Cytokinetics Q4 2024 Earnings Call Transcript

Quartr
Provided by Quartr
February 27, 2025

Key Takeaways

  • Regulatory progress for aficamten includes FDA NDA acceptance (PDUFA 09/26/2025), EMA MAA validation (Day-120 questions due April 2025) and China NMPA priority‐review acceptance, enabling parallel review in the U.S., Europe and China.
  • Commercial readiness is peaking with U.S. launch planning for up to 150 sales reps, launch of the unbranded “HCM Beyond the Heart” awareness campaign, payer engagement and patient support programs, and expansion of key leadership roles in Western European markets.
  • Global partnerships were secured with Bayer (€50 million upfront plus milestones and royalties for Japan) and Sanofi (up to $150 million in milestones plus low-to-high-teens royalties for Greater China), extending aficamten’s reach in major non-U.S. markets.
  • The clinical pipeline advanced with top-line MAPLE-HCM results expected in Q2 2025 (potential label expansion), ongoing enrollment in ACACIA-HCM, HCM extension studies, Phase III COMET-HF in HFrEF, Phase II AMBER-HFpEF and a Phase I study of CK-089 in neuromuscular disease.
  • Financial strength remains robust with $1.2 billion in cash/investments, Q4 2024 revenue of $16.9 million driven by upfront licensing payments, and 2025 GAAP operating expense guidance of $670–710 million (ex-stock compensation $550–600 million), supporting launch and R&D through multiple years.
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Earnings Conference Call
Cytokinetics Q4 2024
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Operator

Good afternoon and welcome to Cytokinetics fourth quarter 2024 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 to questions after the presentation. We will allow for only one question per participant. I will now turn the call over to Diane Weiser, Cytokinetics Senior Vice President of Corporate Affairs. Please go ahead.

Diane Weiser
Diane Weiser
Senior VP of Corporate Affairs at Cytokinetics

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. Andrew Callos, EVP and Chief Commercial Officer, will address commercial readiness activities for aficamten. Fady Malik, EVP of R&D, will provide updates related to recent regulatory interactions and the clinical development program for aficamten. Isaac Ciechanover, EVP, Corporate Development and Chief Business Officer, will provide an update on recently announced business development deals in the context of our corporate development. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates regarding omecamtiv mecarbil, CK-586, and our earlier stage development pipeline. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the past quarter and discuss our 2025 financial guidance, and finally, Robert will review expected key milestones for the year ahead.

Diane Weiser
Diane Weiser
Senior VP of Corporate Affairs at Cytokinetics

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 2024 financial results filed on Form 8-K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call, and now I will turn the call over to Robert.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you, Diane, and thanks to all for joining us on the call today. The fourth quarter of 2024 was an exceptionally productive quarter that rounded out a successful year. Most notably, we made major strides towards potential regulatory approvals and subsequent commercial launches of aficamten across multiple geographies. Our NDA was accepted by FDA, our MAA was validated by EMA, and our NDA was accepted by the NMPA in China with priority review. Now, with regulatory submissions on file in the U.S., Europe, and China, we're engaging in parallel regulatory interactions that may deliver aficamten to patients around the world. With our PDUFA date of September 26, 2025, our commercial readiness activities in the United States are reaching a peak, while we also lay the foundation for our go-to-market activities in Europe.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

In the nearer term, we expect to continue already ongoing activities with FDA in support of their review of the NDA. We have been responding to questions as well as preparing for clinical site and other inspections, and we recently submitted our 120-Day Safety Update to FDA. In March, we expect to participate in a Mid-Cycle Meeting with FDA. Ahead of that meeting, I want to level set that we do not plan to share detailed updates following that meeting, given that the FDA review of the NDA will still be ongoing. However, we maintain our expectation for a differentiated label and mitigation profile for aficamten were it to be approved by FDA.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

In both SEQUOIA-HCM and FOREST-HCM, in patients with oHCM, we observed a favorable overall safety profile, LVEF stability, rapid dose titration, as well as a lack of treatment interruptions related to episodes of heart failure or heart failure hospitalizations related to LVEF. Nor did we observe any clinically meaningful drug-drug interactions. We believe all of these characteristics are consistent with the intrinsic properties of aficamten. Moving on to the regulatory review of aficamten in Europe, following the validation of our MAA in late December, we expect to continue to engage with EMA during their review by responding to requests for information and preparing for inspections. Our next key milestone for these regulatory interactions with EMA is receipt of the Day 120 List of Questions expected in April. As you know, we plan to commercialize aficamten ourselves in the U.S. and Western Europe.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

In other key geographies in the fourth quarter, Sanofi acquired, with our participation from Corxel, the rights to develop and commercialize aficamten in China. Additionally, in November, we announced our new collaboration with Bayer that entails a license agreement for aficamten in Japan. These two strong pharmaceutical company partners in the two leading markets outside the U.S. and Europe both align with Cytokinetics in their commitment to cardiology, and each brings great expertise, resources, and reach to enable us to hopefully deliver aficamten to a greater number of HCM patients in need and contribute to our goal to reach patients globally with our medicines. Simultaneously, we're advancing our later stage development program for aficamten with multiple ongoing potential label expansion clinical trials.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

In the near term, we expect to share top-line results from MAPLE-HCM in Q2, and if positive, data from this trial may represent, again, a label expansion opportunity for aficamten following potential FDA approval. Meanwhile, we continue to expand our specialty cardiology franchise and innovative pipeline advancements, ensuring that we're more than simply a one-product company. In Q4, we started COMET-HF, a confirmatory phase III clinical trial of omecamtiv mecarbil in patients with heart failure with severely reduced ejection fraction, and more recently, we started AMBER-HFpEF, a phase II clinical trial of CK-586 in patients with heart failure and preserved ejection fraction. Our successes over the past quarter reflect our clear vision, strategic execution, and responsible investment in our muscle biology platform.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

