All right, great. I'm Max Skorer, a biotech analyst with Morgan Stanley. Before we get started, I'd like to read some quick disclosures. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, I am happy to welcome the Cytokinetics team. With us today is Fady Malik, Head of R&D, Sung Lee, CFO, and Andrew Callos, Chief Commercial Officer. Just from the top, there's a lot of exciting things that have both happened with Cytokinetics this year. Looking forward, we've got the PDUFA date. Maybe I'll just open it up to the team here if you have any opening comments.
Sure. Thank you, Max, for having us. I might just start with the forward-looking statement. We'll be making forward-looking statements and refer you to our SEC filings for that. We don't take any obligations to update them. You know, we're coming here off the European Society of Cardiology conference over Labor Day weekend, where we presented in full the primary results of MAPLE-HCM, which was our clinical trial of Aficamten as monotherapy versus the current first line of therapy, metoprolol. I think that was quite a watershed moment for the field in that the performance of the beta blocker was much poorer than expected. This is a therapy people have used for decades with very little evidence supporting its use. We weren't surprised that Aficamten outperformed it.
Really, the basis for the use of the beta blocker as a standard of care was, I would say, undermined by the data that we presented in Aficamten. Lots of people left the meeting with questions about what do they do with their patients on beta blockers, how do they adequately maybe think about their treatment paradigms more objectively, potential updates to guidelines in the future, and things like that. On top of that, we saw data from Odyssey, which was the Bristol Myers Squibb trial of Camzyos (mavacamten) in non-obstructive HCM with some promising evidence of benefit there. We can discuss that as well. You know, as we kind of roll into the last quarter of 2025, we're looking forward to our PDUFA date at the end of the year.
Obviously, having a late cycle meeting this month and with lots of preparations ongoing for launch and then rolling into next year, other approvals potentially in Europe, maybe a China approval coming even before FDA approval this year. The next six to eight months are shaping up to be pretty exciting and transformative ones for Cytokinetics.
Great. Thank you. Maybe we just touch on MAPLE first. If you can give kind of the high-level data set. The fact what struck me, and I think highlighted by KOL feedback, is the fact that beta blockers in regards to exercise capacity, it also deteriorated and it was significant with Aficamten. Any highlights there? Maybe if you can call out key KOL feedback, that'd be great.
Sure. In MAPLE, we assessed exercise performance as a primary endpoint. It was probably not that surprising that beta blockers caused a decrease in exercise performance. That's been seen in other conditions. It's even been seen in a small study of non-obstructive HCM, rather of obstructive HCM patients. What was really more surprising was the lack of effect of the beta blocker on reducing the obstruction, the LVOT gradient. There was almost no effect of the beta blocker on that. That's fundamentally the rationale for using the beta blocker in obstructive HCM. Lack of impact on the underlying cause of symptoms. The increase in BNP was also a bit surprising. Patients reported a fair number of adverse events that were a consequence of the beta blockade.
We pushed the dose in the trial just so we could say that the beta blockers had a fair shot at it, but it also led to several down titrations and discontinuations of the beta blockers. I think when you walked the floor and spoke with KOLs afterwards, this was presented in front of an audience of about 4,000 people in the most prestigious session of the meeting. You got the sense that they were just questioning the basis for the use of this drug for their first line of therapy and how that might ultimately, the standard of care may evolve in HCM.
Potentially, this would be submitted as a supplemental application after the PDUFA date in December. Overall, this is a significant milestone. How is it kind of shaping Cytokinetics' positioning in HCM overall? What's your approach going into the potential launch in December?
From a commercial point of view, when the SNDA goes in, this is not a new indication. It just further elucidates the effect of beta blocker. It is in the public domain. We're obviously focusing on long-term Sequoia. When we talk to physicians, when we do formal research or anecdotally, when we talk to KOLs, a few takeaways are, one, that beta blockers will probably still be used in the near-term first line, more driven by payers, but the call to action to add Aficamten a lot sooner than they would have otherwise. Two, there are many cardiologists who don't prescribe cardiac myosin inhibitors today. They do use beta blockers. There are around 10,000 cardiologists who are 80% of the market, and about 80% of those 10,000 cardiologists aren't writing cardiac myosin inhibitors. This would get more of them on board.
