Okay, welcome everyone to the Leerink Global Healthcare Conference. I'm Roanna Ruiz, one of the senior biotech analysts here at Leerink, and just want to welcome everybody. I'm really excited to introduce Cytokinetics, a member of the management team. With me here today, I have Robert Blum, CEO, and Andrew Callos, EVP and CCO. Thanks for joining us.
Thank you.
Yep. I think I'll kick it to you, Robert. You have a couple of slides you wanted to go through for intro?
Yeah, just to create a level set, we put together a few slides that hopefully will provide a nice backdrop for the conversation we're going to be having. I'll be talking about the company. As we talk about our company, it's patients like Eric who inspire us to do the good science that we do for the benefit of ultimately potential new medicines. I'll be making some forward-looking statements. I refer you to our SEC filings with regard to caveats to those statements. Of course, we're not going to undertake any obligation to update those statements, but encourage you to take a look at those things. Cytokinetics is a company that has been pursuing a mission since I started the company now over 25 years ago.
We're focused on new medicines that improve the health span of people with devastating cardiovascular and neuromuscular diseases by sticking to our roots, our expertise in muscle biology. We're addressing where we believe that expertise translates to a novel pharmacology of muscle function. Here's our pipeline. It's a pipeline of potential new medicines, all of which have been discovered by our scientists. This is organic to how we think about science and biology and pharmacology. As you can see, cardiac myosin, which is a mechanical chemical enzyme that drives the mechanics of cardiac muscle contractility, forms the cornerstone of our pipeline. We've got multiple programs in later stages of development, all of which read on cardiac myosin, foremost amongst which is an inhibitor of cardiac myosin called aficamten, which is pending FDA regulatory review for the potential treatment of obstructive HCM.
aficamten is also the subject of other clinical trials, including one that should read out in Q2 called Maple, also in oHCM, and also other studies ongoing in nHCM and pediatric oHCM. Cardiac myosin also forms the basis of our interest in activating cardiac muscle for severe forms of advanced heart failure and inhibiting it in the form of HFpEF, heart failure with preserved ejection fraction. Here you've got three programs all directed to one molecular target, and that forms the cornerstone of not only our pipeline, but also our business strategy, a franchise emerging in specialty cardiology, as we'll talk more about. It's not the whole story. We also have other programs underneath the hood. I doubt we'll have time to talk about them, but they relate to other interests in cardiovascular and neuromuscular medicine. Here's our vision 2030.
It speaks not only to where we've been, but where we're going. We expect by 2030 to have brought not one, but at least two, potentially more products into the armamentarium of patient care. Our goal is to be advancing approved products at the same time, and this perhaps distinguishes us from many companies today. At the same time, we're significantly augmenting pipeline in muscle biology. How we think about go-to-market matters. You'll hear more from Andrew, our Chief Commercial Officer, in a moment, but we expect to be launching our own medicines in North America and Europe at the same time through partnerships in Japan and China, and reaching over 100,000 patients by the time 2030 rolls around, all while still leading in the way of culture with focus to equitable access, as you'll hear more about our company over time.
Ours is a company that thinks about not only science and pipeline, but also how you get there and relying principally on non-equity dilutive capital to do it. We've set a high watermark, we would argue, amongst peer group companies in terms of how we've augmented balance sheet. You can see here that Cytokinetics recently reported cash and cash equivalents of approximately $1.2 billion on our balance sheet, with still ample access to additional capital, as would not come at the expense of equity shareholders through deals we've done, including, I believe, more deals with Royalty Pharma than any other company, and on terms that we think are very much in the interest of low cost of capital and high capital efficiency. We think about being good stewards of shareholder capital, and we can speak more to that if you have questions. Here's the news flow.
This is a company, because of pipeline, that has quite ample news flow this year and the next couple of years as we build out on our business. You can see highlighted here in green things that you can expect of us this year, specifically as it relates to a potential regulatory approval here in the United States for aficamten in oHCM, additional clinical trial data in Maple this year, completing enrollment of Acacia, as would be occurring later next year, and things like that that we can speak to as you may have interest. Last year, at the end of the year, we announced some key deals. We announced a deal in Japan for aficamten with Bayer. We announced a deal in China with Sanofi as they stepped into the shoes of a prior partner, a company called Ji Xing or CORXEL, as it was renamed.
