My name is Eduardo Martinez. I am an equity research associate in the biotechnology space, and today we have the pleasure of hearing from Mr. Robert Blum, CEO of Cytokinetics. Please join me in welcoming him to present this morning.
Good morning. My apologies for our being a couple of minutes late. I'm gonna share with you over the course of about eighteen to twenty minutes an update on Cytokinetics. We're appreciative of the conference organizers inviting us to present, and we'll be making some forward-looking statements. I'll draw your attention to our SEC filings for caveats to those statements and remind you that we don't undertake an obligation to update them. But where we're at now, and certainly this is a company very different than when we presented here a year ago, is a company that's executing extremely well on a strategy that's been in place for now over twenty-five years, to focus to one area of biology and bring forward new medicines as relates specifically to cardiovascular and neuromuscular conditions related to impaired muscle function.
We were involved in muscle biology long before it became fashionable. What we're doing here is advancing a pipeline of drug candidates discovered by our scientists. These are small molecule modulators of proteins involved in the mechanics of muscle contractility, in particular, those that either inhibit or activate cardiac myosin, the mechanochemical enzyme responsible for generating cardiac contractility and muscle force in cardiac tissue. Lead amongst these is aficamten, a next-in-class cardiac myosin inhibitor. It will be the subject, hopefully very soon, of an NDA submission as pertains to a potential first approval in the treatment of obstructive HCM, as we pursue additional expansion of potential label as relates to NHCM as well. You see here also we have a cardiac myosin activator, omecamtiv mecarbil, that has already been the subject of a positive Phase 3.
We're about to embark on a confirmatory study that could hopefully bring that also to patients. And this morning, we announced advancement of CK-586, a second cardiac myosin inhibitor, from P hase 1 into Phase 2, that round out our specialty cardiology pipeline. That'll be the focus of today's presentation. I'll highlight what are some very meaningful catalysts and elements of news flow over the next couple of years. Today, Cytokinetics is roughly a $7-$8 billion-dollar company, depending on how you think about shares outstanding. And we hope to be in a position where that could double or triple over the next couple of years as we advance the pipeline and our go-to-market activities. And we think we're on a very important inflection point for shareholders and all stakeholders, as this science is now delivering on the potential for new medicines.
We have a strong financial position, thanks in part to deals we did in the second quarter, pulling in additional capital, both in the form of an equity financing, as well as a structured deal affording us access to additional capital at a low cost of capital from Royalty Pharma. Bottom line is, at the end of June, we reported approximately $1.4 billion in cash and cash equivalents, with, as you can see here, access to additional capital as we make continued progress that we believe is consistent with a company in a competitive market for cost of capital. We believe we've done right by fortifying the balance sheet, and we're also attending properly to how we deploy that capital.
Here's how we think about a specialty cardiology franchise anchored in those large patient populations suffering from severe cardiac disease that's rooted either in the hyper or hypocontractility of cardiac muscle, with focus initially to obstructive HCM, which is treated by a relative few number of cardiologists, and where we believe, with a sales force of roughly 125 to 150 people in North America, we can get to the roughly 8 to 10 thousand cardiologists who we believe are gonna be largely responsible for the treatment of not just, OHCM, but also NHCM, and as we build that same commercial infrastructure, it's only a modest incremental gain for our interest in heart failure, both reduced and preserved.
So this lays out how we think about a specialty cardiology business rooted in a lean sales and marketing infrastructure directed to a specialty cardiology segment. And you can see how specialty cardiology distinguishes from broader cardiology, where we think the biopharma space is advantaged as we go to a more high-touch, focused, specific, specialized cardiac commercial strategy. So aficamten is the lead horse. We're looking at both obstructive and non-obstructive. Right now, in terms of diagnosed patients, it's probably two-thirds, one-thirds, and you can see these are large but still orphan indications, and we do believe it lends itself to the type of specialty model that we're focused on, especially with a next-in-class cardiac myosin inhibitor. You may know that we played a hand in the launch and the discovery of MyoKardia and mavacamten, respectively. MyoKardia ultimately acquired by BMS.
