CYTK - NASDAQ

Thank you for standing by, and welcome to this Cytokinetics, Incorporated Fourth Quarter 2025 Earnings Call. This call is being recorded and all participants are in a listen-only mode. After the speakers' remarks, we will open the call to questions. We will allow for one question per participant. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. And if you would like to withdraw your question, press star 1 again. I would now like to turn the call over to Diane Weiser, Cytokinetics, Incorporated Senior Vice President of Corporate Affairs. Please go ahead.

Good afternoon, and thanks for joining us on the call today. Robert I. Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Andrew M. Callos, EVP and Chief Commercial Officer, will discuss the commercial launch of MYCorzo in the U.S. and readiness in Europe. Fady Malik, EVP of R&D, and Stuart Kupfer, SVP and Chief Medical Officer, will provide updates related to our clinical development programs. Sung H. Lee, EVP and Chief Financial Officer, will provide a financial overview of 2025 and discuss our 2026 financial guidance. Robert will then make closing remarks and review 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. These include statements regarding expected timing and potential outcomes of clinical trials, including ACACIA-HCM, expectations regarding regulatory interaction and the potential for regulatory approval, expectations regarding commercial performance, and statements about our financial guidance and capital allocation. 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 2025 financial results filed on Form 8-K that was furnished to the SEC today and our annual report to be filed on Form 10-K in the coming days. We undertake no obligation to update any forward-looking statements after this call. I will now turn the call over to Robert I. Blum.

Thank you, Diane, and thanks to all for joining us on the call today. The 2025 marked a defining moment for Cytokinetics, Incorporated with the FDA approval of MYCorzo for the treatment of adults with symptomatic obstructive HCM, the first medicine we have advanced from discovery to commercialization. In fact, in the span of a single week, Cytokinetics, Incorporated received approvals for MYCorzo in both the U.S. and China, plus a positive opinion from CHMP for MYCorzo in the European Union, that latter milestone preceding last week's announcement of the European Commission's approval of MYCorzo in the EU. Together, these milestones represent the culmination of years of focused scientific, clinical, and regulatory execution and we now turn the page onto a new chapter for Cytokinetics, Incorporated as a global commercial-stage biopharmaceutical company. More importantly, the approval of MYCorzo offers a new treatment option to patients living with obstructive HCM, a serious condition that can profoundly impact quality of life. As Andrew will discuss, since the FDA approval in December, our teams have been focused on executing a disciplined and deliberate commercial launch. Our ongoing priority is to implement the systems, the education, the promotion, and market access pathways to support physicians, patients, and payers while also building initial and sustainable launch velocity and momentum. While it is still early, we are encouraged by our progress thus far and the initial engagements we are seeing from the cardiology community. In fact, the level of interest in MYCorzo as a new treatment option is high. With an eye toward the longer-term U.S. commercial launch trajectory, during the first quarter we submitted the supplemental NDA for MAPLE-HCM to the FDA. We expect FDA to conclude its review of the sNDA in Q4 2026. We believe that the potential inclusion of results from MAPLE-HCM into an expanded label for MYCorzo could boost category penetration depth and breadth, so more patients may ultimately benefit. Of course, we also anticipate the readout of results from ACACIA-HCM in non-obstructive HCM and we are on track for top line announcement in the second quarter of this year. nHCM is a different patient population with significant unmet medical need. Should this trial prove positive, it could also represent a potential growth driver for MYCorzo. Outside the U.S., following the recent approval of MYCorzo in the EU, we have now shifted into full execution of our commercial readiness planning, with our first planned launch in Germany expected in the second quarter. Additionally, during the fourth quarter of last year, Health Canada accepted for review the New Drug Submission for aficamten, and a potential approval for aficamten in Canada could come later this year. As we look ahead, we enter this next phase of our corporate development with strong momentum and also solid financials. The progress we delivered last year positions us well for continued growth and value creation while we also keep a close eye on capital structure and capital allocation. Sung will speak to our financial guidance and position as we ended 2025, as well as operating expense guidance for 2026. That guidance reflects the priorities of launching MYCorzo and advancing our muscle biology pipeline, both with disciplined execution and attention to capital efficiencies. We are confident in the foundation we are building for our specialty cardiology franchise and to deliver for both patients as well as shareholders. I am going to now turn the call over to Andrew.