What it does is it increases penetration, i.e., the number of patients who would be on a cardiac myosin inhibitor over time, and it increases our preference share when we've studied a profile of Aficamten to include MAPLE-HCM data. I think it's pretty promising in that we can get a broader set of the cardiology community engaged in treatment, get Aficamten, if it's approved, added sooner. It'll get added to guidelines. I think if it does in 2027, that is our base case of that. If it does get added to guidelines, I think that'll further propel some of that activity.
You said 2027, that's base case.
Base case is our best guess. I mean, we don't control that, obviously.
Yeah. Are there any gating factors in regards to getting that on label? What would be the bold case in that scenario? Just a quick.
Timing-wise?
Yes.
I think you can assume we will be filing it quickly after approval. It's about a 10-month review, so toward the end of 2026.
Okay. That's very helpful. Moving over to the potential launch, the PDUFA date in December. You have a late cycle review this month. Is there any expectation that you'll put something out regarding that late cycle review or any commentary around that or expectations?
As we did with the mid-cycle meeting, I mean, we committed to updating on our quarterly earnings call, next quarterly call being November. I would anticipate a more detailed update at that time. I don't anticipate necessarily anything detailed in the meantime. These are very fluid discussions. Despite there being a late cycle meeting, we're always in constant exchange with FDA with regards to different things. We'll plan to focus in the quarterly call and give maybe more substantive updates at that time.
Okay. Maybe this is a good opportunity just to ask, how are interactions going with the regulators? Is everything consistent? Any changes there?
Yeah. I mean, the review team has remained pretty constant. We get a lot of questions about that. The review team and their members have been the same throughout the process. They're pretty experienced with the mechanism of action. They're very, very knowledgeable now, obviously, about Aficamten and its profile. I just would characterize our interactions as productive and have been progressing normally through the course of the last few months.
Okay. I believe you just said in regards to having fluid discussions, ongoing discussions with regulators, will this be the first formal meeting where they basically give their response to the REMS that the team submitted?
No. I mean, when we submitted the REMS, we got comments back from them that were stylistic and editorial and things like that. The REMS have to kind of follow the label. The label ultimately has to get finalized. If there are any discrepancies, they have to be reconciled at the end. We seem to have good alignment between label and REMS. As we move forward, as we continue to negotiate a final label, that will finalize itself shortly thereafter. They are moving together in parallel, probably is the best way to put it, and they'll get finalized in parallel.
Okay. In regards to the potential label, the proposed REMS, I don't want to push you too far on details, but I'm just trying to think about how potentially it could be differentiated from Camzyos. I know there's differences in drug-drug interactions, the titration schedule, but anything you'd like to comment there?
Yeah. I'm just going to comment on our clinical trial experience and what we've put out in the public domain as a means of thinking about it. When you look at the way that Aficamten has been dosed in all of its clinical trials, including MAPLE-HCM, including Faurescu, including Sequoia, this was done in such a way that basically, the patients would start the drug every couple of weeks with some flexibility now in Faurescu, where it's every two to six weeks. They can come in, have an echo, potentially up-titrate. Every echo either leads to a titration or leads to an entrance into the maintenance phase if the target dose has been reached. Treatment down titration is the means by addressing EFs less than 50%, above 40%. Treatment interruptions have been very rare.
We don't expect necessarily any differences when we get to labeling because obviously, the clinical data will inform the label. Drug interactions, we published or we presented those data at the American College of Cardiology some time ago. The data demonstrated that there were multiple pathways of Aficamten metabolism. It's hard to block them all at the same time. Blocking any one pathway doesn't lead necessarily to a large increase in Aficamten exposure. We expect any labeling around drug-drug interactions to be consistent with that profile that we see, which is altogether, we think, quite differentiated and should ultimately lead to a differentiated label.
Okay. Based on the fact that Camzyos, the REMS was updated this year, it's been on the market for a bit. What kind of learnings are you taking from that launch and applying to your own launch or specifically in the U.S., patient demographics you're targeting, physicians, community setting? Where could you be differentiated in regards to Camzyos?
When we look at it from a launch point of view, we have our campaign. We've spent the last probably four or five months finalizing what that campaign would be to communicate that differentiation. I won't get into details of where the differences are. Obviously, Fady just described them from our phase three study. We do have differentiation in efficacy, safety, REMS, and patient support, assuming that the label and REMS program is finalized the way we're expecting. That campaign will communicate that very clearly to physicians. I think what we've learned, and I think we've all been students of launch, our commercial team is very experienced in launch. We've all launched many products. The key is to get a core set of physicians on board first. That'll be likely the centers of excellence to make sure that they're communicating their experience to the next kind of level of cardiologists.
