Everyone, my name is Cory Kasimov, one of the Senior Biotech Analysts here at Evercore ISI, and it's my pleasure to host our next discussion with Cytokinetics. As you can see, we have CEO Robert Blum, along with Steve Heitner, who heads up Cardiovascular Research, and Chief Commercial Officer Andrew Callos. So thank you guys for being here today, and Robert, I'm going to hand it over to you. I know you have some slides you'd like to start with, and we can go from there.
Yeah, so just to set the table for Cytokinetics and the conversation we're going to have, I'll make some forward-looking statements, refer you to our SEC filings. For those of you who may not know the company briefly, our company is committed to muscle biology and specifically building out the vertical around specialty cardiology, and core amongst those programs in specialty cardiology is aficamten, a cardiac myosin inhibitor that we announced yesterday as the subject of an NDA on file with FDA, PDUFA date September 26 next year for the potential treatment of oHCM, and aficamten is also being studied in other settings, including nHCM, as well as we have two other cardiac myosin modulators, another inhibitor, CK-586, being developed in a form of heart failure called HFpEF, and omecamtiv, a cardiac myosin activator being developed in a form of heart failure called HFrEF.
These three programs, all directed to one molecular target, form the cornerstone of our emerging specialty cardiology franchise. We have other muscle biology programs described on that slide. The company is very well equipped from a resource standpoint, financials. We've got north of $1 billion in cash and cash equivalents. Importantly, we've already engineered access to additional capital through Royalty Pharma deals such that we have access to an additional $500 million. Why is that important? As we think about going to market, we want to make sure shareholders understand our access to capital and our ability to deploy, and we can be capital efficient and maintain a good discipline with regard to OpEx. The company has quite a number of new milestones and substantial opportunities to unlock and reward shareholders over the next couple of years. You can see them depicted here.
I'm pleased to announce here at this conference that not only did we, as announced yesterday, get the NDA on file with U.S. FDA for aficamten with regard to oHCM, but in this fourth quarter, we've already filed with EMA, the MAA, to be enabling of regulatory review in Europe as well, so now aficamten is on file in each of U.S., Europe, and China. That's not a small feat for a company of our stage and maturity, but we think it underscores the commitment to aficamten, as is the cornerstone of this emerging specialty cardiology franchise, and again, as you can see, lots of opportunities for milestones and news flow. Cytokinetics and thinking about specialty cardiology is taking a different approach to cardiovascular medicine than other peer group companies. We're focused on where we can have a higher return on investment.
These are large opportunities, but concentrated in terms of customer segments where Cytokinetics, with limited investment in sales and marketing infrastructure, can produce a high return on sales and shareholder equity. As I mentioned, aficamten is the cornerstone, and not only the study SEQUOIA that's already read out positively supporting a potential approval in oHCM, but MAPLE, a study comparing aficamten to beta blockers in oHCM, is due to read out in the first half of next year. ACACIA should be completing enrollment in 2025 to read out in 2026. CEDAR, a study in adolescence, and FOREST, the open label extensions. Lots of potential news flow still to come with aficamten. About two weeks ago, we announced a licensing collaboration with Bayer for aficamten in Japan.
Economics that we think set a high watermark for companies in the pre-commercial stage in cardiology in Japan, and not only good economics, but a partner that we think is well equipped to execute in terms of bringing aficamten to patients in Japan, and we do believe our interests are nicely aligned, the cardiovascular area being of key importance to Bayer. Here's my last slide, upcoming milestones. In addition to the announcement yesterday, we announced today the start of a phase three confirmatory study of omecamtiv in patients with heart failure and reduced ejection fraction. We're looking forward to starting a phase two study of CK-586 in HFpEF and the MAPLE study, as I mentioned, in the first half of next year. Not only is Cytokinetics a company flipping the page to commercialization for aficamten in oHCM, but substantial, meaningful milestones for aficamten and other cardiovascular programs in other indications.
With that, I'll turn it over back to you, Cory, to engage in some conversation.
Perfect. Thanks. It's a great job of setting the stage, and it's awesome to see how productive the team has been. Let's not surprisingly start with aficamten and look towards the potential introduction commercially of the product next year. You know, as we kind of do that, what aspects of the product's profile are docs pointing to in your engagement with them and your market research in terms of what you think is the most important, what are the most important differentiators versus Bristol's, Camzyos?
