Earnings Call Transcript - CYTK Q1 2024

Operator, Operator

Good afternoon, and welcome to Cytokinetics' First Quarter 2024 Conference Call. This call is being recorded. I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Affairs. Please go ahead.

Diane Weiser, SVP of Corporate Affairs

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer will begin with an overview of the quarter and recent developments. Fady Malik, EVP of R&D, will provide updates related to aficamten, focus to SEQUOIA-HCM, FOREST-HCM and recent interactions with FDA. Stuart Kupfer, SVP and Chief Medical Officer will provide additional updates regarding the ongoing clinical trials of aficamten, MAPLE-HCM and ACACIA-HCM and will also discuss progression of CK-586 and our emerging pipeline. Andrew Callos, EVP and Chief Commercial Officer, will speak about commercial readiness activities for aficamten. Sung Lee, our new EVP and Chief Financial Officer is with us today, but just listening alongside us as this is his first day at Cytokinetics. Robert Wong, VP and Chief Accounting Officer will provide a financial overview of the past quarter. And finally, Robert Blum will review our corporate development strategies before closing the call by reviewing expected key milestones for the year. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements contained in our SEC filings, including our current report regarding our first quarter 2024 financial results filed on Form 8-K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call. And now I will turn the call over to Robert.

Robert I. Blum, President and CEO

Thank you, Diane, and thanks for joining us on the call today. In the first quarter, we made substantial progress executing on our muscle biology-focused portfolio, anchored by the broad development program of aficamten. On the heels of positive top line results from SEQUOIA-HCM, our pivotal Phase III clinical trial of aficamten in patients with obstructive hypertrophic cardiomyopathy, we are running at full throttle in preparation for an ambitious set of presentations and publications scheduled to occur over the course of the year. In addition, we are laser-focused on regulatory submissions in the second half of the year, continued conduct of the ongoing clinical trials program, accelerating our commercial readiness activities and further expanding our pipeline. While top line results of SEQUOIA-HCM announced last December included a comprehensive high-level view of the safety and efficacy of aficamten, a priority of ours is to present more fully the results from SEQUOIA-HCM at a major medical meeting. Recently, we announced that, that forum will be the European Society of Cardiology's Heart Failure 2024 Congress in Lisbon next week, Monday, May 13, where we will have 3 late-breaking clinical trial presentations related to SEQUOIA-HCM. Along with the primary results, we have 2 other late-breakers with data from additional analyses from SEQUOIA-HCM on which Fady will elaborate. He will also lay out the steady stream of presentations and publications that we anticipate sharing related to aficamten throughout 2024 as we believe will nicely elaborate on its next-in-class profile. During the first quarter, we also engaged meaningfully with FDA ahead of our planned submission of an NDA for aficamten in the third quarter of this year. We convened 2 meetings with FDA in the month of February, including a first meeting to review the results of SEQUOIA-HCM and a second pre-NDA meeting to cover specific topics related to our submission. We are pleased with the agency's feedback, and we look forward to additional discussions to occur this quarter, which will address specific questions we are posing relating to potential REMS scenarios. We've also been preparing for our planned submission of an MAA with EMA expected in the fourth quarter of this year. Moreover, in 2024, many other work streams and activities were pushed into the next phase of execution, notably commercial readiness activities, which Andrew will speak about in more detail. And while SEQUOIA-HCM represents the forward edge of the Phase III development program for aficamten, we now have 2 other ongoing Phase III clinical trials evaluating aficamten, which each represent additional opportunities to expand the clinical evidence use case and hopefully reach more patients in need. Of course, we're also continuing our ongoing open-label extension study, FOREST-HCM, to collect longer-term data on the safety and efficacy of aficamten. And as Stuart will elaborate, MAPLE-HCM, the Phase III clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy is expected to complete enrollment in the third quarter. This trial will provide an evidence-driven answer to the question clinicians are beginning to ask with the emergence of cardiac myosin inhibitors, that is, which drug do we initiate first? MAPLE-HCM may be an important opportunity for aficamten as we hope it may inform a critical change in treatment practice as could be outlined in emerging guidelines. Stuart will also share an update on ACACIA-HCM, our Phase III clinical trial of aficamten in patients with non-obstructive HCM and he'll also describe a third late-stage clinical trial called CEDAR-HCM, which is now open to enrollment in a pediatric population of patients with oHCM. We are especially pleased to maintain a strong financial position at the end of the first quarter, alongside of our maturing R&D programs. As I'll speak to in more detail later in this call, we believe that we are in an advantaged position in terms of our options for accessing diversified capital to further fuel our science for the benefit of patients and to deliver increasing shareholder value. And lastly, we were pleased to recently announce that we had finalized our search for a new CFO. And as you hopefully saw from the 8-K we issued, I'm pleased to welcome Sung Lee to our team. When we began our search, we had several key criteria for the ideal candidate including previous experience in both large and midsized biopharma companies, global commercial finance experience and a track record of innovative financing deals. Sung brings all of that and more, and we couldn't be happier to have him join our team. Prior to Cytokinetics, Sung was CFO of Vir Biotechnology and also MorphoSys AG and Sangamo Therapeutics. Previously, he built his career expertise over 14 years at Gilead, where he served in various roles obtaining leadership expertise in tax, accounting, operations and IR. You will hear from Sung in our Q2 earnings call. And for those of you who don't already know him, you'll soon have a chance to meet him at our upcoming conferences and one-on-one meetings. And with that, I'll turn the call over to Fady, please.

