Cytokinetics Q4 2024 Earnings Call Transcript

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Provided by Quartr
February 27, 2025
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Operator

Good afternoon, and welcome to Cytokinetics Fourth Quarter twenty twenty four 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.

Operator

Please go ahead.

Diane Weiser
Diane Weiser
Senior Vice President 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 Kalos, EVP and Chief Commercial Officer, will address commercial readiness activities for afikamten Fadi Malik, EVP of R and D, will provide updates related to recent regulatory interactions in the clinical development program for afikamten Isaac Sihanover, 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-five eighty six 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.

Diane Weiser
Diane Weiser
Senior Vice President of Corporate Affairs at Cytokinetics

And finally, Robert will review expected key milestones for the year ahead. 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 twenty twenty four financial results filed on Form eight K that was furnished to the SEC today. We undertake no obligation to update any forward looking statements after this call.

Diane Weiser
Diane Weiser
Senior Vice President of Corporate Affairs at Cytokinetics

And now, I will turn the call over to Robert.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you, Diane, and thanks to all for joining us on the call today. The fourth quarter of twenty twenty four 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 afacamten 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.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Now with regulatory submissions on file in The U. S, Europe and China, we're engaging in parallel regulatory interactions that may deliver afacamfet to patients around the world. With our PDUFA date of 09/26/2025, 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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

In the

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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 one hundred and twenty 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 misreadigation profile for afikamten were it to be approved by FDA.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

In both Sequoia HCM and Forest HCM, in patients with O HCM, 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 affikamten. Moving on to the regulatory review of Afikamten 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 Afikamten ourselves in The U.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

S. And Western Europe. In other key geographies in the fourth quarter, Sanofi acquired with our participation from Korzell, the rights to develop and commercialize Afikampton in China. Additionally, in November, we announced our new collaboration with Bayer that entails a license agreement for Afikamten in Japan. These two strong pharmaceutical company partners in the two leading markets outside The U.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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 afacamten 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 afacamten with multiple ongoing potential label expansion clinical trials. 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 afikamten following potential FDA approval.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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 COVID HF, a confirmatory Phase III clinical trial of omecamtiv in patients with heart failure with severely reduced ejection fraction. And more recently, we started AMBER HFATH, a Phase two clinical trial of CK-five eighty six 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. This year, we're approaching a defining moment with key milestones ahead that will shape our future.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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 afikantan are well underway with significant momentum in 2024 and setting up what is the final stretch towards a 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 afacamten galvanizing and activating new cardiologist prescriptions, securing access and an affordable co pay for people with HCM and providing exceptional patient support.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

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 acycantin 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 afacamten. 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.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Initial engagement metrics with the website and emails 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 in 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 apacamten, which is currently being tested with HCPs. To support our goal of ensuring product and market access post approval, we have continued our engaging with payers while advancing implementation of our robust patient support program.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

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 are 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 ready activities in international infrastructure to support a potential European approval of afacamten.

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 French and The UK, 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 UK and Western EU markets. I'm pleased with the progress we've made to prepare for both The U. S. And European commercial launches of apicamten and where we are positioned today on our commercial readiness roadmap.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

With that, I'll turn the call over to Fady.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Thanks, Andrew. As Robert mentioned, we recently submitted the one hundred and twenty day safety update to FDA with an additional ten months of safety data from FOREST ACM. These longer term data are consistent with the previously presented data from FOREST ACM and the safety profile of afacamten as reflected in the NDA submission with we believe no evidence of an increased risk of EF excursions or heart failure events. As FDA reviews the NDA, we're continuing to answer their questions and prepare for clinical site and other inspections. As Robert mentioned, we also expect to participate in a mid cycle meeting with FDA in March.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Moving on to our work in the fourth quarter to expand the evidence base for apicamten at the American Heart Association Scientific Sessions in November, we presented data from two pre specified analyses of SEQUOI 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 afikamten. 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 and scientific discussions related to OHCM and apicamten and notified payers of our PDUFA date. Scientific engagement with HCM specialists also continued with discussions focused on the results from SEQUOI HCM, including the primary results and secondary data analyses. Now shifting to the ongoing clinical trials program for apicamten.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Having completed enrollment in Maple HCM in the third quarter of last year, we continue to conduct a 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 will provide an opportunity to elevate apukamten as a potential monotherapy for the treatment of OHCM following approval. Meanwhile, we've continued to conduct ACATIA HCM pivotal Phase III clinical trial in non obstructive HCM, CDER HCM and pediatric population of patients with symptomatic OHCM and of course, FORST HCM, the ongoing open label extension clinical study. Horace HCM continues to grow with now over 400 patients enrolled, nearly three hundred patients have at least a year of follow-up and over ninety have two years of follow-up.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