Sure. So I'll start, but I'm going to turn it over to my colleagues as well. Aficamten was designed to be a next-in-class drug opportunity where we believe the first-in-class drug, BMS's Camzyos, is doing a very fine job, but it's still limited in terms of where it's being used and for which types of patients. Aficamten was designed, engineered from the laboratory to be next-in-class. We had a hand in the discovery of mavacamten. We know it quite well, and aficamten was designed with properties that render it potentially next-in-class and as could be expanding of the category. That speaks to clinical trials data that makes a business case for expanded use and a labeling and a commercial strategy that affords that same advantage.
That's where maybe I'll ask Steve, who leads our cardiovascular clinical research, to talk about how we've, with the SEQUOIA and FOREST studies, been able to demonstrate data that we hope will be category expanding. Then maybe Andrew can speak to what our market research teaches us and where aficamten may play a role there.
So from a differentiation standpoint, what we've managed to demonstrate already in SEQUOIA-HCM are a few things. Firstly, from an efficacy standpoint, you know, the drug is very well tolerated. We have a low incidence of low ejection fraction events, and none of those ejection fraction events were associated with either a heart failure episode or a need to interrupt treatment. It was simply managed by down titration. That was a hypothesis before we conducted SEQUOIA-HCM, and now that hypothesis has been proven.
The other aspects that we did demonstrate in SEQUOIA, which do differentiate from mavacamten, is that it seems that aficamten is not inhibited in terms of its efficacy by the use of concomitant beta blockers, whereas from the EXPLORER HCM study, it did seem that the treatment effect of mavacamten was somewhat blunted by concomitant beta blocker use. Moving to the FOREST data, we incorporated what we believe and others believe are a real-world utilization of aficamten, so the prescribers are able to integrate clinical data, how the patient's feeling, what they're able to do, and what their biomarkers look like into the dosing decisions, and we've shown that in that real-world situation, we are seeing the same, if not lower, low ejection fraction event rates and the same safety profile that we saw in the placebo-controlled SEQUOIA trial.
Taking that one step further, we demonstrated that perhaps, you know, the monitoring schedule that was initially incorporated in FOREST was, you know, overly echo heavy. We took that to the FDA. We showed them that many of the echocardiograms that were being done in FOREST were not leading to treatment-related decisions. And the FDA enabled us to reduce that monitoring strategy such that we're now only monitoring patients every six months, as well as increase the window of titration such that patients have the added flexibility within that clinical trial. And we're hoping that that will read out into what might find its way into a label.
Yeah, I think Steve summarized it. What we hear in research, efficacy, speed of onset with or without beta blockers, safety, drug-to-drug interaction, and zero heart failure hospitalizations or symptoms of heart failure, and very few treatment, you know, downgrades in terms of dosing. And then from a monitoring perspective, less frequent echoes, a broader window of echoes, and lack of drug-to-drug interaction monitoring. So the combination of those are really what makes the difference in preference of research.
Okay, that's great. I want to talk again on the commercial front. I mean, you guys are about to encounter this notion out there, emerging mid-cap biotech company launching its first product, going up against like big bad, big pharma, right? How do investors get confidence in sort of the dedicated sales organization you're creating going up against Bristol, who's obviously well established?
Yeah, firstly, it's not a zero-sum game. We don't have to compete with Bristol for both companies to do well in this category. Right now, there's roughly 400-500 physicians accounting for 80% of the prescriptions for Camzyos, and that represents, you know, roughly 10% of the eligible patients to be treated. So there's plenty of opportunity for both companies to do well. With that said, I think Cytokinetics has a competitive advantage. This will be the third time in my career that I've brought forward a next-in-class cardiovascular medicine. The other two times, it became a category leader. And I think there's a lot to be said for focus, discipline, relationships with opinion leaders, and a bespoke patient experience. And that's what will guide Cytokinetics in its commercial strategies. This is all that matters to us. We're very, very committed to seeing this to be successful.
Cytokinetics has had a couple of years to build an organization that has high continuity, high conviction. And this is a specialty cardiovascular marketplace. This is not your typical market where frequency and reach make the biggest difference. In this case, it's going to be about the patient experience, the label, the risk mitigation strategy, how we can create something that's unique for physicians, pharmacists, and patients. And Andrew and his team have been working on that already for a few years. And I think we've been able to attract and retain talent, the very best of people within the cardiovascular space to make it happen. I don't know if there's anything you want to add.
Yeah, I mean, I think probably it's not a resource-intensive business model. You don't need a lot of field force. It's not share of voice. You're not competing for market access. You don't need to do DTC TV. So you can spend. This is a perfect business model for a biotech to compete in. We're creating a very bespoke customer experience designed to the HCM. We're focused on the physicians that matter, 10,000 out of 80% of the market. So it actually sets us up to do better than a big pharma because of that focus and because we're designing everything around a ficamten as compared to it making it fit into a bigger model.