Fady Malik, EVP of R&D

Thanks, Robert. Top of mind for all our late-breaking clinical trial presentations next week at Heart Failure 2024 in Lisbon. The presentations include, of course, the primary results of SEQUOIA-HCM, which will provide a complete view of the results related to the baseline characteristics, the primary and secondary endpoints, subgroup analyses and select exploratory endpoints. There will also be 2 additional late-breakers on other data analyses from the trial, one will elaborate on the dosing and safety experience in SEQUOIA-HCM and another is a deep dive into the improvements in exercise capacity affected by aficamten based on a detailed review of the CPET data. These presentations will not only expand on what was in the top line press release, but go further in providing an in-depth look at this very rich data set and its implications for clinical practice. As Robert mentioned, our presentations next week represent only the beginning of our plan to fully dissect the results from SEQUOIA-HCM and build a comprehensive picture of the differentiated profile that continues to emerge for aficamten. We have an aggressive plan that starts with HFA and lays out over the course of the year, a series of presentations and publications that will further elaborate on the efficacy and safety of aficamten. You can expect presentations at the European Society of Cardiology, The Heart Failure Society of America and the American Heart Association Meeting as well as accompanying publications in leading medical journals. These include deeper dives into the echocardiographic, Kansas City cardiomyopathy questionnaire data, CMR data, cardiac remodeling and biomarker data as well as an integrated analysis of efficacy. We look forward to sharing more as the year progresses. Shifting to FOREST-HCM. Last month at ACC, we shared additional 48-week data from 46 patients with obstructive HCM and FOREST-HCM that showed the treatment with aficamten is associated with sustained improvements in resting and Valsalva left ventricular outflow tract gradient, NYHA functional class, NT-proBNP and measures of cardiac structure and function. Furthermore, occasions of low left ventricular ejection fraction were very infrequent and were not associated with treatment interruptions or heart failure events. These data continue to reinforce the safety and efficacy of longer-term treatment with aficamten and oHCM. With nearly 300 patients currently enrolled in FOREST-HCM, we look forward to reporting more longer-term data in the future. Importantly, during the quarter, we had many opportunities to engage with KOLs and treating clinicians in the community to discuss the results generated to date from the program for aficamten. Feedback has been incredibly positive, and we believe that once presented and published, the full results will reaffirm this enthusiasm. Specifically, our therapeutic medical science liaisons have interacted with over 500 health care professionals and completed profiling of physician practices with HCM treatment programs. At the same time, our managed health care medical science liaisons engaged integrated delivery networks or IDNs around the results of SEQUOIA-HCM and finalized work to build our payer clinical value narrative. On the regulatory front, as Robert mentioned, during the first quarter, we held 2 meetings with FDA ahead of our NDA submission. During the second quarter, we plan to engage FDA once again, this time for a type B meeting focused specifically on potential risk mitigation. While this is a topic that came up in both of our previous meetings, this next engagement affords us the opportunity to elaborate on the safety and pharmaceutic properties of aficamten, discuss their potential impact on different approaches to manage risk and gain insight into FDA's perspective on these matters. In these discussions with FDA, our position is that the benefit/risk profile of aficamten merits an approach to risk mitigation that's reflective of the safety profile of aficamten as demonstrated in SEQUOIA-HCM and FOREST-HCM. Altogether, we remain optimistic and we believe these discussions will inform our proposal for a differentiated approach to risk mitigation in our NDA. As we've previously shared, we're planning for a rolling submission for the NDA, which will provide FDA the opportunity to begin their review of completed modules. We expect to begin and complete the submission during the third quarter. As I'm sure you'll appreciate, there is a tremendous amount of work that goes into an NDA and our teams are working diligently towards this very important milestone for the company. Meanwhile, we're also preparing our marketing application, which we expect to submit to EMA in the fourth quarter of this year and are coordinating with our partner, Ji Xing in China to support their plans to submit an NDA as well. During the quarter, we are pleased to welcome a new Head of Regulatory for Europe who will lead regulatory strategy and product registration in Europe and support the launch readiness activities. While SEQUOIA-HCM is taking center stage at the moment, it's followed and supported by additional clinical trials and the development program for aficamten that we believe have the potential to expand the utility of cardiac myosin inhibitors. I'll hand it over to Stuart to elaborate more on these additional clinical trials as well as provide an update on our earlier-stage clinical development pipeline.