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 apikamten 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, such that we expect it to eventually represent nearly half of HCM 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
Executive Vice President of Research & Development 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 afikamten as we approach the potential approval and the launch of afikamten 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, Daddi. As Robert mentioned, we secured two new partnerships in the fourth quarter, which together will support the development and commercialization of Afikampton in critical global geographies. We were pleased to enter into a collaboration and licensing agreement with Bayer for the development and commercialization of epikamten in Japan. This deal stands alone in terms of its favorable economics for a cardiovascular drug. EUR fifty million in upfront payments to Cytokinetics, eligibility to receive an additional million tied to milestones through the commercial launch, million in commercial milestone payments from buyer upon their achievement of certain sale milestones and tiered royalties on net sales of epicanthine in Japan.

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

To support the potential marketing authorization of epicanthine 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. Bio, 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 apicamten to patients in Japan. Additionally, during the fourth quarter, Sanofi acquired exclusive rights to develop and commercialize apicamten from Quaraxel, formerly Xijin in China. Through this transaction Cytochrome Netix remains eligible to receive up to $150,000,000 in development and commercial milestone payments from Sanofi and royalties in the low to high teens on sales of apicamten 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 Coraxel. Over the years, we have enjoyed a highly productive collaboration with Coraxel and now we are pleased to partner with Sanofi harnessing their expertise in cardiology to bring epikamten to patients in China. Both of these recent deals serve to expand the potential reach of epikamten in key geographies worldwide. Now with partners onboard in China and Japan and our own commercial infrastructure scaling in The U. S.

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

And Europe, we're turning our attention to how we may further expand our geographic reach with afikamten and how we may also catalyze external R and D activities and pursue new business objectives to augment our existing pipeline alongside innovation from our own labs. 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 02/1930, 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 afikamten to more patients worldwide, as well as how we may augment our R and 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.

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

Now, I'll hand it over to Stuart.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & 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, a cardiac myosin activator. During the quarter, we started COMMON HF, a confirmatory Phase three clinical trial in patients with symptomatic heart failure with severely reduced ejection fraction less than thirty percent. 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.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

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. Investigators with prior experience with omicanthin macarbil have been reaching out to us regularly to inquire about participating in COMMOD HF. And our steering committee is now fully seated with the foremost heart failure leaders from countries where the trial will be conducted.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Now I'll move on to CK-five eighty six, our next cardiac myosin inhibitor. In January of this year, we began AMBER HEPAF, a Phase II placebo controlled double blind trial evaluating the safety, tolerability of pharmacokinetics and pharmacodynamic profile of CK-five eighty six in patients with symptomatic heart failure with preserved ejection fraction and LVEF greater than or equal to sixty percent. AMBER HFpEF is expected to enroll approximately sixty patients in three twelve week dose escalation cohorts with doses ranging from one hundred and fifty to six hundred milligrams once daily. Potential treatment benefits of CK-five eighty six include increased cardiac relaxation leading to improved diastolic function, improvement of heart failure symptoms and increased exercise capacity. And we expect to build a body of evidence in support of these outcomes through this trial.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

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 one study of CK089, a fast skeletal muscle troponin activator. The study comprises of both single and multiple ascending dose cohorts. CK089 arose from our pioneering research in neuromuscular disease and was optimized by our prior learnings. CK089 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
Senior Vice President & Chief Medical Officer at Cytokinetics

We expect to complete this Phase one 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
Executive VP & 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 twenty twenty four with approximately $1,200,000,000 in cash, cash equivalents and investments compared to $1,300,000,000 at the end of the third quarter of twenty twenty four. Cash, cash equivalents and investments declined by approximately $60,000,000 during the fourth quarter of twenty twenty four and benefited from the receipt of $52,400,000 or €50,000,000 payment from Bayer for the exclusive license to develop and commercialize Apicamten in Japan. Moving on to the income statement.