This year, we're approaching a defining moment with key milestones ahead that will shape our future as multiple programs advance in our specialty cardiology franchise alongside progress in our early stage neuromuscular pipeline, as well as continued innovation in our research labs. We're poised to drive meaningful progress to positively impact the lives of patients, as well as create enduring value for shareholders who support our mission. With that, I'll now turn the call over to Andrew.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Thanks, Robert. Our launch preparations for aficamten are well underway, with significant momentum in 2024 and setting up as the final stretch towards the potential U.S. approval and launch of our first medicine in September. The priorities we are guiding towards for a successful launch are as follows: broadening category awareness and effectively communicating the differentiated attributes of aficamten, galvanizing and activating new cardiologist prescriptions, securing access and an affordable copay for people with HCM, and providing exceptional patient support. Of note, we are pleased to see continued category expansion of the number of patients treated with a cardiac myosin inhibitor, or CMI. Continued market growth and broad awareness is good news for Cytokinetics as it reflects a growing opportunity for aficamten to capture what is largely still an untapped market. Cytokinetics will be focused on increasing market awareness and category penetration and broader cardiology adoption for CMIs with aficamten.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Toward that objective, in the fourth quarter, we are proud to drive increased education and awareness of HCM with the launch of HCM Beyond the Heart, an unbranded disease awareness campaign featuring real people with HCM. In October, we launched a campaign directed to HCPs to inspire them to look deeper for HCM and practice whole-person care. Initial engagement metrics with the website and email are above industry benchmark for our target audience. In January, we expanded HCM Beyond the Heart, inclusive of patients, incorporating a website, educational tools, and resources focused not just on the condition, but on the impact it has on a patient's lives beyond their heart. This represents another exciting milestone as we move forward toward the PDUFA date later this year. Meanwhile, we continue developing and refining our branded HCP promotional campaign for aficamten, which is currently being tested with HCPs.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

To support our goal of ensuring product and market access post-approval, we have continued our engagement with payers while advancing implementation of a robust patient support program. This includes contracting with strategic partners, determining the size and approach of our customer-facing nurse navigator team, and creating a bespoke patient experience offering. We also advanced operational planning for our sales force, including finalizing the sales training curriculum and sales territory configurations and deployment, and we finalized our sales representative recruiting process, which will be initiated in late Q1. Beyond the U.S. launch, we're also scaling up commercial launch readiness activities in international infrastructure to support a potential European approval of aficamten.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

At the end of last year, we hired key leadership positions in Europe, inclusive of leaders in marketing, finance, human resources, and in-country leadership in both France and the U.K., following our previous hiring of a leader in Germany earlier in the prior year. Recent planning activities are ahead of a potential European approval, including validation of our reimbursement strategy and initial preparation of dossiers for HTA submission across the U.K. and Western E.U. markets. I'm pleased with the progress we've made to prepare for both the U.S. and European commercial launches of aficamten and where we are positioned today on our commercial readiness roadmap. With that, I'll turn the call over to Fady.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Thanks, Andrew. As Robert mentioned, we recently submitted the 120-Day Safety Update to FDA with an additional 10 months of safety data from FOREST-HCM. These longer-term data are consistent with the previously presented data from FOREST-HCM and the safety profile of aficamten as reflected in the NDA submission, with, we believe, no evidence of an increased risk of EF excursions or heart failure events. As Robert mentioned, we also expect to participate in a Mid-Cycle Meeting with FDA in March.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Moving on to our work in the fourth quarter to expand the evidence base for aficamten, at the American Heart Association scientific sessions in November, we presented data from two pre-specified analyses of SEQUOIA-HCM and one analysis of FOREST-HCM, expanding on our activities to make data from this program available to the medical community. These presentations included analyses of post-exercise oxygen uptake recovery, patient quality of life, and guideline eligibility for septal reduction therapy, all favorably impacted by aficamten. In addition to disseminating data during the quarter, our managed healthcare MSL team continued pre-approval information exchange to actively engage national and regional payers in scientific discussions related to oHCM and aficamten and notified payers of our PDUFA date. Scientific engagement with HCM specialists also continued with discussions focused on the results from SEQUOIA-HCM, including the primary results and secondary data analyses.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Now shifting to the ongoing clinical trials program for aficamten, having completed enrollment in MAPLE-HCM in the third quarter of last year, we continue to conduct the trial, collect data, and progress towards database lock. We're on track to share top-line results in the second quarter of this year, which we expect to be followed by a presentation of the full results at a subsequent medical meeting. If the results of MAPLE-HCM are positive, it'll provide an opportunity to elevate aficamten as a potential monotherapy for the treatment of oHCM following approval. Meanwhile, we've continued to conduct ACACIA-HCM, pivotal phase III clinical trial in non-obstructive HCM, CEDAR-HCM in pediatric population of patients with symptomatic oHCM, and of course, FOREST-HCM, the ongoing open-label extension clinical study. FOREST-HCM continues to grow with now over 400 patients enrolled.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Nearly 300 patients have at least a year of follow-up, and over 90 have two years of follow-up. We're pleased to report that patient enrollment in ACACIA-HCM has progressed rapidly over the last few months thanks to our highly engaged sites. We've completed site activations in North and South America, Europe and Israel, and are pleased with the blinded baseline characteristic of the population. Results from this trial represent a key future milestone for the potential label expansion trajectory for aficamten into non-obstructive HCM. While today representing about one-third of the HCM population, nHCM appears to be growing at a faster rate than oHCM in terms of diagnoses, so it's an important segment of the population that needs to be addressed, in particular because nHCM lacks effective medical or surgical therapy unlike oHCM.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Overall, from a clinical development perspective, our work in the fourth quarter wrapped up a truly monumental year, highlighted by numerous data presentations and publications in high-impact journals. We look forward to building on and publishing that growing clinical evidence in support of aficamten as we approach the potential approval and launch of aficamten in oHCM this year. Now I'll turn it over to Isaac.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

Thanks, Fady. As Robert mentioned, we secured two new partnerships in the fourth quarter, which together will support the development and commercialization of aficamten in critical global geographies. We were pleased to enter into a collaboration and licensing agreement with Bayer for the development and commercialization of aficamten in Japan. This deal stands alone in terms of its favorable economics for a cardiovascular drug: EUR 50 million in upfront payments to Cytokinetics, eligibility to receive an additional EUR 90 million tied to milestones through the commercial launch, EUR 490 million in commercial milestone payments from Bayer upon their achievement of certain sale milestones, and tiered royalties on net sales of aficamten in Japan.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

To support the potential marketing authorization of aficamten in Japan, Bayer will conduct a phase III clinical trial in Japanese patients with oHCM to support SEQUOIA-HCM and FOREST-HCM, while Cytokinetics plans to expand both ACACIA-HCM and CEDAR-HCM into Japan. As you know, we have been pursuing a deal like this in Japan for some time. Bayer, like Cytokinetics, has a deep commitment to cardiology and, through this process, ultimately rose to the top of the right partner who is well equipped to bring aficamten to patients in Japan. Additionally, during the fourth quarter, Sanofi acquired exclusive rights to develop and commercialize aficamten from Corxel, formerly Ji Xing in China. Through this transaction, Cytokinetics remains eligible to receive up to $150 million in development and commercial milestone payments from Sanofi and royalties in the low to high teens on sales of aficamten in China.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

