...Good morning. Welcome to the second day of the Cantor Global Healthcare Conference. I'm Charles Duncan. I'm a senior analyst here, and I'm really excited to introduce this next presenting company. This is Cytokinetics, so Cytokinetics, I have covered for a long time, and I have to tell you, in the last year, it's been really an interesting story. Very topical, on top of mind for a lot of investors, and I'm certain that it will do so in the next year as well, so with me, I have Mr. Robert Blum, the company's CEO. Some of you know him. Robert, thanks for joining us.
Thank you.
And Dr. Fady Malik, the company's head of R&D. So we're gonna talk about the future in terms of especially a specialty-driven cardiovascular company and a new vision for that. So Robert, why don't you share with us a few slides, talk about that vision, and then I'm gonna ask you a few pointed questions.
Sounds very good. Thank you, Charles. Thank you to the conference organizers for inviting us back to provide an update on the company. I'll be making some forward-looking statements. I'll draw your attention to our SEC filings with regard to caveats to those statements, and we don't undertake obligation to update these forward-looking statements. But I do wanna talk to you about Cytokinetics, where we are and where we're going. And here on this slide, you see a pipeline, a pipeline of novel mechanism drug candidates rooted in one biology under the supervision and following the vision of my colleague, Fady Malik, who over many years working together, has overseen the discovery and the characterization and development of these drug candidates that are coming closer and closer to market. Aficamten, the lead amongst these, is a cardiac myosin inhibitor.
It's the subject of an ongoing rolling NDA submission that will be completing relatively soon. We expect that to be enabling of what we hope a first potential drug approval in 2025 as we go to market with this next-in-class opportunity that is driving forward the build of our specialty cardiology franchise, but coming in right behind it is aficamten in another indication of nHCM as well as other drug candidates, one in phase III, omecamtiv. We're developing that for advanced heart failure, soon to be the subject of a confirmatory phase III study to be underway, and CK-586 entering phase II with phase I data having recently been presented.
These three drug candidates, all modulators of an enzyme called cardiac myosin, form the cornerstone of the business we're building, with other drug candidates coming in behind it and an ongoing research commitment to be expanding in muscle biology. Thanks to some deals we did in Q2, we are now in Q3 with a strong financial position, over $1 billion on our balance sheet. We reported $1.4 billion, but that also doesn't even consider access to capital, and I think we've not only fortified our capital structure with added cash, but also enabled access to capital at a lower cost of capital, market competitive cost of capital, as we continue to advance our pipeline.
We think we've done this in a way that's very shareholder sensitive and cognizant of shareholder interests, and I think we proceed now with a stronger financial position to execute on the milestones you'll be hearing about. As we look forward over the next couple of years, we have an abundance of catalysts, to use a investor word, that we think drive value for shareholders, but at the same time, these are things that we know are in the interests of furthering our business. Things like clinical trial readouts, things like regulatory submissions and potential approvals, as well as other expansions of our business as we go to market, and we think we're on the cusp of turning the page onto an important next chapter for the business as the next couple of years will highlight meaningfully important milestones.
We're building something that doesn't exist amongst peer group companies, a specialty cardiology franchise, and we use those terms very selectively because in pharma and in biopharma, there are certainly cardiology companies, companies that have made a meaningful impact in the treatment of cardiovascular disease. But we think we're building something that's something unique amongst peer group companies, in that we're looking at building a business, a business that has quite substantial upside in terms of revenue and P&L impact, but for which the infrastructure required to build that is lean and where we think that we'll have not just one, not just two, but not just three programs advancing to this concentrated customer segment, where we think this is not only in the interests of shareholders, but in the interest of patients and physicians who treat those patients.
We do believe that the return on investment, the return on shareholder equity, is more reflective of what's typically seen amongst specialty companies or orphan drug companies, but for which there's enduring value, enduring as it relates to our science and our prospects. And we're directing these opportunities to concentrated customer segments, but they're not ultra-orphan size. We're talking about hundreds of thousands of patients, but for which the physician segment that treats them is concentrated. Hence, when we talk about hypertrophic cardiomyopathy, 100,000- 200,000 patients in the United States. Advanced heart failure, over a million patients in the United States. Patients with HFpEF, but supra normal ejection fraction, again, close to a million patients in the United States.
