Earnings Call Transcript - CYTK Q4 2023

Operator, Operator

Good afternoon and welcome to everyone to Cytokinetics Fourth Quarter 2023 Conference Call. I will now hand the call over to Diane Weiser, Senior Vice President of Corporate Communication and Investor Relations at Cytokinetics. Please proceed.

Diane Weiser, SVP of Corporate Communication and Investor Relations

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 focused to SEQUOIA-HCM and FOREST-HCM; Stuart Kupfer, SVP and Chief Medical Officer, will provide additional updates for aficamten relating to SEQUOIA-HCM and MAPLE-HCM, and will also discuss CK-586 and CK-136; Andrew Callos, EVP and Chief Commercial Officer, will discuss commercial readiness activities for aficamten; Robert Wong, VP and Chief Accounting Officer, will provide a financial overview of the past quarter; and finally, Robert Blum will provide discuss our 2024 financial guidance and 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 is contained in our SEC filings, including our current report regarding our fourth quarter 2023 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 Blum, President and CEO

Thank you, Diane. And thanks for joining us on the call today. The fourth quarter of 2023 represented a transformational inflection point for our company. As we turned the card on SEQUOIA-HCM, our Phase 3 clinical trial of aficamten for the potential treatment of patients with hypertrophic cardiomyopathy or HCM. The results exceeded our already high expectations, and we began 2024 firing on all cylinders with renewed commitments to preparing for regulatory interactions and submissions with urgency, executing on the broad clinical development program following behind SEQUOIA-HCM, as well as activating the next phase of commercial readiness activities. On today's call, Fady will discuss our plans for presentation and publication of primary and other results of SEQUOIA-HCM, which will further elaborate on the efficacy and safety of our next in class cardiac myosin inhibitor. And as well, we'll discuss how we're moving swiftly towards regulatory submissions across the globe. As important as SEQUOIA-HCM is to our path to commercialization, there's much more in our pipeline that we believe will meaningfully unlock shareholder value as the company continues to mature. Stuart will provide an update on the progress of MAPLE-HCM and ACACIA-HCM, the additional Phase 3 clinical trials of aficamten, which will provide an on-ramp to potentially expanding the utility of cardiac myosin inhibitors as a first line treatment for obstructive HCM, as well as potentially providing a new treatment option for the growing number of patients with non-obstructive HCM. As you will hear, there's been increased enthusiasm and activity surrounding these trials on the heels of the positive results from SEQUOIA-HCM. However, much still remains ahead of us to bring aficamten to patients, but I'm confident in our ability to execute on our ambitious strategies. As you'll hear in more detail, we ended 2023 with a strong balance sheet thanks to reduced spending during the year. In the last quarter and earlier this year, we also added to our cash balance with an infusion of capital from our aftermarket or ATM equity vehicle. We're pleased to be reporting our financial guidance today with approximately two years of cash runway when accounting for both our cash on hand and cash available to us while projecting an increase in our expected operating expenses in 2024. Recently, we announced the retirement of Ching Jaw from his position as CFO in order to attend to his personal health. Ching's departure is unrelated to our business prospects and on mutually good terms with the company. On behalf of our senior leadership team, we support his decision for his well-being and we express our gratitude for his many contributions to our company. Ching built a strong team that many of you may know, including Robert Wong, VP and Chief Accounting Officer, as well as Matt Yang, VP of Corporate Finance and FP&A. Together with the teams they have assembled, we're confident that Ching's departure will have minimal impact on day-to-day financial operations. Libby Schnieders, our SVP of Business Development, who has served our company for well over 20 years, continues to lead business development, so we do not foresee any impact on that front. Furthermore, in anticipation of Ching having to attend to his health, in the fourth quarter of 2023, we brought on a seasoned consultant who previously served as CFO of a public biopharma company and who has extensive experience in financial planning and structured finance transactions. They will continue to work with me through this transition as we've already initiated a national search for Ching’s replacement, so we expect we’ll bring in international commercial and capital allocation experience compatible with maturing operations. Cytokinetics is looking ahead to a bright future in 2024 and beyond. As we turn the page towards potential commercialization of the first medicine arising from our pioneering and leading muscle biology research, we have more to come as we continue to prosecute our R&D programs. We're fortunate to be where we are today. But it is not by coincidence, it's a result of meticulous planning, risk mitigation, strategic foresight, perseverance and dedication. We're building a specialty cardiology company, leading with aficamten as the foundation, and we have the pipeline, the passion, and the people to make that vision happen, as we believe we’ll further reward shareholders. With that, I'll turn the call over to Fady, please.