Cytokinetics is now also eligible to receive additional payments in connection with the execution of the agreement between Sanofi and Corxel. Over the years, we have enjoyed a highly productive collaboration with Corxel, and now we are pleased to partner with Sanofi, harnessing their expertise in cardiology to bring aficamten to patients in China. Both of these recent deals serve to expand the potential reach of aficamten in key geographies worldwide. Now, with partners on board in China and Japan, and our own commercial infrastructure scaling in the U.S. and Europe, we're turning our attention to how we may further expand our geographic reach with aficamten and how we may also catalyze external R&D activities and pursue new business objectives to augment our existing pipeline alongside innovation from our own labs.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

To that end, our goal is to bring additional new chemical entities into clinical development through external innovation, seeking complementary potential therapies to support our late-stage cardiovascular franchise and emerging neuromuscular pipeline. As stated in our Vision 2030, we also seek to expand into new modalities through a combination of both building internal capabilities and identifying external collaborations with industry partners and academic institutions. In the year to come, you can expect more activity on the business and corporate development fronts at Cytokinetics as it relates to bringing aficamten to more patients worldwide, as well as how we may augment our R&D pipeline in more ways that read on progress towards our stated vision. I look forward to sharing more of these matters as they progress. Now I'll hand it over to Stuart.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

Thanks, Isaac. I'm pleased to provide updates on the later-stage development programs within our specialty cardiology franchise, as well as our earlier-stage neuromuscular clinical research. I'll start with omecamtiv mecarbil, our cardiac myosin activator. During the quarter, we started COMET-HF, a confirmatory phase III clinical trial in patients with symptomatic heart failure with severely reduced ejection fraction, less than 30%. Since starting the trial, we've seen a great deal of enthusiasm from our investigators who recognize the considerable unmet need in this high-risk population and are eager to enroll patients. Currently, this trial is enrolling in the United States, and regulatory submissions have been completed in Canada, the U.K., and the rest of Europe.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

Investigators with prior experience with omecamtiv mecarbil have been reaching out to us regularly to inquire about participating in COMET-HF, and our steering committee is now fully seated with the foremost heart failure leaders from countries where the trial will be conducted. Now I'll move on to CK-586, our next cardiac myosin inhibitor. In January of this year, we began AMBER-HFpEF, a phase II placebo-controlled double-blind trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of CK-586 in patients with symptomatic heart failure with preserved ejection fraction and LVEF greater than or equal to 60%. AMBER-HFpEF is expected to enroll approximately 60 patients in three 12-week dose escalation cohorts with doses ranging from 150-600 mg once daily. Potential treatment benefits of CK-586 include increased cardiac relaxation leading to improved diastolic function, improvement of heart failure symptoms, and increased exercise capacity.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

We expect to build a body of evidence in support of these outcomes through this trial. Our goal is to complete enrollment of the first two cohorts in the second half of the year. Finally, beyond our specialty cardiology franchise, during the fourth quarter, we were pleased to begin a phase I study of CK-089, a fast skeletal muscle troponin activator. The study comprises both single and multiple ascending dose cohorts. CK-089 arose from our pioneering research in neuromuscular disease and was optimized by our prior learnings. CK-089 is designed to amplify skeletal muscle response to nerve input, extending time to fatigue and increasing muscle force and power, with potential therapeutic application to a specific type of muscular dystrophy.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

We expect to complete this phase I study within 2025 and look forward to keeping you updated on our progress in this key area of clinical research as it underscores a second vertical for our company. With that, I'll pass it to Sung.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Thanks, Stuart. We're pleased to report our fourth quarter and full year 2024 financial results. Starting with the balance sheet, we finished the fourth quarter of 2024 with approximately $1.2 billion in cash, cash equivalents, and investments compared to $1.3 billion at the end of the third quarter of 2024. Cash, cash equivalents, and investments declined by approximately $60 million during the fourth quarter of 2024 and benefited from the receipt of $52.4 million, or EUR 50 million payment from Bayer for the exclusive license to develop and commercialize aficamten in Japan. Moving on to the income statement, the revenues in the fourth quarter of 2024 were $16.9 million compared to $1.7 million for the same period in 2023. The revenues for the full year of 2024 were $18.5 million compared to $7.5 million in 2023.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Total revenues in the fourth quarter of 2024 and full year 2024 benefited from a $15 million upfront payment from Corxel in connection with the assignment of Corxel's rights for the development and commercialization of aficamten in Greater China to Sanofi. R&D expenses for the fourth quarter were $93.6 million compared to $85 million for the same period in 2023. R&D expenses for the full year of 2024 were $339.4 million compared to $330.1 million in 2023. The increase year over year for both the fourth quarter and full year was primarily due to advancing our clinical trials and higher personnel-related costs, including stock-based compensation. G&A expenses for the fourth quarter of 2024 were $62.3 million compared to $44.1 million for the same period in 2023. G&A expenses for the full year of 2024 were $215.3 million compared to $173.6 million in 2023.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

The increase year over year for both the fourth quarter and full year was primarily driven by investments toward commercial readiness and higher personnel-related costs, including stock-based compensation. Net loss for the fourth quarter of 2024 was $150 million, or $1.26 per share, compared to a net loss of $136.9 million, or $1.38 per share for the same period in 2023. Net loss for the full year of 2024 was $589.5 million, or $5.26 per share, compared to a net loss of $526.2 million, or $5.45 per share in 2023. Turning now to our financial guidance for 2025, we expect our GAAP operating expense, which is comprised of R&D and SG&A expenses, to be between $670 million and $710 million. Stock-based compensation included in the GAAP operating expense is expected to be between $110 million and $120 million.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Excluding stock-based compensation from GAAP operating expense results in a range of $550 million-$600 million. Our capital allocation priorities remain the same, and our resources will be focused on the following. First, on preparing for the potential U.S. commercial launch of aficamten in September of this year, including the hiring of up to 150 sales reps in the U.S. in the third quarter of 2025. Second, on advancing our pipeline with important label expansion opportunities for aficamten and clinical trials of Omecamtiv mecarbil and CK-586. And third, on investments in our muscle biology platform. The anticipated year-over-year growth in operating expense will primarily be driven by the investments toward commercial readiness for the potential launch of aficamten for patients with obstructive HCM.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Our strong balance sheet and access to further capital position us well to execute on our strategy, which we believe could lead to sustainable growth driven by a specialty cardiology franchise. With that, I'll hand it back to Robert.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you, Sung. Our progress in the fourth quarter 2024 has set the stage for a pivotal year ahead. As we approach the potential U.S. approval and commercial launch of aficamten in 2025, we are strategically aligning our longer-term vision while sharpening our operational focus for near-term milestones and progress. With the right infrastructure, capabilities, partners, and team in place, we are confident in our ability to execute and achieve multiple successes within our growing reach.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Earlier this year, we laid out our Vision 2030, our five-year strategic objectives designed to propel Cytokinetics to become the leading muscle-focused specialty biopharmaceutical company intent on meaningfully improving the lives of patients through global access to innovative medicines. Vision 2030 serves as an aspirational roadmap made up of five objectives: innovation, ignition, impact, inspiration, and ingenuity. These objectives articulate how we want to deliver product approvals, achieve broader access to our medicines, promote more equitable access, and advance our pioneering research to benefit patients, shareholders, and employees. Aligned with this vision for our future, we recently announced the appointment of Robert Landry to our board of directors. Bob brings over three decades of financial and operational expertise in the pharmaceutical industry, most recently serving as Regeneron's chief financial officer for 11 years, during which time he helped guide the company as it scaled and commercialized medicines globally.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