Thanks, Robert. Our U.S. commercial launch process began immediately following FDA approval of MYCorzo in December. We have built our customer support systems around a team of HCM navigators who serve patients in a one-on-one relationship. These navigators started taking calls within days of approval, ensuring patients and HCPs had support. Immediately following FDA approval in December, we launched our patient and HCP marketing campaigns, leveraging surround-sound assets and activations such as quick start guides, patient brochures, websites, and social media advertising to help drive awareness and educate patients. Our sales representatives, whom we call Cardiovascular Health Specialists, began engaging with HCPs immediately following the New Year’s holiday and certifications within the MYCorzo label. Within weeks of approval, the online portal for the MYCorzo REMS program went live and MYCorzo became available for prescription. On that same day, we also launched “Corzo & You,” our patient support program offering personalized support, access, reimbursement assistance, and affordability programs for eligible patients, including a free trial program, bridge program, co-pay assistance, and patient assistance program. On the first day of product availability in channel, HCPs began to be certified in REMS and patients enrolled in Corzo & You. Within days of availability, the first prescriptions for MYCorzo were dispensed. In January, we also hosted our first national speakers’ broadcast with strong attendance from across the U.S. This was only the start of what will become an extensive peer-to-peer physician education program, which is a key element of our strategy to ensure HCPs are aware of this new treatment option. All of these integrated commercial launch programs were synchronized to roll out and support our ambitious plans for MYCorzo in the United States. While we are still early in our launch, so far customer feedback has been positive. HCPs have expressed enthusiasm for another cardiac myosin inhibitor as a treatment option for obstructive HCM, with particular interest in the clinical evidence demonstrating sustained reduction in obstruction and improvement in symptoms with no treatment discontinuation due to ejection fraction drops as observed in SEQUOIA-HCM. Our understanding is that a substantial portion of HCPs also appreciate the flexible dosing and ability to rapidly titrate as early as every two weeks, the adaptable monitoring schedule that allows for echos to be completed within a two- to eight-week window, and that drug-to-drug interaction counseling is not required as part of the REMS for MYCorzo. While it is still early in our launch, we are encouraged by the initial level of engagement, REMS certification, and overall demand. Within three weeks, we had over 700 HCPs REMS-certified across HCM specialty and non-specialty centers, a leading indicator of HCPs planning to prescribe MYCorzo. And as mentioned, patients were on therapy within the first week that MYCorzo was available. The level of demand in REMS patient enrollments and therapy is so far reinforcing our conviction in the commercial prospects for MYCorzo. In addition, we have already achieved over 12,000 customer engagements, including our Cardiovascular Account Specialists having engaged over 95% of the 700 HCPs who account for the majority of CMI prescribing today. Our current focus remains on educating HCPs on the prescribing information, preparing them for the REMS requirements, and encouraging them to identify patients for MYCorzo. From market research conducted post launch, we have learned that on an unaided basis, 90% of HCPs surveyed are aware of MYCorzo, the majority of which have stated they plan to prescribe MYCorzo for their obstructive HCM patients. They further state they recognize the potential benefits of the MYCorzo clinical profile for efficacy, safety, and tolerability as well as the differentiated REMS and dosing flexibility. As we have stated, starting with our Q1 earnings call, we will report on three key metrics to measure the pace and velocity through our launch: number of HCPs who are actively writing prescriptions, the volumes of prescriptions an HCP writes, and the number of patients on MYCorzo. We see these as leading indicators of launch depth and breadth that will read on our overall progress. As we continue this launch, our goal for MYCorzo is to achieve greater than 50% of CMI new patient preference share by 2026. We also intend to grow the overall CMI category. Our confidence is based on three launch drivers: clinical evidence, our bespoke patient support services, and the differentiation of our REMS program. First, the clinical evidence from SEQUOIA-HCM supports that MYCorzo is associated with rapid and sustained reduction in obstruction and improvement in symptoms, that it provides flexibility to titrate as early as two weeks with a flexible monitoring schedule for both patients and HCPs, and was not associated with treatment interruptions or clinical heart failure events. Second, our patient support program called Corzo & You provides a single point of contact for patients to deliver an experience that balances empathy and individual connection with consistency and seamlessness. And third, the MYCorzo REMS program allows for the flexibility to titrate as early as two weeks with echo monitoring required within a two- to eight-week window following dose initiation and any subsequent dose change, with no DDI monitoring. Importantly, a patient’s dose may be titrated after each echo with no delay. These three launch drivers are what we believe will fuel the uptake for MYCorzo and preference share. Driving access for patients is also a high priority. We have been engaging with payers for some time ahead of FDA approval to educate them on the evidence from our clinical trial as well as the clinical and economic burden of obstructive HCM. We have already met with all key payers earlier this year following approval. Our goal is to have Medicare access comparable to Camzyos in the first quarter and commercial access comparable to Camzyos by Q4 2026. In Europe, with EC approval for MYCorzo now secured in the European Union, we are moving quickly toward our first European commercial launch in Germany, planned in the second quarter. Our German medical and commercial teams are hired, and launch plans are accelerating. We also now have hired country leads in all EU4 countries and the UK to prepare for subsequent European launches in later 2026 and in 2027. We also continue to advance European commercial readiness activities, including preparing HTA dossiers for all key European markets. It is a privilege to be in the position of launching MYCorzo globally, and it is our priority to establish awareness and confidence. As proven by other launches, the early work of establishing awareness and confidence in access is critical to unlocking long-term momentum and velocity. We are encouraged by initial engagement and are focused on converting these engagements into consistent, scalable execution with positive commercial success as the year progresses. And with that, I will turn the call over to Fady to address our medical and clinical development activities.