We believe mavacamten, the first-in-class compound, is an excellent drug. We discovered it. We know it quite well. But, we believe aficamten is next in class, and you can see here some of the aspirational profile that we built into aficamten. As was demonstrated to have meaningful, clinically relevant safety and efficacy in its pivotal clinical study, SEQUOIA, announced topline in December 2023, and as presented in full at the heart failure meetings in Europe and published concurrently in the New England Journal in Q2 2024, and here you can see clinically relevant and meaningfully large effects on peak VO2, as measured change from baseline at 24 weeks, and that's on top of standard of care, and these effects were consistent across every subgroup that we evaluated as pre-specified in this trial.
Moreover, the effects were supplemented by statistically relevant and clinically meaningful effects on every pre-specified subgroup. So we consider this to be a quite compelling story for efficacy as measured in that pivotal study. And here you can see a responder analysis, as was another way of thinking about these data in support of a potential NDA submission. The safety data suggests that aficamten, layered on top of standard of care, is well-tolerated, and we believe that will translate, we hope, into a distinct and differentiated risk mitigation profile for this next-in-class opportunity. And as you can see, even as we've continued patients into FOREST, the open-label extension, we continue to see no treatment interruptions, no heart failure events, all effects on EF below 50, reversible and addressed with dose-down titration, no dose terminations.
We think that this augurs well for how FDA may hopefully look at risk mitigation with a potential approval and labeling. SEQUOIA forms the basis of an NDA submission. We gave guidance previously that we'll be seeking to submit an NDA in the third quarter, so that's this month. We expect to be announcing in the fourth quarter when that NDA may hopefully be accepted for filing. Similarly, we're pursuing a submission with EMA later this year, and you'll hear more about our strategies as relates to regulatory filings and potential approval over time. We do believe that aficamten can demonstrate an aspirational profile as we've researched this next in class, and we think this could translate to category growth and enhanced awareness, as could be beneficial to patients and stakeholders.
We're doing a lot of other studies with aficamten. I've talked about SEQUOIA and FOREST, the open-label extension. We expect to be reading out MAPLE in 2025. That's another study in OHCM, as could potentially affect guidelines and positioning of aficamten, as could ultimately be in first-line management of these patients. ACACIA is a study in NHCM that should hopefully conclude enrollment next year, read out in 2026. CEDAR is a newer study in pediatric patients. This all speaks to our confidence as we're advancing aficamten, and as we should, as next in class could be enabling of category growth. And here's how we think about growth over time. This is a category for which we're beginning to see wider adoption, but still it's roughly 400 cardiologists responsible for about 80% of the prescriptions for the existing cardiac myosin inhibitor.
And we think it's incumbent upon Cytokinetics to bring forward aficamten, as can grow this category, more patients benefiting more prescribers. And we believe we can do that with a focus to those concentrated customer segments, as you see depicted here, and as we've seen time and time again, next-in-class cardiac medicines opening the category to broader community cardiologist awareness and adoption. And that's how we're thinking about gating investment spend with the NDA submission and potentially its acceptance for filing. As we roll through a potential mid-cycle review, we'll gear up for the hiring of salespeople next year in 2025 and other go-to-market activities. So aficamten, as I've discussed, represents an anchor for the foundation of this specialty cardiology business, and analysts have projected that this could be, for us, a multi-billion dollar category.
We see this as opening the door for the rest of our business, omecamtiv being a potential next opportunity. Around the time, two to three years into the aficamten launch, we might be asked by shareholders, "So what's next?" And we do believe omecamtiv represents low-hanging fruit for what could be the next opportunity also directed to specialty cardiology, and in this case, severe heart failure with reduced ejection fraction. Omecamtiv was the subject of a positive phase 3 study, GALACTIC. Over 8,000 patients reported in the New England Journal. And FDA indicated, as did EMA, good, but not good enough, and we want to see a confirmatory study. So we recently announced we will be doing a confirmatory study of omecamtiv. That should be underway later this year...
We expect it to be a concentrated focus study, roughly two thousand patients, intended to recapitulate what we saw in four thousand patients in the eight thousand-patient study, previously announced. So we do think this is, you're on the five-yard line, it's first and goal, and you've got an opportunity to bring it into the end zone, as you can build on what we already know from omecamtiv in GALACTIC. And that is that while the effect size was clinically relevant and statistically significant in the overall population, it was approximately double in the more severely ill patients, as reflected on this slide. With increasing severity, lower ejection fraction, we saw increased effect size. We want to amplify that now in a confirmatory study.
