Cytokinetics Inc (CYTK) 2025 Q4 法說會逐字稿

Thank you for standing by, and welcome to the Cytokinetics fourth quarter 2025 earnings call. This call is being recorded (Operator Instructions). 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 Callos, EVP and Chief Commercial Officer, will discuss the commercial launch of Myqorzo in the US 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 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 response 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 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.

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 Myqorzo 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 Myqorzo in both the US and China, plus a positive opinion from CHMP for Myqorzo in the European Union. That latter milestone preceding last week's announcement of the European Commission's approval of Myqorzo in the EU.

Together, these milestones represent the culmination of years of focused scientific, clinical and regulatory execution and we now turn the page on to a new chapter for Cytokinetics as a global commercial stage biopharmaceutical company.

More importantly, the approval of Myqorzo 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 Myqorzo as a new treatment option is high. With an eye towards the longer-term US 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 Myqorzo 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 a 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 Myqorzo.

Outside the US, following the recent approval of Myqorzo 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 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 and as well as operating expense guidance for 2026. That guidance reflects the priorities of launching Myqorzo 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 US commercial was process began immediately following FDA approval of Myqorzo on December 19 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 are taking calls within days of approval, ensuring patients and HCPs had 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 drugstores, websites and social media advertising to help drive awareness and education.

Our sales representatives, whom we call cardiovascular account specialist began engaging with HCPs immediately following the New Year's holidays and certifications within the Myqorzo label. Within reach of approval, the online porter portal for the Myqorzo -- program went live and Myqorzo became available for prescription.

On that same day, we also launched Myqorzo and you, our patient support programming offering personalized support, access and reimbursement assistance and affordability programs for eligible patients, including a free trial program, Ridge program, Coke 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 Myqorzo and you. Within days of availability, the first prescriptions from Myqorzo were dispensed. At the end of January, we also hosted our first national speaker broadcast with strong attendance from across the US. 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 Myqorzo in the United States. While we are still early in our launch so far, customer feedback has been positive, as 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 canceling is not required as part of the REMS for Myqorzo.

While it's still early in our launch, we're encouraged by the initial level of engagement, REM certification and overall demand. Within three weeks, we had over 700 HCPs now REM-certified across HCM specialty and nonspecialty senators, a leading indicator of ACT's planning to prescribe Myqorzo. And as mentioned, patients were on therapy within the first week that Myqorzo was available. The level of demand in Repaint enrollments and therapy initiation is so far reinforcing our conviction and the commercial prospects for Myqorzo.

In addition, we have already achieved over 12,000 customer engagements, including our cardiovascular account specialist having engaged over 95% of the 700 HCPs who account for the majority of CMI prescribing today. Our current focus remains on educating HCPs -- prescribing information, preparing them for the REMS requirements, and encouraging them to identify patients for Myqorzo.

From market research conducted post launch, we have learned that on an ad basis, roughly 90% of HCP's surveyed are aware of Myqorzo, the majority of which have stated they plan to prescribe Myqorzo for their obstructive HCM patients. They further state they recognize the potential benefits of the Myqorzo 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 Bureau launch. The number of HCPs are actively writing prescriptions, the volumes of prescriptions and HCP rights and the number of patients on Myqorzo, we see this as leading indicators of launch depth and breadth that will read on our overall progress.

As we continue this launch, our goal for Myqorzo is to achieve greater than 50% of CMI new patient preference share by the end of 2026. We also intend to engrave the overall MI category. Our confidence is based on three launch drivers: clinical evidence are bespoke patient support services and the differentiation of our REMS program.

First, the clinical evidence from SEQUOIA-HCM supports that Myqorzo is associated with rapid and sustained reduction in obstruction and improvement in symptoms, that it provides flexibility that type -- really 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 Myqorzo in 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 Myqorzo 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 Myqorzo and preference share. Driving access for patients is also a high priority. We've been engaging with payers for some -- 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 was to have Medicare access comparable to Camzyos in the first quarter and commercial access comparable Camzyos Q4 2026.

