Cytokinetics Inc

NASDAQ:CYTK

Earnings Call Analysis

Cytokinetics Poised for Regulatory Filings

Cytokinetics starts 2024 strong, working towards their first regulatory approvals within 18 months. They plan to submit New Drug Applications (NDA) to the FDA and Marketing Authorization Applications (MAA) to the EMA for aficamten in Q3 and Q4 respectively. Major milestones include presenting SEQUIOA-HCM results in Q2, completing MAPLE-HCM enrollment in Q3, continuing ACACIA-HCM enrollment, and moving forward with go-to-market strategies. The company intends to expand their pipeline beyond obstructive Hypertrophic Cardiomyopathy (HCM) and is eyeing severely ill and underserved markets. Success hinges on their innovative science, operational efficiencies, and wise capital management.

Overview of the company's strategy and clinical trials

The company aims to establish aficamten as a potential next-in-class treatment option for Hypertrophic Cardiomyopathy (HCM). They shared plans to present efficacy and safety data for aficamten from their FOREST-HCM trials, demonstrating its potential over a follow-up period of one year. The company has engaged the FDA in preparatory interactions for a New Drug Application (NDA) which they plan to submit in Q3 2024, receiving favorable feedback on their proposed submission plan. They also intend to submit a marketing application to the European Medicines Agency (EMA) in Q4 2024, coordinating with partner Ji Xing in China for related submissions. The company's therapeutic medical science liaisons have focused on profiling HCM treatment programs to support medical education activities, positioning aficamten among healthcare professionals.

Progress in Clinical Trials

Clinical trials MAPLE-HCM and ACACIA-HCM are ongoing, evaluating the potential superiority of aficamten as monotherapy compared to metoprolol in patients with obstructive HCM, with MAPLE-HCM enrollment expected to be completed in Q3 2024 and results expected in 2025. A trial for symptomatic nonobstructive HCM is also underway, with plans to complete enrollment by 2025. The expanded evidence from these trials could extend the potential indications and benefits of aficamten to a broader population of HCM patients underserved by current treatment options.

Commercialization and Market Strategy

The company's patient services hub design involves comprehensive patient support, including facilitation, education, and reimbursement support. Initial conversations with specialty pharmacies and service hub providers commenced in Q4 2023 to build a differentiated patient services hub targeted for Q2 2024 alongside their aficamten submissions.

Financial Standpoint

The company has reduced spending to strengthen its financial position. For 2024, they anticipate revenue in the range of $3 million to $5 million, with operating expenses between $420 million to $450 million, and net cash utilization approximately $390 million to $420 million. They also consider strategic options for financing and partnerships to enhance shareholder value, being eligible for two additional loan tranches under a development funding agreement following positive SEQUOIA-HCM results.

Expansion and Future Goals

The company is extending their research and development pipeline beyond aficamten and obstructive HCM with new compounds, aiming to address severely ill and underserved populations. Building a sustainable specialty cardiology company is part of their future vision, starting with regulatory filings for aficamten in both the US and Europe in 2024. They aim to drive shareholder value by maximizing opportunities in their pipeline, with a long-term goal of achieving a company value of $15 billion to $20 billion by pursuing a variety of value-creation strategies.

European Market Potential and Regulatory Strategy

A greater patient prevalence in Europe suggests a notable market opportunity for aficamten, albeit with an expected price point 15% to 25% lower than in the U.S. Following approval, Germany will be the first launch market in Europe, with launches in other European countries trailing. The company foresees a potential commercial presence in Europe approximately a year behind the U.S., outside of Germany.

Earnings Call Transcript 2023-Q4

[Operator]

Good afternoon, and welcome, ladies and gentlemen, to Cytokinetics' Fourth Quarter 2023 Conference Call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. At the company's request, we will open the call for questions and answers after the presentation. We will allow for only one question per participant and ask that you adhere to this request. I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Communication and Investor Relations. Please go ahead.