Thanks, Andrew. In support of the launch of MYCorzo, our medical affairs organization continued to expand its engagement with the HCM community ahead of and now during our commercial launch. The field medical affairs team has been in place for several years now, working with our clinical trial sites during the conduct of SEQUOIA-HCM and MAPLE-HCM, building deep relationships across the HCM community. Immediately upon approval of MYCorzo, our U.S. field medical teams, including Therapeutic Medical Scientists and Managed Health Medical Scientists, were fully trained and operational, allowing them to hit the ground running and engage in 2026. Since approval, our U.S. TMS team has rapidly scaled scientific engagement, conducting over 500 interactions with HCPs in support of MYCorzo. Our U.S. MHMS team, in collaboration with our U.S. payer account managers, has expanded engagement by conducting more than 50 access-related interactions, reinforcing the economic profile, clinical profile, and safety considerations most relevant to access decision makers. At the ACC next month, our presence will underscore our leadership in HCM, with accepted oral and poster presentations covering the real-world treatment implications, additional data from MAPLE-HCM, and important safety and efficacy analyses drawn from our late-stage clinical programs. Supportive of our global development strategy, our partner Bayer completed enrollment in CAMELLIA-HCM, a Phase 3 clinical trial of aficamten in Japanese patients with obstructive HCM. Additionally, we completed enrollment of the Japanese cohort of non-obstructive HCM patients in ACACIA-HCM, both intended to support potential marketing authorization for aficamten in Japan. During the fourth quarter, we presented additional data from MAPLE-HCM in three late-breaking sessions at the HCM Society Scientific Sessions and the Scientific Sessions. Responder analyses showed that significantly more patients on aficamten achieved a positive response compared to patients on metoprolol. Additionally, treatment with aficamten resulted in significantly greater improvements than metoprolol on symptoms and cardiac biomarkers. The results from MAPLE-HCM have resonated strongly across the cardiology community, highlighting the evolving thinking around the standard-of-care treatment in HCM and the need for new therapies. Now I will hand it over to Stuart to speak more about ACACIA-HCM as well as our ongoing development programs in heart failure.

Thanks, Fady. Our next important data readout will come from ACACIA-HCM, the pivotal Phase 3 clinical trial of aficamten in patients with nHCM. We remain on track to share top line results of the primary cohort, which excludes Japan, in the second quarter. We anticipate the top line press release will remain relatively high level so as not to jeopardize presentation of the full results at a potential medical congress later in the year. nHCM is a highly underserved patient population with no approved therapies. We look forward to reporting the results of ACACIA-HCM and to evaluating whether aficamten can demonstrate a clinically meaningful benefit for these patients. As with any pivotal trial, a range of outcomes is possible, and we will provide a thorough review of the results at an upcoming medical congress following the top line release. As we previously guided, the conduct of ACACIA-HCM remains within its design parameters and closeout is going according to plan. Given our expertise and experience in designing and managing trials in HCM, we believe that we have successfully executed a well-designed clinical trial. We continue to be confident in ACACIA-HCM and look forward to seeing the results in the second quarter. Now moving on to our clinical development programs in heart failure. During the quarter, we continued conduct of COMMUN-HF, the confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction less than 30%. We now have 100% of U.S. sites activated and over 90% of European sites activated. We soon plan to expand the trial into China to increase the global footprint of this important clinical trial. We also continued AMBER-HFpEF, the Phase 2 clinical trial of olicamtiv, in patients with symptomatic heart failure with preserved ejection fraction of at least 60%. We continued enrollment in cohort one of AMBER-HFpEF and expect to complete enrollment in this first quarter. After an interim safety review is conducted, we may assess whether to begin to enroll in cohort two for evaluation of a higher dose. We are encouraged by the continued progress and execution across these ongoing clinical trials, reinforcing our focus on disciplined development and advancing innovative medicines within our emerging specialty cardiology franchise. And with that, I will pass it to Sung. Thanks, Stuart.