I think we do have a profile in Aficamten that likely can expand the market to a broader set of cardiologists. When I say likely expand the market, I do believe it will expand the market. Likely, what does that mean in 2026? Can we do it as quickly as in 2026? MAPLE will help a lot with that, especially if guidelines get updated faster than we were expecting. If Acacia is positive, that'll certainly help with that. There are lots of reasons to believe that acceleration could occur beyond what maybe a base case launch could look like. Finally, we've been really focused on HCM, Aficamten, this patient population, this treatment journey. We've designed a patient treatment program around it. We've been interacting with the KOLs. They know us very well. We know them very well.
I think we have a competitive advantage in that we have that level of focus as an organization and a business model that's specialty that you don't need large field forces and a lot of resources to compete in.
In many ways, with MAPLE potentially on the label, that's where the inflection could come from expanding beyond centers of excellence to community setting. Do you think that's a reasonable expectation?
Yeah, I think that's a very reasonable expectation.
Okay. Without providing specific guidance or launch metrics, how are you communicating to investors, the investing community in regards to what 2026 looks like in regards to the launch?
In November, at our earnings call, we'll probably describe that better in terms of the metrics. You can imagine it's going to be things like the number of patients treated, the number of patients that are being converted to commercially paying patients, the number of physicians who have been certified in the REMS program. There will be a couple of metrics that we talk about that are early indicators of greater launch success. I think the first year of Camzyos (mavacamten)'s launch had around 4,000, the first 12 months, I believe, had around 4,000 patients. I think that would be a minimum that we would expect. I certainly think for reasons around MAPLE, the patient support program, the areas of differentiation, the ability to expand, I certainly believe we could do better than that. We'll have to see how the label and the REMS play out as well.
Okay. That's very helpful. Moving on, you noted it, Fady, at the beginning in regards to Odyssey, Camzyos, the data in non-obstructive HCM. Is there anything you'd like to call out there before maybe some questions on that program?
Sure. I mean, I think what we saw at Odyssey was that the underlying basis for believing that a cardiac myosin inhibitor would impact the physiology of HCM in a positive way was confirmed. We saw improvements in echocardiographic measures of cardiac relaxation. We saw decreases in NT-proBNP, which is also a reflection of poly-filling pressures of the heart. That physiologic basis for believing that there would be a clinical benefit to that was solidified in a very large and global population of HCM patients. The clinical outcomes data were not statistically significant in terms of their statistical testing plan, but there were positive trends on both endpoints that were, again, encouraging. One of the endpoints was confounded by a large placebo effect.
I think all of those things portend well for the case of potentially being positive down the road with certain improvements in the way the study is potentially conducted or the product's dose and things like that.
Could you speak to the patient journey for someone with non-obstructive HCM? What does it look like? What are the diagnostic criteria? My sense from both your presentation and reviewing the Odyssey data, it seems like it could be a heterogeneous population, but any commentary around that would be helpful.
Sure. You know, the obstruction in obstructive hypertrophic cardiomyopathy gives you a very specific and kind of unusual feature by which to say those patients have obstructive hypertrophic cardiomyopathy. The non-obstructive patients don't have the obstruction. What they have, though, are thickened ventricles. They generally have geometries that are not very normal-looking, asymmetric hypertrophy, for instance, or the hypertrophy is concentrated at the apex, or they have mid-cavitary obstruction, things like that. This is not, in general, something like you see in heart failure with preserved ejection fraction, where the hypertrophy is more concentric looking. It's more of a visual thing. We have our physicians that are HCM experts look at every single echo that is a part of the qualification process as patients get screened into the study. I think I have pretty good control of that.
The patient journey is also a bit different because obstructive hypertrophic cardiomyopathy can be recognized early because of a murmur. You need a stethoscope, listen to somebody's heart, you hear a murmur. Even if you don't know what the murmur is, it does suggest that perhaps you should image the heart and see what's going on, and that leads to an echocardiogram. Hopefully, the echocardiogram leads to a diagnosis. Non-obstructive HCM is silent. There's no murmur. The symptoms are often mistaken for other things, and other things can present very similarly. It takes, you know, these patients tend not to get recognized until later in their disease, until they've had substantial symptoms for quite some time. I think that just is a call to action for us to improve diagnostic rates and elevate the diagnosis and the sort of differential diagnosis.
Available therapies, if the Aficamten does become available for that, often change that dynamic, and they improve diagnostic rates and recognition of disease.