[Diane Weiser, executive]

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 ACACIA-HCM and MAPLE-HCM, and will also discuss CK-586 and CK-136. Andrew Callos, EVP and Chief Commercial Officer, will speak about 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 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 I. Blum, executive]

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 turn the card on SEQUOIA-HCM, our Phase III 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 a broad clinical development program following behind SEQ-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, how we're now moving swiftly to regulatory submissions across the globe. And then Andrew will comment on how we're prudently planning for differentiated commercial positioning for our next-in-class opportunity. 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 III 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 provide a new treatment option for the growing number of patients with nonobstructive HCM. As you'll hear, there's been an 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 at-the-market or ATM equity vehicle. We're pleased to be reporting our financial guidance today with approximately 2 years of cash runway when accounting for both our cash on hand and cash available to us and despite 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 to 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. He'll continue to work with me through this transition as we've already initiated a national search for Ching's replacement that we expect will bring international commercial and capital allocation experience compatible with maturing operations. Cytokinetics is looking ahead to a bright future in 2024 and also beyond. And as we turn the page towards potential commercialization of the first medicine arising from our pioneering and leading muscle biology research with 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 happen that vision as we believe will further reward shareholders. With that, I'll turn the call over to Fady, please.

[Fady Malik, executive]

Thanks, Robert. During the quarter, we shared topline 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 at 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 prespecified 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 prespecified 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 1 class improvement in New York Heart Association functional class at weeks 12 and 24; the change in provoked left ventricular outflow tract 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 of 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 8 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%, 5 patients or 3.5% on aficamten compared to 1 patient or 0.7% on placebo. Importantly, there were no instances of worsening heart failure or treatment interruptions due to low LVEF. While these topline 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 analysis 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, over the coming months 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, examining the breadth of improvements patients experienced in SEQUOIA-HCM. In another, 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 on other metrics of exercise capacity, cardiac remodeling from the CMR sub-study, echocardiographic measures of systolic and diastolic function and cardiac structure, symptoms and 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 SEQUIOA-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 1 year of follow-up in FOREST-HCM. Last month, we shared data at CMR 2024 from the cardiac magnetic resonance or CMR sub-study of FOREST-HCM. The results showed the 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 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 1-year mark and beyond. Regarding regulatory engagements, during the month of February, we held 2 meetings with 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 PDI 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 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 partner 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 and 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 topline results from SEQUOIA-HCM have been well received by the HCM community of physicians and patient advocates who foresee that they represent what can be 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. Now I'll hand it over to Stuart to elaborate more on additional clinical trials progress we are making with aficamten and provide an update on our earlier-stage clinical development pipeline.

[Stuart Kupfer, executive]

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 2 ongoing Phase III clinical trials of aficamten, MAPLE-HCM and ACACIA-HCM. We're pleased to see that screening and enrollment is 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 U.S. sites are now activated, and we've now activated sites in the U.K., 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 when we hope to be commercially launching 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. We're developing aficamten to capitalize on this next-in-class potential and MAPLE-HCM factors importantly into that strategy. ACACIA-HCM, the pivotal Phase III clinical trial of aficamten in patients with symptomatic nonobstructive HCM, is currently focused on study start-up, but we have the necessary IRB approvals in the U.S., and the EU, 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 to complete enrollment in 2025. ACACIA-HCM represents an important opportunity for aficamten and tests the 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 thankfully 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 in the HCM patient population and impact 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 in development for the potential treatment of a subgroup of patients with heart failure with preserved ejection fraction or HFpEF. Having completed analyses of the single ascending dose data, we proceeded to the multiple ascending dose portion of the study. We expect to complete the Phase I study in this quarter and subsequently shared data in the second quarter of this year, with plans to begin a Phase II clinical trial in the second half of the year. We believe that the positive Phase II data we generated for aficamten in patients with nonobstructive HCM support the development of CK-586 in a population of patients with HFpEF. This condition has many parallels to nonobstructive 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 SGLT2 inhibitors, the first evidence-based therapies demonstrating some benefit in those with HFpEF, 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 analysis of the single and multiple ascending dose cohorts in the Phase I study of 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 in 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 look forward to sharing more progress soon. With that, I'll turn the call over to Andrew.