We are pleased to report our fourth quarter and full year 2025 financial results. Starting with the balance sheet, we finished 2025 with approximately $1,220,000,000 in cash, cash equivalents, and investments, compared to $1,250,000,000 at the end of 2024. The 2025 year-end balance includes $100,000,000 in proceeds from the drawing on tranche five of the Royalty Pharma multi-tranche loan. Excluding the proceeds from this loan, cash, cash equivalents, and investments would have declined by approximately $134,000,000 during 2025. Turning to the income statement, total revenues in Q4 2025 were $17,800,000 compared to $16,900,000 for the same period in 2024. Total revenues for the full year 2025 were $88,000,000 compared to $18,500,000 in 2024. Total revenues for the full year 2025 benefited primarily from the successful completion of the technology transfer totaling $52,400,000 to Bayer in 2025 and the recognition of $15,000,000 in milestones in 2025 related to the approvals of MYCorzo in the United States and China under the Sanofi license agreement. As we announced previously, MYCorzo became available to patients near January, and as such, we expect to report product sales of MYCorzo with our Q1 2026 results. R&D expenses for the fourth quarter were $104,400,000 compared to $93,600,000 for the same period in 2024. R&D expenses for the full year 2025 were $416,000,000 compared to $339,400,000 in 2024. The increase from 2024 to 2025 was primarily due to advancing our clinical trials, higher personnel-related costs including stock-based compensation, and medical affairs activities. G&A expenses for Q4 2025 were $91,700,000 compared to $62,300,000 for the same period in 2024. G&A expenses for the full year 2025 were $284,300,000 compared to $215,300,000 in 2024. The increase from 2024 to 2025 was primarily driven by investments toward commercial readiness, including the hiring of our U.S. sales force primarily in 2025, and higher non-sales personnel-related costs. Net loss for Q4 2025 was $183,000,000 or $1.50 per share compared to a net loss of $150,000,000 or $1.26 per share for the same period in 2024. Net loss for the full year 2025 was $785,000,000 or $6.54 per share compared to a net loss of $589,500,000 or $5.26 per share in 2024. Turning now to our financial guidance for 2026. As this is our first year of launching MYCorzo, we are not providing product sales guidance at this time. In terms of expense, we expect our GAAP combined R&D and SG&A expense to be between $830,000,000 and $870,000,000. Stock-based compensation included in the GAAP combined R&D and SG&A expense is expected to be between $120,000,000 and $130,000,000. Excluding stock-based compensation from the GAAP combined R&D and SG&A expense results in a range of $700,000,000 to $750,000,000. The GAAP combined R&D and SG&A expense does not include the following: collaboration expenses, including reimbursed expenses and cost of inventory sales of aficamten to partners; subject to the results of ACACIA-HCM and regulatory review, potential costs related to commercialization of aficamten in nHCM; and the effect of GAAP adjustments as may be caused by events that occur subsequent to publication of this guidance, including, but not limited to, business development activities. Our capital allocation priorities are as follows: first, launching MYCorzo in the U.S. and funding commercial readiness activities in Europe; second, advancing our pipeline with important label expansion opportunities for aficamten and ongoing clinical trials of omecamtiv mecarbil and olicamtiv; and third, investments in our muscle biology platform and pipeline. We will continue to be disciplined in our approach to capital allocation and remain good stewards of capital as we embark as a global commercial-stage company. With that, I will hand it back to Robert.

Thank you, Sung. Before we open the call to questions, it is worth pausing to reflect on what this moment represents for Cytokinetics, Incorporated. After years of focus, discipline, and unwavering commitment to our science, we have crossed an important threshold from pursuing possibilities to delivering impact. The approval of MYCorzo marks the beginning of a new chapter, one for which our work impacts the daily lives of patients and the decisions made in clinics around the world. This is a moment we have been working toward for nearly 28 years at Cytokinetics, Incorporated, and it reflects unstoppable resilience, dedication, and a rigorous focus on translating our science into medicine for the benefit of patients. With that transition comes a deeper sense of purpose and dedication to our core values, which define how we do what we do. Chief amongst them is our value of “Patients are our North Star,” and during the fourth quarter, we announced our support for a three-year initiative led by the American Heart Association to address disparities in access to care, diagnosis, and treatment for people living with HCM. Through this longstanding commitment, we hope to help close the gaps between evidence, guidelines, implementation, and equities in health care delivery for HCM. Progress at this stage is not only about innovation, but also about our responsibility to show up for patients and the communities we serve. What we have discussed today reflects years of focused work across the organization from discovery and development through regulatory, manufacturing, and now commercial execution. What made all of this possible was the enduring dedication and the passions from our employees, for which I have endless gratitude. As we enter this next chapter as a commercial-stage company, our focus remains clear: execute ambitiously, advance our pipeline, and deliver meaningful, longer-term impact for patients and shareholders. Now I would like to share our 2026 milestones. For aficamten, we expect to report top line results from ACACIA-HCM in the second quarter 2026. We expect to launch MYCorzo in Germany in the second quarter 2026. We expect to receive potential FDA approval of the supplemental NDA for MAPLE-HCM by Q4 2026. We expect to complete enrollment in the adolescent cohort of CEDAR-HCM in Q4 2026, and we expect to receive potential approval from Health Canada in the second half of this year. For omecamtiv mecarbil, we expect to continue patient enrollment and the conduct of COMMUN-HF through 2026. For olicamtiv, we expect to complete enrollment in cohort one of AMBER-HFpEF in Q1 2026 and complete enrollment in cohort two of AMBER-HFpEF by 2026. And finally, for our preclinical development and ongoing research, we expect to continue ongoing preclinical development and the research activities directed to additional muscle biology-focused programs. Operator, with that, we can now open up the call to questions, please.

Thank you. And just as a reminder, please one question. Your first question comes from Tessa Romero with JPMorgan. Please go ahead.

Hello, good afternoon, Robert and team. Thanks so much for taking ours this afternoon. So one from us on ACACIA. Is it true that the study will be successful if at least one of the endpoints reaches statistical significance? And then along these lines, in your study protocol, did you specify which endpoint you would need to hit to properly claim success? In other words, either KCCQ or peak VO2, or is either fine? Thank you.

I will start, and I will turn it over to Fady and Stuart. To define success, you have to also consider with whom you are engaging. And, obviously, the clinical community is going to have one set of expectations and interests, as might FDA, but also they could diverge. But it is true as we have designed this clinical trial, it will be deemed positive if it hits on either or both of the prespecified clinical trial endpoints. With that, I will also turn it over to Fady and Stuart if they want to add anything.