I think this is enabling of us to think about the global presence of aficamten in over 80%-90% of eligible patients with OHCM. Cytokinetics is thinking boldly and broadly as it relates to ensuring access to aficamten promptly upon approvals. As we prepare to go to market, we've been in preparation with commercial readiness activities, not only medical affairs, but also as we engage with payers. We recently launched an unbranded disease awareness campaign, initially to healthcare professionals, more recently to patients. I encourage you to take a look at these websites and knowing that we're investing in market development through these initiatives. I think it's really important to know Cytokinetics to understand how we think about go-to-market. Andrew will speak to this in great more detail.
We have been a good student of learnings of other companies, including first-time biotech launch companies. We believe we've already implemented strategies that have demonstrated to have been successful for biotech companies that are their first-time commercial launch companies. This is not our first rodeo. Me and others, we've done this already several times before, and we've taken learnings from those experiences to be enabling of a specialty cardiology approach to building our franchise. We're thinking about multiple programs.
We're thinking about how we approach market access differently, how we're thinking about omnichannel precision marketing differently, how we're thinking about the patient experience, and ultimately nurse navigators and other ways that we engage with HCPs in their offices, specialty distribution channels, and other fit-for-purpose ways of enabling a very focused, disciplined way of addressing a highly concentrated customer segment, as we would believe could translate into initial launch velocity and enduring commercial sales. Happy to get into more detail about that. As I mentioned, it's not just about aficamten in its first studies, but other ongoing studies. We're investing quite amply in additional clinical trials, some of which you might even say sound a bit like phase IV studies that we've accelerated into earlier timeframes so that we can hit the market at a stride and demonstrate already, we hope, category growth and hopefully preferential share.
Maple should be contributing to that, as well as could Acacia in non-obstructive HCM in Q2 2025 and completing enrollment later this year, as depicted on this slide. Here are the milestones for this year. I won't go into each of these individually. I think I've already touched on most of them. To know Cytokinetics again is to recognize how we expect to go to market in the United States with approval hopefully anticipated in Europe next year, in China later this year, and at the same time with other catalysts that could be contributing to augmenting of the story with Maple and Acacia to follow. That is at the same time we're advancing omecamtiv mecarbil in phase III, CK-586 in phase II, CK-089 in phase I.
Cytokinetics is a story of not only, we hope, impact in terms of commercialization this year, but also pipeline growth and enduring value for shareholders as we build out our franchise verticals. With that, I'll turn it back to you for Q&A.
Sure. Sounds great. That was a really good overview. I guess to kick off, I did notice you put out a bit of a release earlier this morning with some regulatory updates. Just want to level set here for the audience. Could you just talk about some of those updates and where things stand for aficamten in particular?
Yeah, so knowing we were going to have lots of one-on-one meetings this week and also three investor conferences this week, our lawyers counseled us that it would be good to level set from a Reg FD standpoint to ensure that everybody has the same access to the same information. We announced this morning that we recently did convene a meeting with FDA, a mid-cycle meeting. During that meeting, a couple of things. One is FDA has made clear that it does not expect an adcom for aficamten, that we are on timeline for a late-cycle meeting in June. Coming out of the meeting, same as going into the meeting, Cytokinetics continues to believe that if aficamten is approved, that we should expect a differentiated label and risk mitigation profile. We are pleased.
That is about it in terms of how we are going to be able to comment on what has been occurring with ongoing FDA interactions.
Yep. Got it. Okay, great. Just thinking about aficamten, since it's a big driver of a lot of the investor conversations I've had over time. In terms of Sequoia and the phase III trial and putting out more granular data updates, more interesting updates later this year, I mean, what's your plan in terms of publications, medical meeting presence, and how does that tie in well to commercial education, et cetera, ahead of a potential AFI launch?
This is one of those things that I think is incredibly important at Cytokinetics and, frankly, is a competitive advantage. Cytokinetics is a company that's both been a pioneer and a leader in this space. It is evidenced not just in the clinical trials that we're doing, but the scientific evidence that's been published. Last year, we published over a dozen manuscripts in support of aficamten's evidence to support go-to-market. We do believe that this is somewhat unusual and provides us support as our medical affairs colleagues and our eventual commercial colleagues will be calling on customers. You should expect more of that from us, not just with regard to additional analyses from Sequoia, but from Forest. We now have hundreds of patients in Forest- HCM, the open label extension, that are out beyond one and two years.