Fady Malik, EVP of R&D

Thanks, Robert. During the quarter, we shared top line results from SEQUOIA-HCM, which as Robert said, exceeded our expectations. It was a truly extraordinary milestone reflective of an incredible commitment from so many, including our investigators, study staff, patients and of course, our teams at Cytokinetics. The results of SEQUOIA-HCM showed that treatment with aficamten significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake or peak VO2, measured by cardiopulmonary exercise testing, by a least square mean difference of 1.74 milliliters per kilogram per minute with a p-value of 0.000002. The treatment effect with aficamten was consistent across all pre-specified subgroups, reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy. Statistically significant and clinically meaningful improvements with a p-value of less than 0.0001 were observed across all 10 pre-specified secondary endpoints, including the Kansas City Cardiomyopathy Questionnaire clinical summary score at weeks 12 and 24, the proportion of patients with a greater than or equal to one class improvement in New York Heart Association functional class at weeks 12 and 24, the change in provoked left ventricular outflow track gradient and proportion of patients whose gradient fell below 30 millimeters of mercury at weeks 12 and 24, as well as exercise workload and guideline eligibility for septal reduction therapy. These positive results reflect rapid and sustained improvements in symptoms, functional capacity and heart failure status. Aficamten was well tolerated with an adverse event profile comparable to placebo. Treatment emergent serious adverse events occurred in eight patients or 5.6% on aficamten and 13 patients or 9.3% on placebo. Core echocardiographic left ventricular ejection fraction or LVEF was observed to be less than 50% in five patients or 3.5% on aficamten compared to one patient or 0.7% on placebo. Importantly, there were no instances of worsening heart failure or treatment interruptions due to low LVEF. While these top line results provide a relatively comprehensive look at the overall effect of treatment with aficamten, we have an extensive plan to share the primary results and additional analyses in more detail in a series of published manuscripts and presentations. We hope the first of these to occur at Heart Failure 2024, the annual meeting of the Heart Failure Association of the European Society of Cardiology, taking place in May in Lisbon. Along with the primary results from SEQUOIA-HCM, we plan to present and publish key data that may lend support to the differentiated profile of aficamten. One important analysis is to examine the clinical effectiveness of aficamten in patients across several endpoints in aggregate, looking at the breadth of improvements patients experienced in SEQUOIA-HCM. In another analysis, we plan to elaborate on the dosing and safety experience from SEQUOIA-HCM, which we believe informs the potential safety and monitoring needed in the clinical environment. In addition to these important analyses from SEQUOIA-HCM, we have a robust scientific communications plan over the coming year that includes manuscripts and congress presentations that will further elaborate on the effect of aficamten and other metrics of exercise capacity, cardiac remodeling from the CMR substudy, echocardiographic measures of systolic and diastolic function and cardiac structure, symptoms, quality of life and cardiac biomarkers. We look forward to sharing these analyses with you in 2024, starting in Q2. I'd like to acknowledge the tremendous efforts by our steering committee and internal teams to support and execute on this ambitious plan of publications and presentations. Shifting over to FOREST-HCM, the Open Label Extension Clinical Trial of aficamten, we can report that over 90% of the patients eligible from REDWOOD-HCM and SEQUOIA-HCM have enrolled in FOREST-HCM, representing nearly 300 patients that will contribute to our understanding of the effects of long-term treatment with aficamten. Please note that this does not include patients from the China cohort of SEQUOIA-HCM. These patients will eventually make their way into a China-specific open-label extension clinical trial. In April, at the American College of Cardiology annual Scientific Sessions, we will present the efficacy and safety of aficamten in the first cohort of patients with symptomatic obstructive HCM that have completed one year of follow-up in FOREST-HCM. Last month, we shared data at CMR 2024 from the cardiac magnetic resonance, or CMR substudy of FOREST-HCM. The results showed that treatment with aficamten for 48 weeks resulted in cardiac structural remodeling, improvements in cardiac function and stabilization of myocardial fibrosis, demonstrating that aficamten has potential disease-modifying effects and the ability to improve the architecture of the heart in patients with obstructive HCM. While this analysis is small, only 16 patients were eligible at the time of this data cut, we plan to expand on these data in the future as more patients reach the one-year mark and beyond. Regarding regulatory engagements, during the month of February, we held two meetings with the FDA ahead of our expected submission of an NDA in the third quarter of this year. A first meeting to review the results of SEQUOIA-HCM and a second pre-NDA meeting, providing an opportunity to align on the content and format of the NDA. We're pleased with the FDA's feedback, supporting the sufficiency of our proposed NDA submission package and the receptivity to a rolling submission plan. We believe that the positive readout for SEQUOIA-HCM, along with the favorable pharmacologic and DDI profile of aficamten continue to support the opportunity to achieve differentiated labeling and risk mitigation. We look forward to providing future updates regarding our interactions with the FDA this year. As to regulatory planning and interactions in Europe, we're similarly ready for submission of our marketing application in the fourth quarter of this year, and plan to meet with EMA in Q2 to inform preparations. Similarly, we're coordinating with our partners, JI XING in China to collaboratively support JI XING's plan to submit an NDA. Overall, our proactive planning in 2023 has enabled us to capitalize on the positive results from SEQUOIA-HCM and to proceed with urgency towards global regulatory submissions, as well as to consider expedited pathways consistent with our aggressive planning scenarios. Alongside all of this, from a medical affairs perspective, during the quarter, our therapeutic medical science liaisons continued profiling of HCM treatment programs, while our managed healthcare medical science liaisons began development of our payor clinical value proposition. We also continued our support of medical education activities at medical conferences. As Robert said, the strength of the specialty cardiology company we are building is anchored in the power of our research engine and development pipeline with aficamten, if approved, leading the way. The top line results from SEQUOIA-HCM have been well received by the HCM community of physicians and patient advocates who foresee that they represent a meaningful advance in care. We're grateful for their support and we look forward to continuing to engage with them as we work to establish aficamten as a potential next-in-class treatment option for patients with HCM. I'll hand it over to Stuart to elaborate more on additional clinical trials progress we're making with aficamten and provide an update on our earlier-stage clinical development pipeline.