I think the only thing to add is that either endpoint is considered equally positive.

Either one is positive, the trial would be considered positive. One is not weighted more heavily than the other.

Your next question comes from the line of Roanna Ruiz with Leerink Partners. Please go ahead.

Good afternoon. Afternoon, everyone. Hello. So a question for me. I was thinking about MYCorzo and its initial launch in cardiologist engagement. Could you share any color on how long it is taking sites and clinical centers to get through the REMS certification and start to prescribe? Are the field reps noticing anything so far in their detailing?

I will start again and turn it over to Andrew. And we very purposely are focusing on engagements, inputs, if you will, on this call because it is early in the launch. But we are indeed impressed by how many HCPs have already been REMS-certified and the speed at which that happened shortly after product was in channel. And I will ask Andrew to elaborate.

Sure. So the REMS certification, as you are maybe aware, is a quick self-study training and a 10-question Q&A that is scored. It takes 10 to 20 minutes generally for cardiologists, sometimes even faster. So it has really not been a barrier to be REMS-certified. I think there are many HCPs and cardiologists we were talking to that were waiting for MYCorzo to be approved and had patients that were also waiting, and, you know, we have gotten strong engagement across a broad base of cardiologists, both in centers of excellence and outside of centers of excellence in not only REMS certification, but also getting patients REMS-certified and prescribing. And, also, to add, knowing that this is not the first but now the second cardiac myosin inhibitor, these cardiologists were accustomed to a REMS, were awaiting one, and when we did launch and have product in channel, I think they were poised, well-positioned to move swiftly with REMS certification, and we are seeing evidence of that.

Got it. Thanks.

Your next question comes from the line of Mayank Mamtani with B. Riley Securities. Please go ahead.

Hello, Mayank.

Yes. Good afternoon, team. Thanks for taking our questions, congrats on a very productive recent few months. So on ACACIA, if I may, could you comment on your placebo arm response expectations for both KCCQ and peak VO2? And if you would expect consistency to what we have seen in preceding nHCM trials? And if you could also comment on whether you would expect a similar NT-proBNP reduction that you saw in the earlier OLE experience at the time point that you have here, and if you expect that to be correlated to the exposure that you may have from a dose intensity standpoint?

I am going to ask my colleagues to answer your question, but I will remind you and also them that as we are approaching the conclusion of the study, and as we would be expecting to proceed to database lock and unblinding, we should answer your question with regard to what was the original design expectations. And I want to make certain that we are not in any way front running anything that might be understood regarding the progress of the trial, rather its design and conduct.

It is important to realize that we are still blinded to the data, so we have really no clue as to what the placebo arms are doing. But based on past experience, the peak VO2 arm generally—the placebo response—is close to zero.

It may be a little higher, may be a little lower, but in our prior studies the placebo response—there is not much of a placebo response to peak VO2, and, again, we based ACACIA’s design on—

A placebo response in line with our prior studies. You know, expect four to five points, perhaps six points. But just to—

Emphasize, the statistical design of the study does not rely on the magnitude of the placebo response. It relies on the difference between the active—

Response and the placebo response. And so that difference in the case of KCCQ, which we powered the study on, was five points—

Difference between placebo and active. And then your last, I think, point was with regards to NT-proBNP.

We certainly would not have any—

Expectations that are different from what we observed in the Phase 2 or the open-label extension with regards to how NT-proBNP has declined during treatment with aficamten, but we are blinded to those data as well.

Thank you, team.

Your next question comes from the line of Joe Pantginis with H.C. Wainwright. Please go ahead.

Hey, Joe.

Hey, everybody. Thanks for taking the questions. So a question on early market uptake, and I am glad Andrew made an earlier comment as well that I wanted to ask. So with regard to the U.S. first, Andrew, you made some comments about—and previously about patients that docs have been having in—wanted to know if there is any uptake there that you thought might have been in line or even quicker than expected. And secondly, with regard to ex-U.S., you know, China, for example, what would you describe as any commercial differences? I know you have started to put a team there or potential headwinds that you could expect versus what you would see in the United States? Thanks.

Andrew, do you want to take that?

Sure. So maybe start backwards. China is partnered—Sanofi is commercializing in China. We are not doing that. So that is an important element. I think back to the U.S. patients in reserve, I think that the demand we are seeing and where we are seeing it from is what we were expecting. So we were not surprised by the patient demand. I think it will be reflected in research we were seeing when we were doing primary market research pre-approval—things like demand studies, things like awareness studies—that there was broad awareness. The physicians certainly were aware of not only SEQUOIA, but also MAPLE that were presented at congresses. So I think we are where we were expecting to be knowing that we have been in the market with product for about three weeks.

Maybe I can just add to the point of Andrew’s market research, but also as equity research analysts from Wall Street have done their own surveys, there was clear evidence that the current cardiac myosin inhibitor category was only penetrated 15% to 20% at most and that there would be a large number of patients still eligible for treatment. What we heard, what analysts heard, is that there would be a number of patients that could be started promptly and the early evidence would suggest that there were patients that were held awaiting a potential approval. And we will be in a position to comment more about that in time.