Here you see some of the attributes of those sicker patients and the effect size, the hazard ratio, the statistical significance that informs how we're approaching this next confirmatory study, a study that FDA has reviewed and we think will be underway later this year. Here's a high-level look at what that study might ultimately look like, and we'll have more to say about it over the course of the next several months. We're looking again at a concentrated customer segment. While there are over six million patients in the United States with heart failure, half have reduced ejection fraction. About a third of that half have more severe advanced heart failure, and we think there's an opportunity here that's not being well served by existing standard of care.
Still over a million patients in the United States who may benefit, and for where we may even be afforded, higher price potential, as these are patients who are the frequent flyers in U.S. hospitals, oftentimes at high cost to Medicare. So that's how we're thinking about omecamtiv. CK-586, the third of this triangle of cardiac myosin modulators, we announced this morning phase I data for this distinct cardiac myosin inhibitor. It has a slightly different mechanism of action than does aficamten, whereas aficamten is acting at the ATPase binding site, and therefore is calcium-dependent in the way it inhibits cardiac myosin.
CK-586 binds to a different allosteric site, has effect to the regulatory complex, and therefore, we believe may have certain advantages as we look not to the advancement of this drug in hypertrophic cardiomyopathy, but in patients with heart failure and preserved ejection fraction, but those more severely ill, those with hypercontractility more anatomically similar to NHCM, patients who may, benefit from this mechanism but aren't likely to benefit from SGLT2 inhibitors. As we've seen, these patients are not your ones who have more of the metabolic syndrome, heart failure, and preserved ejection fraction, but rather the more severely ill hypercontractile, as described here.
And we've already seen in phase I data, described in this morning's press release, a shorter half-life compared to aficamten, a shallow PK/PD relationship, and one with dose-linear, PK, such that we believe once-daily dosing, is the way we should approach patients with heart failure and preserved ejection fraction. And here you can see some of the phase I data that, were announced this morning, and we do believe this augurs well for advancement into a phase II study later this year in heart failure with preserved ejection fraction. Lastly, I'll summarize our financials. Here's the financial guidance that we announced with our Q2 earnings call, and you can see it's reflected in GAAP OpEx, and this is for this year, twenty twenty-four.
And as you can see for that, combined with our balance sheet, which I described earlier, we have good, ample cash runway as we execute on these milestones, many of which we've already ticked off, but others still following. And you can see a number of things that contribute to news flow and hopefully catalysts for shareholder value as we roll into the remaining months of twenty twenty-four, and we can expect in twenty twenty-five, hopefully our first commercial launch. With that, I'll thank you for indulging me as I went through that pretty quickly. We've got a couple of minutes for questions, if you might have them. Sure.
You've made the argument that the, I'm not sure I remember the name, but the aficamten is superior to the one that's on the market.
So I don't think I can make a statement like that, because that would be comparative, and they've never been compared head-to-head, and-
Yeah, that's my question.
... regulators and lawyers would tell you, you shouldn't, and I don't. But for which we've designed into aficamten certain next-in-class properties, and as we've learned, the current cardiac myosin inhibitor, which is an excellent drug, is being used, and there's high adherence and compliance, but its use is affected by an existing REMS program that in market research has indicated to be an impediment to use. So our hope is that aficamten may ultimately be approved for marketing, and that FDA would hopefully see it as unique with its safety, tolerability, and efficacy profile, and where labeling and a potential REMS may enable a distinct risk mitigation profile and how that may contribute to wider adoption, that's to be determined.
But FDA has already, in our open label extension, which is ongoing, been permitting of, wider windows than was practiced in SEQUOIA for uptitration of aficamten. And in the maintenance phase, after one achieves target dose, less frequent echo monitoring than was, the case in SEQUOIA. That suggests to us that FDA seemingly is comfortable with the safety profile of aficamten, and as hopefully augurs well for how they might approach labeling upon approval. But that's still to be determined, subject to FDA review.
Dosing interval the same?
No, the dosing interval is not the same. The half-lives are not the same, so, the way in which one uptitrates is not the same. There's different properties of aficamten that render its dosing, we would argue, addressing some of the issues that cardiologists have indicated a want for pertaining to flexibility, pertaining to speed of onset, speed to get to target dose, rapid reversibility, absent of drug-drug interactions that are clinically meaningful, and the kinds of things that you would expect of us in designing a potential next-in-class drug.