Cytokinetics, Incorporated

Thank you for standing by and welcome to the cytokinetics fourth quarter 2025 earnings call. This call is being recorded and all participants are in a listen only mode. After the speaker's 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'd like to withdraw your question, press star one again. I would now like to turn the call over to Diane Weiser, CytoKinetics Senior Vice President of Corporate Affairs. Please go ahead.

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 discuss the commercial launch of MyCorso in the U.S. and readiness in Europe. Patty Malek, EVP of R&D, and Stuart Kupfer, SVP and Chief Medical Officer, will provide updates related to our clinical development programs. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of 2025 and discuss our 2026 financial guidance. And finally, 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, without limitation, statements regarding expected timing, potential outcomes of clinical trials, including ACACIA HCM, expectations regarding regulatory interactions and the potential for regulatory approval, expectations regarding commercial performance, and statements about our financial guidance and capital allocations. 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 filing, including our current report regarding our fourth quarter 2025 financial results filed on Form 8K that was furnished to the SEC today and our annual report to be filed on Form 10K in the coming days. We undertake no obligation to update any forward-looking statements after this call. And now, I will turn the call over to Robert.

Thank you, Diane, and thanks to all for joining us on the call today. The fourth quarter of 2025 marked a defining moment for cytokinetics with the FDA approval of mycorrhizal for the treatment of adults with symptomatic obstructive HCM, the first medicine we've advanced from discovery to commercialization, in fact, In the span of a single week, cytokinetics received approvals for mycorrhizal in both the US and China, plus a positive opinion from CHMP for mycorrhizal in the European Union. That latter milestone preceding last week's announcement of the European Commission's approval of mycorrhizal 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 as a global commercial stage biopharmaceutical company. More importantly, the approval of mycorrhizal 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's still early, we are encouraged by our progress thus far and the initial engagements we're seeing from the cardiology community. In fact, the level of interest in mycorrhizal as a new treatment option is high. With an eye towards 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 mycorrhizal 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 nonobstructive HCM, and we're on track for top-line announcement in the second quarter of this year. is a different patient population with significant unmet medical need. Should this trial prove positive, it could also represent a potential growth driver for mycorrhizal. Outside the US, following the recent approval of mycorrhizal in the EU, we've 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 Affy Campton, and a potential approval for Affy Campton 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 end in 2025, as well as operating expense guidance for 2026. That guidance reflects the priorities of launching myCORSO and advancing our muscle biology pipeline, both with disciplined execution and attention to capital efficiencies. We're confident in the foundation we're building for our specialty cardiology franchise and to deliver for both patients as well as shareholders. And with that, I'm going to now turn the call over to Andrew, please.