Thank you.

Your next question comes from the line of Cory Kasimov with Evercore. Please go ahead.

Hey, Robert. Hey, guys. Thanks for taking the question. So I had a follow-up on ACACIA and wanted to also ask between these two primary endpoints of KCCQ and peak VO2, and we think specifically about U.S. investigators. Is there a view from, like, domestically on whether one of these endpoints is more important than the other? I know the original primary was KCCQ—does that—is that a reflection of how U.S. physicians are thinking about it? And then from that standpoint, I know how it is, again, powered, but what is considered to be a clinically meaningful change from a physician point of view? Thank you.

So here again, I am going to remind our colleagues of the fact that we chose to have co-primary endpoints not because we originally thought one was more important than the other, but rather because regulatory authorities wanted to see a harmonization across the study as could be best achieved by putting equal weight and emphasis to the two co-primaries. Maybe Fady and Stuart, I will ask you if you want to say anything else.

I will just add I do not think physicians will lean one way versus the other. I think they will look at the totality of the evidence and not just the primary endpoints, but also the secondary endpoints that include NYHA class, and other metrics of exercise, biomarkers, and things like that. So, you know, in this field, there are no treatments for non-obstructive HCM. Physicians are looking for improvements in their patients’ status, and there are many dimensions—

Upon which they can improve, and, you know, I think they and also regulators will look at the totality of the data. To answer your question about minimally important differences, for this being in HCM, and to reiterate what Fady said, there is no approved drug for these patients in this population. What is going to be considered important and clinically meaningful is going to be hopefully a function of this trial, as we learn what is concordant—how the endpoints move together, and what ultimately defines larger magnitude improvements versus what may be otherwise. So I think we are going to learn a lot from this study that is going to be informing the clinical literature and hopefully what ultimately may be medical guidelines. But we do not have reference standards or benchmarks that we can point to. Instead, this study is intended to test those hypotheses and determine what should be important and meaningful.

That is helpful. Thank you both.

Your next question comes from the line of Salim Syed with Mizuho. Please go ahead.

Great. Thanks for the question, guys. One for us just on the disclosure. When you said high level, should we be thinking more along the lines of how Bristol had their press release for Odyssey, which was just completely qualitative? I think it was just one sentence like, did not hit on the dual primaries. Or should we be thinking somewhere more along the lines of SEQUOIA, how you guys did it, which had a lot of numbers in it, or somewhere in between. And if it is all qualitative, would you be willing to comment on each of the co-primaries in the press release? Thank you.

Ultimately, this will be a function of the data and what is deemed material, and also what would be, upon receipt of those data, what can be negotiated with the medical congress. Disclosing more would be an objective if that can be permitting of the full presentation at an important medical meeting. And in the case of SEQUOIA, we disclosed more, but at the expense of being able to present it at the medical congress where it would have been more appropriate. So we would like to be able to do both: disclose as much as we can, but still preserve the opportunity to present at the appropriate next-level congress. If it is going to be more qualitative, I imagine we will have to speak to both endpoints. I do not think we could speak to one and not the other. But in terms of what would be contained beyond that, I think it all depends on the data, magnitude of effect, p-values, and what we can be enabling of at a congress. Fady, anything you want to add?

The presentation of the data is important to the academic community, and in the past, I would say that if you look at the presentation of MAPLE at the ESC Congress last year, it was tremendously impactful that way. So there are many considerations and important trade-offs here—

In terms of all the stakeholders involved.

We are fully aware of the significance and the importance of these data both to the medical community as well as to the Wall Street community. And we are going to try to do our best.

Okay. Got it. Thanks so much, guys.

Your next question comes from the line of Yasmeen Rahimi with Piper Sandler. Please go ahead.

Thank you so much for all the color. My question is just related on ACACIA also. I think, you know, one of the questions we have been getting is have you done payer work or uptake work to understand whether the usage would still be strong if you showed a three-point placebo-adjusted difference in KCCQ, or just commentary—as long as you have a statistical separation, the magnitude of delta difference in KCCQ is irrelevant. Appreciate color, and I will jump back in the queue.

Maybe that is a question for both Fady and Andrew. In terms of your specific example of a three-point difference in KCCQ, I assume you picked that number arbitrarily. But maybe, Fady and Andrew, if you want to tackle that.

Let me just start by saying that in MAPLE and SEQUOIA, you see a range of strength of response. And while the average response, say, in your example of three, may represent an all-comers average response, you see responses that are far larger than that, and, obviously, you see some patients that do not respond very much at all.

And so I think in a lot of ways, the—

The average number that is coming out of the trial will certainly color how physicians maybe look at the importance of the results, but—

We also enrolled 500 patients in the study, and many of them will go into open-label extension, and—

Many of these investigators will have a chance to evaluate on their own—are patients improved? And I think ultimately, this will be probably a case of: if you try it and you have a sizable response, and it is important to you, then continue therapy; and if you do not, then you do not have to continue therapy. And it is a little different than drugs where we treat to lower risk, where you do not really know if you are the one that is going to benefit from the drug, and thereby absolute differences are far more important to understand your potential benefit.