[Andrew Callos, executive]

Thanks, Stuart. During the quarter, ahead of our announcing the results from 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 patients' overall mental health, social engagement and other aspects of everyday life. We also tested a range of product profiles and 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 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 at our patient services hub. Access in particular is a key focus for us. Aligned with our company values at 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 and 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 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 payor in 2023 to introduce Cytokinetics. This field-based payor account team will continue to further engage in 2024 to share the results from SEQUOIA-HCM and ensure payors 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 our 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 CRO from the FDA, we maintained the infrastructure that has 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 onboard the majority of U.S.-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 ATP 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 to spending and gating cost 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 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 our 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, executive]

Thanks, Andrew. We ended the fourth quarter with $655.4 million in cash and investments, which included $162.9 million that we raised through our at-the-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 I. Blum, executive]

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 U.S. 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 2 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 multipronged 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 nondilutive approaches. Our priority remains focused on business development. And as you know, 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 long-standing 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 as would benefit shareholders while also preserving important shareholder value in major markets of value for aficamten. And 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 2 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 1 year following our receipt of the results, which occurred in late December. The second tranche of $100 million will become available to us were we to choose to draw on it, subject to the satisfaction of certain conditions, most notable of which is the acceptance of an NDA submission for aficamten in the United takes. 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 3 to 5 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. And next then, we expect CK-586 to advance through proof of concept in 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 as 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 maximal value and controlling that which we can control. We believe that can be best 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 now 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 FDA, and in Q4 an MAA with EMA. We expect to be more precise as timing goes to our Q1 earnings call and especially as it relates on positioning and other aspects contained within the content of those submissions. And 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. And our vision of building a specialty cardiology company is now being realized, and we're well positioned for success. With that, I'd now like to share our expected 2024 milestones. For aficamten, we expect to present primary results from SEQUIOA-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 continue advancing 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 I study in Q2 2024. And finally, for CK-136, we expect to complete a Phase I study in the second quarter of this year. And Operator, with that, we can now open up the call, please, to questions.

[Operator]

[Operator Instructions] Our first question comes from Mayank Mamtani with B. Riley Securities.

[Mayank Mamtani, analyst]

Good afternoon, team. Thanks for taking our questions and hope for Chang's well-being too. 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 EFFICIENCY, Heart Failure Congress, you'd probably have about 150 patients go through the titration phase. I'm just curious if -- 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 I. Blum, executive]

I'll turn that call, that question rather, over to Fady.

[Fady Malik, executive]

Thanks. I can't give you the exact number of patients that will be available. But we also, besides of the number of patients who have extended follow-up in FOREST at the time of NDA submission, we'll also have the opportunity to submit an update at the Day 120 timepoint. There's a Day 120 safety update where we can expand the dataset. 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]

Understood. And as a related question, just quickly, the ACACIA-HCM, I'm glad you narrowed the timeline there. I was just curious, based on everything we know on dosing, safety, cardiac remodeling data, just your confidence level for that, what you could report there. Also recognizing that a threshold could be set from the other HCM study early part of next year. Thanks again for taking the questions.

[Fady Malik, executive]

Well, I think based on the results that we saw in Phase II and the predictability of dosing and the safety profile we saw of aficamten in SEQUOIA, we feel very confident with the outcomes and potential outcomes in ACACIA. I think all of them read well on the likelihood of that trial reading out positively, and we'll continue to conduct it in a way that helps us get to the best answer.

[Robert I. Blum, executive]

Thank you for the question. Just a reminder, please, one question per analyst, please. Next question, please?

[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 for -- and I believe it's the first time you guys are using that terminology, if I'm not mistaken, rolling submission for aficamten. 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? Thank you.

[Robert I. Blum, executive]

Yes. I'll answer that question. You're right, we are using that terminology for the first time, and that's coming out of our recent meetings with 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. And in that regard, they were amenable to our recommendation that we do it in a rolling basis. We're going to be submitting most of the modules earlier than 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 timepoints we need to collect in order to be able to finalize those submissions. But all this speaks to, we think, a focus forward in 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.

[Fady Malik, executive]

As it relates to MAPLE, no, we don't expect that those data will be contained in this submission. MAPLE won't read out until next year.

[Operator]

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

[Fatima Amanat, analyst]

Fatima Amanat on behalf of Ashwani from UBS. Just a general quick question. In terms of cardiology in general, just a high level, is portfolio level contracting common? Like would such a practice mean that companies with a broad set of offerings may get favorable benefit of scale in the long run?