Stuart Kupfer, SVP and Chief Medical Officer

Thanks, Fady. I'll start with our 2 ongoing Phase III clinical trials, MAPLE-HCM and ACACIA-HCM. We believe both of these trials have the opportunity to expand the potential benefit of aficamten to additional patients with obstructive and non-obstructive HCM and to elevate aficamten in treatment guidelines. MAPLE-HCM, which is evaluating the potential superiority of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM is on track to complete enrollment in the third quarter. Over 75% of our global sites are activated, and we're expecting sites in China and South America to join MAPLE-HCM soon. By the end of the second quarter, we expect to be at approximately 50% of target enrollment and foresee a large increase in enrollment in the third quarter. The results from SEQUOIA-HCM have provided a strong tailwind for enrollment in our ongoing trials, including MAPLE-HCM, and we've observed strong enthusiasm from sites for completing the trial and getting us across the finish line. We expect MAPLE-HCM to read out in 2025, around the time when we hope to be commercially launching aficamten, and a positive outcome will provide the evidence base to potentially position aficamten in guidelines for use as first-line therapy in obstructive HCM. ACACIA-HCM, the pivotal Phase III clinical trial of aficamten in patients with symptomatic non-obstructive HCM is also entering what we will expect to be a rapid phase of site activation and enrollment. During the second quarter, we're meeting with many of our investigators and study staff at their sites around the world, and we recently held a successful investigator meeting in San Francisco. Given positive results from Cohort 4 of REDWOOD-HCM, clinicians are enthusiastic about the promise of aficamten for the potential treatment of patients with non-obstructive HCM. And we look forward to continuing enrollment this year towards a goal of completion in 2025. Turning our attention to another important patient population. Just this morning, we announced the start of yet another clinical trial of aficamten called CEDAR-HCM, a randomized double-blind, placebo-controlled trial and open-label extension evaluating the efficacy of pharmacokinetics and safety of aficamten in a pediatric population with symptomatic obstructive HCM. CEDAR-HCM will enroll 2 cohorts, approximately 40 adolescents aged 12 to 17 years will be enrolled in the initial cohort. A second younger cohort of up to 10 children aged 6 to 11 years will begin enrollment after data from at least 20 adolescent patients supports safety and dose selection in the younger cohort. In the cohort in adolescents, the treatment regimen for aficamten will be the same as that for adults, that is once daily doses of 5 to 20 milligrams individually selected based on echocardiographic parameters. Primary and secondary endpoints will be evaluated after 12 weeks of double-blind treatment. The primary endpoint is change in Valsalva left ventricular outflow tract gradient, and secondary endpoints include change in resting gradient, pharmacokinetic measures, cardiac biomarkers and symptoms. After 12 weeks of double-blind treatment, all patients will roll over into an open-label extension. While pediatric HCM may be rare, it's associated with a high risk of heart failure and serious arrhythmias. HCM tends to present similarly in children and adolescents as it does in adults and is associated with shortness of breath, fatigue and poor exercise tolerance, impacting overall quality of life. We're optimistic, given the results from SEQUOIA-HCM in adults, that aficamten may prove promising for this key segment of the HCM population. During the second quarter, we'll also be starting a Phase I study to evaluate the pharmacokinetics, safety and tolerability of aficamten in healthy Japanese participants to advance our global clinical program in that geography. Additionally, during the first quarter, we advanced CK-586, another cardiac myosin inhibitor, in development for the potential treatment of a subgroup of patients with heart failure with preserved ejection fraction, or HFpEF. Earlier today, we announced top-line data from the Phase I study of CK-586, which showed that CK-586 was safe and well tolerated in healthy participants with generally linear pharmacokinetics. These findings are supportive of advancing the program to a Phase II clinical trial, which we expect to begin in the fourth quarter of this year. We plan to present the data from the Phase I study in more detail at a medical congress in the second half of the year. We believe CK-586, which has a different mechanism of action than aficamten, has the potential to further unlock the potential biology of myosin modulation for patients with high unmet need. Finally, further work continued in the past quarter on our earlier stage programs that we expect to mature from our labs into the clinic later this year and next, extending beyond muscle contractility for the areas of muscle metabolism and energetics. These emerging programs are an important part of our long-term vision as we continue to pioneer the field of muscle biology and pharmacology. And toward that end, we're pleased to be sponsoring a dedicated muscle biology symposium here in South San Francisco next Friday called CLIMB, Contemporary Landscapes in Muscle Biology. This 1-day event will bring together scientists, researchers and emerging professionals to share innovative research in the field of muscle biology. The goal of this gathering is to foster collaboration, facilitate networking opportunities and promote scientific and interdisciplinary dialogue with the ultimate goal of driving advancements in the understanding and treatment of muscle-related diseases and disorders. With that, I'll turn the call over to Andrew.

Andrew Callos, EVP and Chief Commercial Officer

Thanks, Stuart. After sharing top line results from SEQUOIA-HCM at the end of last year, in the first quarter, we began the design and build phases of our go-to-market strategies. We worked to refine our market development campaign, which we plan to launch at HFSA later this year and initiated the design and build of our comprehensive patient support services program as well as our specialty distribution strategy. We continue to strengthen our commercial team with new hires, including a U.S. Patient Marketing Lead and a Head of Germany, which, if approved, is the first European country where we plan to launch aficamten. In 2024, hiring in our commercial organization and in Europe will remain modest with more hiring expected in 2025 and 2026, gated to regulatory milestones in the U.S. and EU and reimbursement levels on a country-by-country basis in the EU. On that topic, we are pleased to continue to see more positive health technology assessments for the CMI class during the last several quarters, including from Germany, France and the U.K., which signals a potentially positive forecast for the future reimbursement of aficamten across key countries, if approved in Europe. During the quarter, we continued to build the value proposition for aficamten for various stakeholders, including payers and HTAs by generating data around health economics and outcomes research or HEOR. In the first quarter in recent weeks, our team published and presented 8 HEOR abstracts on topics including the impact of ethnicity, sex, region and payer health care coverage on outcomes in HCM, medical therapy usage post septal myectomy and long-term cost of care for patients with symptomatic obstructive HCM. Our findings around patient outcomes and costs related to obstructive HCM further underscore the clinical and economic unmet need for this growing patient population. Looking ahead, after we present and publish the primary results from SEQUOIA-HCM next week, we will continue engagement with U.S. payers. Our payer and medical account team began dialogues with every major payer in 2023. And beginning in Q3 of this year, we plan to initiate pre-approval information exchange with every major payer to review the results of SEQUOIA-HCM, so the payers understand the clinical meaningfulness of the results as well as the cost and outcome burden of obstructive HCM. I'm pleased with our progress for commercial readiness so far in 2024. As I've spoken to before, the obstructive HCM market has a highly concentrated customer base, which is typical for specialty cardiology. Unlike biopharma companies that have come before us who did not perform to market expectations, we believe our focus on specialty cardiology anchored by aficamten should enable us to successfully reach the subset of cardiologists who treat approximately 80% of the obstructive HCM patients. We believe that we are uniquely advantaged for success, and we're keeping our foot on the gas across our commercial readiness preparations this year. Just as our company successfully built a formidable R&D organization that cultivated the robust pipeline we have discussed today, we're well on our way toward building an equally outstanding commercial organization poised to stand shoulder to shoulder with our highly respected R&D colleagues. Together, we are pioneering new frontiers of success, driven by our shared vision and mission to help patients. And with that, I'll turn the call over to Robert Wong.