Stuart Kupfer, SVP and Chief Medical Officer

Thank you, Fady. In addition to sharing positive results from SEQUOIA-HCM, during the fourth quarter, we continued enrollment and are building momentum with our two ongoing Phase 3 clinical trials of aficamten, MAPLE-HCM and ACACIA-HCM. We're pleased to see that screening and enrollment are accelerating and have been catalyzed by the announcement of results from SEQUOIA-HCM. In MAPLE-HCM, which is evaluating the potential superiority of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, nearly all US sites are now activated and we've now activated sites in the UK, France, Italy, the Netherlands, and Israel. We expect to complete enrollment in MAPLE-HCM in the third quarter of this year, which would enable results from MAPLE-HCM to be available in 2025 concurrent with our hopes for a commercial launch of aficamten. We believe that if MAPLE-HCM were to read out positively, it would provide support for the positioning of aficamten as a first-line therapy for patients with obstructive HCM. Developing aficamten to capitalize on its next-in-class potential and MAPLE-HCM factors importantly into that strategy. ACACIA-HCM, the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic non-obstructive HCM, is currently focused on study startup. We have the necessary IRB approvals in the US and the EU, and we're progressing our clinical trial application through the new harmonized procedure. We plan to hold investigator meetings for North America, South America, and Europe in the second quarter, and look forward to continuing enrollment in this trial through 2024 with the objective of completing enrollment in 2025. ACACIA-HCM represents an important opportunity for aficamten and tests a key therapeutic hypothesis for expanding the evidence to support cardiac myosin inhibition in a growing population of patients underserved by current treatment options. We believe that the results from SEQUOIA-HCM and REDWOOD-HCM faithfully add confidence to what we can expect from ACACIA-HCM, and our optimism is shared by clinical investigators. Both clinical trials have the potential to expand the utilization of aficamten and the HCM patient population, impacting treatment guidelines. At the same time, we're pleased with the progress of our clinical trials of aficamten. In the past quarter, we also advanced our earlier-stage development pipeline, notably with CK-586, our cardiac myosin inhibitor developing for the potential treatment of a subgroup of patients with heart failure with preserved ejection fraction or HFpEF. Having completed analyses of a single ascending dose data, we proceeded to the multiple ascending dose portion of the study. We expect to complete the Phase 1 study in this quarter and subsequently share data in the second quarter of this year with plans to begin a Phase 2 clinical trial in the second half of the year. We believe that the positive Phase 2 data we generated for aficamten in patients with non-obstructive HCM support the development of CK-586 in a population of patients with HFpEF. This condition has many parallels to non-obstructive HCM. Currently in the United States, there are about 3.6 million people with HFpEF, which is expected to increase to 4.8 million by 2033. Approximately 30% to 40% of these patients present with characteristics that may make their condition amenable to cardiac myosin inhibition. Even with SGLT-2 inhibitors, which are the first evidence-based therapies demonstrating some benefit in those with HEpEF, there is still a high residual risk of cardiovascular events and a clear need for additional effective therapies. Additionally, during the past quarter for CK-136, our cardiac troponin activator, we continued analyses of the single and multiple ascending dose cohorts in the Phase 1 study with healthy participants and expect to complete the study in the second quarter of this year. In 2024, we plan to share more updates from our early stage pipeline and our research. As more programs mature from our labs into the clinic, we will report on how in recent years we've extended our focus and muscle biology beyond muscle contractility to also include other programs entering development, representing potential innovations in muscle metabolism and energetics. While aficamten represents the most important near-term value driver for our company, our early stage pipeline and emerging programs from ongoing research demonstrate productivity against our Vision 2025. The long-term goal is to cement our leadership in muscle biology adjacent to exciting developments and treatments for cardiometabolic syndromes. We'll look forward to sharing more progress soon. With that, I'll turn the call over to Andrew.