Those data continue to demonstrate, we believe, the same properties that we engineered into aficamten as could be potentially differentiating. Moreover, Maple reading out in Q2, you'll see those data presented and published hopefully soon. I think it's a hallmark of how we do business that Cytokinetics is continuing to advance the science.
Yep. Got it. Drilling down a bit more, there has been a lot of discussion around Camzyos' REMS from Bristol and how that might have been a limiting factor in the uptake of that program. Could you just talk about what are your view of the REMS requirements for that product? Could that be generalized to the CMI class or just remind us of some of the differentiation points for AFI where things could be different?
Yeah, so I'm going to ask Andrew to speak to this primarily, but what I'll say is this. We think that BMS is doing a great job with regard to Camzyos. At the same time, they're demonstrating that cardiac myosin inhibition is a very effective therapeutic strategy. There are roughly 550-600 physicians accounting for over 80% of the Camzyos prescription volume. Those numbers are impressive, especially as it relates to repeat prescriptions and patient adherence. These are things that are demonstrating that for their first-in-class drug, they're doing all the kinds of things you'd expect of a new cardiovascular medicine. It's incumbent upon Cytokinetics, upon a potential approval and launch, to expand the category. That's where our strategy has always been.
With that, I'm going to turn it over to Andrew to talk about where the REMS fits into this and how we might perceive to be differentiated.
Sure. I mean, as Robert alluded to, there's a little over 550 cardiologists who are really driving mavacamten in over 80% of their volume. To get out to beyond the specialized centers into general cardiology, our research tells us that the REMS is a major factor that that's a slow process. There are elements of REMS that are echoes, that there are a number of echoes required to get up to a maintenance dose. There's a percentage of patients who actually have to go down in dose from 5 mg to 2.5 mg . There's a drug-to-drug interaction monitoring required. There's a pretty narrow window between when an echo occurs and when a patient can get the next prescription. Collectively, it does add some level of administrative challenge to offices to get a patient on steady-state dose.
That said, I think what we hear is that patients and cardiologists in general say that mavacamten works well, that it does take some time, as I alluded to. If you could lower that administrative burden, if you can get a patient from an efficacy point of view faster to maintenance dose, if there's less requirements relative to a risk management program, that should unlock more of the market. The market's pretty linear right now. I think there's about 1,400 patients per quarter being added, maybe about 15,000, our estimate number of total patients on mavacamten. The market opportunity is probably over 100,000. There are New York Heart Association Class II-III patients. Our expectation is about 80% or more of the market for obstructive HCM will be available.
If we go to the cardiologist, we'll start in those same 550 likely, but if we can expand to another several hundred physicians, then you'll start to see maybe the market grow in terms from this linear growth stage more to a high growth stage over time.
Yep. Got it. In the context of the CMI class growing with potential approval of AFI, and I know you cannot speak directly to what FDA input yet, I was curious going into continuing this review process for AFI, what are your goals in terms of presenting information to the FDA or what do you hope that they garner from all the package that you've provided them so far?
We announced with our earnings call that we recently submitted the Day 120 update. You're seeing in real time how the Forest open label study of aficamten is a real-world experience. What I'm especially encouraged by is we've yet to see any excursions relating to ejection fraction that contribute to a heart failure diagnosis or a hospitalization. That to me underscores the fact that we're doing the right thing by how we approached dose up titration and dose maintenance and that this is in aficamten, if approved, hopefully a potential medicine that can be enabling with more confidence and ease of use and flexibility. It can't stop there. We have to demonstrate to physicians, nurses, pharmacists, and patients that the experience with aficamten, like in the open label extension, is one that can be engendering confidence.
We have to design something that's tailored for patients and that is recognizing of how patients identify with their disease. That is what I think ultimately matters. I hope that our label will be reflective of this experience that we're trying to create for patients that would ultimately be enabling of more physicians, more patients to get comfortable with a medicine sort of this. Again, it's all as driven by science.