Robert Wong, VP and Chief Accounting Officer

Thanks, Andrew. We ended the quarter with approximately $634.3 million of cash on the balance sheet, which represents 2 years of forward cash runway, including capital we expect to be available to us under our deal with Royalty Pharma upon satisfaction of conditions. Our first quarter 2024 R&D expenses increased to $81.6 million from $79.4 million in the first quarter of 2023, primarily due to spending on our cardiac myosin inhibitor programs, offset by lower expenses for our skeletal muscle programs in the prior year. Our first quarter 2024 G&A expenses were $45.5 million down from $49.7 million in Q1 2023 due primarily to higher pre-commercial expenses in the prior year. With that, I'll hand it back over to Robert Blum.

Robert I. Blum, President and CEO

Thank you, Robert. As you've heard, our cohesive biology anchored by cardiac myosin inhibition continues to drive shareholder value and growth as we execute on our plan to advance to the next tier of biopharmaceutical companies. In the near term, we remain focused on elaborating on the positive results from SEQUOIA-HCM in presentations and publications, as well as preparing for the successful launch of aficamten if approved, in 2025, while also continuing to invest in expanding our promising pipeline directed to our plans to build a specialty cardiovascular franchise. In 2024, we've been focused on parallel opportunities to sustain and grow our company by diversifying access to capital and strengthening our balance sheet, and we're prepared to execute on a series of primarily non-dilutive transactions such as comes with partnering and structured financial engineering. We hope to have more to say about these initiatives as they come to closure and commit to ensure not only access to diversified sources of capital, but that we also focus on capital efficiencies as we deploy capital towards advancing our pipeline and emerging commercial business. Our priority remains our ongoing business development campaign for aficamten in Japan. During the quarter, we continued discussions with multiple parties and with momentum, we hope to consummate a deal. We're also looking at restructuring and expanding current financial instruments and deals to lower our overall cost of capital and potentially monetize additional R&D progress. We expect to remain diligent about the different levers we can pull as could be enabling of us in a principally non-equity dilutive manner to continue to augment shareholder value, and may also consider equity financing at the right time as part of a broader capital access strategy. Shaping our business conduct today and into the future is our pledge to corporate responsibility. And recently, we were proud to release our Second Annual Corporate Responsibility Report, which highlights our actions and progress against our goals of keeping patients at the center of our work, advancing a high-integrity, diverse and inclusive culture and supporting sustainable communities. As we look at our longer-term goals and vision, which will be articulated in our Vision 2030 early next year, the company we aspire to be is a sustainable commercial enterprise with an enduring R&D organization. Our vision is to maintain our pioneering leadership in muscle biology and pharmacology and is grounded in financial stewardship and doing what's right for the patients we serve. Now I'll recap our upcoming milestones. For aficamten, we expect to present the primary results from SEQUOIA-HCM at the European Society of Cardiology Heart Failure 2024 Congress next week. We expect to submit an NDA to the FDA in Q3 2024 and an MAA to the EMA in Q4 2024. We expect to complete enrollment in MAPLE-HCM in Q3 2024 and continue enrollment in ACACIA-HCM throughout 2024. We expect to continue enrollment in CEDAR-HCM in 2024 and to begin a Phase I study of aficamten in Japanese healthy volunteers in Q2 2024, and we expect to continue advancing our go-to-market strategies for aficamten. For CK-586, we expect to present primary data from the Phase I study at a medical meeting in the second half of this year and to start a Phase II clinical trial in Q4 2024. And for preclinical development and ongoing research, we expect to initiate clinical development with another muscle-directed compound later this year as well as continue our research on expanded muscle biology activities. Operator, with that, we can now open up the call to questions.

Operator, Operator

Our first question will come from Charles Duncan from Cantor Fitzgerald.

Unknown Analyst, Analyst

This is Charles. Congratulations on all the progress made in the quarter. I have a question regarding CK-586. Based on the Phase I results released this morning, what will be the starting dose and escalation strategy for the Phase II clinical study? Additionally, how do you plan to monitor safety and efficacy in the study?

Robert I. Blum, President and CEO

So it's a bit premature in light of the fact that we haven't announced the design for the Phase II study. But maybe Fady and Stuart can speak in general terms about how we think about dose escalation and the types of assessments that we might be considering for the Phase II study.

Fady Malik, EVP of R&D

Yes. I mean, I'll just say that all the doses that were in the press release were well tolerated. We didn't find a maximally tolerated dose. We didn't need to push it that high. We've had a clear pharmacodynamic response, and that was enabling us to decide on how to proceed to Phase II. I think we'll have more to say on specific doses and things, but you can expect Phase II to be really a dose-finding study in patients with heart failure and preserved ejection fraction, those that will resemble patients that we'll study in Phase III. And right now, in terms of monitoring and the dosing schedule and how we're going about it, I'm going to probably remain quiet on that until we are ready to be more forthcoming with those details.

Robert I. Blum, President and CEO

But what you can expect is that we're borrowing from learnings as it relates to aficamten in nHCM for application to CK-586 in HFpEF. And we believe that there are similarities in patient populations as well as endpoints for clinical evidence of effect. So we'll have more to say about that later in the year.

Operator, Operator

And our next question will come from Paul Choi from Goldman Sachs.