Thanks, Robert. Our U.S. commercial launch process began immediately following FDA approval of myCORSO on December 19th last year. We have built our customer support systems around a team of HCM navigators who serve patients in a one-on-one relationship. These navigators start taking calls within days of approval, ensuring patients and HCPs have support. Immediately following the FDA approval in December, we launched our patient and HCP marketing campaigns, leveraging surround sound assets and activation, such as quick start guides, patient brochures, websites, and social media advertising to help drive awareness and education. Our sales representatives, whom we call cardiovascular account specialist, began engaging with HEPs immediately following the New Year's holidays and certifications within the mycorrhizal label. Within weeks of approval, the online porter portal for the mycorrhizal REMS program went live, and mycorrhizal became available for prescription. On that same day, we also launched mycorrhizal in you, our patient support programming offering personalized support, access and 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, ACPs began to be certified in REMS and patients enrolled in myCORSO and you. Within days of availability, the first prescriptions from myCORSO were dispensed. At the end of January, we also hosted our first national speakers broadcast with strong attendance from across the US. 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 ACPs 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 myCORSO 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 myCORSO. While still early in our launch, we're encouraged by the initial level of engagement, REMS certification, and overall demand. Within three weeks, we had over 700 HCPs now REMS certified across HCM specialty and non-specialty centers, a leading indicator of HCPs planning to prescribe mycorrhizal. And as mentioned, patients were on therapy within the first week that mycorrhizal was available. The level of demand in REMS patient enrollments and therapy initiation is so far reinforcing our conviction in the commercial prospects for mycorrhizal. In addition, we have already achieved over 12,000 customer engagements, including our cardiovascular health specialist having engaged over 95% of the 700 HEPs who account for the majority of CMI prescribing today. Our current focus remains on educating HEPs on the prescribing information, preparing them for the REMS requirements, and encouraging them to identify patients for micortisone. From market research conducted post-launch, we have learned that on an aided basis, roughly 90% of HCPs surveyed are aware of mycorrhizal, the majority of which have stated they plan to prescribe mycorrhizal for their obstructive HCM patients. They further state they recognize the potential benefits of the mycorrhizal clinical profile for efficacy, safety, and tolerability, as well as the differentiated REMS and dosing flexibility. As we've stated, starting with our Q1 earnings call, we will report on three key metrics to measure the pace and velocity of our launch. The number of ACPs who are actively writing prescriptions, the volumes of prescriptions an ACP writes, and the number of patients on myCORSO. 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 myCORSO is to achieve greater than 50% of CMI new patient preference share by the end of 2026. We also intend to enroll 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 myCORSO is associated with rapid and sustained reduction in obstruction and improvement in symptoms, that it provides flexibility to take red 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 MyCords Doing You, which 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 mycorrhizal REMS program allows for the flexibility to titrate as early as two weeks with echo monitor required within a two- to eight-week window following dose initiation and any subsequent dose change with no DDI monitoring. And 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 mycorrhizal and preference share. Driving access for patients is also a high priority. We've been engaging with payers for quite 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 CAMS-ISIS in the first quarter and commercial access comparable to CAMS-ISIS by Q4 2026. In Europe, with ECA approval for myCORSO now secured in the European Union, we are moving quickly towards 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's a privilege to be in the position of launching myCORSO globally, and it is our priority to deliver. 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're 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'll turn the call over to Fadi, who addresses our medical and clinical development activities.

Thanks, Andrew. In support of the launch of myCORSO, our medical affairs organization continued to expand its engagement with the ACM 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 myCORSO, our U.S. field medical teams, including therapeutic medical scientists and managed health medical scientists, were fully trained in operational allowing them to hit the ground running and engage ACPs at the start of 2026. Since approval, our US TMS team has rapidly scaled scientific engagement, conducting over 500 interactions with ACPs in support of myCORSO. Our US MHMS team, in collaboration with our US payer account managers, have 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 III clinical trial of Apikampton 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 Apikampton in Japan. During the fourth quarter, we presented additional data from Maple HCM and three late-breaking sessions at the HCM Society Scientific Sessions and the AHA Scientific Sessions. Responder analysis showed that significantly more patients on africansin achieved a positive or complete response compared to patients on metoprolol. Additionally, treatment with africansin 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'll hand it over to Stuart to speak more about Acacia HCM, as well as our ongoing development programs in heart failure.

Thanks, Paddy. Our next important data readout will come from Acacia HCM, the Pivotal Phase III clinical trial of Afikantin 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 athecampin can demonstrate a clinically meaningful benefit for these patients. As with any pivotal trial, a range of outcomes is possible. And we'll 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 and heart failure. During the quarter, we continued conduct of COMET-HF, the confirmatory phase three clinical trial of Omicantamacarbal in patients with symptomatic heart failure with severely reduced ejection fraction, less than 30%. We now have 100% of US 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 AmberHefPeth, the phase two clinical trial of Eulacanthin in patients with symptomatic heart failure with preserved ejection fraction of at least 60%. We continued enrollment in cohort one of AmberHefPeth 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 higher dose We're encouraged by the continued progress and execution across these ongoing clinical trials, reinforcing our focus on discipline development and advancing innovative medicines within our emerging specialty cardiology franchise. And with that, I'll pass it to Sung.