Yep. I hear you. You also mentioned two phase III trials coming up that we should watch for, both Maple and Acacia. Could you just give us an overview of what do you hope to see in these two different trials and how would it be important for expanding aficamten's opportunity in the future?
I'll turn to Andrew about this, but firstly, I'll say we were very encouraged by data from Sequoia, which demonstrated that for patients both on and off beta blockers, that those receiving aficamten did better than placebo counterparts. That's indicative of what we hope will be confidence going into the readout of Maple, where we're doing a head-to-head comparison of patients on aficamten versus those on beta blockers. Beta blockers, for those of you who don't know, tend to be used first line for these patients, A, because they're cheap and they've been around for a long time, but there's no clinical evidence to support their use in terms of increased exercise capacity. We do believe that this could be meaningfully incremental if aficamten shows superiority to beta blockers, especially as it relates to guideline-directed treatment and how payers might see aficamten.
We're looking to Maple to be enabling of increased confidence. In Acacia, we're studying in a population called non-obstructive HCM, whereas Andrew can comment, we're seeing a more rapid growth of prevalence. Andrew, might you speak to both where you see Maple and Acacia fitting in?
Sure. It is important to understand from a market point of view, New York Heart Association Class II-III is the patients that we have studied, and they are the ones that would be candidates for a CMI. Over 90% of patients today are on a beta blocker or a calcium channel blocker, most on a beta blocker. We talked about the importance of unlocking cardiology, general cardiology outside the specialized centers where 80% of prescribing is today. There are those physicians. In market research, there are a couple of kind of key findings.
One, there is a segment of physicians who feel like beta blockers are good enough. They are not educated on CMIs or they are not convinced. When they would see head-to-head data, if you put a profile in front of them that says the head-to-head data that shows superiority, it unlocks more physicians in terms of activating them to prescribe.
The impact that has on that broader set of cardiology as well as those that are already prescribing, it does two things. One is it expands the market. If you look at peak penetration of what a CMI market will be for eligible patients, that increases with the addition of a second data set. When you look at a preference share of available treatments, the preference share for aficamten increases as well. A second data set confers more assurance that efficacy, safety, real world in a second study provides a little more confidence that it just was not a single study. It really grows the market and increases share, and it should unlock more prescribers from a Maple point of view. From a payer point of view, Maple should also increase or influence guidelines.
Once guidelines come in play, then that's when we can start to hopefully unlock payers over time, but that takes more time. From a non-obstructive, so when we looked at this market maybe two or three years ago in terms of Epi, the obstructive versus non-obstructive was about a 60/40, with obstructive being 60% of the population. Obstructive population is growing with the population, so it's fairly flat, very, very small level of increase. Non-obstructive is increasing at double-digit rates. Non-obstructive is probably approaching now 50/50 in terms of the market and likely will overtake obstructive in terms of the overall number. Non-obstructive is turning out to likely be a larger opportunity than we were originally anticipating. We're going to be publishing from HEOR point of view later this year that Epi data, that analysis and what those numbers look like overall.
I think another critical point is these are the same prescribers. So we're building a field force to focus on 10,000 cardiologists who are 80% of diagnosis and prescribing of all therapies, including generics. They would be the same prescribers, obstructive, non-obstructive. So our go-to-market strategy, when you look at Sequoia, when you add on Maple, when you add on a different population of Acacia, it's all the same infrastructure and same field force expanding this market.
I'm going to sing Andrew's praises for a minute because one of the reasons why he was so attractive to join us as our Chief Commercial Officer, and this was four years ago, is that he had co-led the development and co-promotion of Eliquis when he was then at Pfizer after 23 years working together with BMS, understands what a next-in-class drug coming into a market can do for a category. Eliquis is one of those archetypal examples of a cardiovascular medicine that made a huge impact with the introduction of a new medicine as a second entrant and how that grew the category for the benefit of all patients.
Yep. Got it. I know, Andrew, you alluded to some possible guideline updates that could be favorable after Maple and/or Acacia readout. Could you just help frame for the audience timelines of that, if there's any way to know when those could kick in? I know it's a moving target, but how are you thinking about this possibly happening for only AFI, or could there be a CMI class update? What are the pushes and pulls there?