Kyuwon Choi, Analyst

It’s great to see Sung again and continue our collaboration. I have a question about MAPLE. Regarding your timing comments about enrolling the trial by the third quarter this year, you should be able to access some data by the middle of next year at the latest. Therefore, I'm wondering if you have any plans to submit interim or partial data or potentially the complete data as part of your NDA filing to strengthen your case for your proposed REMS or label. Your thoughts on this would be appreciated.

Robert I. Blum, President and CEO

Good question. I'll ask Fady to comment.

Fady Malik, EVP of R&D

Yes. So the trial will remain blinded until it reads out in 2025. But that said, during an NDA review, there's something called a 120-day safety update. And so we'll be submitting aggregate safety data from ongoing trials like MAPLE and ACACIA as well as updated safety and efficacy data from FOREST-HCM. So there will be more data, if you will, to consider and to cement if the safety profile of aficamten during the NDA review.

Operator, Operator

Our next question will come from Srikripa Devarakonda from Truist Securities.

Srikripa Devarakonda, Analyst

Aficamten is still in early stages of launch, and I may be jumping the gun here in terms of we have to wait for aficamten to get approved. But just thinking a little bit long term, if approved, aficamten would still have a significant proportion of the market left to penetrate, but I was wondering about the potential of patients to switch from mavacamten to aficamten? If they're either concerned about the safety or not satisfied with the efficacy, that may not be your base case, but I was just wondering if there is a possibility?

Robert I. Blum, President and CEO

So it's interesting. I think analysts have been polling opinion leaders about that very matter, and we'll leave that to the equity research community to make its own conclusions from those surveys. But it's certainly our primary strategy to be expanding the category for aficamten as could be applicable to a broader array of patients and physicians who prescribe for those patients and not otherwise to focus on patient switches, but maybe I could ask Andrew to speak about how he's thinking about the broader category growth and penetration.

Andrew Callos, EVP and Chief Commercial Officer

Yes, Robert, to elaborate on what you mentioned, we anticipate that a significant portion of the market will remain open to us. Our focus will primarily be on educating physicians and the wider cardiology community about aficamten so they can make well-informed decisions regarding patient treatment. We do not plan to promote or market switches in any way. If such changes occur, they will be addressed during the discussions between physicians and patients.

Robert I. Blum, President and CEO

We are focused on learning from other cardiovascular brand launches and next-in-class strategies and how that benefits both patients and shareholders. It is essential for us to concentrate on where cardiac myosin inhibition can still be applicable to a wider range of patients to accomplish our scientific goals and mission.

Operator, Operator

Our next question comes from Tessa Romero from JPMorgan.

Tessa Romero, Analyst

So we saw that you have an upcoming meeting with the FDA this quarter. Curious on your latest thinking on what you will provide us all in terms of how that meeting goes on your interactions around a risk mitigation plan here? And like, will there be a disclosure before you begin the NDA filing or not? And what could that look like? And then second quick question is just on the epidemiology side for HCM. We attended ACC and one of our key takeaways was around the focus on improving diagnosis. Where are you today on the right number, what the patient number is that could be addressable at the time of the launch? And how does this number expand if one includes the pediatric population?

Robert I. Blum, President and CEO

Sure. So I'll tackle the first one. Maybe Fady will add something to that, and then we'll ask Andrew to comment on numbers 2 and 3. As it relates to our strategy, we do not intend to provide feedback on a play-by-play basis with regard to regulatory interactions, especially as it relates to REMS. We do expect to come out of the meeting with FDA with clarity on what we might choose to do in connection with the potential REMS and we'll give some general update with our next earnings call but not otherwise, after the meeting itself. We believe that it's in the interest of transparency to at least provide some general updates, but not so specifically as that may affect the actual review and discussions we're having with FDA. And as you know, ultimately, it won't be until perhaps a mid-cycle review that the FDA gives us a sense of what they're thinking, and that's ultimately what's most actionable. And it will be at that point if this drug, hopefully, will be approvable that we'll be in a negotiation around a potential REMS or other risk mitigation strategies. So I don't think it's in anyone's interest to foreshadow that before we've even submitted the NDA. Fady, anything you want to add to that?

Fady Malik, EVP of R&D

Yes. I think these discussions are generally more about direction rather than commitments. They help the FDA become familiar with the data as we understand it, but they'll need to conduct their own review. Therefore, any disclosures may not be particularly helpful as things can change during the review process. We want to avoid creating confusion regarding the direction of our progress.

Robert I. Blum, President and CEO

To be clear, however, we do expect to float different scenarios, different risk mitigation strategies as could read on a potential REMS and it won't be until after that meeting that we make a decision about how to approach that in the course of submitting an NDA in Q3. And with that, maybe I'll turn it to Andrew to answer questions 2 and 3.

Andrew Callos, EVP and Chief Commercial Officer

Sure. So on the diagnosed, so I'll just stick to obstructive HCM. There's 200,000 patients today diagnosed, of those 130,000 would be eligible for treatment as defined by New York Heart Class II or III. The like most rare diseases, that number in terms of the true prevalence is likely underrepresented where many patients are not diagnosed, but probably the true prevalence is 3 or 4 times that number. It's also not uncommon once an available treatment is on the market, guidelines are updated to include that available treatment, there's education and publications by pharmaceutical companies, you'll start to see those rates go up, and we're expecting that to be the case. In terms of the pediatric population, so of the 200,000 obstructive HCM diagnosed patients in the U.S., and Europe is similar, there's around 6,000 to 8,000 pediatric patients with HCM. So I'm assuming that's probably we don't have a breakout of New York Heart Class for the pediatric population. But assuming it's probably 50% to 60% of that population would be eligible for treatment. So hopefully, that answers your question.

Operator, Operator

And our next question will come from Roanna Ruiz from Leerink.

