert. Yeah, so the answer to your question is, yeah, there's flexibility. There sure is. And you can see also, obviously, sequoia was the pimple trial upon which OHCM was approved, Kim Zalas was approved for OHCM. And obviously there's tremendous flexibility in the label and it does not reflect exactly what was done in the study. And that was based on the same kind of thing that we did here with Forrest with NHCM, which is that physicians have oversight. They can integrate clinical judgment, not just physicians, nurses, NPs, whatever is taking the patient, but also there's not just a flexible window, two to six weeks also, but they get to decide whether they're going to actually increase the dose or decrease the dose. They don't have to increase the dose, even if patient meets the criteria for dose increase, so they can execute on their own judgment. And that's something that we're actually looking into to see where that clinician judgment is playing out within our studies. And obviously, we're going to discuss that with appropriate regulators to inform on how best to form the label. So yeah, simple answer. Absolutely. We are not tied 100% to how the pivotal study was structured, which was a forced every two week titration computer algorithm, which unfortunately is how you have to run clinical trials in order to keep them blinded.

Okay. That's very helpful. Maybe I'll refocus this back to my, my corzo launch and obstructive disease where you are today. Strong start so far. I know since your 2Q update call, folks will be interested to get a sense of, you know, how the cadence of new patient starts is trending and as well as dispensations relative to sort of that trend that you were seeing back in May and June. And similarly, how conversion to pay prescriptions has evolved since the 2Q update.

So we can't here provide an inter-quarter update, but I will say that Q2 was a really strong quarter. You saw how, from a standpoint of metrics and outputs, we came out of the gate very strong. We continue to believe that we're on track to do similarly in Q3 and hopefully continue to exceed expectations. The things you're asking about, for instance, time to paid script from prescription continues to be a hallmark of how we are delivering and executing well on this launch. i think it's true that the street had expected that that might take as many as 60 days when in fact it's demonstrated in q2 to be just a few weeks so we like where we situate there and we'll continue to manage to that we're continuing to see the same kinds of things that we think we have pointed the street to monitor as would be evidence of meeting or exceeding expectations.

Robert, you actually, you know, began in your opening remarks talking about how you're expecting by year end to be, you know, the leading or to lead new to brand share by the end of the year. Can you talk a little bit about what is driving physician and patient decision-making when choosing between the two first-line CMI options today? And to what extent do you see upside beyond that? Let's call it 50% threshold of new to brand share.

So I'll ask Tricia to comment on that, but I'll set her up by reminding folks that we designed into Affecampton certain attributes that could, upon approval, hopefully render it a medicine that would be viewed as enabling of convenience, flexibility, and other attributes that play to physician and patient experience. And upon approval, we received a label and a REMS that was differentiated in its category. And now I'll ask Tricia to comment on what's driving a preferential share of new scripts.

Yeah, exactly to that point. I know we communicated even prior to launch the two areas that we wanted to deliver on were clinical differentiation and REMS differentiation. And we believe, based on all of the insights that we've gathered to date from the prescribing community, that they are recognizing that differentiation across the brand in regards to the clinical profile, efficacy, safety, but also the differentiation that's enabled with MyCorso for REMS. I think what we're excited to see is, to the points that were raised, is we are already driving 40% new to brand share coming out of June. We are also seeing that we are deeping the penetration of the prescribing deeper into the community with a large portion of our prescriptions in quarter two coming from HCPs that previously were low prescribers or CMIs or had never previously prescribed a CMI. And because of the profile that we're offering in regards to the flexibility that our REMS offered, also the exposure to the maple data, which really calls into question some of the historical behaviors of utilizing beta blockers that my course was able to show statistical significance versus and really key endpoints is really driving some of that utilization deeper in the HCP prescribing community and leading to the share and the differential share that we're driving towards.

If we fast forward a year from now, how do we think about the scale of your marketing campaign and obstructive HCM and sort of the promotional spend relative to where it's at today. And is DTC part of that longer term marketing strategy?

So I'll ask Tricia, but also Sung maybe to comment on how we're thinking about dialing up certain activities, but also overall OPEX and where that should be pointing.

Do you want the head of marketing or the head of finance to answer that question first? Sure.

Eric, I think it's important as a company, We're early days in launch and we keep all options open, but with regard to the OPEX trajectory, it is fair to think that SG&A, specifically commercial expenses, will continue to increase as we prepare for a potential launch in NHCM. Recall that was a key driver of our OPEX guidance increase for 2026. And, of course, next year you would get a full year impact ahead of the launch and for years thereafter. I also want to call out we have important launches to conduct in Europe. We're just at the very beginnings of this with a launch in Germany over the summer. And, of course, the U.K. is next later in Q4 with other large countries coming online in 2027. So the field force for those countries have not been brought on board yet. So that would be a reason for a further incremental increase in SG&A.