Sung Lee
Sung Lee
Executive VP & CFO at Cytokinetics

The revenues in the fourth quarter of twenty twenty four were $16,900,000 compared to $1,700,000 for the same period in 2023. The revenues for the full year of 2024 were $18,500,000 compared to $7,500,000 in 2023. Total revenues in the fourth quarter of twenty twenty four and full year 2024 benefited from a $15,000,000 upfront payment from Korzell in connection with the assignment of Korzell's rights for the development and commercialization of Afikantin in Greater China to Sanofi. R and D expenses for the fourth quarter were $93,600,000 compared to $85,000,000 for the same period in 2023. R and D expenses for the full year of 2024 were $339,400,000 compared to $330,100,000 in 2023.

Sung Lee
Sung Lee
Executive VP & CFO at Cytokinetics

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 and A expenses for the fourth quarter of twenty twenty four were $62,300,000 compared to $44,100,000 for the same period in 2023. G and A expenses for the full year of 2024 were $215,300,000 compared to $173,600,000 in 2023. 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 twenty twenty four was $150,000,000 or $1.26 per share compared to a net loss of $136,900,000 or $1.38 per share for the same period in 2023.

Sung Lee
Sung Lee
Executive VP & CFO at Cytokinetics

Net loss for the full year of 2024 was $589,500,000 or $5.26 per share compared to a net loss of $526,200,000 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 and D and SG and A expenses to be between $670,000,000 and $710,000,000 Stock based compensation included in the GAAP operating expense is expected to be between $110,000,000 and $120,000,000 Excluding stock based compensation from GAAP operating expense results in a range of $550,000,000 to $600,000,000 Our capital allocation priorities remain the same and our resources will be focused on the following. First, on preparing for the potential U. S.

Sung Lee
Sung Lee
Executive VP & CFO at Cytokinetics

Commercial launch of efikamten in September of this year, including the hiring of up to 150 sales reps in The U. S. In the third quarter of twenty twenty five. Second, on advancing our pipeline with important label expansion opportunities for afikamten in clinical trials of omecamten mecarbil and CK-five eighty six 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 afikamten for patients with obstructive HCM.

Sung Lee
Sung Lee
Executive VP & 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 specialty cardiology franchise. With that, I'll hand it back to Robert.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you, Sung. Our progress in the fourth quarter twenty twenty four has set the stage for a pivotal year ahead. As we approach the potential U. S. Approval and commercial launch of Afikamten in 2025, we are strategically aligning our longer term vision, while sharpening our operational focus for near term milestones and progress.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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. Earlier this year, we laid out our Vision 02/1930, 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 2,030 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.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Bob brings over three decades of financial and operational expertise in the pharmaceutical industry, most recently serving as Regeneron's Chief Financial Officer for eleven years, during which time he helped guide the company as it scaled and commercialized medicines globally. 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 apicamten and the execution of our ongoing clinical trials programs.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Last year, we raised over $1,000,000,000 between existing cash and access to new capital and which affords us the runway to execute The U. S. Launch of apicamten, while also advancing our R and 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.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

For Afikamten, we expect to advance NDA review activities with FDA to support the potential U. S. Approval of Afikamten in the second half of this year. We expect to advance go to market strategies and prepare to commercially launch afikamten in The U. S.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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 twenty twenty six. We expect to coordinate with Sanofi to support the potential approval of Afikampton in China in the second half of twenty twenty five, 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 CDER HCM also in the second half of twenty twenty five.

Robert I. Blum
Robert I. Blum
CEO, President & Director 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-five eighty six, we expect to complete enrollment of the first two patient cohorts in AMBER HFpEF in the second half of this year. And for CK089, we expect to complete the Phase one 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. And our first question will come from Paul Choi from Goldman Sachs. Your line is open.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Good afternoon.