We're pleased to have him join our board at this time in our corporate development. Looking at the year ahead in 2025, we will continue to focus on FDA approval and U.S. commercial launch readiness for aficamten and the execution of our ongoing clinical trials programs. Last year, we raised over $1 billion between existing cash and access to new capital, which affords us the runway to execute the U.S. launch of aficamten while also advancing our R&D pipeline and making investments in a fiscally prudent, capital-efficient way to build enduring value for shareholders. I'm optimistic about what our future holds in 2025. So now I'll recap our upcoming milestones. For aficamten, we expect to advance NDA review activities with FDA to support the potential U.S. approval of aficamten in the second half of this year.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

We expect to advance go-to-market strategies and prepare to commercially launch aficamten in the U.S. in the second half of this year, subject to approval by the FDA. We expect to continue go-to-market plans in Germany and expand commercial readiness activities in Europe in 2025 in preparation for potential approval by the EMA in the first half of 2026. We expect to coordinate with Sanofi to support the potential approval of aficamten in China in the second half of 2025, pending approval by the NMPA, and we expect to report top-line results from MAPLE-HCM in Q2 of this year. We also expect to complete enrollment of ACACIA-HCM in the second half of this year and to complete enrollment of the adolescent cohort in CEDAR-HCM also in the second half of 2025.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

For omecamtiv mecarbil, we expect to continue patient enrollment in COMET-HF through 2025 to enable completion of enrollment in 2026. For CK-586, we expect to complete enrollment of the first two patient cohorts in AMBER-HFpEF in the second half of this year. And for CK-089, we expect to complete the phase I study this year. And finally, for our preclinical development and ongoing research, we expect to continue ongoing preclinical development and research activities directed to additional muscle biology-focused programs. Operator, with that, we can now open the call to questions, please.

Operator

Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we do ask that you kindly limit yourself to one question at this time. Please stand by while we compile the Q&A roster. And our first question will come from Paul Choi from Goldman Sachs. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good afternoon.

Khalil Fenina
Khalil Fenina
Equity Research Analyst at Goldman Sachs

Hi, everyone. Good afternoon to you too. This is Khalil calling in for Paul. I guess our question could be on MAPLE-HCM. If the results are positive, how should we think about the timeline for a potential label expansion, assuming approval in September? And then how would the positive results fit into the company's marketing strategy in the interim? Thank you so much.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

So I'll turn first to Fady to answer the first part, and then to Andrew, the second part, please.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Yeah, hi. I think in terms of timing to label expansion, we would certainly be looking at the results and deciding whether to-with the timing for that, I would expect it to come into 2026 as opposed to 2025, given our PDUFA date right now is September 26th of 2025, but I think it'll all depend on timing and whatever else is going on at that time.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

In terms of the marketing strategy, the second study really offered confirmatory evidence of a primary study, both safety and efficacy, which is reassuring to physicians seeing a lot of the same primaries and secondaries. It opens up a cohort of cardiologists who really treat with beta blockers alone. There's really about 2,000 cardiologists of 500 or with the vast majority of prescribers of CMI today. And per our market research, this would open up to more prescribers who many of them feel like maybe beta blockers is good enough. And it offers that additional evidence and maybe even influencing guidelines and move treatment to first line over time, but that certainly takes a lot longer.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Yeah, just to maybe echo what Andrew is saying, sorry, just to add a comment to Andrew's, I do believe that MAPLE-HCM, were it to be positive, could contribute to more category growth as potentially more cardiologists would be more comfortable prescribing a cardiac myosin inhibitor. And on top of that, we would hope it would add to more category penetration for aficamten into that larger market. But I would consider it more incremental than transformative to what we would hope would be the label opportunity provided by SEQUOIA-HCM.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Great. Thank you.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. And our next question will come from Cory Kasimov from Evercore ISI. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Corey.

Cory Kasimov
Cory Kasimov
Senior Managing Director and Fundamental Research Analyst at Evercore ISI

Hey, good afternoon, guys. Hey, good afternoon. Thanks for taking the question. So following up on Andrew's prepared comments on market expansion, I think it's pretty well established that HCM is a highly underdiagnosed condition. So curious kind of as to your expectations as to how this changes over time when there's two companies on the market educating and promoting the benefits of cardiac myosin inhibitors. If it really is on the order of 70% to even 80% of patients as yet undiagnosed, is there a good proxy of where this rate may get to, say, three to five years from now? Thank you.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you. I'll turn to Andrew, please.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Sure. So great question. I think, as you know, when guidelines get adjusted, when studies are out, when us and others are at conferences where physicians go to learn about emerging data, those certainly increase penetration of market and increase diagnosis with awareness and education. I think what we've seen over the last few years is obstructive HCM has continued to increase diagnosis rates around with population, but the non-obstructive is growing at a double-digit rate. So I think over time, non-obstructive may be even 50/50 or slightly larger than obstructive in terms of overall patient population. The estimate we have right now is about 30% or so of the population is diagnosed. And given these rates and kind of where they're going, that certainly could be in the 50% range in the next, say, three to five years.

Cory Kasimov
Cory Kasimov
Senior Managing Director and Fundamental Research Analyst at Evercore ISI

Perfect. Thank you.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Now, in terms of comps, we're reviewing the landscape as well. And I do believe that the amyloidosis space and the pulmonary arterial hypertension space both afford comps in terms of what a next-in-class drug could mean in terms of increased diagnosis and also category penetration. We look at those as good proxies.

Cory Kasimov
Cory Kasimov
Senior Managing Director and Fundamental Research Analyst at Evercore ISI

All right. Sounds good. Appreciate it. Thanks, guys.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Thank you. Our next question will come from Salim Syed from Mizuho. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Salim.

Salim Syed
Salim Syed
Managing Director and Senior Biotechnology Analyst at Mizuho

Great. Hey, Robert. Thanks for the question. One question we're getting a lot on, I'm sure you guys are as well. We'd just love to get your view. It's just the upcoming Edgewise data set, the 28-day. We just sort of love to see how you're framing it, anything you're looking out for there. And also just related to that, do you think there's any even remote possibility that if they were to progress, come out of this without any REMS at all? Thank you. Based on the preclinical data, at least. Thank you.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah, it's a very slippery slope, obviously, that we won't go down to comment on another company's ongoing development program. But I still appreciate the question. With that said, it's early days, and I'll turn to Fady to comment on this matter much as he's been asked by others, but I would suggest that we let the data and evidence speak for itself. Fady?