Roanna Clarissa Ruiz, Analyst

So a follow-up on the CEDAR-HCM trial in pediatric patients. Could you talk a bit about the unmet need there for an agent like aficamten in this particular segment of the HCM market? And how long might it take to actually complete that trial? And do you have any thoughts on the regulatory path forward, assuming that you have positive data from CEDAR?

Fady Malik, EVP of R&D

The pediatric population is smaller than the adult population, but there is a notable unmet need. As Andrew mentioned, they generally have similar treatment options available, but surgery is less preferred in younger patients. The introduction of a myosin inhibitor would be a significant option for these patients, especially since the disease can be quite aggressive when it manifests early. Over time, we may gather insights into how the disease stabilizes rather than progresses in this subgroup, which might be more susceptible to rapid progression. The FDA typically aims to expedite the review process for pediatric patients. We anticipate positive results since the primary endpoint is the reduction of the left ventricular outflow tract gradient. While we are not yet specifying the timeline for trial completion, we believe it will progress swiftly, allowing us to file this as part of the supplemental NDA.

Operator, Operator

Our next question will come from Salim Syed from Mizuho.

Salim Syed, Analyst

I want to welcome and congratulate Sung. It's nice to reconnect with you, Sung. Regarding 586, I'm aware this may be better suited for Fady. Can you provide any insights on the Phase II design? Specifically, Fady, is there anything from the Phase I trial that suggests how this compound may stand out compared to the MyoKardia 224 compound and how that insight might influence the differentiation in the upcoming Phase II study?

Fady Malik, EVP of R&D

It's a challenging question to answer, Salim, because we don’t have much information about 224 and have not shared many details about 586. I can say that our goal is to make dosing of 586 simpler than aficamten, and we believe it has some unique properties that could help achieve that as developed during Phase I.

Stuart Kupfer, SVP and Chief Medical Officer

I think the only thing I'll really add is that CK-586 was designed to target what we consider more vulnerable population. These patients have had many comorbidities, perhaps more at risk of some decreases in ejection fraction, for example. And we think CK-586 has properties that would make these patients more manageable and less prone to that or other risks. And so, again, those details will be more forthcoming.

Operator, Operator

And our next question will come from Jeff Hung from Morgan Stanley.

Lee Hung, Analyst

Congratulations, Sung, on your new role. For CEDAR, what are the expectations for the dose range that's likely to be sufficient for most pediatric and adolescent patients? If they end up being a similar dose range as the patients from SEQUOIA, would you expect a higher rate of ejection fraction excursion because of the differences related to age?

Robert I. Blum, President and CEO

Stuart, do you want to take that one?

Stuart Kupfer, SVP and Chief Medical Officer

Sure. Thanks for the question, Jeff. So as we mentioned, the doses in adolescent patients are exactly the same as the doses that we're studying in adults, between 5 and 20 milligrams. And again, what's important is that the dose selection is individualized based on achievement of target gradient and maintaining a normal ejection fraction. In terms of younger children, the key question will be really what is the safe starting dose. And the plan will be to, as I mentioned, evaluate doing an interim analysis, evaluate 20 patients, adolescent patients, pharmacokinetics and safety and determine for younger children, what is a safe starting dose. And that's the basic strategy. And so with that in mind and individualized dose selection, we don't anticipate that the benefit/risk ratio in children will be just as good as we're observing in adults.

Operator, Operator

Next question will come from Mayank Mamtani from B. Riley Securities.

Mayank Mamtani, Analyst

Also pleased to see Sung join the team. Just maybe on the next Monday's ESC Heart Failure Congress data, could you please clarify if you could get the patient level and safety analysis relative to maybe what we saw at the top line? And also obviously curious to see how much of the dose titration and the responder rate of patients staying at higher efficacious doses is helpful to having that peak VO2 number that seems to be on the higher side and not connected to the baseline characteristics that we had initially thought. If you could clarify that, that would be great.

Fady Malik, EVP of R&D

Yes, Mayank. I mean, I think most of your questions will be addressed in those presentations. Remember the 3 of them, one will speak a lot about dosing and safety. And so we'll show the characteristics of patients at the various doses and how safety is related to that. With regards to peak VO2, can't really comment. I'm not sure that there is a dose-specific analysis. But you got to remember these patients were not randomized to dose, they were randomized to a dosing strategy, and they achieved a dose based on their individual response to the drug. And so in that way, we, in a lot of ways, consider them just all part of the same dosing strategy.

Operator, Operator

Our next question will come from Jason Butler from Citizens JMP.

Jason Butler, Analyst

And congrats on all the progress. Just wondering if you could give us an update on regulatory progress for China and what next steps are there?

Robert I. Blum, President and CEO

Jason, I'll take that one. In light of that, we're making very good progress, but we aren't in a position yet to be specific until such time as we and Ji Xing, our partner are aligned on setting those expectations. So I do hope that we'll be able to say something with the next earnings call.

Operator, Operator

Our next question will come from Jason Zemansky from BofA.

Cameron Bozdog, Analyst

This is Cameron Bozdog on for Jason. So you've discussed the potential of a novel drug and it's based on a risk algorithm. I mean, could you kind of elaborate a little bit on what this could look like? Have you received any feedback from regulators on this point? And then if you could maybe touch on your base case assumptions currently for number of echoes likely to be required in both titration and then in the maintenance setting as well?

