Cytokinetics, Incorporated (CYTK) Earnings Call Transcript & Summary

Welcome again to Citi's Back to School Biopharma Conference. I'm Eric Joseph, 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 hopping into Q&A, I can 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 MYQORZO 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 MYQORZO 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 4 years. But I do think the market is embracing of aficamten 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 aficamten and MYQORZO oHCM and nHCM today. And as time permits, hopefully, we can also speak about our financial picture and our outlook for the pipeline.

Great. Yes. We hope we'll touch on all of 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 nonobstructive HCM market. If we're looking at estimates, the prevalence would seem to be roughly an even split between obstructive and nonobstructive disease if you're looking at the total HCM market. But nonobstructive 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 in HCM?

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

Can you hear me? Is this on? Yes. Thanks. This is Dan Jacoby, Clinical Research here at Cytokinetics. And I'm also a hypertrophic cardiomyopathy physician for many years, I -- this was a major part of my practice. I ran clinical trials, and 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 1,000 patients, and I was more 70-30 nonobstructive 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 nHCM 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, aficamten 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.

Yes. 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 the -- 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 in 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 III 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 is -- what data points, I guess, are resonating most with the treating community?

Yes, we had an opportunity to engage with a number of physicians following the full data readout at ESI -- 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 how would it be managed in the real-world context?

Yes. I think I'll just go ahead and take this. So look, we're going to be looking to bring forward more published data on this cohort so people can better understand it. But in the interim, okay, I think there's a couple of thoughts here. One is, and I think everybody is 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. Master, ] I think, pointed out during the investor conference at ESC. You asked about predisposing factors. We -- 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 an 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 seem to have advanced disease. Maybe they weren't the most ideal patients for the study and end up having heart transplant. So we'll get some of that data in more detail out. The overall message is that these patients 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 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 in the placebo group that hadn't been exposed to aficamten previously that rolled over into FOREST and then were titrated on to aficamten. So this was new exposure to aficamten. Those -- that cohort only had 2 episodes of heart failure, right, in that whole cohort. So it's 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. And actually, once we get 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-HCM if we were looking at their sort of baseline 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 MYQORZO, how should we be thinking about the addressable nHCM population eligible for MYQORZO by their symptom severity or treatment history? I guess is there -- should we think about going to market treating a patient population that looks like what the study indicated? 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 -- 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 nonobstructive 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 nonobstructive disease. One caveat to that, who has symptoms and who doesn't have symptoms is always a judgment call. 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 they can 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.

Yes. 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. If you think about oHCM, it's not specified to a certain NYHA class, it's asymptomatic 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 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 nonobstructive disease. I know it's a very forward-looking question given that the sNDA hasn't been filed yet, but maybe you can sort of speak to what commercial prep we should be thinking about in the lead up to a potential expanded 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 aficamten, 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 rightsized 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.

Yes. So with the positive ACACIA 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 o and nHCM, 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 a Cytokinetics prior to oHCM approval.

Okay. Okay. I think it's still a reasonable question to ask whether 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 nonobstructive HCM. But assuming that it's required, but if it were, would that process be more streamlined than the one you're currently navigating for in support of obstructive today with...

So I'll take that. With regard to streamlining, the current REMS for aficamten/MYQORZO 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, aficamten 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 2 different REMS for 2 different indications for the same drug. So we're assuming base case 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 employ 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 monitoring and guidance to dosing reflected in label.

Do you have -- okay, I just wonder whether you kind of have flexibility to depart a little bit from the titration protocol as set forth in the ACACIA study when it comes to the recommended escalation relative to the language that may end up in the 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 up-titrated in ACACIA versus how up titration is occurring in FOREST.