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Yeah. Hi, Salim. I think it's still, as Robert said, early in the program. I think in order to understand the safety profile of a drug that's going to be used in thousands of people, you're going to need hundreds of people's worth of data. And until you understand that, it's premature to comment, even if I were to comment on their eventual safety profile and monitoring. So I'll probably just leave it there.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

We're looking forward to seeing the data. Obviously, these data will be telling as to whether there is an opportunity to land a new mechanism treatment in oHCM that would be potentially differentiated. We're very pleased with the data we have supporting aficamten, both as it relates to efficacy as well as safety, ease of use, and other things that were designed into aficamten consistent with intrinsic properties, and as we look forward to potential approval and potential commercial launch, we're very confident that we're situated in a very positive place. With that said, we'll take a look at these data as they may come out later, I guess, in the first quarter from what we gather.

Salim Syed
Salim Syed
Managing Director and Senior Biotechnology Analyst at Mizuho

Okay. Perfect. Thank you so much.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. Our next question comes from James Condulis from Stifel. Your line is open.

James Condulis
James Condulis
Associate Vice President of Biotechnology Equity Research at Stifel

Hey. Thanks so much. Good afternoon. Thanks for taking my question and congrats on all the progress. I just want to ask one kind of quick question on the REMS. And totally appreciate there's only so much you can say, but wanted to get your thoughts on if you expect mavacamten's REMS to be eased in the US as well. And sort of if that happens, how does that change how you sort of think about the range of scenarios for kind of what aficamten's REMS looks like? Again, sort of in that scenario, would you define differentiated REMS as still differentiated in sort of the maintenance setting as well? Or does that become more about some of the other aspects of the REMS? Just curious what you can share there. Thanks.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah. Here again, I'm going to be careful not to make any comparative statements. But I will say we noted with interest the BMS earnings call and its reporting on the changes as it relates to EMA label. And we'll look forward to learning, I guess, in Q2 how FDA may respond to an application to ease certain restrictions relating to the existing REMS for mavacamten, Camzyos. We've done a lot of market research, and there are points of differentiation that we continue to believe are quite meaningfully important for aficamten as are consistent with intrinsic properties. And echo frequency is one of those, but so are there several others. And maybe I'll ask Andrew to comment on the market research we've done and our expectations for a differentiated risk mitigation profile if approved.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Yeah. Thanks, Robert. So differentiation, I mean, maybe we'll just start with the data. The data should inform the label, which is our guidelines for claims around differentiation. There are many aspects of differentiation that we're exploring and that are going well from a market research point of view. This could be one of them, or this could be in parallel, but there's others. I think if this does get relaxed for the whole category, this is actually good for the category. The vast majority of patients are not treated today with a CMI. If less frequent monitoring in the maintenance phase gets more patients on board with a CMI, gets more physicians to treat with a CMI, it's kind of high tide lifts all boats. So we look forward to what the FDA has to say. I believe the date is April.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

We'll certainly go from a differentiation given how our label is informed by the data.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

We've said this many times, that our goal is to ensure that more cardiac myosin inhibitors are used by more cardiologists for more patients. And still, to our estimates, there are over 80% of eligible patients who could stand to benefit from use of a cardiac myosin inhibitor. And with prevalence growing, that number increases. We believe strongly that aficamten, if approved, will have a differentiated profile, both as it relates to label and risk mitigation. So we'll wait and see. I hope that answers your question.

James Condulis
James Condulis
Associate Vice President of Biotechnology Equity Research at Stifel

Yep. I appreciate the color. Thank you.

Operator

Thank you. Our next question will come from Tess Romero from JPMorgan. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hey, Tess.

Tess Romero
Tess Romero
Biotechnology Equity Analyst at JPMorgan

Hi, Robert and team. Thanks for taking our questions tonight, and look forward to ACC. So do you think based on your physician and KOL interactions that it is appreciated that there is not the same pharmacogenomic and DDI liability with aficamten as there is with Camzyos due to the way that the drug is metabolized related to a patient's CYP2C19 genotype versus yours? If not, how do you think you will go about educating doctors around this point? And then relatedly, to be clear, will any monitoring be needed by the pharmacy around concomitant meds with aficamten? Thanks so much.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good questions. Maybe I'll ask Fady and Stuart to comment, and then Andrew if he wants to add anything.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

I think, Tess, your question really ultimately is going to depend on the labeling that we achieve with aficamten. But I think physicians that we've interacted with, even that have conducted our clinical trials, recognize a difference, say, that the drug interaction profile of aficamten doesn't involve 2C19, that it has very few meaningful drug interactions. And they certainly have been educated to that fact and act accordingly. The monitoring of concomitant medications is something that's always done. There's no drug in the universe that is not susceptible at all to any drug interactions, even aficamten, but any drug interactions we have would be reasonably rare and uncommon. And physicians would be educated on those as well. But I doubt that there's necessarily a need for a monitoring program or anything like that. We haven't done that in our clinical trials and haven't had any issues to date.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

For clarification, you asked about pharmacy. Stuart or Andrew, do you want to comment on that?

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Pharmacy.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Education.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

I mean, we're not expecting, I think, in our base case that from any REMS program that pharmacy monitoring would be part of a REMS program where a pharmacy has to call a patient and talk about existing drugs and potential drug interactions. That is not something that we're anticipating.

Tess Romero
Tess Romero
Biotechnology Equity Analyst at JPMorgan

Thank you, guys.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. Our next question comes from Leonid Timashev from RBC Capital Markets. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good afternoon.

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

Hey, guys.

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

Yep. Thanks for taking my question. I wanted to ask on the endpoints for ACACIA-HCM and maybe some comparison to the competitor in nHCM study. And I don't mean to corner you into commenting on someone else's study, but I guess, can you talk about any potential differences in KCCQ-23 versus KCCQ-12 and maybe why you settled on a single primary focusing on KCCQ rather than also including pVO2 as a primary and sort of whether that was based on your own diligence of your own data or in consultation with the FDA? Yeah, just any thoughts there would be appreciated. Thank you.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Sure. I'll ask Fady and also Stuart if he wants to comment.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Yeah. Well, like I say, I think the KCCQ is a patient-reported outcome. We examined the impact of aficamten on KCCQ in our phase two study in nHCM. And while that was an open label experience, there was a meaningful impact on KCCQ. That said, I think that regulators in general would like to see an impact of a drug on more than just KCCQ. They'd like to see improvements in exercise and in NYHA class, a consistency, if you will, across functional and symptomatic endpoints. And ACACIA is currently designed has both. It has an exercise endpoint as a secondary endpoint, as KCCQ as a primary endpoint. As you pointed out, ODYSSEY has a dual primary endpoint with both pVO2 and KCCQ in parallel assessed as part of a primary. I think, practically speaking, there's not that much of a difference between the two approaches.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

They are both designed to assess the strength of the evidence with respect to a patient-reported outcome and other functional metrics. And I think regulators clearly want to see a consistency across both of those domains.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hopefully, that answers your question, Leo.