Paul Choi
Paul Choi
Analyst at Goldman Sachs

Hi, everyone. Good afternoon to you too. This is Kahlil 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 potential label expansion assuming approval in September?

Paul Choi
Paul Choi
Analyst at Goldman Sachs

And then how would the positive results fit into the company's marketing strategy in the interim? Thank you so much.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Yes, hi. I think in terms of timing to label expansion, we would certainly be looking to 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 09/26/2025. But I think it all depends on timing and whatever else is going on at that time.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

And in terms of the marketing strategy, the second study really offers 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 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

Got it. Maybe ask what Andrew is saying.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Sorry, just to

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

add a comment to Andrew's. I do believe that maple HCM were 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 afikamten 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.

Paul Choi
Paul Choi
Analyst at Goldman Sachs

Great. Thank you.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you.

Operator

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

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Hello, Cory.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Good afternoon, guys.

Cory Kasimov
Senior Managing Director at Evercore

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 under diagnosed 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 seventy percent to even eighty percent of patients as yet undiagnosed, is there a good proxy of where this rate may get to say three to five years from now?

Cory Kasimov
Senior Managing Director at Evercore

Thank you.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Sure. It's a great question. I think as you know, when guidelines get adjusted, when studies are out, when us and others are at congresses where physicians go to learn about emerging data, those certainly increased penetration of market and increased 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 maybe even be fifty-fifty or slightly larger than obstructive in terms of overall patient population.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

The estimate we have right now is about thirty percent or so of the population is diagnosed. And given these rates and kind of where they're going that certainly could be in the fifty percent range in the next say three to five years.

Cory Kasimov
Senior Managing Director at Evercore

Perfect. Thank you.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes, 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
Senior Managing Director at Evercore

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Hello, Salim.

Salim Syed
Managing Director, Equity Research at Mizuho Securities

Great. Hey, Robert. Thanks for the question. One question we're getting a lot on, I'm sure you guys are as well, I would just love to get your view, is just the upcoming EDGEWISE dataset, the twenty eighth day, we just sort of look to see how your framework in it, anything you're looking out for there and also just related to that.

Salim Syed
Managing Director, Equity Research at Mizuho Securities

Do you think there's any even remote possibility that they 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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes, 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 Fadi to comment on this matter much as he has been asked by others. But I would suggest that we let the data and evidence speak for itself. Fadi?

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Yes. Hi, Selim. I think it's still, as Robert said, early in the program, I think in order to understand the safety profile of the 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 I. Blum
Robert I. Blum
CEO, President & Director 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 afikamten, both as it relates to efficacy, as well as safety, ease of use and other things that were designed into apicamten 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
Managing Director, Equity Research at Mizuho Securities

Okay, perfect. Thank you so much.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you.

Operator

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

James Condulis
Associate Vice President - Biotechnology Equity Research at Stifel Nicolaus

Hey, thanks so much.

James Condulis
Associate Vice President - Biotechnology Equity Research at Stifel Nicolaus

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 U. S. As well and sort of if that happens, like how does that change how you sort of think about the range of scenarios for kind of what Afacamten's REMS looks like?

James Condulis
Associate Vice President - Biotechnology Equity Research at Stifel Nicolaus

Again, sort of like 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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes. 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, Chemsaios. We've done a lot of market research and there are points of differentiation that we continue to believe are quite meaningfully important for Afikampton as are consistent with intrinsic properties. An echo frequency is one of those, but so are there several others.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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

Thanks, Robert. So differentiation 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.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

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 the CMI. If less frequent monitoring in the maintenance phase gets more patients on board with the CMI, gets more physicians to treat with the CMI. It's kind of high tide lifts all boats. So, we look forward to what the FDA has to say.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

I believe the date is April and we'll certainly go from a differentiation given how our label is informed by the data.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

But 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 eighty percent 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 afikamten, if approved, will have a differentiated profile, both as it relates to label and risk mitigation. So we'll wait and see, but I hope that answers your question.

James Condulis
Associate Vice President - Biotechnology Equity Research at Stifel Nicolaus

Yes, I appreciate the color. Thank you.