Thanks, Stuart. We're pleased to report our fourth quarter and full year 2025 financial results. Starting with the balance sheet, We finished the fourth quarter of 2025 with approximately $1.22 billion in cash, cash equivalents and investments, compared to $1.25 billion at the end of the third quarter of 2025. The 2025 year-end balance includes $100 million 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 million during the fourth quarter of 2025. Turning to the income statement, total revenues in the fourth quarter of 2025 were $17.8 million compared to $16.9 million for the same period in 2024. Total revenues for the full year of 2025 were $88 million compared to $18.5 million in 2024. Total revenues for the full year 2025 benefited primarily from the successful completion of the technology transfer totaling $52.4 million to Bayer in the second quarter of 2025 and the recognition of $15 million in milestones in the fourth quarter of 2025 related to the approvals of Mike Corso in the United States and China under the Sanofi License Agreement. As we announced previously, mycorrhizal became available to patients near the end of January, and as such, we expect to report product sales of mycorrhizal with our Q1 2026 results. R&D expenses for the fourth quarter were $104.4 million compared to $93.6 million for the same period in 2024. R&D expenses for the full year of 2025 were $416 million compared to $339.4 million 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 the fourth quarter of 2025 were $91.7 million compared to $62.3 million for the same period in 2024. G&A expenses for the full year of 2025 were $284.3 million compared to $215.3 million 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 the fourth quarter of 2025 and higher non-sales personnel related costs. Net loss for the fourth quarter of 2025 was $183 million or $1.50 per share compared to a net loss of $150 million or $1.26 per share for the same period in 2024. Net loss for the full year of 2025 was $785 million or $6.54 per share compared to a net loss of $589.5 million, or $5.26 per share in 2024. Turning now to our financial guidance for 2026. As this is our first year of launching myCORSO, 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 million and $870 million. Stock-based compensation included in the GAAP combined R&D and SG&A expense is expected to be between $120 million and $130 million. Excluding stock-based compensation from the GAAP combined R&D and SG&A expense results in a range of $700 million to $750 million. TAB, Mark McIntyre, The gap combined r&d and sg and a expense do not include the following collaboration expenses which can include reimburse expense expenses and cost of inventory sales about the camp into partners. TAB, Mark McIntyre, subject to the results of acacia HCM and regulatory review potential costs related to commercialization about the camp and then an HCM and. the effect of gap 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 myCoreZone in the U.S. and funding commercial readiness activities in Europe. Second, advancing our pipeline with important label expansion opportunities for Affycampton and ongoing clinical trials of Omecampton-McCarville and Oolacampton, 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'll hand it back to Robert. Thank you, Sung.

Before we open the call to questions, it's worth pausing to recognize what this moment represents for cytokinetics. After years of focus, discipline, and unwavering commitment to our science, we've crossed an important threshold from pursuing possibilities to delivering impact. The approval of myCORSO 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've been working towards for nearly 28 years at cytokinetics, 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 healthcare 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've 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'd like to share our 2026 milestones. For AFI Camden, we expect to report top-line results from Acacia HCM in the second quarter, 2026. We expect to launch myCORSO in Germany in the second quarter, 2026. We expect to receive potential FDA approval of the supplemental MDA for Maple HCM by Q4, 2026. We expect to complete enrollment in the adolescent cohort of CDER HCM in Q4, 2026. And we expect to receive potential approval from Health Canada in the second half of this year. For Omicant and McCarville, we expect to continue patient enrollment and the conduct of Comma HCF through 2026. For EULA-CAMPTON, we expect to complete enrollment in cohort one of AMBER-HEF-PEF in Q1, 2026, and complete enrollment in cohort two of AMBER-HEF-PEF by the end of 2026. And finally, for our preclinical development and ongoing research, we expect to continue that 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. If you would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. And if you'd like to withdraw that question, again, press star 1. And just as a reminder, please one question. Your first question comes from Tess Romero with JP Morgan. Please go ahead.

Hello, Tess. Good afternoon, Robert and team. Thanks so much for taking our question 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 CO2 or is either fine? Thank you.

So I'll start and I'll turn it over to Fatty and Stuart. To define success, you have to also consider with whom you're 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 that as we have designed this clinical trial, it will be deemed positive if it hits on either or both of the pre-specified clinical trial endpoints. With that, I'll also turn it over to Fadi and Stuart if they want to add anything.

I think the only thing to add is that either endpoint is considered equally positive. So if either one's positive, the trial, would be considered positive. There's not one, one's not weighted more heavily than the other.

Thanks for the question. Thank you.

Your next question comes from the line of Rowanna Ruse with LearRink Partners. Please go ahead.

Good afternoon.

Good afternoon, everyone. Yep. Hello. So a question for me, I was thinking about my course, though, and its initial launch and cardiologist engagement. And could you share any color on how long it's taking sites and clinical centers to get through the ram certification and start to prescribe? And are the field reps noticing anything so far in their detailing?