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

That's great. Thank you.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. And our next question will come from Akash Tewari from Jefferies. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Akash.

Zaki Molvi
Zaki Molvi
Senior Associate of Biotech Equity Research at Jefferies

Hi. This is Zaki on for Akash. Thanks so much for taking the question. So in terms of non-obstructive HCM, so it looks like Bristol's ODYSSEY and your ACACIA trial, you're both looking to dose patients up to achieve higher exposures. And so when I look at Redwood cohort 4, it looks like the final proBNP levels are similar to mavacamten's lower dose cohort. So I think the key question is whether you can actually show more efficacy by getting patients onto the 20-mg dose in ACACIA. So based on the SEQUOIA data you've seen so far, how easily do you think you can actually keep patients on the 20-mg dose without EF issues for the whole 36-week period? And also, is there any sense on whether slower titration like we're seeing in ODYSSEY might be better in the nHCM population?

Robert Blum
Robert Blum
President and CEO at Cytokinetics

That's a multi-part question, and I'll ask Fady and Stuart to tackle it.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Maybe I'll take it. I think just to be simple and concise, the Redwood data, we dosed patients between five and 15 mg. 85% of the patients got up to 15 mg, and were there within six weeks of initiation of therapy. Many of those patients were still eligible to up-titrate to 20 mg. I don't think fundamentally there's any difference between the cardiac function of an nHCM patient and an oHCM patient. One could expect a similar dose distribution in the two groups, perhaps even a bit skewed to the high side in nHCM because you don't stop titrating based on achieving the targets with respect to gradients. What we saw in Redwood was that NT-proBNP decreased in a dose-dependent manner. The higher doses produced greater decrements in NT-proBNP.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

And so I think the strategy that we've adopted in ACACIA is built very tightly on what we did in Redwood. It's a one-to-one. The dosing strategy is almost the same. The speed of dosing is almost the same. And I think all of those things are helpful when you design a phase III study on the basis of a phase two study. So I think we're pretty confident with how we've addressed dosing in that trial.

Zaki Molvi
Zaki Molvi
Senior Associate of Biotech Equity Research at Jefferies

All right. Thank you guys so much.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thanks.

Operator

Thank you. Our next question will come from David Lebowitz from Citi. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, David.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hi. This is Ike Lee on for David Lebowitz. Thanks for taking the question. We are wondering if you can orient us on expectations, particularly on the exercise capacity primary endpoint heading into the MAPLE-HCM readout. Are we looking for a similar level of benefit this time head-to-head versus beta blockers as we did in SEQUOIA-HCM, something like 5%-8%, maybe 10% improvement over baseline exercise capacity? And is there any change in the level of clinical meaningfulness for this one as opposed to the trials run before since the endpoint is the same? Thanks.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good questions. We'll probably want to answer them in terms of how the study was designed, what it was powered to demonstrate. And I'll ask Fady to comment on that, please.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Sure. So MAPLE was designed as a trial to assess the impact of aficamten and metoprolol on exercise capacity. And it's powered to about a 2.0 difference between the two. As we had in SEQUOIA, achieved 1.75. I think that's a pretty reasonable expectation. 1.75 was very, very highly statistically significant. I think when you get to questions of clinical meaningfulness, anything above one is thought to be clinically meaningful. And certainly, the 1.74 that we achieved in SEQUOIA is we consider that clinically meaningful. There are data that show that mortality and morbidity are potentially tied to peak VO2, and then changes in peak VO2 of that magnitude have substantial impacts on long-term morbidity and mortality. So I think any of those changes, 5%-8%, 10%, would represent clinically meaningful differences between the two.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

And again, as I said earlier, it's not necessarily just going to be all about what's the difference between peak VO2, but it's going to be a consistency of treatment effect across endpoints. It's going to be safety. It's going to be tolerability. All of those things, I think, should be considered in considering how aficamten performs as monotherapy compared to metoprolol performing as monotherapy.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thanks for the question.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. And our next question will come from Sean McCutcheon from Raymond James. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Sean.

Sean McCutcheon
Sean McCutcheon
VP at Raymond James

Hi, guys. Good afternoon, and thanks for taking the question. Maybe to build on the last question. For MAPLE, you're enrolling patients with a percent predicted peak VO2 of less than 100%, whereas in SEQUOIA, for the most part, outside of one patient, you are enrolling less than 80% predicted. How should we be thinking of this patient population as it relates to obstruction-driving exercise capacity deficits and how that contrasts with SEQUOIA, if at all? Thanks.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

Hi. This is Stuart Kupfer. I think that what we observed in SEQUOIA-HCM was that that threshold, less than 90% or less than 80%, did not make a significant difference in terms of the incapacity of these patients. I think it was apparent that because of the degree of obstruction and the fact that these patients were significantly symptomatic, they already had a significant deficit in their exercise capacity. So we just realized we could relax that criteria and still enroll patients with quite significant deficit that we believe that these patients could benefit from aficamten treatment.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thanks, Sean.

Sean McCutcheon
Sean McCutcheon
VP at Raymond James

Thank you.

Operator

Thank you. And our next question will come from Kripa Devarikonda from Truist Securities. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Kripa.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hi. It's actually Alex from Kripa. Thanks, and we are excited about the progress in 2025. One commercial question for us. We've heard with mavacamten that treatment by cardiologists in their practice centers may be limited to insufficient numbers of monitoring equipment to adjust the large volumes that they see, and patients have been referred to more specialist centers. Wanted to know on your end, have you heard this? Is there potential for future treatment with aficamten to be administered by a broader range of HCPs? And does your market research highlight any bottlenecks related to equipment readiness in target markets outside the U.S. as well as the U.S.?