Andrew Callos, EVP and Chief Commercial Officer

Thanks, Stuart. During the quarter, ahead of our announcing the results for SEQUOIA-HCM, we continued commercial readiness activities for aficamten. Throughout 2023, our focus was on learning the first phase in our go-to-market approach. We commissioned multiple market research studies seeking insights from nearly 850 healthcare professionals and more than 160 patients with obstructive HCM, which revealed that the HCM patient journey can be complex and challenging. Furthermore, HCM can also negatively impact a patient's overall mental health, social engagement, and other aspects of everyday life. We also tested a range of product profiles in market research prior to our receipt of the results from SEQUOIA-HCM. The tested attributes most closely resembling the actual SEQUOIA-HCM results revealed that healthcare professionals would perceive the results from SEQUOIA-HCM favorably and would drive the use of aficamten if approved across a broad range of obstructive HCM patients. These learnings are informing the strategic decisions we're making around the target product profile, positioning potential customer profiles in our patient services hub. Access, in particular, is a key focus for us aligned with our company values of keeping patients at the forefront of all we do. We're designing a comprehensive patient support program to facilitate and support patients in transitioning to treatment with aficamten, inclusive of patient education resources, reimbursement support, and affordability programs for eligible patients. In the fourth quarter of 2023, we held initial conversations with specialty pharmacies and patient service hub providers to support our build of a differentiated patient services hub. Now that we have results from SEQUOIA-HCM this year, we are advancing to the second and third stage phases of our go-to-market strategy, design, and build. This year, we plan to build our patient support services access strategy, inclusive of distribution model, contracting approach, and pricing. Our seasoned account manager team is fully staffed and interacted with every major payer in 2023 to introduce Cytokinetics. This field-based payer account team will continue to further engage in 2024 to share the results from SEQUOIA-HCM and ensure payers understand the clinical meaningfulness of the results. In 2024, we also plan to finalize our product positioning and launch our market development and education campaign while we develop our branded marketing campaign in support of a potential 2025 promotional launch. As we previously shared, we began building our commercial capabilities in the United States prior to the potential FDA approval and launch of omecamtiv mecarbil. After receiving the CRL from the FDA, we maintained the infrastructure that had been built and further refined the team and activities to prepare for what now will be our first commercial launch with aficamten. Today, we have on board the majority of US-based headquarter personnel that we expect to need, including marketing, field sales leadership, and individuals leading insight generation, market analysis, commercial strategy, systems, and operations. We expect to expand the team in 2025 with HCP customer-facing positions gated appropriately alongside the regulatory process for aficamten. In Europe, having hired key leadership positions last year, including our Head of Europe and Head of Market Access, we plan to only modestly expand our EU staff in 2024 while maintaining a disciplined eye on spending and gating costs of regulatory submissions and feedback from health technology assessments or HTAs. It is encouraging to see favorable benefit assessment from HTAs in both Germany and France related to cardiac myosin inhibitors as a new treatment option for patients with obstructive HCM, and we believe this bodes well for the future reimbursement of aficamten if approved across major European markets. Overall, I'm very pleased with the foundational commercial readiness work that we've completed ahead of sharing the results of SEQUOIA-HCM last year, which sets us up to nimbly advance into the next phase of our planning in 2024 and can enable us to capitalize on what we believe will be differentiated positioning for aficamten in the treatment of patients with obstructive HCM. And with that, I'll turn the call over to Robert Wong.

Robert Wong, VP and Chief Accounting Officer

Thanks, Andrew. We ended the fourth quarter with $655.4 million in cash and investments, which included $162.9 million that we raised through the after-market equity vehicle in the quarter. Following the quarter close, we raised approximately $83 million net through yesterday with our ATM equity vehicle, which is not reflected in our year-end balance. Our fourth quarter 2023 R&D expenses increased to $85 million from $75 million in the fourth quarter of 2022, primarily due to spending on our cardiac myosin inhibitor programs. Our fourth quarter 2023 G&A expenses were $44.1 million, down from $54 million in Q4 2022 due primarily to lower outside spending on commercial activities, offset by higher personnel-related costs including stock-based compensation. Overall, our net cash burn in 2023 was $414 million relative to what was our initial 2023 guidance of $420 million to $450 million. We believe we proved to be good stewards of shareholder capital by reducing spending ahead of the results of SEQUOIA-HCM at the end of the year, which puts us in a stronger financial position to begin 2024. Now, I'll hand it over to Robert Blum to review our financial outlook, 2024 guidance, and corporate development strategies.