But yet, where we can get to these patients with lean sales and marketing infrastructure, we're talking about 100-150 sales reps in North America, a similar number in Europe, and where we think we'll have also a good ability to leverage what could be strengths with payers. We think this is a sustainable business and a very valuable business, as could be rewarding of shareholders. We reported on SEQUOIA data recently in Q2, presented and published in the New England Journal. I'm pleased to say today, we're announcing that we've recently completed enrollment in the MAPLE-HCM study. MAPLE-HCM is a study that we expect could read out concurrent with a potential commercial launch, both SEQUOIA and MAPLE-HCM reading on the opportunity in obstructive hypertrophic cardiomyopathy.
We're enrolling the ACACIA study, CEDAR study, and FOREST is the trial, the open label extension around which all of these studies are feeding. And as you can see, a major commitment to the further development of aficamten across oHCM and nHCM, for which we have orphan designation across both. And we do believe that, this commitment to clinical research underscores the both pioneering leadership we have in this space and the integrity and credibility of which we've established also in this space. And as you can see here, what we're doing in oHCM, together with nHCM, together in HFrEF and HFpEF, represents, we believe, the cornerstones of the business we're building across specialty cardiology opportunities, and I'm sure we'll have more to say about that. And last slide, the milestones, you can look forward to them this year.
The next most important one will be the completion of the rolling NDA submission, the readout of further results from SEQUOIA and FOREST, as well as, as I announced today, completion of enrollment in MAPLE, and you'll hear more about these other milestones between now and the end of the year. And with that, Charles, we'll be open to questions.
Super! Come in, have a seat, and we have a few. But you've had such a, such a busy year, and so I'm gonna ask you what seems to be a softball, but it's actually a tough question, especially for you folks, because I'm asking you for one, one thing that you're most proud of having accomplished in this, in this last year. What do you think was the, the biggest kind of aha moment that turned over a card that said, "We have something here?
So maybe we can answer that, each of us-
Sure
... because I-
There could be two.
My answer might be different from Fady's.
Yes. Right. Right.
I'm very pleased with how we're scaling the company, and for which, as we transition from R&D to a commercial enterprise, we've fortified the executive leadership team with some key additions and fortified the balance sheet in order to be able to execute on the plans under Fady's supervision. Very often, biotech companies do this in a way that is short-sighted, and they get it wrong, and they go from R&D to commercial in a way that subtracts ultimately from their leadership in the marketplace and their ability to continually sustain innovation. And I think we've preserved team continuity of vision, and we've been able to access resources, both financial and human, in a way that's hopefully providing a seamless transition into the commercial space, which is no obvious thing.
Mm-hmm.
How you do that and preserve culture and maintain continuity is typically where people get it wrong, and I think we've done that extremely well.
You've made some good observations, and I'll come back around to that with regard to other companies.
But Fady may have a different way of answering the same question.
Please. Yeah, Fady.
I think, as the R&D person, I'm gonna just reflect on the pipeline as it is expanded.
Mm-hmm.
You know, last year, we obviously were all very focused on aficamten, kind of ignoring the rest of the things that we were building, and this year you can see how that work is now expanded into a pipeline of positioning omecamtiv to, you know, begin a confirmatory study, doing CK-586, so it can begin its phase II study this year. And obviously, the clinical program with aficamten has expanded, and there are a couple of things coming out of research in the next, you know, 12-16 months, I think people will be interested in. So I think the...
You know, being able to keep your eye focused on the ball, which is aficamten, but at the same time, you know, build on that foundation, build the rest of the house, so to speak, in R&D, I think I'm most proud of our team's been able to accomplish there.
Both of you have touched on one important differentiator that I see for your company now, that perhaps I didn't see in the past, or certainly I have not seen with other companies that have become revenue generator companies, and that is this concept of sustainable growth, potentially sustainable growth, not necessarily through in-licensing or whatever, but a homegrown pipeline based on a biologic platform. So most of the audience knows Cytokinetics, but just take a moment to reflect on the kind of, you know, foundations of Cytokinetics and how you come to deploy this novel biological platform for drug discovery?