Operator

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

Operator

open.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Hey, Tess.

Tessa Romero
Tessa Romero
Equity Analyst at J.P. Morgan

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 afikamcin as there is with Kamzios 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 afikansan?

Tessa Romero
Tessa Romero
Equity Analyst at J.P. Morgan

Thanks so much.

Robert I. Blum
Robert I. Blum
CEO, President & Director 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
Executive Vice President of Research & Development at Cytokinetics

I think, Jess, your question really ultimately is going to depend on the labeling that we achieved with apicamten. But the, 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 apicamten doesn't involve 2C19, that it has a very few meaningful drug interactions and 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 at the Campton, but any drug interactions we have would be reasonably rare and uncommon. And physicians would be educated on those as well.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

But I doubt that there's necessarily need for a monitoring program or anything like that. We haven't done that in our clinical trials and haven't had any issues

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

I mean, we're not expecting I think in our base case that a 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.

Tessa Romero
Tessa Romero
Equity Analyst at J.P. Morgan

Thank you, guys.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Thank you.

Operator

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

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

Good afternoon, guys. Yes. Thanks for taking my question. I wanted to ask on the endpoints for Acacia and maybe some comparison to the competitor in HCM study. And I don't mean a quarter unit commenting on someone else's study, but can you talk about any potential differences in KCCQ23 versus KCCQ12?

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

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. Just any thoughts there would be appreciated. Thank you.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Sure. I'll ask Fady and also Stuart if he wants to comment. Yes. Well, let me say

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

I think the KCCQ is a patient reported outcome. We examined its impact the impact of afikamten on KCCQ in our Phase II 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 like to see improvements in exercise and in NYHA class, a consistency, if you will, across functional and symptomatic endpoints.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

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, Odysee has a dual primary endpoint with both peak VO2 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. They both are both designed to assess the strength of the evidence with respect to a patient reported outcome and other functional metrics.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

And I think regulators clearly want to see consistency across those both of those domains. Hopefully that answers your question, Leo.

Leonid Timashev
Leonid Timashev
Biotechnology Analyst at RBC Capital Markets

That's great. Thank you.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Thank you.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Hello, Akash.

Zaki Molvi
Zaki Molvi
Senior Associate, Biotech Equity Research at Cytokinetics

Hi. This is Zaki on for Akash. Thanks so much for taking the question. So in terms of non instructive HCM, so it looks like Bristol's ODDyssey and your ACACHA trial, you're both looking to dose patients up to achieve higher exposures. And so when I look at Redwood cohort four, it looks like the final proBNP levels are similar to MAVERICK's lower dose cohort.

Zaki Molvi
Zaki Molvi
Senior Associate, Biotech Equity Research at Cytokinetics

So I think the key question is whether you can actually show more efficacy by getting patients onto the twenty milligram dose in Acacia. So based on like the SEQUOIA data you've seen so far, how easily do you think you can actually keep patients on the twenty milligram dose without EF issues for like the whole thirty six week period? And also, is there any sense on whether slower titration like we're seeing in Odysee might be better in the NHCM population?

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

That's a multipart question and I'll ask Fady and Stuart to tackle it.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Well, maybe I'll take it. I think just to be simple and concise, the Redwood data, we dosed patients between five and fifteen milligrams, eighty five percent of patients got up to fifteen milligrams and were there within six weeks of initiation of therapy. Many of those patients were still eligible to up titrate to twenty milligrams. And I don't think fundamentally there's any difference between the cardiac function of an NHM patient and an OHCM patient. So 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.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

And what we saw in Redwood was that NT proBNP decreased in a dose dependent manner. The higher doses produced greater decrements in NT proBNP. And so I think the strategy that we've adopted in ACATIA is built very tightly on what we did in Redwood, right? 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 three study on the basis of a Phase two study.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

So I think we're pretty confident with how we've addressed dosing in that trial.

Zaki Molvi
Zaki Molvi
Senior Associate, Biotech Equity Research at Cytokinetics

Thank you guys so much.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Thanks.

Operator

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

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Hello, David.