Yeah, I mean, if it's a little bit of crystal balling, then I mean, I'll go from our colleague Dan, who's with us today, our VP of clinical development, that tells me that guidelines are trying to move forward towards annual updates as compared to maybe every three or four years. With his data set, is it conceivable that guidelines could be updated in early 2026 to include? My experience is what they would probably say CMIs, but with an asterisk pointing to data. The other difference is if guidelines do say CMIs with an asterisk pointing to Maple, from a promotional point of view, a pharmaceutical company needs evidence to promote a given claim. We would have that evidence to promote that claim. To my knowledge, BMS is not running such a study.
I think from a preference point of view or from an execution point of view, we would be able to show both data sets. This is a confirmatory data set, maybe with higher levels of peak VO2, but confirmatory safety, confirmatory efficacy. I think that speaks volumes for cardiologists. In my experience, I've been in the cardiology market for sales and marketing for a long time. When you see evidence over evidence, especially with long-term data, this really does give assurance to some cardiologists. Cardiologists generally take longer to get on board with newer therapies, and this certainly could accelerate that.
Got it. I know this is more than just a one product story, so it's not all about AFI. I did want to ask a bit about some of your pipeline development products as well. We've got CK-586, which is advancing. We've got omecamtiv. Maybe could you give us a little bit of highlights about where those stand and what to look forward to next?
Yeah, heart failure is the number one reason why people in the United States are hospitalized. It's growing with the aging demographics, and it represents already 6 million to 7 million patients in the United States. There are new medicines that are making a dent in heart failure, certainly SGLT2s and GLP-1s and otherwise, Entresto, a $7 billion-$8 billion a year drug, but for which on the extremes, those patients with severely reduced ejection fraction or those patients with supernormal ejection fraction, hypercontractility, it's our assertion that those medicines are not demonstrating effects that would address the high unmet need. We've positioned omecamtiv mecarbil for severely ill heart failure patients with reduced ejection fraction. It was already the subject of a positive phase III study in over 8,000 patients, but admittedly, where the effect size in a less sick population was more modest.
We're now doing a confirmatory study as requested by FDA in a sicker population. As that study is now in phase III and enrolling, we're very excited about where that represents upside. On the other side of the spectrum are those patients with hypercontractile ventricles and heart failure with preserved ejection fraction. There we think a cardiac myosin inhibitor could also play a meaningful role. These patients look like the non-obstructive HCM patients in a lot of ways. We have very encouraging data to support the use in nHCM. We've advanced a second cardiac myosin inhibitor, CK-586, into phase II, and that study is now enrolling. We have omecamtiv mecarbil in phase III, CK-586 in phase II. It's those three programs that represent three legs of a stool for a franchise strategy that speaks to who we are at Cytokinetics in terms of business.
We do believe that we are in a position by 2030 to be advancing three potential medicines to patients and as would be addressing unmet needs across different patients with impaired cardiovascular muscle function, but all as would be generally prescribed by the same concentrated cardiology physician base. We do not have to scale sales and marketing necessarily because we are talking about relatively the same customers, and we think that is core to strategy.
Yep. Got it. I know we're close to time. Just want to pause here, see if anybody in the audience has any questions that they might want to jump in with. I think the question was, do you see Edgewise as a possible competitor? What are your thoughts there?
I do not want to talk about comparators or competitors. What I will say is we're very science and data-driven, and we'll look forward to seeing data from both Camzyos and the Edgewise 7500 compound as they come forward. We believe that the bar is very high that was set by aficamten in terms of what would be expected clinical profile. One needs a lot of data here in order to be able to make statements about where one would be positioned. What I will say is with aficamten, we have a 5 mg and a 10 mg dose for which if we only studied those two doses, we would see rapid gradient reductions, no EF excursions, and one might conclude that those drugs were sufficient, those dose strengths sufficient to address a majority of patients without the need for echo monitoring.
We do not believe that addresses the diversity of patients that some require higher doses, and we do believe that FDA is not likely to consider no echo monitoring for patients with oHCM, especially since these patients get echo monitored once or twice a year already. We think that aficamten occupies the sweet spot for what would be positioning as would set the bar high for any other competitive threat.
I don't see any other questions, so I'll probably wrap it there so we can get to other sessions. Thanks again, Robert and Andrew, for joining us. It was a really great discussion.
Thank you very much.
Thank you.
Thank you.