So you've known us longer than any other equity research analyst, and you know that Fady and I have worked together for 26 years.
Mm-hmm.
And over the course of 26 years, you build something meaningfully significant, not just in terms of culture, purpose, values, and mission, but in terms of biology and science, and how that can deliver on the promise of innovation. And I do think that we've built this company from the beginnings. We've architected it and built it very differently. As we go to market with aficamten, hopefully in 2025, we look over our own shoulder at a pipeline of organically generated drug candidates rooted in the same biology for which we have already relationships with key opinion leaders-
Yeah
... regulatory authorities, and ultimately, the marketplace that can deliver something of enduring value.
Mm-hmm.
We think about commercialization not as we graft it on to the R&D enterprise-
Mm
... but as something that's part of a continuum-
Mm-hmm
... as we deliver it for patients. How we do that and how we show up in our community of patients is just as important as how we've been engaging with scientists and physician scientists, and KOLs all these years, and I think that pays dividends into the marketplace. We think about the velocity of commercial launch differently. We think about the ways we layer in revenues and how that ultimately reflects on the P&L growth differently, and this is not something like it's an unnatural act, to go to market and then find the next act. The next act is the low-lying fruit that comes from our own pipeline. Fady may have more to say.
Insights provided from this long endeavor? Any-
You know, obviously, it's to persevere, to keep your eye on the ball. You know, as best you can, to stay in control of what you develop. No one knows, you know, what has the expertise that we do in the area that we've invented and developed. To be forthcoming with what you have done in a way that is credible and honest, and you know, we've been very good about publishing and presenting our works completely. You can see that in the half dozen publications just to come out in the first eight months of this year, and so I think those principles really are what guide us.
I like the strategy and long-term thinking. Let me ask you about the use of, the very specific use of the word specialty cardiovascular. So, you know, everyone has a heart, so these are not areas where precision medicine has worked all that well, although recently there have been, you know, some interesting targets, particularly come along. Do you detect a change in an ability to use biomarkers and novel targets to really provide impactful medicines for cardiovascular patients? And then I wanna talk to you about what that means in terms of commercialization and your ability to compete.
I think what you've seen in cardiology is that, you know, for the diseases of the heart, where there's a good molecular understanding of what drives the disease, there's now a willingness to pursue those conditions. You see that with HCM drugs, where, you know, the etiology was uncovered in the late 90s. You see that now with the ATTR drugs and-
Yeah
... the cause there. Some of the gene therapies that are attacking some of the smaller cardiomyopathies. So there's been a willingness to pursue diseases that fall out of atherosclerosis and hypertension and, you know, atrial fibrillation, the big ones, and I think that provides a broader... That, you know, develops this field of specialty cardiology, so to speak-
Mm-hmm
... with some of the most impactful treatments that are developed. And probably the challenge now is to begin to translate those approaches to some of those bigger conditions that we've, you know, obviously, are very important for society for us to conquer.
You know, over 20 ago, and you'll remember this, we made a commitment to muscle biology.
Yeah.
We did so with the foresight, knowing that, increasingly, as the population aged and as advances in genomics and other areas of science were bearing on opportunities, that we were gonna be in a position to be both a pioneer and a leader, and that that would extend from a laboratory to marketplace. That was at a time when a lot of companies were moving away from cardiology, but for which we knew that we had, under Fady's vision, know-how and expertise that would lend itself to the building of a franchise business. While it's taken us a while to get here, and we like to joke, nobody's gonna ever accuse us of being an overnight success, here we are, and we've built this portfolio that's gonna provide some rapidity to the way we go to market.
What we've established along the way, to Fady's point, is integrity and credibility with the key opinion leaders that's gonna translate into product adoption. As we have differentiated programs moving to patients, we're gonna be in a good position, I think, to establish a meaningfully significant commercial position... For anybody who's questioning, and we get this question a lot: how do you compete with BMS?
I was gonna ask you.