Robert I. Blum, President and CEO

Sure. It's premature to speak to the second part of your question, the number of echoes is a function of conversations that we're still going to be having with FDA. But I think there's no scenario by which we expect a similar REMS. I think in light of the fact that the dosing strategy employed in SEQUOIA-HCM and continuing in FOREST-HCM is itself differentiated. And therefore, that ties to the risk mitigation strategy. It's, I think, going to be clear that there will be a different kind of REMS program. And with that, we expect to have conversations with FDA about what that could look like in a concrete way as will be informed by how we might approach risk mitigation in an NDA submission. And there are different ways to approach risk mitigation, as you know. Some of that can be handled by labeling. Some of that can be handled in an informational REMS. Some of that may require ETASU REMS. And the current cardiac myosin inhibitor is the subject of an ETASU REMS. And our objective is to understand how FDA thinks about risk in light of not just the EF excursions as seems to be the focus of Wall Street, but also as pertains to ADME properties, drug-drug interaction properties, pharmacokinetic properties that speak to half-life and shape of the curve with regard to pharmacodynamics, all these things factor into how one approaches risk mitigation. And I do think we're going to be in a position, as is our base case, to have a differentiated profile for risk mitigation. I think that's the best I can do today, but we do hope to have more to say down the road.

Operator, Operator

Our next question comes from Carter Gould from Barclays.

Carter L. Gould, Analyst

I'm going to ask a somewhat unfair question since the AHA and ACC HCM guideline was just released this afternoon. However, I believe you probably had an idea of what would be included. So, at a high level, is there anything surprising in there? And I might provoke Diane and the operator, but for Andrew, when considering the importance of guidelines moving forward, how significant is the differentiation between mavacamten and aficamten based on your previous case study work?

Robert I. Blum, President and CEO

Yes. So good on you for noting that those guidelines dropped just today. I will ask Fady and Andrew both to comment from their perspectives in light of your questions. And you did get a grin out of Diane, by the way.

Fady Malik, EVP of R&D

I received the guidelines just two hours before this call and actually didn't see them until midway through. So I'll do my best to address your question. From a brief review, it seems they refer to a class of myosin inhibitors. There wasn't anything particularly surprising; they seem to follow the same approach as the EMA and ESC guidelines, placing cardiac myosin inhibitors after first-line therapy with beta blockers for patients who do not respond to that initial treatment. This is why we are conducting the MAPLE study, to potentially demonstrate the benefits of starting with cardiac myosin inhibitors first. Hopefully, the data from this study will help shape future guidelines. There are certain points in the guidelines where they mix issues related to cardiac myosin inhibitors that are actually specific to certain compounds and not to the class as a whole. I won’t go into detail, but if you read the guidelines, you should be able to identify those points. Some of this information may need clarification in the future, and we will do our best to ensure that the relevant data gets into the hands of those who create the guidelines. We were not aware of the contents of these guidelines and do not participate in that process, but we can certainly ensure that the data is accessible to them, and I expect that will happen.

Andrew Callos, EVP and Chief Commercial Officer

The only thing maybe I was going to add to your question was around the guidelines. Certainly, that's credibility when talking to physicians around evidence, that certainly adds credibility to payers to cover, especially if it's a first-line therapy. Additional studies certainly give more strength to a guideline as well. And I think probably extremely important is, if a guideline, as an example, talks about, say, first-line therapy because of data like MAPLE, having that data and that evidence and being able to talk to physicians about it as compared to not having that evidence and not being able to talk to physicians about it, I think is a big difference. So I think the guideline helps maybe to summarize with credibility to various stakeholders and probably most importantly lets us as a pharmaceutical company talk to physicians and payers about the evidence relative to aficamten if we get approved.

Operator, Operator

Our next question comes from Yasmeen Rahimi from Piper Sandler.

Yasmeen Rahimi, Analyst

As we approach the Cardiology Heart Failure Congress on Monday, you've mentioned that the data improves the more you analyze it. Do you think that with Monday's data release or full disclosures, it will become even clearer that aficamten excels in efficacy, not just in its safety profile? I'd appreciate your insights on this, and I'll rejoin the queue afterward.

Robert I. Blum, President and CEO

So to be clear, we did not conduct a head-to-head comparison of aficamten with mavacamten and it would not be appropriate to imply that we did. With that said, we believe the profile of aficamten in SEQUOIA as it relates to efficacy, safety, convenience and all those things that factor into its next-in-class profile will be supported by the evidence as would be indicative of our belief that aficamten can become the cardiac myosin inhibitor of choice, ultimately, if approved. With that said, that's ultimately for you to determine once you see the data. The results will be available not just in presentations, but in publications and not just at the European Heart Failure meeting, but throughout other meetings later this year. And I do believe that these results are reaffirming of our expectations.

Operator, Operator

Our next question comes from Akash Tewari from Jefferies.

Unknown Analyst, Analyst

This is Amy on for Akash. Just one on CK-586. Do you think the drug will need LV ejection fraction monitoring? And what are you seeing in your healthy volunteer data that either supports or doesn't support this requirement?

Stuart Kupfer, SVP and Chief Medical Officer

I can take that question. We developed CK-586 as a potential way to administer treatment to HFpEF patients without the need for routine echo monitoring. However, we need to gather data to ultimately back this up, and it's too early to say for certain if we will succeed. The profile we observed in Phase I was encouraging in that regard. We will have more insight as we continue our exploration of this drug in Phase II.

Operator, Operator

Our next question will come from Serge Belanger from Needham.

Serge Belanger, Analyst

You've had 2 meetings with the FDA so far and another one coming up, I guess, later this quarter. What are your current thoughts regarding the potential for a priority review or in the AdCom?

Robert I. Blum, President and CEO

Yes. So neither of those are in our base case assumptions, we believe that as a next-in-class profile it would be more exceptional to assume priority review. It's certainly possible, but that's not something that we're banking on, so to speak. And as it relates to an AdCom, we don't expect one, but one can be surprised by those things. And for the fact that the data are, we believe, quite compelling. There's already a very effective cardiac myosin inhibitor on the marketplace that did not have an AdCom. I think it would be unusual to now have an AdCom for a next-in-class compound. But I guess it's theoretically possible, it's not our base case assumption.