In Europe, with DCA approval for Myqorzo 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 legion in all EU four countries and the UK to prepare for subsequent European launches in later 2026 and in '27.

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 Micro 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 Fady to address our medical and clinical development activities.

Thanks, Andrew. In support of the launch of Myqorzo, 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 Myqorzo, our US 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 HCPs at the start of 2026.

Since approval, our US TMS team has rapidly scaled scientific engagement, conducting over 500 interactions with HCPs that supported Myqorzo. 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 and 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 our global development strategy, our partner Bayer completed enrollment to Camelia-HCM, a Phase III clinical trial of aficamten in Japanese patients with obstructive HCM. Additionally, we completed enrollment of the Japanese cohort of non-obstructive HCM patients and ACACIA-HCM, both intended to support potential marketing authorization for aficamten in Japan.

During the fourth quarter, we presented additional data from MAPLE-HCM and three late-breaking sessions at the HCM Society Scientific Session and the AHA scientific sessions. Responder analysis show that significantly more patients on aficamten achieved a positive or complete response compared to patients on metoprolol.

Additionally, treatment with aficamten resulted in significantly greater improvements to -- 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 and 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 III clinical trial of aficamten patients with an HCM. 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 shows 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, the 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 in heart failure. During the quarter, we continued conduct of Code-HF, the confirmatory Phase III clinical trial of omecamtiv mecarbil in patients with symptomatic heart failure which 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 AMBER-HFpEF, the Phase II clinical trial of ulicamten 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 2 for a valuation of higher doses. We're 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'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 Myqorzo in the United States and China under the Sanofi license agreement.

As we announced previously, Myqorzo became available to patients near the end of January. And as such, we expect to report product sales of Myqorzo 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 and 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 and was primarily driven by investments towards commercial readiness, including the hiring of our US sales force, primarily in the fourth quarter of 2025 and higher nonsales 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 it is our first year of launching Myqorzo, 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. The GAAP combined R&D and SG&A expense do not include the following: collaboration expenses, which can include reimbursed expense 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 and 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 Myqorzo in the US 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 ulacamten; 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 Myqorzo 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 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 or 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 and access to care, diagnosis and treatment for people living with HCM.

Through this long-standing 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 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 aficamten, we expect to report top line results from ACACIA-HCM in the second quarter 2026. We expect to launch Myqorzo in Germany in the second quarter 2026. We expect to receive potential FDA approval of the supplemental NDA for MAPLE-HCM and 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 common HCF through 2026. For ulacamten, we expect to complete enrollment in Cohort 1 of AMBER-HFpEF in Q1 2026 and complete enrollment in Cohort 2 of AMBER-HFpEF 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.

(Operator Instructions)

Tess Romero, JPMorgan.

Hello, sir. Good afternoon. Thanks so much for taking my questions this afternoon. So one from us on ACACIA. Is it true that the study will be successful, if at least one of the end points reaches statistical significance. And then along these lines, in your study protocol, did you specify which endpoint would be you would need to hit to be claim -- 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 Fady 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 interest as mid 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 prespecified clinical trial end points.

With that, I'll 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, but either one is positive, the trial would be considered positive. There's not one is not weighted more heavily than the other. Thank you.

Roanna Ruiz, Leerink Partners.

Yeah. Good afternoon, everyone. So a question for me. I was thinking about Myqorzo and its initial launch in cardiologist engagement. And could you share any color on how long it's taking sites and centers to get through the REMS 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 purposefully 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'll ask Andrew to elaborate.

Sure. So the REM certification, as you're maybe aware, is a quick self-study training and attend question-and-answer that scored, it takes 10 minutes 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 Myqorzo to be approved and had patients that were also waiting. And we've gotten strong engagement across a broad base of cardiologist 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 in channel I think they were poised, well positioned to move swiftly with REMS certification, and we're seeing evidence of that.

Got it. Thanks.

Thank you.

Mayank Mamtani, B. Riley Securities.

Hello, Mayank.