Analyst

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 breed out. Are we looking for a similar level of benefit this time head to head versus beta blockers as we did in Sequoia, something like 5% to 8%, maybe 10% improvement over baseline exercise capacity?

Analyst

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 I. Blum
Robert I. Blum
CEO, President & Director 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
Executive Vice President of Research & Development at Cytokinetics

Sure. So, MAPLE was designed as a trial with a to assess the impact of apicamten and metoprolol on exercise capacity and it's powered to about a two point zero difference between the two. And as we add in Sequoia achieved 1.75, I think that's 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.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

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, five percent to eight percent, ten percent would represent clinically meaningful differences between the two. 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.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

All of those things I think are should be considered in considering how apicamten performs as monotherapy compared to metoprolol performing as monotherapy. Thanks for the question.

Analyst

Thank you.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Hello, Sean.

Sean McCutcheon
Sean McCutcheon
Vice President - Biotechnology Equity Research at Raymond James Financial

Hi, guys. Good afternoon. Thanks for taking the question. Maybe to build on the last question. For MAPFLE, you're enrolling patients with percent predicted HCO2 of less than 100%, whereas in SEQUOIA, for the most part, outside of one patient, you are enrolling less than 80% predicted.

Sean McCutcheon
Sean McCutcheon
Vice President - Biotechnology Equity Research at Raymond James Financial

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
Senior Vice President & Chief Medical Officer at Cytokinetics

Hi, this is Stuart Kupfer. I think that what we observed in Sequoia was that threshold less than 90 or less than eighty percent 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 that we could relax that criteria and still enroll patients with quite significant deficit that we believe that apicamten that these patients could benefit from apicamten treatment. Thanks John.

Sean McCutcheon
Sean McCutcheon
Vice President - Biotechnology Equity Research at Raymond James Financial

Thank you.

Operator

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

Analyst

Hi, Doctor. Alex on Vicrippa. Thanks. We are excited about the progress in 2025. One commercial question for us.

Analyst

We've heard with mavacamten that treatment by cardiologists in the 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 Ophi 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.

Analyst

S. As well as The U. S?

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes. 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.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

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 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. And because Europe has a single payer system generally by country and they 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.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

It's difficult sometimes to distinguish between what's cause and effect or which the cart and which is the horse. We do believe that a majority of Chemsios 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 afacamthan 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.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

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

Analyst

Yes, it makes a lot of sense. And thanks. We're all looking towards the year ahead.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Thank you.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Good afternoon.

Roanna Ruiz
Senior Managing Director, Biotechnology 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 and D pipeline, curious of any color on stage of asset mechanisms, indications, etcetera that you'd be interested in internally or externally? And how would you balance that with your current cash runway expectations today?

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes. 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 the landscape both of what's 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
Executive VP & CFO at Cytokinetics

Yes. And Ruana, 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 $1,200,000,000 Also, we have access to further capital, as you know, from Royalty Pharma up to $500,000,000 We'll also benefit from some near term milestones from the BD deals we closed last year related to Afikamten ex U. S. So we're in a very strong position here. Specific to this year, we expect cash utilization to be in the low $500,000,000 s.

Sung Lee
Sung Lee
Executive VP & CFO at Cytokinetics

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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes. And just to elaborate a little bit, our focus to be clear remains on AffyCampton 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 02/1930 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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

That's not our intention.

Roanna Ruiz
Senior Managing Director, Biotechnology Analyst at Leerink Partners

Understood. Thanks.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Thank you.

Operator

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

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

Hello, Joe.

Joseph Pantginis
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

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, something you anything you might be that you can share regarding COMET HF and the enrollment trajectory, say, related to GALACTIC, since there are additional screening criteria?

Joseph Pantginis
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Thanks.

Robert I. Blum
Robert I. Blum
CEO, President & Director 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.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Thanks, Joe. So as you know, we began enrollment in COMED HF late last year and we have an advantage of leveraging all the information we have from GALACTIC 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 omicathic macarbil will be even more effective in these higher risk patients. And so enrollment is proceeding as estimated. We will continue to roll through the year.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

We plan to complete enrollment next year. And so studies are proceeding according to plan.