Operator, Operator

Our next question comes from Ash Verma from UBS.

Ashwani Verma, Analyst

I have 2. So regarding just the presentation on Monday, like from your perspective, what do you think is the bar for the LV at less than 40% event from the SEQUOIA study? What level of LV less than 40% would give you the conviction that the FDA could actually indeed be discerning in viewing your safety profile as differentiated from Camzyos? And then second, on the oHCM market, just in the long run, do you think fundamentally, there is a lot of diagnosis expansion that you could drive? oHCM is sometimes compared to ATTR binders, and that has seen pretty significant diagnosis expansion? Just if you can frame what's the difference between the 2.

Robert I. Blum, President and CEO

So I might ask Fady to speak to the comments about EF below 40%, but recognizing our top line press release already speaks to some of those matters.

Fady Malik, EVP of R&D

Yes, I wanted to mention that we have not encountered any treatment discontinuations for ejection fraction below 40%. The protocol required action if such cases were observed. We will provide further details in the presentation, but I believe having a sample size of 0 or 1 is not significantly helpful. Understanding what does not happen is valuable and supports the safety profile. We have never experienced heart failure due to aficamten, and treatment interruptions have been nearly nonexistent. Overall, these factors are quite encouraging for potential future labeling. We did not fully grasp your second question, which we can address now.

Ashwani Verma, Analyst

Yes. Just quickly, I mean, in terms of like just the diagnosis expansion of oHCM, right, I mean, one could argue that, yes, it has a high unmet need, but the mortality and mobility burden is not as high as something like ATTR which has seen a significant diagnosis expansion. So do you believe that in the long run, you could potentially drive a lot of diagnosis expansion? I mean, this one has been doing a lot and other marketing campaigns are still not driving any kind of a meaningful inflection on Camzyos. So just trying to understand if this oHCM market is sort of where it is? Or could we see a material expansion in the long run?

Robert I. Blum, President and CEO

Yes. I don't think the disease burden here is defined by mortality incidents as much as symptom burden and other matters that read on functional life and quality of life. And it's very clear that patients who receive a cardiac myosin inhibitor are very adherent and compliant with their therapy. Look at the data for Camzyos. These are patients who are benefiting substantially from receiving a new therapy and want to stay on that therapy. And I do believe that that's ultimately going to be defining on what could be the opportunity for category expansion. Andrew, anything you want to add to that?

Andrew Callos, EVP and Chief Commercial Officer

Yes. I would say that's probably part of the remit of what we're doing in a QoR. If you think about some of the secondary endpoints like improvement in New York Heart Class Association, improvement in KCCq, reduction for the need of septal therapy and surgery, all those speak to improvement in health outcomes and improvement in cost savings. So I think you'll start to see some more publications and us talking to that and then merging that with large data sets to show the impact it can have on larger populations. So it may be not as obvious as something as ATTR, but it's certainly something I think you're going to see over time that the expertise that we have in the QoR around this area will certainly lead to what you're describing.

Operator, Operator

And our next question will come from Sean McCutcheon from Raymond James.

Sean McCutcheon, Analyst

Can you comment on the patients you will enroll in the Phase II study for CK-586 or maybe what subset do you think has the clearest pathophysiologic rationale and how you're thinking about the Phase II in terms of parsing the HFpEF subsets and maybe broad strokes on the size of the opportunity in those restrictive populations?

Fady Malik, EVP of R&D

Yes. Sure. I'll ask Stuart to answer that, but in sort of general terms, I'll just mention ahead of time that as Robert said earlier, the non-HCM patients that responded so well in the Phase II study kind of provide a human model of the type of HFpEF patients we want to study with CK-586, and maybe Stuart can expand on those characteristics generally.

Stuart Kupfer, SVP and Chief Medical Officer

Yes. Thanks, Fady. I think that's correct. We believe that a subgroup of patients with severe diastolic dysfunction may largely be composed of patients with hypercontractility, and some of these individuals develop ventricular wall thickening similar to those with non-obstructive HCM. The outcomes we observed in Phase II and the REDWOOD-HCM study inform the potential benefits and improvements in diastolic function for this subgroup with HFpEF. We will be evaluating patients who have a relatively high ejection fraction and some degree of ventricular wall thickening, who are symptomatic and experiencing functional and symptomatic heart failure related to their condition, to determine if these patients could benefit from treatment. This is generally the population we will be focusing on.

Robert I. Blum, President and CEO

Andrew, do you want to speak in general terms approximately around how we're thinking about the subsets of HFpEF from a prevalence standpoint?

Andrew Callos, EVP and Chief Commercial Officer

Yes. HFpEF, just all probably from our press releases, around half of the overall market. We're describing here is a subset of HFpEF in the upper range of ejection fraction. And I think once we start to learn more in Phase II, we'll probably hone in more of exactly the size of that subset and where the cutoff is.

Operator, Operator

And I am showing no further questions from our phone lines. I'd now like to turn the conference back to Robert Blum, President and CEO, for closing remarks.

Robert I. Blum, President and CEO

Thank you, operator, and thank you to the analysts for some excellent questions. We're excited to have shared this update with you, especially as it pertains to our expanded focus on the development program for aficamten. And at the same time, we believe that we're being good financial stewards as we think about capital diversification and capital deployment and efficiencies. And we're looking forward to updating you on continued progress including with our presentations next week, Monday, May 13 at the European Heart Failure meetings and afterwards. We thank you for your interest in Cytokinetics and we'll look forward to the next earnings call. Operator, with that, we can now conclude the call.

Operator, Operator

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.