So I hope that helps from a medical perspective. Fady.

And from a demand point of view, provided that the study is statistical and that MYCorzo would be approved for non-obstructive, the care demand is driven, you know, significantly higher. You know, we hear things like HCPs being able to use one product across all of HCM, not worrying whether it is oHCM or nHCM, especially given the profile that you know and we know from SEQUOIA. That would drive up use both in oHCM, obviously, as well as nHCM. So it has a significant impact on nHCM, and maybe not significant, but definitely an impact on oHCM as well.

And I think, just to maybe culminate here, simply achieving clinical significance is not alone enough. The magnitude of change needs to be meaningful, especially relative to an instrument like KCCQ where there is history of a placebo effect. So our goal is to demonstrate with this trial, above and beyond a placebo effect, a meaningful impact on KCCQ.

Your next question comes from the line of James Condulis with Stifel. Please go ahead.

Good afternoon. Congrats on all the progress, and thanks for taking my question. Actually wanted to ask one about HFpEF, and I was curious, in the context of ACACIA, how important or meaningful you think an ACACIA win would be helping to kind of de-risk that broader HFpEF opportunity given some of the overlap in kind of pathology here. And just curious if you could also help frame out kind of when we may see initial data there and what a win looks like. Thanks so much.

Good question, and I am going to ask Stuart to comment, but I will also highlight that we learned a lot from what we can glean from those data from ODYSSEY. And that obviously has impact and implication to what we hope to see with our study, ACACIA. But to your point, ACACIA can also inform what we might expect from HFpEF and the translation of this mechanism of a cardiac myosin inhibitor to an adjacent population. That is certainly our objective. And with that, I will ask Stuart maybe to comment.

Thank you, James. You hit upon an important evidence base that really informed this hypothesis about the potential benefit of a CMI in patients with HFpEF and, more specifically, those patients with hypercontractility. So, you know, many of the features structurally are similar between patients with non-obstructive HCM and with HFpEF and hypercontractility. So I think the outcome of ACACIA could further inform the potential benefit of a CMI in HFpEF. With respect to when we expect results from AMBER-HFpEF, I think it is a little bit too soon to say that, but we will continue updating you in terms of the progress of the trial.

But underscoring what Stuart said around hypercontractility, ensuring that everybody appreciates that the way we are thinking about HFpEF is not the entirety of that population, but those whose disease and anatomy is defined by hypercontractility, and that is where we believe there is an adjacency to nHCM. Thank you for the question. Your next question comes from the line of Jason Butler with Citizens. Please go ahead.

Hi. Thanks for taking the question. Just wondering if you could give us any color on the centers that are signing up in the REMS program right now. Are you getting any health care prescribers that are either not current CMI prescribers or have never prescribed CMI? Or is it fair to say the majority of the sign-up are current CMI prescribers?

Thanks for the question. The majority are current CMI prescribers, but we do have prescribers who are REMS-certified who are not CMI prescribers today, and we do have prescribers that are first-time CMI prescribers as well. But as you would think, the majority are current CMI prescribers.

And that tracks with the ways in which our Cardiovascular Account Specialists are focusing their energies. As Andrew commented in his prepared remarks, our activities are more focused to those targeted cardiologists who are already high-volume prescribers, and that is where he commented on percent engagements. But it is nice to see that already we are seeing outside of that circle use of a cardiac myosin inhibitor where it had not been previous.

Great. Thank you.

Your next question comes from the line of Maxwell Skor with Morgan Stanley. Please go ahead.

Great. Thank you for taking my question. So assuming positive ACACIA readout, how should we think about any incremental uplift to the obstructive HCM launch trajectory in 2026? If you can maybe quantify or speculate that would read through. And also, can we expect ACACIA to read out in the early part of the second quarter or maybe later on in the second quarter? Thank you.

I will tackle that latter question and ask Andrew to do the former. We are not going to guide to when in second quarter. I imagine analysts will do their own math and make their own handicapping and projections, but we are not going to comment on that. And then I will ask Andrew to speak to your first question.

Yeah. I mean, I think, obviously, we are not going to be promoting or talking about 15% to 20% uplift. To be able to comment on the data, we will have to do additional market research to assess how that might inform use in HCM and what kind of spillover there may be, but underscoring we intend to be very much by-the-book compliant with regard to what our field colleagues would be able to speak to.

Your next question comes from the line of Serge Belanger with Needham. Please go ahead.

Hi, good afternoon. Thanks for taking my questions. I will pile on ACACIA too—seems to be the topic du jour. So I know you are still blinded to almost all the data, but I think in the past, you have talked about monitoring the variability in the endpoints. So just curious if there has been any change in that variability in what you can glean from that? Thanks.

I will turn to Fady, but I will emphasize yet again that in light of the fact that we are now nearer to what would be database lock and unblinding, we cannot comment on something like what you asked with regard to standard deviation. Rather, instead, we can comment on what the study was designed to demonstrate.