Robert Blum, President and CEO

Thank you, Robert. Today, we announced our financial guidance for 2024. The company anticipates revenue will be in the range of $3 million to $5 million, operating expenses will be in the range of $420 million to $450 million, and net cash utilization will be approximately $390 million to $420 million. In terms of capital allocation, our priorities are focused on benefiting patients and enriching shareholder value anchored by a prudent spending plan that balances advancing our commercial strategy with investment in our pipeline. Our foremost priority is advancing regulatory submissions for aficamten in obstructive HCM and ensuring commercial preparedness in key markets like the US and Europe. Secondly, in continuing MAPLE-HCM and ACACIA-HCM, we plan to maximize the therapeutic potential of aficamten. And finally, we remain focused on growing our pipeline inclusive of CK-586 and bolstering our R&D platforms to sustain future innovation. Inclusive of the approximately $83 million net raised in recent weeks through our ATM as well as cash available to us under our loan agreement with Royalty Pharma, our current cash balance of $655 million at the end of last year represents approximately two years of forward cash runway based on our financial guidance and projected 2024 operating expenses and net cash utilization. With positive results from SEQUOIA-HCM in hand, we've been looking at the arc of capital requirements leading up to potential approvals and the global commercial launch of aficamten, as well as sustaining and growing R&D through profitability. As such, we continue to focus on a multi-pronged approach to accessing capital that enables us to pull several different levers over time. As has been our history, we plan to monetize our R&D progress and preserve shareholder value via partnering, as well as structural finance engineering and other non-dilutive approaches. Our priority remains focused on business development, and we've been focused on a Japan deal for aficamten. We're in active discussions with multiple parties, and I'm pleased with how that deal campaign is looking. Moreover, we're considering partnering CK-586 for the potential treatment of HFpEF, while also preserving key rights for Cytokinetics in both co-development and co-commercialization. We believe that our longstanding leadership in the area of cardiac myosin modulation for the treatment of severe cardiovascular diseases has enabled us to look at partnering in an advantaged way that benefits shareholders while also preserving important shareholder value in major markets for aficamten. Additionally, we may consider restructuring our debt and other novel ways to build on the momentum from SEQUOIA-HCM in structured finance transactions that we believe would augment shareholder value and, importantly, would not subtract from it. I'll remind you that through our transaction with Royalty Pharma, we remain eligible for two additional loan tranches under our development funding agreement. The first tranche of $75 million became available upon our sharing positive results from SEQUOIA-HCM, and we remain eligible to draw down for one year following our receipt of the results, which occurred in late December. The second tranche of $100 million will become available to us, should we choose to draw on it subject to the satisfaction of certain conditions, most notably of which is the acceptance of an NDA submission for aficamten in the United States. As we are now a company valued between $8 billion and $10 billion, we have an ambitious yet practical and realistic plan to increase shareholder value over the next three to five years, to that which would be upwards of $15 billion to $20 billion. How do we get there? By unlocking the value in our pipeline and maximizing our opportunities. It starts with aficamten in North America and Europe based on the results from SEQUOIA-HCM. From there, we hope to increase value as MAPLE-HCM and ACACIA-HCM read out results that now have higher probability of technical success. Next, we expect CK-586 to advance through proof-of-concept and HFpEF, with additional upside coming from our earlier stage pipeline. I also want to take a moment to address recent M&A speculation relating to Cytokinetics. Since sharing the positive results from SEQUOIA-HCM, Cytokinetics has been rumored to be an acquisition target. While we will not and cannot comment on specific speculations, let me please be clear about one thing, we did not initiate nor do we have a sale process ongoing. However, as responsible fiduciaries to our shareholders, I can assure you that we thoroughly evaluate options that are presented. And as you heard me say a moment ago, we continue to advance business development discussions. We're optimistic about how those discussions are proceeding, and we're committed to building a sustainable specialty cardiology company that starts with executing against our goal of bringing new medicines to patients. We take great care in fulfilling our duty to shareholders by ensuring that we're doing the right thing to deliver maximum value and controlling that which we can control. We believe that can best be achieved by advancing our innovative science, ensuring operational efficiencies, and thoughtfully and prudently managing and deploying capital to maximize shareholder value. We're beginning 2024 in an advantaged position. We have turned the page to the next chapter of the Cytokinetics story, and the work we're undertaking will set the stage for our first potential regulatory approvals we hope within the next 18 months. In the second half of this year, we expect to submit regulatory filings in both the United States and Europe for aficamten. You heard from Fady, in Q3, an NDA with the FDA, and in Q4 an MAA with the EMA. We expect to be more precise as timing goes to our Q1 earnings call and especially as it relates to positioning and other aspects contained within the content of those submissions. We have ambitious goals beyond obstructive HCM, as well as beyond aficamten, including expanding our development pipeline with new compounds arising from our research extending beyond the contractility of muscle to the energetics, growth, and metabolism of muscle. Each of our programs in muscle biology has been designed to potentially address severely ill and underserved populations in need of new therapies. Our vision of building a specialty cardiology company is now being realized and we're well positioned for success. With that, I now would like to share our expected 2024 milestones. For aficamten, we expect to present primary results from SEQUOIA-HCM at a medical conference in Q2 2024. 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. We expect to complete enrollment of ACACIA-HCM in 2025 but continue its enrollment in 2024. And we expect to advance our go-to-market strategies for aficamten. For omecamtiv mecarbil, we expect the CHMP to issue an opinion regarding the MAA in Q2 2024. For CK-586, we expect to share data from the Phase 1 study in Q2 2024. Finally, for CK-136, we expect to complete the phase one study in the second quarter of this year. Operator, with that we can now open up the call to questions.

Operator, Operator

Our first question comes from Mayank Mamtani with B. Riley Securities.

Mayank Mamtani, Analyst

So just quickly on the pre-NDA meeting that occurred, I was just curious how much of the FOREST-HCM data would be part of that submission? I believe by the ESC heart failure congress, you'd probably have about 150 patients to go through the titration phase. Just curious how much of that is going to be important as part of the pre-NDA meeting and eventually make it into the NDA submission?