Yeah. So I'll 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 REM certified and the speed at which that happened shortly after product was in channel. And I'll ask Andrew to elaborate.

Sure. So the REM certification, as you may be aware, is a quick self-study training and a 10 question and answer. that scored it takes um you know 10 to 20 minutes generally for cardiologists sometimes even faster so it's really not been a barrier to be rem certified i think the 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've gotten strong engagement across a broad base of cardiologists both in centers of excellence and outside of centers of excellence in not only REM certification but also getting patients REM 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 and channel, I think they were poised, well positioned to move swiftly with REM certification. And we're seeing evidence of that.

Got it. Thanks.

Thank you. Your next question comes from the line of Mayank Mantani with B Reilly Securities. Please go ahead.

Hello, Mayank. Yes, good afternoon, Dean. Thanks for taking our questions and congrats on a very productive recent few months. So if I may, could you comment on your placebo arm response expectations for both TCCQ and PBO2 and, you know, if you'd expect consistency to what we've seen in proceeding And if you could also comment on whether you'd expect a similar pro-BNP reduction that you saw in the earlier Redwood experience at the time point that, you know, you have here, and if you expect that to be, you know, correlated to the exposure that you may have from a dose intensity standpoint.

So I'm going to ask my colleagues to answer your question, but I'll remind you and also them that as we're approaching on 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're not in any way front running anything that might be understood regarding the progress of the trial, rather its design and conduct.

Yeah, it's 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 PPO2 arm generally, the placebo response is close to zero. You know, it may be a little higher, it may be a little lower, but in our prior studies that placebo response, there isn't much of a placebo response to PPO2. And again, we based Keisha's design on a placebo response in line with our prior studies. You know, you expect four to five points, perhaps six points. But just to emphasize, the statistical design of the study doesn't 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, the difference between placebo and active. And then your last, I think, point was with regards to NPT-proBNP. We certainly wouldn't have any that are different from what we observed in the phase two or the open-label extension with regards to how NT-proBNP has declined during treatment with afecamtin, but we're blinded to those data as well.

Thank you, Dean.

Your next question comes from the line of Joe Pant-Guinness with HC Wainwright. Please go ahead.

Hey, Joe. Hey, everybody. Thanks for taking the questions. So a question on early market uptake, and I'm 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 reserve. Wanted to know if there's 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, you know, any commercial differences? I know you have started to put a team there or potential headwinds that you could expect versus what you see in the United States. Thanks.

Andrew, do you want to take that?

Sure. So maybe start backwards. China is partnered. Sanofi is commercializing China. We're not doing that. So that's an important element. I think the back to the U.S. Patients in Reserve, I think that the demand we're seeing and where we're seeing it from is, you know, what we were expecting. So we were not surprised by the patient demand. I think it was reflected in research we were seeing when we were doing primary market research, pre-approvals, 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're where we were expecting to be, knowing that we've been in the market with product for about three weeks.

But also like just. Sorry.

Maybe I can just add to the point of Andrew's comment, 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'll be in a position to comment more about that in time. Thank you.

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

Hi, Corey. 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. Is that a reflection of how U.S. physicians are thinking about it? And then from that standpoint, I know how it's powered, but what's considered to be a clinically meaningful change, again, from a physician point of view? Thank you.

So here again, I'm going to remind our colleagues with regard to what were the original design requirements, but I'll also say that the fact that we chose to have co-primary endpoints was 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, Fatih and Stuart, I'll ask you if you want to say anything else.

Yeah, I'll just add, I don't think physicians will lean one way versus the other. I think they will look kind of 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. You know, in this field, there are no treatments for non-obstructive HCM. Physicians are looking for improvements in their patient 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 evidence.

I'll just add that to answer your question about minimally important differences, for this being in HCM, and to reiterate what Sadi said, there is no approved drug for these patients in this population. What's going to be considered important and clinically meaningful is going to be hopefully a function of this trial as we learn what's concordant, how the endpoints move together, and what ultimately defines larger magnitude improvements versus what may be otherwise. So, I think we're going to learn a lot from this study that's going to be informing the clinical literature and hopefully what ultimately may be medical guidelines. But we don't 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's helpful. Thank you both.