Yes. Good afternoon, team. Thanks for taking our questions then. Congrats on a productive recent few months. So ACACIA, if I may. Could you comment on your placebo arm response expectations for both KCCQ and PVO2? And if you'd expect consistency to what we've seen in preceding HCM trials? And if you could also comment on whether you'd expect a similar proBNP reduction that you saw in the earlier Edward 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?

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 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 it's 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 PPO 2 arm, generally, placebo response is close to 0, maybe a little higher, maybe a little lower, but in our prior studies that placebo response, there isn't much of a placebo response to PPO 2.

And again, we based ACACIA design on a placebo response in line with our prior studies, expect 4 to 5 points, perhaps 6 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 5 points difference between placebo and active.

And then your last thing point was with regards to NT-proBNP, we certainly wouldn't have any expectations that are different from what we observed in the Phase II or the open-label extension with regards to how NT-proBNP has declined during treatment with came but we're blinded to those data as well.

Thank you, team.

Joe Pantginis, H.C. Wainwright.

Hey, Joe.

Hey, everybody. Thanks for taking So a question on market uptake, and I'm glad Andrew made an earlier comment as well that I wanted to ask. So with regard to the US first, Andrew, you made some comments about and previously about patients docs have been having in reserve. I wanted to know if there is any uptick there that you thought might have been in line or even quicker than expected.

Secondly, with regard to ex US, 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 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 US patients and reserves I think the demand we're seeing and where we're seeing it from is what we were expecting. So we were not surprised by the patient demand.

I think it will reflected in research we were seeing when we were doing primary market research, preapprovals, 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.

Cory Kasimov, Evercore.

Hi, Cory.

Hey, Robert. Hey, guys. Thanks for taking the questions. So I had a follow-up on ACACIA and I want to also ask between these two primary endpoints of KCCQ and peak VO2. And we think specifically about US 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 with KCCQ, is that a reflection of how US 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 end points 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 Fady and Stuart will 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 NY class and other metrics of exercise, biomarkers and things like that.

So in this field, there are no treatments for nonobstructive physicians are looking for improvements in their patient status and there are many dimensions upon which they can improve. And I think they and also regulators will look at the totality of that.

I'll just add -- 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'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 end points 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.

Salim Syed, Mizuho.

Great. Thanks for the questions, 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 hit on the dual primaries.

Or should we be thinking somewhere more along the lines of SEQUOIA. Had 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.

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 KCCQ and needed to 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 at Congress. Fady, anything you want to add?

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 was tremendously impactful that way. So there are many considerations and important trade-offs 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.

Yasmeen Rahimi, Piper Sandler.

Thank you so much for all the color. My question is just related to ACACIA also I think one of the questions we've been getting is, would -- have you done payer work or uptake work to understand whether the usage would still be strong as you showed a 3-point placebo-adjusted difference in KCCQ or just commentary as long as you have a statistical separation and the magnitude of delta difference in KCCQ is irrelevant. I appreciate color and I'll jump back in the queue.

So maybe that's a question for both Saudi and Andrew. In terms of your specific example of a 3-point difference in KCCQ, I assume you picked that number arbitrarily, but maybe Fady and Andrew, if you want to tackle that?

Let me 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 don't respond very much at all.

And so I think in a lot of ways, the average number that's 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 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 potential benefit. So I hope that helps from a medical percent.

Thank you, Fady.

And yes, from a demand point of view, provided that the study is statistical and that Myqorzo would be approved for non-obstructive. The care demand is driven significantly higher. We hear things like AAPs being able to use one product across all of ATM, not worrying whether it's OEM or nHCM, especially given the profile that you know and we know from SEQUOIA that it would drive up use, both in OEM obviously as well as in HCM. 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. 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 a 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.

James Condulis, Stifel.

Good afternoon.

Hey, thanks for taking my questions. Good afternoon. Congrats on all the progress and thanks for taking my questions. I actually wanted to ask one about HFpEF. And I was curious in the context of Acacia, how important or meaningful you think in ACACIA win would be helping to kind of risk that broader HFpEF 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 we learned a lot from what we can glean from those data from Odyssey. And that obviously has impacted 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's certainly our objective. And with that, I'll ask Stuart maybe to comment.