Robert Blum, President and CEO

So I'll pass that question over to Fady.

Fady Malik, EVP of R&D

So I can't give you the exact number of patients that will be available. But we also, besides the number of patients who have extended follow-up in FOREST at the time of the NDA submission, we'll also have the opportunity to submit an update at the day 120 time point. There's a day 120 safety update, where we can expand the dataset. So we fully expect the number of patients with up to a year of follow-up to be perfectly adequate for their review.

Mayank Mamtani, Analyst

I have a quick question about the ACACIA-HCM. I'm glad you narrowed the timelines. Based on what we know about dosing safety and cardiac remodeling data, how confident are you in the findings you can report? Also, is it possible that a threshold could be established from the HCM study early next year?

Robert Blum, President and CEO

Based on the results we observed in Phase 2, as well as the predictability of dosing and the safety profile demonstrated in aficamten and SEQUOIA, we are very confident about the potential outcomes in ACACIA. Overall, we believe all indicators suggest a positive result for that trial, and we will continue to conduct it in a manner that allows us to reach the best conclusion.

Operator, Operator

Our next question comes from the line of Salim Syed with Mizuho.

Salim Syed, Analyst

Robert, I just wanted to focus on, maybe this is for Fady as well, but on the rolling submission. What exactly is going in, because I believe it's the first time you guys are using that terminology, if I'm not mistaken, rolling submission for aficamten. So what exactly is going in first and then what is the piece that you plan to submit later? And then curious also if the rolling submission if that in any way encompasses the potential to submit the MAPLE-HCM data, because you're going to get that before an approval decision?

Robert Blum, President and CEO

So I'll answer that question. So you're right, we are using that terminology for the first time and that's coming out of our recent meetings with the FDA. We're very encouraged by what appears to be a leaning forward and willingness to consider these data sooner. We're looking at how we might accelerate submission. In that regard, they were amenable to our recommendation that we do it on a rolling basis. We're going to be submitting most of the modules earlier, and what's going to be the long pole in the tent, so to speak, in terms of what will be coming in later, will be some of the CMC data that we're still in the process of finalizing in light of the fact that there are certain time points we need to collect to finalize those submissions. But all this speaks to, we think, a forward-focused connection with a submission that could be started sooner. Keep in mind that the actual filing doesn't change. That ultimately depends on the final modules as they are then submitted, but it certainly allows the review to begin. As it relates to MAPLE, I know we don't expect that those data will be contained in this submission. MAPLE won't read out till next year.

Operator, Operator

Our next question comes from the line of Ashwani Verma with UBS.

Unidentified Analyst, Analyst

Just a general quick question about cardiology. At a high level, is it common for companies to engage in portfolio level contracting? Would this practice potentially allow companies with a wide range of offerings to benefit from economies of scale over time?

Robert Blum, President and CEO

Your question is whether we might face a disadvantage by launching with a single product compared to payers who might be working with multiple products. Is that correct?

Unidentified Analyst, Analyst

Yes.

Robert Blum, President and CEO

From a payer point of view, no, I don't believe we're at a disadvantage. Payers aren't managing this category. It's a rare disease, there are over 120 payors in the US, each payer only has a very limited number of patients. It's not a significant budget impact. It's a high unmet need. There's one product in the market, a second product. These usually aren't payer-managed categories from a cardiology point of view. The focus of a subset of cardiologists is what we will focus on those that diagnose and treat HCM as a subset of overall cardiology and are highly motivated to treat the disease. So they are going to be more focused on the products and patients relative to the disease. By all means, I think we'll compete fine and it's not going to be a disadvantage.

Operator, Operator

Our next question comes from the line of Maya Iskandarani with Barclays.

Carter Gould, Analyst

This is Carter. Maybe for Robert and Fady, the commentary on the REMS sort of referenced SEQUOIA, PK and the DDI profile all of which we've known for a while, I guess now. But can you comment if the FDA interactions in any way shifted or reaffirmed your belief in that differentiated label for REMS?

Robert Blum, President and CEO

Yes, I'll just comment very briefly. It’s premature because those conversations will continue, but reaffirming our view that between positioning, labeling, lesser REMS, and other things that read on safety and risk mitigation, that we’ll be in a position to have a very constructive, fruitful conversation with the FDA.

Operator, Operator

Our next question comes from the line of Paul Choi with Goldman Sachs.

Paul Choi, Analyst

My question is regarding your recent meeting with the FDA. Can you confirm if there were any preclinical or clinical testing requirements specified by the agency? Additionally, how much of this needs to be coordinated with EMA requirements ahead of a potential MAA filing, in addition to the NDA?

Robert Blum, President and CEO

We don't believe there are any other studies that are required. Hopefully that addresses your question.

Operator, Operator

Our next question comes from the line of Tess Romero with JP Morgan.

Adi Jayanthi, Analyst

I'm Adi on for Tes. So we just wanted to ask, is there any data from SEQUOIA that you are yet to see at this point?