[Robert I. Blum, executive]

I don't understand that question. Might you repeat it, please?

[Fatima Amanat, analyst]

Sure. Yes. I'm just trying to understand, like in the cardiology space, is portfolio level of contracting coming? Like do you think companies that have like a broad set of diverse portfolio in cardiology, they have like a larger benefit compared to companies that are focused on single assets?

[Robert I. Blum, executive]

I see. Your question is, are we going to be potentially disadvantaged because we'll be launching with a single product relative to payors I assume who might have multiple -- who might be contracting around multiple products, is that right?

[Fatima Amanat, analyst]

Yes.

[Stuart Kupfer, executive]

From a payor point of view, no, I don't believe we're at a disadvantage. Payors aren't managing this category. It's a rare disease. There's over 120 payors in the U.S. Each payor only has very limited number of patients. It's not a big budget impact. It's a high unmet need, there's one product in the market, a second product. These usually aren't payor 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 HSM as a subset of overall cardiology and highly motivated to treat the disease. They're going to be more focused on the products, the patients relative to the disease. By all means, I think we'll compete fine and it's not going to be a disadvantage.

[Operator]

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

[Carter L. Gould, analyst]

This is Carter. Thanks for taking the question, Robert. Maybe for Robert and Fady, the commentary on the REMS sort of reference, SEQUOIA, PK and the EDI 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? Thank you.

[Robert I. Blum, executive]

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 FDA. Next question, please.

[Operator]

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

[Kyuwon Choi, analyst]

My question is with regard to your recent meeting with the FDA, can you maybe just confirm for us if there were any either preclinical or clinical testing requirements that were specified by the agency? And if indeed there are any, how much of this needs to be coordinated with EMA requirements ahead of a potential MAA file in addition to NDA?

[Robert I. Blum, executive]

Sure. We don't believe there are any other such studies that are required. I believe that addresses your question well. Thank you.

[Operator]

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

[Adhiraj Chauhan, analyst]

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

[Robert I. Blum, executive]

I'll turn that over to Fady.

[Fady Malik, executive]

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

[Robert I. Blum, executive]

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

[Operator]

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

[Yasmeen Rahimi, analyst]

I guess it's been now 2 months since the topline data. Have you had a chance to complete all your ramp preparation by hiring the consultants, reviewing the data on an integrated basis, coming up with a package and kind of laying out sort of the proposal? Like could you maybe give us some color on which of these activities have been completed? What is left to do? How much of the proposal I guess is in a finishing process? And thank you again for allowing me to ask my question.

[Robert I. Blum, executive]

Thank you, Yasmeen. I'll take that one. 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 be enabling of aficamten to be accessed by a greater number of physicians for a greater number of patients. And as it relates to how that REMS may be positioned, situated, what would be the elements of it, that's something that I think will be the subject of negotiation at the end of the day, 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 is certainty around what that looks like.

[Yasmeen Rahimi, analyst]

Got it. Thank you so much, Robert, and keep up the amazing work. I'll be -- I'll go back in the queue.

[Operator]

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

[Jason Butler, analyst]

This is Jose for Jason. You mentioned that the data from FOREST-HCM demonstrate favorable structural remodeling. Can you speak to the potential long-term functional benefits of such 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? Thank you.

[Robert I. Blum, executive]

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

[Stuart Kupfer, executive]

Yes, this is a really key question that we are anxious to investigate certainly in the long term. Because what we hypothesize is that cardiac myosin inhibition will result in the long term, very favorable remodeling and hopefully normalization. The cardiac structure and function that we anticipate, that that will mediate, confer lifelong benefit for patients in terms of symptomatic and functional improvement. And we could also hypothesize reduced risk of cardiovascular events.

[Fady Malik, executive]

I might just add that the data we reported in January is really just the first taste of the CMR cohort, which I think is the largest cohort of patients that will undergo serial CMRs at one -- at yearly or every other yearly intervals. And so, the number, the length of time, those data will mature as the years go on and I think give us a very good sense of how the cardiac structure changes over time.

[Stuart Kupfer, executive]

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 close to the launch next year.

[Robert I. Blum, executive]

And those are not the kinds of things that one talks about at this point in time. Next question, please.