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah. So we noted your equity research analyst note to that effect and where some of the echo infrastructure was perhaps impeding adoption beyond centers of excellence. Maybe I'll ask Andrew to comment on what he's learned from market research with regard to that and how that may or may not extrapolate to learnings in Europe.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Sure. So we looked at ECHO capacity across the U.S., both within specialized centers, academic centers, city centers, as well as community. And it is currently not a burden or anything that's kind of reducing the capacity is not allowing patients to potentially get treated. So I think there's other challenges with starting treatment outside maybe academic centers and centers of excellence, but it's not related to ECHO capacity largely. When we looked at Europe, Europe is a more concentrated market than the U.S. Typically, Europe, you have to start in a hospital, in a community center. It's not as diverse in terms of the number of physicians' offices you have to go to, usually going actually to a center.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Because Europe has a single payer system generally by country, and as part of the reimbursement process for a specialty medication, it's pretty typical for prescribing to be limited to one of these institutions, and these institutions have capacity as well.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

It's difficult sometimes to distinguish between what's cause and effect or which is the cart and which is the horse. We do believe that a majority of Camzyos use currently is amongst a concentrated number of prescribers who happen to be in centers of excellence. And with more experience comes ability to navigate through a REMS program. So can you extrapolate that to mean that there's less of an issue outside of centers of excellence? We look at this as experience with cardiac myosin inhibitors in general is correlated with broader and more adoption of the existing cardiac myosin inhibitor. Our hope is if aficamten is approved, that we can contribute to more education, more awareness, more category growth and expansion beyond centers of excellence, as could be a rising tide to lift the class.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

That could hopefully confer benefit to aficamten as we hope it becomes a category leader independent of what may be any concerns relating to ECHO capacity. I hope that helps.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Yeah. Makes a lot of sense, and thanks. We're all looking towards the year ahead.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. Our next question comes from Roanna Ruiz from Leerink Partners. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good afternoon.

Roanna Ruiz
Roanna Ruiz
Senior Research Analyst at Leerink Partners

Hi. Good afternoon, everyone. So a slightly different question from me. I was curious if you could elaborate a bit more on your future goals for, I think you mentioned BD and corporate development in the coming years. It sounds like you're willing to consider augmenting your R&D pipeline. Curious of any color on stage of asset mechanisms, indications, etc., that you'd be interested in internally or externally. And how would you balance that with your current cash runway expectations today?

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah. So I'll ask Isaac to comment first, followed by Sung, and then I may have a few comments after that.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

Sure. Thanks so much for the question. The most important thing for us is to make sure that we continue to focus on our expertise in the muscle biology and be able to look at a landscape both of us being developed externally as well as internally to make sure that we can help advance the most advanced programs that are available. So from a licensing perspective, we have been and are actively in discussions with both academics and research centers where there are preclinical programs, but also looking at early-stage clinical development programs where we can use our own expertise to advance these programs forward. We're obviously looking at that from being prudent from a financial perspective and where we think we can have the greatest impact.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

Our focus has been on small molecules, and as we've made comments earlier in our talk, that being able to look at other modalities is something that is very important to us because we see that happening within the field, and we want to make sure that we are in the forefront.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Yep. And Roanna, in terms of cash runway, we believe we have multiple years of runway as we start the year. And this is supported by our starting cash balance of $1.2 billion. Also, we have access to further capital, as you know, from Royalty Pharma up to $500 million. We'll also benefit from some near-term milestones from the BD deals we closed last year related to aficamten XUS. So we're in a very strong position here. Specific to this year, we expect cash utilization to be in the low $500 millions. So you can kind of work out the math there that with all the things that I've described in terms of sources of capital, we believe we have multiple years on the runway right now.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah. And just to elaborate a little bit, our focus, to be clear, remains on aficamten and our later-stage pipeline, and that's where our investment capital is best deployed. The things that Isaac was referring to are more intentional to augment, complement, and provide adjacency to things we're doing in earlier stage of our research. And the capital investments alongside of that will be modest relative to the overall spend. So this is more about building training wheels for Cytokinetics as we want to execute on our Vision 2030 alongside of the things we're doing organically to provide some inorganic complement, especially as could be adjacent to things we're already doing where we can mitigate risk and with new modalities enable a transition to some non-small molecule approaches. Don't confuse that to mean we're going to go into more expensive modalities like gene therapies and cell therapies.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

That's not our intention.

Roanna Ruiz
Roanna Ruiz
Senior Research Analyst at Leerink Partners

Understood. Thanks.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Operator

Thank you. And our next question comes from Joe Pantginis from H.C. Wainwright. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Joe.

Joe Pantginis
Joe Pantginis
Managing Director of Equity Research at H.C. Wainwright

Hey, everybody. Thank you for taking the question. Good afternoon. So I'm not sure if you could discuss this right now because everything is active, but upcoming to your Mid-Cycle Meeting with the FDA, anything you could discuss about key questions that are still outstanding or any potential rate-limiting steps? And then also with regard to omecamtiv mecarbil, anything you might be that you can share regarding COMET-HF and the enrollment trajectories, say, related to GALACTIC-HF since there are additional screening criteria. Thanks.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Sure. So you answered your own question with respect to ongoing FDA interactions. We can't really comment other than to say that we feel very good about how we're situated in light of the ongoing activities. And as we approach a Mid-Cycle Meeting, we believe we're in a good position to address any questions we may be getting from FDA. As it relates to COMET and enrollment sites relative to GALACTIC, maybe I could ask Fady or Stuart to comment on that.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Thanks, Joe. So as you know, we began enrollment in COMET-HF late last year. And we have an advantage of leveraging all the information we have from GALACTIC-HF in terms of the best investigators to participate in the trial. And we have the advantage of a great data set to draw from demonstrating the, I think, the hypothesis that omecamtiv mecarbil will be even more effective in these higher-risk patients. And so enrollment is proceeding as estimated. We will continue enrollment through the year. We plan to complete enrollment next year. And so studies are proceeding according to plan.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

To your question, we're borrowing a lot of learnings from GALACTIC, and we believe we're in an advantaged situation for having conducted GALACTIC to know where to go for COMET so that trial can enroll rapidly. We'll have more to say about that through the year.

Joe Pantginis
Joe Pantginis
Managing Director of Equity Research at H.C. Wainwright

Thanks again.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Thank you. Our next question comes from Mayank Mamtani from B. Riley Securities. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Good afternoon.

Mayank Mamtani
Mayank Mamtani
Senior Managing Director, Group Head of Healthcare Research and Senior Biotechnology Analyst at B. Riley Securities

Good afternoon, team. Thanks for taking our questions and congrats on the progress. Just maybe switching gears to CK-586 HFpEF study. I think you mentioned the first two cohorts, low and mid-dose level enrolling and completion by end of this year. Could you maybe just talk to if the higher-dose cohort is contingent on completion of the first two cohorts and maybe just what you're looking to learn on both the tolerability and obviously the biomarkers there in the HFpEF study? Thanks for taking our question.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Sure. Maybe I'll ask Stuart to tackle that, please.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

Sure. Thank you. The study is intentionally designed to be flexible. And so as you noted, our intent is to complete the first two cohorts by the end of the year. And based on the information that we retrieve from those two cohorts, then we would consider if we need to proceed with the third cohort or perhaps with a different dose. It is a flexible design, and I think that really strengthens the study. With respect to the endpoints in the trial, first and foremost, we're evaluating safety and tolerability in this HFpEF population. We'll be collecting biomarker data, cardiac biomarkers, NT-proBNP, as well as assessing pharmacokinetics and evaluating effects on ejection fraction. And so those are some of the key endpoints that we'll be evaluating. This is mainly a dose-finding type of study.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you. Hopefully, that answers your question.