Robert Blum, President and CEO

I'll turn that over to Fady.

Fady Malik, EVP of R&D

We've seen the full set of data. I wouldn't say every analysis you could imagine has been completed that may go on for years, to be honest, as we think of new analyses. But all the pre-specified analyses, for example, the clinical study report, have been completed and reviewed in detail.

Robert Blum, President and CEO

You'll also see this laid out in full glory in the second quarter. We expect multiple presentations, multiple publications.

Operator, Operator

Our next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Yasmeen Rahimi, Analyst

I guess, it's been now two months since the top line data. Have you had a chance to complete all your REMS preparation by hiring the consultants, reviewing the data on the integrated basis, coming up with a package and kind of laying out sort of the proposal? Like could you maybe give us a color on which of these activities have been completed, what is left to do, how much of the proposal, I guess, is in its finishing process? And thank you again for allowing me to ask my question.

Robert Blum, President and CEO

I'll take that one. And we are in the process of doing just what you are asking. I don't think that's the kind of thing that we're going to choose to elaborate on publicly, that's obviously something that informs competitive positioning. I do believe, to elaborate on Carter's question, that we're going to be potentially able to consider how we may be differentiated and advantaged in ways that could enable aficamten to be accessed by a greater number of physicians for a greater number of patients. As it relates to how that REMS may be positioned, situated, and what would be the elements of it, that's something that I think will be the subject of negotiation during the review period of an NDA after it's on file. So that's not something I expect we’ll be providing play-by-play visibility to until such time as we believe that there's certainty around what that looks like.

Operator, Operator

Our next question comes from the line of Jason Butler with JMP Securities.

Unidentified Analyst, Analyst

This is Jose for Jason. You mentioned that the data from FOREST-HCM demonstrate favorable structural remodeling. Could you speak to the potential long-term functional benefits of structural remodeling in HCM patients? And as a quick follow-up on aficamten, do your discussions with payors give any insights into the potential risk pricing versus the standard of care?

Robert Blum, President and CEO

So I'll ask Fady or Stuart to address the first question.

Fady Malik, EVP of R&D

This is really a really key question that we are anxious to investigate, certainly in the long term, because what we hypothesized is that cardiac myosin inhibition will result in a long-term very favorable remodeling and hopefully normalization of cardiac structure and function. We anticipate that will confer lifelong benefits for patients in terms of symptomatic and functional improvement, and we could also hypothesize reduced risk of cardiovascular events.

Stuart Kupfer, SVP and Chief Medical Officer

I want to emphasize that the data we shared in January is just an initial glimpse of the CMR cohort, which is expected to be the largest group of patients undergoing serial CMRs annually or every other year. Over time, as we gather more data, we will gain valuable insights into how the cardiac structure evolves.

Robert Blum, President and CEO

From a pricing point of view, we will be sharing SEQUOIA-HCM results with payors once the SEQUOIA-HCM results are published. There is one product on the market today, obviously, that has a list price. We'll be in the range of that list price, whether we're at, slightly above, slightly below, we haven't finalized where we'll be in pricing, but we'll finalize that as we get closer to launch next year. Those are not the kinds of things that one talks about at this point in time.

Operator, Operator

Our next question comes from the line of Joe Pantginis with H.C. Wainwright.

Joe Pantginis, Analyst

So I think my question is more suited for Andrew. I know you guys, from an internal standpoint, don't want to talk about the competitive profile or what you're thinking, but curious from your marketing research and talking to physicians and polling, et cetera. The profile data from SEQUOIA, has it led to any data that you can discuss regarding physicians' willingness to switch from Camzyos early on or needing more real world data in order to get educated about the drug, aficamten?

Andrew Callos, EVP and Chief Commercial Officer

We haven't focused on that. We're completely focused on making sure that patients who are on beta-blockers, calcium channel blockers, not on standard of care, not on disease modifying therapy, are activated towards the CMI, to educate those physicians on ultimately the label and REMS program associated with aficamten soon to be approved. We're going to focus on activating and getting patients on therapy. We're not going to focus on patients that were already on existing therapy, that's really up to a physician patient dialog if they choose to go that route.

Robert Blum, President and CEO

Underscore for a next-in-class opportunity, like we believe aficamten represents, it's incumbent upon us to think about how might this lead to an expansion of the category for the benefit of more patients at the end of the day, and that's where our focus is.

Andrew Callos, EVP and Chief Commercial Officer

And we do think that there are well over 100,000 patients who will be eligible. Our best guess is that the vast majority of those will still be available for CMI treatment when we come to market.

Operator, Operator

Our next question comes from the line of Jeffrey Hung with Morgan Stanley.

Unidentified Analyst, Analyst

This is Catherine on for Jeff. We just had a quick one, I'm just curious from your conversations or interactions with providers. Have they expressed any enthusiasm about the potential for a less restrictive REMS program or have they indicated whether they feel the data might be supportive of that?