Your next question comes from the line of Selim Said 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 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.

So, ultimately, this will be a function of the actual data and what's 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'd like to be able to do both of our KK82, 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'll have to speak to both endpoints. I don't 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 it at Congress. Patty, anything you want to add?

You know, I'll just add that 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 tradeoffs here in terms of all the stakeholders involved.

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

Okay, got it. Thanks so much, guys.

Your next question comes from the line of Yasmine 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 one of the questions we've been getting is, have you done pair 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'll jump back in the queue.

So maybe that's a question for both Sadie and Andrew in terms of your specific example of a three-point difference in KCCQ. I assume you picked that number arbitrarily, but maybe, Sadie and Andrew, if you want to tackle that.

Let me just start, you know, by saying that in, you know, Maple, and sequoia, you see a range of strength of response. 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 don't respond very much at all. And so, I think in a lot of ways, the average number coming out of the trial We'll certainly color how physicians maybe look at the importance of the results, but we also, you know, enrolled 500 patients in the study, and many of them will go in an open-label extension, and many of these investigators will have a chance to evaluate on their own how patients improved. And I think, ultimately, this will be part of the case If you try it, you have a sizable response, and it's important to you, then continue therapy. And if you don't, then you don't have to continue therapy. And it's a little different than drugs where we treat to lower risk, where you don't really know if you're the one that's going to benefit from the drug. And thereby, absolute differences are far more important to understand your potential benefit. So I hope that helps. you know, medical perspective.

Thank you, Patty.

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

And I think just to maybe culminate here, just 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 Condoulas with Stifel. Please go ahead.

Good afternoon. Hey, thanks for taking my question. Afternoon. Congrats on all the progress, and thanks for taking my question. I actually wanted to ask one about ASPF, and I was curious in the context of Acacia, you know, how important or meaningful you think an Acacia win would be helping to kind he risked that broader HFPAF opportunity given some of the overlapping 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'm going to ask Stuart to comment, but I'll also highlight that, you know, we learned a lot from what we can glean from those data from Odyssey. 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 Hef-Pef and the translation of this mechanism of a cardiac myosin inhibitor to an adjacent population. That's certainly our objective. And with that, I'll ask Stuart maybe to comment.

Thank you, James. I mean, you hit upon an important evidence base that really informed this hypothesis about the potential benefit of a CMI in patients with HEP-PEF, and more specifically those patients with hypercontractility. So, you know, many of the features clinically and structurally are similar between patients with non-obstructive ACM and with HEP-PEF and hypercontractility. I think, you know, the outcome of Acacia could further inform the potential benefit of a CMI in Hep-Peth. With respect to when we expect results, you know, from Amber Hep-Peth, I think it's a little bit too soon to say that, but we'll 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're thinking about HFAP is not the entirety of that population, but those whose disease and anatomy is defined by hypercontractility. And that's where we believe there's an adjacency to NHCM. Thank you for the questions.

Your next question comes from the line of Jason Butler with Citizens. Please go ahead.

Hi. Thanks for taking the question. Can you give us any color on the centers that are signing up in the REMS program right now? Are you getting any healthcare prescribers that are either not current CMI prescribers or have never prescribed CMI? Or is it fair to say the majority of the signups are current CMI prescribers? Andrew?

Yeah, sure, so thanks for the question. The majority are current CMI prescribers, but we have, we do have prescribers who are REM certified who are not CMI prescribers today, and we do have prescribers that are first-time CMI prescribers as well. So, but as you would think, the majority are current CMI prescribers.

And that tracks with the ways in which our, cardiovascular count 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's where he commented on percent engagements. But it's nice to see that already we're 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 Score with Morgan Stanley. Please go ahead.

Great. Thank you for taking my question. So, assuming a 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 how that would read through. And also I'll try, 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.

So I'll tackle that latter question and ask Andrew to do the former. We're 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're not going to comment on that and then i'll ask andrew to speak to your first question yeah i mean i think obvious we're not going to be promoting or talking about nhm or acacia if the product's positive and approved but you know given that we would expect that there would be uplift we have seen in market research that there's a halo effect, if you will, on obstructive HCM, probably in the order of magnitude of 15 to 20% uplift.

Great. Thank you. And on the data, we'll 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 past colleagues would be able to speak to.