Robert I. Blum
Robert I. Blum
CEO, President & Director 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.

Joseph Pantginis
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Thanks again.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you.

Operator

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

Mayank Mamtani
Senior Managing Director at B. Riley Securities

Good afternoon. Good afternoon, team. Thanks for taking our questions and congrats on the progress. Just maybe switching gears to CK-five 86, if that 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 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?

Mayank Mamtani
Senior Managing Director at B. Riley Securities

Thanks for taking our question.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Maybe I'll ask Stuart to tackle that please.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Sure. Thank you. So the study is designed intentionally and 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 would treat from those two cohorts then we would consider if we need to proceed with the third cohort or perhaps with a different dose.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

So 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 hep hep 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 to this is mainly a dose finding type of study. Thank you.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Is there any other hopefully that answers your question?

Mayank Mamtani
Senior Managing Director at B. Riley Securities

Yes, it does. Thank you. Appreciate it.

Stuart Kupfer
Stuart Kupfer
Senior Vice President & Chief Medical Officer at Cytokinetics

Thank you.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Hello, Yasmeen.

Yasmeen Rahimi
Yasmeen Rahimi
Sr. Research Analyst at Piper Sandler Companies

Hi, Robert.

Yasmeen Rahimi
Yasmeen Rahimi
Sr. Research Analyst at Piper Sandler Companies

Thank you so much for all the great updates. I guess one of the questions I was wondering about is recently the baseline demographics of the ODiSI 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 Odysee, from Maple continue to grow the uptake of CMIs in this big market.

Yasmeen Rahimi
Yasmeen Rahimi
Sr. Research Analyst at Piper Sandler Companies

I mean, we're talking about a million patients, which which is a big mark, a high addressable population. So if you could just kind of comment around that. I know, AKIA is currently fully in enrollment mode, but maybe if there are any some 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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Thank you. Feddy?

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

Yes. 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 in a 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.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

So I think that it speaks to the fact that there are a lot of highly impacted patients with NHCM. 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 it the effectiveness of CMIs in them should will be elucidated by the results.

Fady Malik
Fady Malik
Executive Vice President of Research & Development at Cytokinetics

But there's similarity in lots of ways to the OHCM patients, I think, bode well for what we might expect to see.

Yasmeen Rahimi
Yasmeen Rahimi
Sr. Research Analyst at Piper Sandler Companies

Thank you, Patty.

Operator

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

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Hello, Charles.

Charles Duncan
Analyst 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, 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.

Charles Duncan
Analyst at Cantor Fitzgerald

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 I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

Yes. 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.

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

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 CorXL and Sanofi. But what we understand is there were multiple parties interested. There's a clear understanding of an unmet need in China. There are no REMS programs in China.

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

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 ASCAMPTEN. 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
Executive VP & CFO at Cytokinetics

Yes. 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 $35,000,000 in total across our partners.

Robert I. Blum
Robert I. Blum
CEO, President & Director at Cytokinetics

And then as I mentioned, they've stepped up in some meaningful ways in terms of timelines, forecasts, manufacturing and supply requirements. 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

Yes, sorry. Yes, 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.

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

So that

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

could

Andrew Callos
Andrew Callos
EVP and Chief Commercial Officer at Cytokinetics

certainly

Executives
    • Diane Weiser
      Diane Weiser
      Senior Vice President of Corporate Affairs
    • Robert I. Blum
      Robert I. Blum
      CEO, President & Director
    • Andrew Callos
      Andrew Callos
      EVP and Chief Commercial Officer
    • Fady Malik
      Fady Malik
      Executive Vice President of Research & Development
    • Isaac Ciechanover
      Isaac Ciechanover
      EVP, Corporate Development and Chief Business Officer
    • Stuart Kupfer
      Stuart Kupfer
      Senior Vice President & Chief Medical Officer
    • Sung Lee
      Sung Lee
      Executive VP & CFO
    • Zaki Molvi
      Zaki Molvi
      Senior Associate, Biotech Equity Research
Analysts
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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.
AI Generated. May Contain Errors.
Earnings Conference Call
Cytokinetics Q4 2024
00:00 / 00:00

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