Mm-hmm.
You stole my question.
We don't. It's not about competing with BMS. Mavacamten, a drug that they're commercializing as CAMZYOS, was discovered in collaboration with Cytokinetics. We know it quite well, and it's a great drug, but it's only being used by roughly 5%-10% of eligible patients. If we're competing with BMS, we both lose.
Yeah.
We need to go to market in a way that enables category growth well beyond where mavacamten is currently being used, and we think aficamten has that next-in-class profile that should be enabling of that.
Excellent. Then, like I said, it did partially address my next question, but it... But I think the other thing that you mentioned was leadership, not only in drug discovery and development, clinical development, but also commercialization. So help us understand the next, call it eighteen months, if you will, or less, because you may have a rapid review with aficamten maybe. Help us understand your route to market. What do you anticipate accomplishing in the next twelve months with regard to commercialization?
Firstly, it should be known that we have prepared for this for several years.
Yeah.
Not just as a company, but for this specific product opportunity, knowing in phase II, where we were targeting with phase III data, and the phase III data even exceed our target product profile. We put in place an organization, home office support and field sales management and payer engagement and medical affairs, that's been in their position for over two years, some of those people over three years. So they've-
Mm
... established relationships. They've maintained those relationships, and they're all geared up and ready to go. Next week, at the Heart Failure Society of America meetings, we're launching a campaign that I think will speak to how we go to market in a way that's very aware of patient opportunity and need and where the market segment speaks to where we can play a meaningfully significant role. We've been engaging with payers already and they're well informed as to what they should expect if this drug is approved. Right now, only roughly 400 physicians are responsible for about 80% of the mavacamten prescriptions.
Okay.
And those are largely coming from centers of excellence, of which there are fewer than 100, and it's incumbent upon us to engage not only the centers of excellence, but for this drug to make its impact the way we intend, we have to be able to demonstrate, with not just efficacy and safety, but convenience and ease of use, why aficamten should be comfortably prescribed by physicians in the communities. And we're gonna be targeting roughly 8,000-10,000 cardiologists, which comprise about 1/3 to 1/4 of all cardiologists, in terms of how we can get that message across, and we do believe we've got a sound strategy for how to make that happen.
I love talking to you because you always choose your words very carefully, and you often will pepper a discussion with information, which I have to listen to and pick up on, and I appreciate you doing that even today. There are a couple of things I wanted to ask you about. One is MAPLE, the other is next week. Next week, or soon thereafter, is the end of the third quarter. You talked about possibly talking more about your go-to-market strategy. Would that coincide with a completed NDA filing, perhaps?
Yeah. So you'll be hopefully very soon hearing about the completion of the rolling NDA submission. We've already submitted several modules, and the final module was simply waiting on some stability time points and data collection from registration batches in order to be able to get that CMC module submitted. And it's our expectation that that'll be very soon. Given that, you'll be hopefully in the fourth quarter hearing about the acceptance of the NDA for filing-
Yeah
... by FDA, and with that, we'll be informed as to whether we have standard review or priority review, if accepted for filing. That would be informing of timelines to potential approval next year.
Mm-hmm.
We're assuming a standard review-
Okay
... but we're asking for a priority review.
Sure.
We'll ask for it, but it's not something we're banking on.
Mm-hmm.
If we get it, we'll be prepared for it, but we're not assuming that. The base case is a standard review, and the upside case is a priority review. Regardless, we'll be ready to launch midyear next year in North America, and we're building out in Europe so that we could be launching in Europe in early 2026. That being contingent both on regulatory but also reimbursement approvals.
Sure. So assuming a standard review, and we'll come back to MAPLE-HCM, but assuming a standard review, could you see an AdCom maybe to evaluate the risk of cardiac myosin inhibitors or anything? Or do you think that an AdCom may not be necessary? And I understand that you have a partner in this debate, and that's the agency.
... Yeah, so we're assuming no AdCom.
Okay.
It's unlikely.
Yeah.
If there is one, we'll be ready.
Yeah.
Mavacamten didn't have one.
Right.
So we're assuming we shouldn't expect one.