Just touching again on the inclusion criteria for Acacia versus Odyssey, I know you've noted previously that you have a team that's reviewing echocardiograms. How confident are you that you've enrolled a differentiated patient population compared to Odyssey?
I wouldn't say that their population was the reason that Odyssey didn't reach statistical significance. I think we've enrolled a population with some more objective measure of exercise intolerance. We have an upper limit on PCO2 that was not in the Odyssey entry criteria; people could have normal or even over normal PCO2s. We both had entry criteria related to KCCQ that required patients to have substantial symptoms, symptom burden. We had maybe a bit higher of an NT-proBNP entry criteria, which is another objective measure of burden of disease. I think these things are fine-tuning things. The review of echoes is important, obviously. Probably the biggest difference will be in dosing density, I would imagine. We piloted the dosing of Aficamten in NHCM patients in phase two and then retested it in the open-label extension. We were able to titrate patients, the majority of them, to the highest doses.
We didn't have patients having to interrupt treatment. Generally, we're able to take that same dosing regimen right into phase three, having road tested it. Hopefully, that will also increase our likelihood of success.
Okay. For the non-obstructive patients, how reflective is the enrollment criteria for Acacia in regards to the overall patient population? Trying to get a sense of the TAM here.
When we designed Acacia, if you think of all of HCM as a pie, Sequoia was really the treatment-resistant population. Patients that were on background therapies still had substantial symptoms. We required a high level of both resting and provoked gradient to get into the trial. MAPLE enrolled patients with obstructive HCM that essentially met, but just the diagnostic criteria, all comers that sort of met those diagnostic criteria for obstructive HCM. What's left are essentially the patients we enrolled in Acacia. These are patients that don't have, they don't meet the diagnostic criteria for obstruction. They have the appropriate wall thickening. They have symptoms, things like that. We tried not to exclude a lot of patients from the trial because, again, we wanted to address the whole pie, not just pieces of it.
Would you say the opportunity is larger, but less defined in regards to which patients would go on therapy right away in non-obstructive?
No. I mean, I think the patient population, again, people that have HCM, what they hope at the end of the day is that Aficamten is a drug indicated for hypertrophic cardiomyopathy, period, end of story. Yeah. Not obstructive or non-obstructive or, you know, cuts in both directions. That is the way it should be. This is a disease of hypercontractility. This is a mechanism that addresses hypercontractility across the whole spectrum of HCM. There shouldn't necessarily be little pockets that are carved out, other than patients that don't have symptoms. I mean, those are the ones that probably are not needing therapy until later in their disease.
And.
Yes, the overall population size, non-obstructive HCM is about half the market, and obstructive HCM, obviously, the other half. From the symptomatic, our expectation is the number is going to be pretty similar, about 130,000, 140,000 that are symptomatic. I think the difference is, obviously, if we are successful there, then none of them would be treated. Beta blockers do not work well. First-line therapy, we really would be the call for, which could fuel further first-line therapy for obstructive HCM over time as well.
Sorry, just going back to the beta blocker dynamic, when do you plan to get feedback from payers? Do you expect the MAPLE data to potentially support shrinking the time patients are on beta blockers to start? Yeah, just any commentary around that.
Guidelines are probably the most impactful thing for payers. I think in reality, we're not trying to position MAPLE-HCM to fuel first-line therapy in the short term. I think what we're trying to fuel is a call to action for those who have HCM who are not on a CMI when Aficamten gets approved to be on Aficamten. That approval should at least get payers to reduce the timeframe. Beta blockers will still be first-line. The ability to add a CMI and accelerate use more quickly from a payer is really the response we're looking for, and from the community of cardiologists to get more of them to write because of the superiority in beta blockers not working for the gradient.
Okay. I'd like to touch on the pipeline also. I know most of the questions have been around Aficamten, but you have a pipeline, expanding pipeline. Is there any highlights or catalysts we should keep an eye out for over the next 12 to 18 months?
Sure. I mean, I think just with Aficamten as a pipeline and a product, right, with Acacia reading out next year, label updates occurring next year and potentially the year after in terms of Acacia. Following that, omecamtiv mecarbil, that trial COMET, which is a trial in severely reduced ejection fraction heart failure patients, will have finished up enrolling. Hopefully, in 2028, we'll read out positively as it is supported by a fairly large, maybe the largest ever clinical trials program supporting a pivotal trial. That is a drug that would add nicely to the Aficamten launch as that story is beginning to mature. The omecamtiv mecarbil data and potentially its launch and approval and things like that would follow soon thereafter. AMBER is a trial in heart failure with preserved ejection fraction.