Robert Blum, President and CEO

Well, we've certainly spoken to providers, and they're optimistic given the safety profile that we've shared with them in the SEQUOIA data. But they really, obviously, don't contribute to the FDA's evaluation of that question. We'll be proposing something based on the findings that we have and the accumulated data that we have. So I would just stay tuned.

Operator, Operator

Our next question comes from a line of Roanna Ruiz with Leerink Partners.

Roanna Ruiz, Analyst

So I was curious if you could discuss the European market opportunity for aficamten a little bit and if there are any similarities or differences that we should think about versus the US, and possible timeline for ramping up more of a commercial presence in Europe?

Robert Blum, President and CEO

From a European point of view, you heard the filing dates, the prevalence in terms of the number of patients is slightly higher just because the overall population is slightly higher. The price point is lower than the US, probably in the range of 15% to 25%, depending on the country. From an opportunity point of view, once approval is achieved, we will launch in Germany. That allows for launch to occur with that approval. Other markets need to submit for reimbursement and pricing negotiation. So in general, Europe will probably be about a year behind in launch in terms of market opportunity outside of Germany.

Operator, Operator

Our next question comes from the line of Srikripa Devarakonda with Truist Securities.

Billal Jahangiri, Analyst

This is Bilal on for Kripa. Is there anything in your data analysis to help predict who would be more susceptible to LVEF drops in patients treated with aficamten, and would that be incorporated into your REMS program? And are you seeing stabilization of LVEF over time?

Robert Blum, President and CEO

Well, the answer to the second part of your question is yes. And we've looked at those data and presented those data; you'll see some of that in FOREST, where you'll see EF over time for up to a year looks very stable. I think the question as to susceptibility factors, I think you can kind of predict, obviously, who might have susceptibility. Those are patients that have after you finish titration, their EFs are 50%, 55%. They're maybe at more risk because they're closer to the cut-off; it's kind of obvious. I think when you look at any sort of monitoring strategy employed in medicine, you generally look at patients that are closer to certain thresholds, and you look at them more carefully than other patients who are more distant from it. So we'll certainly incorporate that into our thinking.

Operator, Operator

Our next question comes from the line of Jason Zemansky with Bank of America.

Unidentified Analyst, Analyst

This is Cameron on for Jason. Congratulations on the quarter and thank you for taking our question. How significant is the use in the community setting for your commercial outlook, particularly regarding the front-line opportunity? What do you think is needed to help community prescribers feel more at ease with administering afi, especially considering it may have a REMS? Additionally, how long do you anticipate this transition will take?

Robert Blum, President and CEO

When you're describing community, I'm assuming you still mean cardiology, community cardiology.

Unidentified Analyst, Analyst

Yes, exactly.

Robert Blum, President and CEO

There's a little over 1,000 prescribers now of CMI. When you look at claims data, there's probably around 10,000 cardiologists who drive diagnosis; about 80% of diagnoses come from a smaller subset of general cardiology. Typically, specialty product launches always go from a core outward, that outward will occur over time. I do think the REMS probably slows it down a bit as education continues to occur, as patients start to show up in general cardiology already on a CMI, that'll accelerate, especially in the maintenance phase. It's hard to say exactly what that point will be, but it'll certainly occur over time given the number of patients that need to be treated.

Operator, Operator

Our next question comes from the line of Serge Belanger with Needham.

Charles Duncan, Analyst

ACC seems a little shortsighted on that last point. Wanted to ask you a couple of quick questions that you may not be able to answer. And one is kind of simple, and that is, do you anticipate an adcom to be called? And the second is harder to answer, and that is, what compels you more pharmacoeconomic modeling supportive of, say, premium pricing or an anchor to a standard of care? I know you're not really talking about pricing, but just your perspective.

Robert Blum, President and CEO

So as it relates to an adcom, we can't know that. What we do know is that there was not an adcom for mavacamten; that doesn't necessarily mean we wouldn't have an adcom. We'll be prepared if there is an adcom, but that's not something that one can know at this juncture, and certainly not until a submission is accepted for filing. As it relates to what we're compelled by in connection with pricing, I'm not going to speak to pricing. But I will say we're quite compelled by what are the HEOR datasets that are being prepared and analyzed and how they relate to value associated with aficamten, and that alongside a number of other factors ultimately contribute to what will be determinants of pricing. I think that's the best I can do for you today.

Operator, Operator

And I'm showing no further questions at this time. I would now like to turn the conference back to Robert Blum, President and CEO for closing remarks.

Robert Blum, President and CEO

Thank you, operator. We covered a lot of ground today, both in our prepared comments and also in our Q&A, so I'll be brief. I'll simply say that with SEQUOIA results, we do believe we've turned an important page onto the next chapter for Cytokinetics. We’ll remain vigilant with regard to execution and doing right by shareholders. At the same time, we're humbled by the science but also leaning forward on the opportunity that aficamten presents, not just as it relates to OHCM, but also as it opens the door we believe on other value creation. We'll look forward to keeping shareholders abreast of that progress. And with that, operator, we can now conclude the call, please.

Operator, Operator

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