[Operator]

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

[Joseph Pantginis, analyst]

I think my question is more suited for -- or most 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, etc., the profile data from SEQUOIA, has it led to any data that you can discuss regarding the 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, executive]

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

[Robert I. Blum, executive]

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, executive]

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

[Operator]

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

[Lee Hung, analyst]

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

[Stuart Kupfer, executive]

Well, we've certainly spoken to providers, and they're optimistic given the safety profile that we shared with them in the SEQUOIA data. But they really obviously don't contribute to the FDA's evaluation of that question. And 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]

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

[Roanna Clarissa Ruiz, analyst]

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 U.S. and possible timeline for ramping up more of a commercial presence in Europe?

[Fady Malik, executive]

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 of the overall population. It's slightly higher. The price point is lower than the U.S., probably in the range of 15% to 25% depending on the country. From an opportunity point of view, once the approval has occurred, we will launch in Germany. That'll allow for launch at approval. Other markets you need to submit for reimbursement and pricing negotiation. In general, Europe will probably be about a year behind in launch in terms of market opportunity outside of Germany.

[Operator]

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

[Srikripa Devarakonda, analyst]

This is [Vilal] 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 in your REMS program? And are you seeing stabilization of LVEF over time?

[Stuart Kupfer, executive]

Well, the answer to the second part of your question is yes, and we've looked at those data, and we've actually presented those data. You'll see some of that in FOREST where you'll see EF over time for up to a year. It 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 may be at more risk because they're closer to the cutoff. It's kind of obvious. And I think when you look at any sort of monitoring strategy that's employed in medicine, you generally look at patients that are closer to certain thresholds. You look at them more carefully than other patients who are more distant from it. We'll certainly incorporate that into our thinking.

[Operator]

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

[Cameron Bozdog, analyst]

This is Cameron Bozdog on for Jason. Congrats on the quarter and thanks for taking our question. How important to your commercial outlook is use in the community setting, especially when looking at the frontline opportunity? What do you think is necessary to make community prescribers feel more comfortable administering afi, especially given it's likely to have a REM? And then how long do you expect this transition to take? Thanks so much.

[Stuart Kupfer, executive]

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

[Cameron Bozdog, analyst]

Yes, exactly.

[Stuart Kupfer, executive]

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 diagnosis is 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 will accelerate, especially in the maintenance phase. Hard to say exactly what that point will be, but it will certainly occur over time given the number of patients that need to be treated.

[Operator]

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

[Serge Belanger, analyst]

I guess my question is regarding the upcoming SEQUIOA presentations. Maybe just talk about the decision to present at the heart failure meeting rather than the upcoming ACC meeting next month. And maybe what kind of additional data and analysis we'll see in those results?

[Robert I. Blum, executive]

Sure. I'll take that one. We knew there was a risk when we top lined the results of SEQUOIA-HCM that we may run afoul of a policy that ACC has regarding acceptance of abstracts and what would be otherwise contained in the public domain when they have that abstract to review. We also knew we had a material obligation to shareholders to disclose that which we did choose to disclose. Our abstract for SEQUOIA was not accepted by ACC, we assume for the reasons that it was already disclosed in large detail in a press release. And therefore, the next meeting is the HFA meeting a month later in May in Lisbon. That's where these data we hope will be presented. That's still to be determined. But at the same time, we expect that it will be presented and potentially published concurrently in and around the second quarter. I hope that answers your question, but we expect not just will these primary efficacy and safety results be presented and published, but more so in connection with other secondary analyses and also some post-hoc analyses. We believe we've got an aggressive communications plan with regard to presentations and publications, and you'll see multiple presentations and publications during that period.

[Serge Belanger, analyst]

Thanks. Look forward to seeing the additional data.

[Operator]

Our next question comes from the line of Charles Duncan with Cantor Fitzgerald.

[Charles Duncan, analyst]

Robert and team, congrats on all the progress. ACC seems a little shortsighted on that last point. I wanted to ask you a couple of quick questions that you may not be able to answer. 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 the standard of care? I know you're not really talking about pricing, but just your perspective.

[Robert I. Blum, executive]

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 the 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 of 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]

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 I. Blum, executive]

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, and 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 we're 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]

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