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

Hey, Serge. Hi, good afternoon. Thanks for taking my questions. I'll pile on Acacia too, seems to be the topic du jour. So I know you're still blinded to almost all the data, but I think in the past you've talked monitoring the variability in the endpoints. So just curious if there's been any change in that variability and what you can glean from that.

Thanks. Yeah, so I'll turn to Fadi, but I'll emphasize yet again that in light of the fact that we're now nearer to what would be database lock and unblinding, We can't 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.

Yeah, the study was designed to demonstrate a five-point delta on KCCQ, assuming a standard deviation of 15 and a PCO2 of 1 with a standard deviation of 3. 90% power with, you know, being able to detect statistically significant differences and differences that are less than that with less power, obviously. And as I stated in the script, the setting remains within its design parameters. And, you know, we won't commit to updating those statements going forward. Got it. Thank you. Thank you.

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

Hello, Jason.

Hi, this is Jackie on for Jason. Congrats on the progress and thanks for taking your question. So real quick, can you report what you've 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 reception been like specifically within these offices? Thank you.

Thank you. Andrew?

Sure. So we're not going to give numbers. We'll 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've seen with physicians is at if not above what we expected internally. In terms of community versus centers of excellence, you know, the 700 physicians that were 80% of the market, That's where the majority is coming from. But there's also strong engagement from the community. There's strong engagement from new prescribers. Probably new prescribers who have never prescribed to CMI, you know, those numbers are higher than we were expecting. I think we're seeing a good balance across all types of prescribers. And the majority, obviously, are the ones that we're calling on and educating. But in the, you know, in our first quarter call, we'll give more color around patients and engage in, you know, centers of excellence versus non-centers of excellence, prescribing death, et cetera. So, you know, more to come, but too early to say with just three weeks of data.

Suffice it to say, it's early innings, but we're pleased.

Understood.

Thank you.

Your next question comes from the line of Krypta Devakonda with Truist Securities. Please go ahead.

Hi, this is Alexon for Krypta. Congrats on the progress. I'm very excited to see how my course's REMS can also improve the patient and physician experience. A question on the REMS. Could there still be an option to modify the REMS requirement in the future? And can cytokinetics go back to the FDA at some point with updated post-marketing data and get it re-reviewed potentially to potentially make it even more favorable?

Yeah, so we've already seen that the FDA was accepting of an opportunity to see real-world evidence data in support of a modification of the CAM-XIOS REMS. But for our REMS, we're not guiding to any changes in the near term, but certainly over a medium to longer term, it's reasonable to expect that real-world evidence could inform changes. What those changes might look like, it would be premature to speak to today. Patty or Stuart, anything you want to add?

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

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

Yeah. Hi there. Thanks, guys. 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 phenotype?

I can talk to, you know, discontinuations. And again, the study was designed to withstand a 10% discontinuation rate. And I think, as I've said in the past, we've been within that metric. my earlier comments reaffirm that but we'll commit to updating that going forward and then um you know we haven't uh released any of the baseline characteristics and so i can't really comment on your last question but what i can say is that our um you know group of hcm specialist physicians review every every echo of every patient that's 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 Lenoded Timashev with RPC Capital Markets. Please go ahead.

Hey guys, thanks for taking my question. I just want to go back to the mycorrhizal launch and the patient. I guess, can you provide any color on the types of patients that are being started versus what you might expect from, you know, the initial Mavicams in the launch? I guess, is there 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'm just curious how doctors are thinking about the initial use of Avacamp and as they now have the ability to use the drug.

Thanks.

Keep in mind, we don't 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 is that we, you know, patient information is protected. We don't see exactly who's put on and for what reason. You know, the data is too early to see if they're switching, et cetera. But I do think we're 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 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 won't repeat those statements other than to say we understand the significance of this as we turn the page onto commercialization, and we want to do the right thing by these patients for the benefit of their care. and do right by healthcare professionals who attend to their care. We also recognize and acknowledge that this is an important milestone for Wall Street as cytokinetics is now a global commercial company, and we take that very seriously as well, and we look forward to providing you insights as we have more substantial information relating to the launch of mycorrhizal in the United States, its expected launch in Germany and other European countries, and we'll 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're doing at cytokinetics. We look forward to keeping you abreast of progress. With that, operator, we can now conclude the call.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.