If we look at how we're planning from a commercial perspective, obviously we have a few things that we're doing right now. We'll certainly resource appropriately into further driving the OHCM launch at the same time as we are planning and preparing for the hopeful entrance of NHCM and the opportunity that we have from a commercial perspective to speak to the entirety of the HCM community. We are looking, and one of the nice opportunities that we have as a cytokinetics is to be really nimble in how we are approaching our business and our business planning. And we're looking at ways in which we can reach the HCPs and the patient community and what would probably be considered some of the more traditional mechanisms, but also innovative ways. We know, especially with our patients, the market is changing. How patients are engaging within their health is changing. So what are those innovative ways in which we can reach our patient community to drive appropriate education?

Additional comment there?

You know, we have a very robust academic publication strategy with our studies. We do that for two reasons. One is because we believe that getting the data out to the community in the most transparent way possible is the best way to facilitate, you know, appropriate and beneficial use of the medicine for patients. But the other reason that we're doing it is because we recognize that the way people access information now is a bit different. And with open evidence and chat HGPT and pick your item, a lot of those engines are integrating evidence themselves. And it's really important to, it's no longer the story that you can just publish in a big journal and say to everybody, here's the big journal publication, and let's just index to that. You have to tell the complete story because people are accessing information that wants to integrate the complete story. And I think we have a very robust team for this. Our academic colleagues are incredible and have published extensively, and we will continue that strategy.

Try and fit in a couple of pipeline questions in the time that we have left. I want to pick up on Oma Captiv in Hefref. You know, I think this is an opportunity that's often overlooked in our discussions with investors. Can you, Robert, maybe just speak to lessons learned from the Galactic FH trial and how your level of confidence in comet HF underway right now kind of has you, sorry, your level of confidence in comet HF being successful in the more narrowly defined population being studied there?

Sure. So for those of you who may not remember, omicamptiv macarble is being developed for the potential treatment of advanced heart failure with severely reduced ejection fraction. This is a concentrated customer segment like HCM, and there may be upwards of a million or more patients in the United States who are frequent flyers in U.S. hospitals with reduced ejection fraction, such as we're studying here, EF below 30. Omicamptiv was the subject of over 30 clinical trials, including Galactic, an over 8,000 patient clinical trial that met its hard clinical endpoint in terms of reduced outcomes and with a P less than 0.05. In today's environment, that might have been approved by FDA, but at that point in time, FDA was looking for two clinical trials if P is less than 0.05, but not less than 0.01. So FDA has asked us to do a confirmatory study. And this confirmatory study is being conducted. It's called COMET, and it's being conducted in a group of patients with EF below 30 compared to galactic EF below 40. In that subgroup pre-specified in Galactic, we saw a doubling of the treatment effect already in roughly 4,000 patients. And now we're doing a study that may be approximately 2,000 patients to reproduce something we've already seen in a study of roughly 4,000 patients as a subset of a group of over 8,000 patients. So when you look at it that way, hopefully like us, you can be pretty hopeful that this should deliver like it already has in patients with severely reduced ejection fraction. This is something where I think there's a meaningful potential for dislocation relative to street expectations. And I do think that Omi-Kamtev, if positive in the Comet study, That study should complete enrollment in 2027, potentially readout in 2028, could generate significant upside potential in terms of maximizing of shareholder value. So we're encouraged by the study, its current enrollment, already what we know from blinded data, and we're looking forward to that study reading out for what could be a new medicine for patients with advanced heart failure where there is no current treatment. that acts directly on heart muscle for those patients.

The screening phase of common, there's a screen in treatment phase, I believe, to common HF. Does that aid in the enrichment of patients that are then followed up in the full?

Excellent question. Excellent question, in particular, because in Galactic, conducted by Amgen, our partner at that time, there were upwards of 15 to 20 percent of patients we found out afterwards who were not either compliant with study med or at exposures that would render the drug at its target levels. And that, unfortunately, in retrospect, was a mistake and a problem. And in spite of that, the study was positive. So upon our design and conduct of Comet, and I'll ask Dan to speak of this, we included a run-in phase, and he can speak to what are the objectives of that run-in phase.

Yeah, thanks, Robert. The run-in phase, it will enable the identification of patients who are not compliant, for whatever reason, with medication, and have those patients not enroll in the study, ultimately, number one. And number two, it's actually another very important point, is that will allow the identification of non-modifiable early events, right? So if someone signs up for the study and a week and a half or two weeks later has a heart failure hospitalization, that's not a modifiable event, but that patient will no longer be included in the study and will not contribute to a non-modifiable event, which would be a bias or a obscuring of actual effect for a treatment effect in the study if that makes sense right we've gone over we'll have to leave it there for time so thanks so much for your time again this afternoon really appreciate it thank you appreciate it very much