Thank you, James. I mean you'll hit upon an important evidence space that really informed this hypothesis about the potential benefit of in patients with HFpEF and more specifically those patients with hypercontractility.

So many of the features clinically and structurally are similar between patients with nonobstructive HCM and with HFpEF and hypercontractility. So I think the outcome of ACACIA could further inform the potential benefit of a CMI and HFpEF. With respect to when we expect results from -- from AMBER-HFpEF, 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 hyper contractility, and ensuring that everybody appreciates that the way we're thinking about FPP 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.

Jason Butler, Citizens.

Hi, thanks for taking my questions. 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 precise CMI? Or is it fair to say the majority of all of the sign-ups are current CMI prescribers?

Andrew?

Yes, 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. But as you would think the majority are carrier CMI prescribers.

And then 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'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.

Maxwell Skor, Morgan Stanley.

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 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, obviously, we're not going to be promoting or talking about an HCM or ACACIA, if the product's positive and approved. But 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. It -- depends 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 cash colleagues would be able to speak to.

Serge Belanger, Needham.

Hey, Serge.

Hi, good afternoon. Thanks for taking my questions. I'll pile on ACACIA 2 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 about monitoring the variability in the end points. So just curious if there's been any change in that variability in what you can glean from that? Thanks.

Yeah. So I'll turn to Fady, but I'll emphasize yet again that in light of the fact that we're now near 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 5-point belt on KCCQ, assuming a standard deviation of 15 and a PF2 of 1 with a standard deviation of 3. 90% power with being able to detect statistically significant differences at the 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 we won't commit to updating those statements going forward.

Got it. Thank you.

Thank you.

Jason Zemansky, Bank of America.

Hello, Jason.

Hi, this is Jackie on for Jason. Congrats on the progress, and thanks for taking our questions. 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?

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, the 700 physicians were 80% of the market. That's where the majority is coming from, but there's also strong engagement from the community.

Their strong engagement from new prescribers probably new prescribers who have never prescribed the CMI, those numbers are higher than we were expecting. So 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 our first quarter call, we'll give more color on pages and engage in centers of excellence versus non centers of excellence, prescribing death, et cetera. So 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.

Crypta Devin Conda, Truist Securities.

Hi, this is -- for Crypta. Congrats on the progress. We're very excited to see how Myqorzo's REM can also improve the patient and physician experience A question on the REMS. Could there still be an option to modify the runs requirement in the future? And could Cytokinetics go back to the FDA at some point with updated post-marketing data and get it rereviewed potentially to potentially make it even more favorable?

Yes. 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 Camzyos 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. Fady or Stuart, anything you want to add?

Yes. The REM itself is quite straightforward in terms of what's required to execute it. But new real-world data will inform potential future modifications to it. But as Robert said, it's still too early to decide what it is that we may pursue. I think we just need some real-world data to understand what maybe our pinch points and how those real-world data would support all three grams at my release those few points.

Ash Verma, UBS.

Yeah. Hi, there. Thanks, guys. This is Natalie on for Ash, and thanks again for taking our questions. 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 LDH phenotype?

I can talk to discontinuations. And again, study was designed to withstand a 10% discontinuation rate. And I think as I said in the past, we've been within that metric. And in my earlier comments, reaffirm that, but we'll commit to updating that going forward.

And then we haven't 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 group of HCM specialist physicians review every echo of every patient that's enrolled in the trial and unless they feel 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.

Leonid Timashev, RBC Capital Markets.

Hey, guys. Thanks for taking my questions. I just want to go back to the Myqorzo launch and the patients. I guess, can you provide any color on the types of patients that are being started versus what you might expect from the initial Nava camps in the launch? I guess is there anything specific about the patients being put on? Is it just new patients? Are there any switches? Is it patients who may be needed higher efficacy or had lower baseline ejection fraction. I guess I'm just curious how docs are thinking about the initial use of aficamten -- have there the ability to use the drug? Thanks.

I'm sorry, just keeping 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, you said exactly what I was going to say is that we -- patient information is protected. We don't see exactly who was put on in for what reason. 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 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 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 Myqorzo 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 two. 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.