Okay, so obviously a lot of attention on what a potential label might look like is something that's going to evolve over the next 10 months or so until your PDUFA. What are your latest thoughts on just how differentiated you think it can be? And what, as you sit here today, would an ideal label look like to you come next September?
So I think it can be highly differentiated. We already know with regard to the absence of certain drug-drug interactions and reproductive toxicology that aficamten should be reflected differently in label. But we also know from FDA, and Steve spoke to this, FDA's willingness to be accommodating of wider dosing windows and less frequent echo monitoring in the open label extension study, that augurs well for a lesser risk mitigation upon potential approval. We haven't had our mid-cycle review meeting yet with FDA, and certainly that'll be reading importantly on what we should expect if approved.
But FDA's already being leaning forward, if you will, in terms of things that they've been permitting of in the conduct of the clinical trials, in the conduct of the open label extension to suggest they understand that these drugs, while with similar mechanism of action, have different risk mitigation strategies, and hopefully that gets reflected in the label.
Okay. All right. So last question on afi before we work in a few on some of your other assets. What has your market research indicated the split may be from prescribers at centers of excellence and, you know, percentage of HCM patients that are seen at those centers?
Current prescribing of CMIs or longer term?
I guess both.
So I mean, currently right now, it's probably about, and what we're saying, centers that are expert in HCM versus not. They don't all have the designation, but they have a focus on HCM. Right now, it's about 60%-65% in those focus centers and maybe about 30%-35% in the non-specialized centers. Over time, you know, there's around, when you look at the ICD-10 codes of HCM, there's two of them. There's around 10,000 of the 30,000 or so cardiologists that are around 80% of the market. Currently, about 1,500 of those 10,000 have prescribed, but 500, as Robert alluded to, are 80% of the market, so the 80/20 rule. So there's only 500 of 10,000, if you will, that are driving the market.
I think where this market will go over time is that the centers of excellence will lead the way as it typically occurs in a drug launch of any category, and the non-specialized centers, the cardiologist in the community center should be over 80%-90% of the market at its peak.
Okay. All right. That's great. So shifting gears here in our last few minutes, I wanted to ask a question on CK-586. So your takeaways from the Camzyos Embark data in HFpEF and how that sort of informs your go-forward efforts and strategy with this molecule.
So I'll ask Steve to comment, but firstly, so for everybody's benefit, CK-586 is a second cardiac myosin inhibitor, different mechanism being studied in a different patient population of heart failure with preserved ejection fraction. I would argue that the best indicator of potential effect is less from the EMBARK study and more from our REDWOOD cohort four in nHCM patients because they borrow so much from one another, HFpEF being a disease that resembles more nHCM. But Steve, how would you speak to that?
You know, just focusing on EMBARK, I would say that it's encouraging. I think that it adds weight to the proof of concept that we did see some encouraging data come out in terms of the biomarker response, and it's given us reassurance that we're on the right track over here. It also underscores that mavacamten is not the right drug for the HFpEF population. I think that BMS has realized that because of the pharmacology and the demographics of those patients, they're more fragile, there's more polypharmacy, and they're older, and I think that mavacamten is not well suited for that, which is why BMS is shifting their focus to 22 4, and I think that the pharmacology of 586 is ideal for these patients based on what we've seen from the phase one.
Okay. All right. So then in our last minute, I wanted to also get in a question on omecamtiv mecarbil. You've already shown in a very large trial that the product is safe and it's also likely effective in this narrower patient population that you're targeting. So at this point, what do you see as the most significant development risks as you go forward with the new study that was just launched?
So this morning, we announced the start of COMET-HF, and I think the biggest risk to your question speaks more to ultimately less properties intrinsic to omecamtiv mecarbil, and more where I see the market going. I think the market for HFrEF is being well served by SGLT2 inhibitors and other drugs like GLP-1s that are being developed for more of your run-of-the-mill heart failure with reduced ejection fraction. Where we believe omecamtiv mecarbil may play a role uniquely is in those severely affected reduced ejection fraction patients, EFs below 30, high BNPs, recent hospitalization, where those drugs don't seem to have a role to play, and that's where omecamtiv mecarbil, by boosting cardiac muscle contractility, we think can augment cardiac performance and do so in a way that's both clinically and importantly pharmacoeconomically important.
Okay. And it ended right as the buzzer went, so very well done. Thank you guys very much for the time and for being with us here today.
Thank you.
Thanks, Cory.