This is a kind of a population where we think non-obstructive HCM is a model of that particular population, thickened hearts, symptomatic, a lot of same features in HCM. We'll see early data from the phase two trial in 2026. If those data are supportive, launching of a sizeable, more sizable trial in 2027. I'd say the next three years have a lot of exciting changes for Cytokinetics on top of transformation of the company into a commercial powerhouse.
Yeah, I think that leads in well. Maybe we can just discuss financials. I believe with over around $1 billion in cash at the end of Q2, additional potential tranches from Royalty Pharma. How are you thinking about capital allocation and any thoughts on business development?
Yeah. Max, our top priority, obviously, is the launch of Aficamten in the US. We're also putting up the commercial infrastructure for a launch in Europe later next year as well. That will be an important priority. With our capital allocation, advancing our pipeline is very important. As Fady said, we have sort of an abundance of opportunities with Aficamten alone, sort of a pipeline and a product. Funding those ongoing studies, taking Acacia across to the goal line, we have the wherewithal to do that. Of course, omecamtiv mecarbil and CK-586. Those are our capital allocation priorities. You mentioned something very important. In addition to the cash balance of $1 billion mid-year, we have important options ahead of us in terms of additional access to capital.
Starting with a $100 million term loan that we've already qualified for, I think it's fair to expect us to take that down before the end of the year. If Aficamten is approved before the end of this year, we would qualify for an additional $175 million. That will be an important source of additional capital. As you know, we retain the vast majority of worldwide rights to Aficamten still, with the exception of Greater China and Japan, where we have partners. That could be an additional important non-equity source of financing, selling the rights to the rest of the world.
Okay. That leads into a couple of quick questions we've been asking several of our companies. With China's recent rise in biotech innovation, how are you thinking about your competitive position here? Will this influence your R&D or BD strategy at all?
I think like every company out there, we certainly look at the entire landscape in terms of opportunities to externally partner or license things. I think that we're certainly not going to be restricted in our view in that way. Maybe just to step back a minute, you know, as a company, we think uniquely positioned not just to launch Aficamten and develop that market, but with other clinical and regulatory milestones in the future. We've maintained a pretty meaningful and productive research group. We have other small molecules that are poised and hopefully will enter development in the near future as our entire pipeline has grown internally from work from our research group. That doesn't mean that we're only thinking to grow our pipeline with internal discovery because obviously, there's a lot of opportunities externally as well. We consider things in China.
We consider things anywhere, really, in order to augment that. You know, our long-term vision is to grow our pipeline over the course of the next five years and add to those three important products that we talked about today.
Would the opportunity potentially, or is the China opportunity becoming more significant now? Is it equal with anything else you can find across the world?
I think we find innovation everywhere. I think we've talked to companies in China around potential partnerships. There are companies in the US we've talked to as well. I don't think there's a tilt necessarily one way or the other, but we'll be as open-minded as anyone else will be.
Okay. I guess last question. Is there anything I missed or is there something you would like to highlight or you think are top of mind among investors?
I think it's a confluence of how our first launch is coming together with a field that has developed a lot of enthusiasm for new therapies. We're seeing other products being developed in HCM. We're seeing the standard-of-care really shift. I think of it as a very opportune time for us to launch Aficamten, which we hope will be a highly differentiated product for HCM and maybe potentially in non-obstructive HCM. The company has positioned itself very well financially. We've had a long time to prepare commercially to launch Aficamten. In many ways, you know, we represent an unusual story in how we've come to this point. Hopefully, we'll continue with that momentum going forward.
I mean.
I'd maybe just add one that the level of energy and excitement at Cytokinetics is really off the charts. One, we have a very differentiated product that we really believe in, in both the profile, the REMS. We're building a patient support program that's very custom to this patient population. Timing is great in that there are many sales representatives on the market or who have recently left organizations who have been focused on cardiology. We have 9,000 applicants for a little over 125 jobs. We have very deeply experienced representatives who know these cardiologists, who have relationships, who will be in these offices. When you combine the commercial team, the know-how, the people on top of the rest of the organization, the differentiation we have in Aficamten, the lifecycle coming with MAPLE-HCM and Acacia, I think there's a lot to be really bullish about in the short term.
You can feel the energy in the company as it's getting closer and closer to launch.
Great. Thank you very much.
All right.
Thanks.
Thank you for having us.