Yeah.
We are expecting a different risk mitigation profile for aficamten.
Sure.
Mavacamten or CAMZYOS was approved with a REMS program. We engaged FDA in Q2 around scenarios pertaining to risk mitigation, and we're submitting with an expectation that, if approved, aficamten will have a different profile.
Sure. Based on, maybe frequency of imaging or monitoring?
Yeah, so Fady can speak to some conversations we had with FDA and some progress we made with regard to FOREST, which we think augurs well for potential labeling upon approval.
Okay. Fady?
Yeah, no, you know, FOREST is the open-label extension-
Yeah
... where we've had, you know, 280 patients enrolled, followed now, some of them as long as three years. So you get a sense of what's the utility of frequency of monitoring.
Yeah.
You always start off monitoring more, and you decide, you know, what really makes sense here, and as we presented at the European Society of Cardiology a couple weeks ago-
Yeah
... the echoes, you know, very few of them have any clinical impact-
Yeah
... less than 1%.
Yeah.
So what is the right frequency? You know, these patients generally get echoes every year.
Mm-hmm.
You know, for now, we think going every other twice a year is probably appropriate.
Mm-hmm.
We, you know, had that discussion as part of our last meeting with FDA and then subsequently amended the FOREST protocol to implement every six-month monitoring as well as some more flexibility around the dose escalation.
Mm-hmm.
So we were, you know, escalating every two weeks. That's 'cause we could escalate that quickly and
Mm-hmm
... but, you know, we didn't want people to think it had to be escalated that quickly.
Right.
And it creates some flexibility for physicians and patients to, you know, put a window in there. So now it's every two to six weeks. After escalation, you come back and have your checkup and decide whether you escalate dose again.
The fact that FDA is permitting of those changes in the open-label extension, even before reviewing our application, would indicate that they recognize that aficamten is different-
Yeah
... and should be assessed uniquely for its own, data and properties.
and that's not just happenstance or luck. You tried to design some differences into the molecule.
Yeah, no, the molecule, you know, has very, very good pharmacokinetic properties, very tight exposure data. Exposure response is, you know, fairly shallow, not meaningful drug-drug interactions. So all of those things, you know, when we look at how do patients' ejection fractions change over time, it's really small. So, you know, sort of once you are at the right dose and the right range, and you've confirmed you're stable, you know, the likelihood is that things aren't gonna change.
Unfortunately, I don't have another half an hour, yet I do have another half an hour worth of questions. I'll fire them off, and we'll talk about another molecule in a second. But the question that I wanted to ask you before we hop off stage. First of all, thank you for announcing the completed enrollment of MAPLE. I'm sure that you planned that with regard to our conference.
Of course.
But congrats to you on that. How do you feel about the enrollment of those patients, and how can that differentiate aficamten in the market?
So MAPLE is a study that you might have thought of as a phase IV-like design, but we accelerated it such that we would have the data when we go to market. That's not by accident. We do believe that it informs guidelines and how real-world use of aficamten may be differentiated in the marketplace. So right now, while there's really no evidence to support their clinical utility, beta blockers and calcium channel blockers are used routinely in these patients, and they're cheap. But we're doing a head-to-head comparison with beta blockers that we think, in many ways, is somewhat stacked in our favor, as we'll expect to see data in the first half of next year. And Fady can speak to sort of how we're already seeing, in FOREST, withdrawal of beta blockers.
Use? Less use?
Yeah-
Yeah.
No, we, you know, we allow, in FOREST, physicians to withdraw background therapy once patients have gotten to their aficamten doses, and those data were also recently presented. They, you know, they show that people get to monotherapy quite frequently when you try and withdraw background therapy, that the effectiveness remains the same. There's no, you know, adverse consequences of it, and it simplifies, you know, their regimens, ultimately.
You have to come back and allow me to do this again 'cause we didn't get to CK-586, which is very different than aficamten. You've got a lot going on. We'd like to talk to you about omecamtiv, my old favorite, but unfortunately, we're out of time. So it's gonna be a busy year. We're looking forward to seeing you again next year and wish you all the best, and thank you.