Mayank Mamtani
Mayank Mamtani
Senior Managing Director, Group Head of Healthcare Research and Senior Biotechnology Analyst at B. Riley Securities

Yeah, it does. Thank you. Appreciate it.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you.

Stuart Kupfer
Stuart Kupfer
SVP and Chief Medical Officer at Cytokinetics

Thank you.

Operator

Thank you. Our next question comes from Yasmeen Rahimi from Piper Sandler. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Yasmeen.

Yasmeen Rahimi
Yasmeen Rahimi
Managing Director and Senior Research Analyst at Piper Sandler

Hi, Robert. Thank you so much for all the great updates. I guess one of the questions that we were wondering about is recently the baseline demographics of the ODYSSEY study was published. And I would love to maybe get Fady's thoughts on that study and what stood out to you. Just some commentary. I appreciate the commentary throughout the call that positive data from ODYSSEY from MAPLE could continue to grow the uptake of CMIs in this big market. I mean, we're talking about a million patients, which is a big market, a high addressable population. So you could just kind of comment around that. I know ACACIA is currently fully in enrollment mode, but maybe if there are any differences that stand out to you as you look at that baseline population would be helpful. And I'll jump back in the queue.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you. Fady?

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

Yeah. Hi. I mean, I think the baseline characteristics were not unsurprising. These are people that have significant symptoms. They have elevated biomarkers, reduced exercise capacity, all of those things that we expect to see in a population that is an HCM population. I think what is surprising is how similar they are to the oHCM patients with the exception of a gradient in the biomarker and other deficits that they have. So I think that it speaks to the fact that there are a lot of highly impacted patients within HCM. We've seen both their trial enroll very well. We've seen our trial enroll very well. This is a condition that's probably not as uncommon as people originally thought. And I think the effectiveness of CMIs in them will be elucidated by the results.

Fady Malik
Fady Malik
EVP of R&D at Cytokinetics

But their similarity in lots of ways to the oHCM patients, I think, bode well for what we might expect to see.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Thank you, Fady.

Operator

Thank you. And our next question comes from Charles Duncan from Cantor Fitzgerald. Your line is open.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Hello, Charles.

Charles Duncan
Charles Duncan
Managing Director at Cantor Fitzgerald

Hey, good afternoon. Hey, Robert and team. Congrats on a great year of progress. Lots of good questions asked, so I will send one in terms of biz dev. I'm just kind of wondering if you could characterize the kind of work that Sanofi did in terms of the China market. It seems like, obviously, it could be quite large. Wondering if you could provide any color on, call it, the unmet need there and how you might see it pace in terms of it being developed. And would you anticipate milestones yet this year in terms of cash payments or even early next year? Thanks.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Yeah. So we've been very impressed by the degree to which Sanofi has jumped in and dialed up and stepped up in meaningful ways. I'll ask Isaac to comment on that and then Sung to speak to your second part of your question.

Isaac Ciechanover
Isaac Ciechanover
EVP, Corporate Development and Chief Business Officer at Cytokinetics

Sure. So as Robert said, we've been very impressed with Sanofi and their process. To be clear, this was a transaction that was done through Corxel and Sanofi. But what we understand is there were multiple parties interested. There is a clear understanding of an unmet need in China. There are no REMS programs in China. So I think from that perspective, it went into Sanofi's value proposition of being able to go and take advantage of all the benefits of aficamten. And so they stepped into the collaboration. I can tell you that since then, we have a very active dialogue with them as part of the potential approval this year. There are, as you know, milestones associated with approval, but again, they depend on that event happening in this calendar year. If not, they'll be pushed into 2026.

Sung Lee
Sung Lee
EVP and CFO at Cytokinetics

Yeah. And Charles, just expanding on the milestone question, we do expect meaningful milestones this year. And I would say these milestones, of course, we have multiple partners here, so I'm not going to be specific to a single partner. But these milestones are tied to clinical and regulatory milestones. So just to give you some color, we could be eligible up to $35 million in total across our partners. And then, as I mentioned, they've stepped up in some meaningful ways in terms of timelines, forecasts, manufacturing, and supply requirements.

Robert Blum
Robert Blum
President and CEO at Cytokinetics

Maybe I'll ask Andrew to comment on market sizing in China. Andrew, are you on mute?

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Yeah. Sorry. Yeah, Charles. So in terms of population, China is also a concentrated market. There's around 400,000 diagnosed patients. And there's a little over 1,000 hospitals where the vast majority, over 80% of those patients are. There's likely a lot more patients in the rural and community settings that aren't diagnosed. So that could certainly.

Executives
    • Isaac Ciechanover
      Isaac Ciechanover
      EVP, Corporate Development and Chief Business Officer
    • Sung Lee
      Sung Lee
      EVP and CFO
    • Robert Blum
      Robert Blum
      President and CEO
    • Fady Malik
      Fady Malik
      EVP of R&D
    • Andrew Callos
      Andrew Callos
      EVP and Chief Commercial Officer
    • Stuart Kupfer
      Stuart Kupfer
      SVP and Chief Medical Officer
    • Diane Weiser
      Diane Weiser
      Senior VP of Corporate Affairs
Analysts
    • Charles Duncan
      Managing Director at Cantor Fitzgerald
    • Salim Syed
      Managing Director and Senior Biotechnology Analyst at Mizuho
    • Leonid Timashev
      Biotechnology Analyst at RBC Capital Markets
    • Tess Romero
      Biotechnology Equity Analyst at JPMorgan
    • James Condulis
      Associate Vice President of Biotechnology Equity Research at Stifel
    • Khalil Fenina
      Equity Research Analyst at Goldman Sachs
    • Analyst 2
    • Joe Pantginis
      Managing Director of Equity Research at H.C. Wainwright
    • Cory Kasimov
      Senior Managing Director and Fundamental Research Analyst at Evercore ISI
    • Analyst 1
    • Sean McCutcheon
      VP at Raymond James
    • Zaki Molvi
      Senior Associate of Biotech Equity Research at Jefferies
    • Mayank Mamtani
      Senior Managing Director, Group Head of Healthcare Research and Senior Biotechnology Analyst at B. Riley Securities
    • Yasmeen Rahimi
      Managing Director and Senior Research Analyst at Piper Sandler
    • Roanna Ruiz
      Senior Research Analyst at Leerink Partners
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