The study was designed to demonstrate a five-point delta on KCCQ, assuming a standard deviation of 15, and a peak VO2 of 1 with a standard deviation of 3.

Ninety percent power, with being able to detect statistically significant differences—

At differences that are less than that, with less power, obviously. And as I stated in the script, the study remains within its design parameters, and, you know, we will not commit to updating those statements going forward.

Got it. Thank you. Thank you.

Your next question comes from the line of Jason with Bank of America. Please go ahead.

Hi. This is Jackie on for Jason. Congrats on the progress, and thanks for taking our question. So real quick, can you report what you have seen thus far this year in terms of patient start forms and also about how much of your early efforts have involved more community practices and what has the uptake been like specifically within these offices? Thank you.

Thank you. Andrew?

Sure. So we are not going to give numbers—we will do that in the first quarter relative to start forms. All I can say is what we said in the script, which is our demand in the three weeks and the engagement we have seen with physicians is at, if not above, what we expected internally. In terms of community versus centers of excellence, the 700 physicians that were 80% of the market—that is where the majority is coming from. But there is also strong engagement from the community. There is strong engagement from new prescribers—probably new prescribers who have never prescribed a CMI—those numbers are higher than we were expecting. So I think we are seeing a good balance across all types of prescribers. And the majority, obviously, are the ones that we are calling on and educating. In our first quarter call, we will give more color around patients and engagement—centers of excellence versus non-centers of excellence, prescribing depth, etc. So, you know, more to come, but too early to say with just three weeks of data.

I see. It is early innings, but we are pleased.

We have already seen that the FDA was accepting of an opportunity to see real-world evidence data in support of a modification of the Camzyos REMS. But for our REMS, we are not guiding to any changes in the near term, but certainly, over a medium to longer term, it is reasonable to expect that real-world evidence could inform changes. But what those changes might look like would be premature to speak to today. Fady or Stuart, anything you want to add?

The REMS itself is, you know, quite straightforward in terms of what is required to execute it. But the real-world data will inform potential future modifications to it. But as Robert says, still too early to decide what it is that we may pursue. I think we just need some real-world data to understand what may be our pinch points and how those real-world data would support altering the REMS as might relieve those pinch points.

Your next question comes from the line of Ashwani Verma with UBS. Please go ahead.

Hi there. This is Natalie on for Ash, and thanks again for taking our question. So just on ACACIA, could you talk about how the discontinuation rate in ACACIA compares to prior studies? And then also for the baseline patient population, could you give us a sense of the percentage of patients that might have the concentric LVH phenotypes?

I can talk to, you know, discontinuations. And, again, the study was designed to withstand a 10% discontinuation rate, and I think as I have said in the past, we have been within that metric, and in my earlier comments, reaffirmed that, but we will not commit to updating that going forward. And then, you know, we have not released any of the baseline characteristics, and so I cannot really comment on your last question. But what I can say is that our group of HCM specialist physicians review every echo of every patient that is enrolled in the trial, and unless they feel it is an echo consistent with hypertrophic cardiomyopathy, the patient would have a query raised to the site to gather more information that might support the diagnosis.

Got it. Thanks so much. Thank you.

Your next question comes from the line of Leonid Timashev with RBC Capital Markets. Please go ahead.

Hey, guys. Thanks for taking my question. I just wanted to go back to the MYCorzo launch and the patient starts. I guess, can you provide any color on the types of patients that are being started versus what you might expect from the initial mavacamten launch? Anything specific about the patients that are being put on? Is it just new patients? Are there any switches? Is it patients who maybe needed higher efficacy or had lower baseline ejection fraction? I guess I am just curious how docs are thinking about the initial use of aficamten as they now have the ability to use the drug. Thanks.

Good evening. Thanks. Just keeping in mind we do not always have insights into patient-level data, but we only hear things maybe a bit more anecdotally. I think “all of the above” may be a way of addressing your question. But maybe, Andrew, you have something else you want to add.

No. I think you said exactly what I was going to say, which is that patient information is protected. We do not see exactly who is put on and for what reason. You know, the data is too early to see if there are switching, etc. But I do think we are seeing all of the above, as Robert said.

And that concludes our question and answer session. I will now turn the conference back over to Robert I. Blum for closing comments.

Thank you, operator, and thanks to all of you for joining us on this call today. Obviously, we reflected on the importance of this moment. I will not repeat those statements other than to say we understand the significance of this as we turn the page on to commercialization, and we want to do the right thing by these patients for the benefit of their care and do right by health care professionals who attend to their care. We also recognize and acknowledge that this is an important milestone for Wall Street, as Cytokinetics, Incorporated is now a global commercial company, and we take that very seriously as well. We look forward to providing you insights as we have more substantial information relating to the launch of MYCorzo in the United States, its expected launch in Germany and other European countries, and we will know more and be able to share more through the remainder of this year. Moreover, as we have access to results from ACACIA, expected in Q2, we look forward to sharing those with you, and we recognize the significance of those too. So thank you for your interest and attention to all that we are doing at Cytokinetics, Incorporated. We look forward to keeping you abreast of progress. With that, operator, we can now conclude the call.