CYTK - NASDAQ

Thank you for standing by, and welcome to the Cytokinetics Q3 2025 Earnings Conference Call. This call is being recorded and all participants will be in a listen-only mode. [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 address commercial readiness activities for aficamten. Fady Malik, EVP of R&D, will provide updates related to the clinical development program and medical affairs activities for aficamten. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates on the clinical development program for omecamtiv mecarbil and ulacamten. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the past quarter. And finally, Robert will provide closing comments and review our expected key milestones for the remainder of 2025. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our third quarter 2025 financial results filed on Form 8-K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call. Now I will turn the call over to Robert.

Thank you, Diane, and thank you all for joining us on the call today. The past quarter was highly productive and defining for Cytokinetics. We made significant progress across the company's priority objectives as we advance towards the end of the year when we hope to achieve our first potential FDA approval of aficamten for patients with oHCM. Our major accomplishments this past quarter were dedicated to preparing for that milestone, including continuing constructive engagements with FDA, completing key commercial launch readiness activities and fortifying our capital structure. During the quarter, we held our late-cycle meeting with the FDA. As we previously disclosed during the meeting, we discussed our proposed REMS program, including elements to assure safe use, or ETASU, as well as anticipated post-marketing requirements. Prior to the meeting, we had received FDA's responses to our proposed REMS and label for aficamten. And based on our exchanges and discussions with FDA to date, we continue to expect a differentiated label and risk mitigation profile for aficamten if approved by the FDA. We've completed all GCP inspections by the FDA with no observations noted. Moreover, to date, we have not been notified of the intention of FDA to conduct pre-approval inspections. We look forward to continuing our dialogue with FDA ahead of the PDUFA date. In recent months, we've also leaned further into commercial readiness with the onboarding of our commercial field sales colleagues and the finalization of promotional campaigns and patient support programs, with objective to further differentiate how we show up commercially. At the same time, in Q3, we achieved an important clinical milestone within the development program for aficamten. We presented the positive primary results from MAPLE-HCM, which demonstrated superiority of aficamten to metoprolol in patients with oHCM, challenging the long-held status quo of treatment in this disease. Our intention is to file a supplemental NDA for MAPLE-HCM following its potential initial FDA approval. But in the meantime, we believe these results may help catalyze certain prescribers and help unlock more of the market upon the initial introduction of aficamten as may result in increased commercial launch velocity. Following closely behind the potential approval and launch of aficamten in the United States is the expected potential approval of aficamten in the EU. During the quarter, we received the Day 120 List of Questions from the EMA, and we subsequently submitted our responses. More recently, we've continued EMA interactions, and we're preparing Day 180 responses. We're encouraged by ongoing interactions, and we expect a final decision from the European Commission in the first half of next year, even possibly on the earlier side of the year, given the pace of our review to date. In parallel, our European launch readiness activities are well underway, focused on market access planning, medical education and engagement with the cardiology community and to ensure a strong foundation for a successful introduction of aficamten in Europe. We also continue to work closely with Sanofi to support the potential approval of aficamten in China to further broaden the global opportunity and reinforce our commitment to making this therapy available to patients worldwide. To achieve all of this, we're fortunate to have a strong balance sheet, which we further bolstered during the quarter through our convertible note offering. As Sung will elaborate, this transaction helps not only to provide additional capital at this important time, but also financial flexibility. And lastly, we continue to build momentum across our broader pipeline at this important inflection point in our corporate development, reflecting our ongoing commitment to sustained innovation and longer term growth. With that, I'll turn the call over now to Andrew, please.

Thanks, Robert. We continue to make strong progress with commercial readiness activities towards the potential FDA approval of aficamten next month. As Robert mentioned, our interactions with the FDA to date have reinforced our expectations for a differentiated risk mitigation profile anchored in REMS and label, and we have confirmed our go-to-market plans and promotional campaign. Following anticipated approval in December, our launch process will begin immediately. Within days, our website, patient navigators, patient support services will go live to begin supporting physicians and patients on their treatment journey. Shortly thereafter, in early January, our fully trained cardiovascular sales and medical teams will be in the field engaging healthcare professionals with full commercial launch, inclusive of product availability and REMS operations to follow. To ensure a seamless and impactful launch, we've invested deeply in assembling the right team and creating the right infrastructure. Over the last several months, we've built a strong and highly experienced cardiovascular sales team with our field sales representatives averaging over 20 years of industry experience and 14 years of cardiovascular experience. These are seasoned sales professionals who understand the nuances of launching a new medicine in a specialized market. Our sales team is on board and completing training to ensure that our full team will be prepared to begin HCP engagement within days of FDA approval. A subset of our sales team has already been in the field since early September, introducing Cytokinetics to key oHCM HCPs and providing disease education. Core to our launch strategy and consistent with the value and our vision of a differentiated patient-centric treatment experience, one that has been built from the ground up specifically for aficamten. Our approach is designed to be simple and integrated across all touch points for both HCPs and patients. At the heart of this model is a highly qualified team of patient navigators who will serve as a central point of contact throughout the patient journey. These navigators are also on board and have completed their training or are completing their training and preparations ahead of their anticipated approval to ensure readiness. We've developed a distinct and compelling promotional HCP campaign that highlights the differentiated characters of aficamten and key attributes of our REMS program. We believe this campaign will clearly communicate the clinical value of aficamten and support broad awareness among cardiologists. Ahead of launch, we continue to engage with payers to educate them on the evidence from our clinical trial as well as the clinical and economic burden of HCM. We remain confident in our ability to see parity access by the second half of 2026. Importantly, our strategy is comparable access with focus to differentiate based on the clinical profile of aficamten, our REMS program and our comprehensive bespoke patient support services. As we stand several weeks out from our potential approval, I'm pleased with our commercial preparation and launch readiness, and I'm confident in our ability to execute quickly and effectively if aficamten is approved. As we look ahead to measuring the pace and velocity of our launch after approval, we will focus on a few key metrics. First, HCP prescribing breadth as measured by the number of HCPs who are actively writing prescriptions. Second, prescribing depth as measured by the volume of prescriptions and HCP writes for aficamten. To achieve rapid uptake, we will quickly engage existing CMI prescribers with an eye to expanding the prescribing universe to those who treat HCM, but have yet to prescribe a CMI. More specifically, our goal for our field-based cardiology account specialists was to reach nearly all of the estimated 650 HCPs or approximately 80% of the HCM prescribing to date within the first few weeks of January. And third metric is the volume of patients on aficamten. We will be closely monitoring and supporting patient uptake, including time of conversion to commercial drug, adherence, compliance and persistency. These measures will provide us early insights into the speed and trajectory of our launch rate of change and overall strength of our commercial execution focused on category growth and overall preferential share in an expanding market. Finally, our attention is not only on the U.S., but also in the EU, where we've made meaningful progress in preparing for potential commercial launch of aficamten in that geography. We recently hired a General Manager for Italy alongside colleagues that are already on board in the U.K., France and Germany and also began recruiting and hiring our full German commercial team inclusive of our field sales reps. In addition, we are preparing dossiers for upcoming discussions with HA bodies across key EU countries, with potential EMA approval expected in the first half of 2026, we remain on track for a launch in Germany in the first half of 2026 with other geographies to follow in '26 and '27. With that, I'll turn the call over to Fady.

Thanks, Andrew. During the quarter, we are pleased to have presented new data that further reinforces the differentiation of aficamten and its potential for patients with HCM. Most notably, at the ESC Congress, we presented positive primary results from MAPLE-HCM, which were simultaneously published in the New England Journal of Medicine. The results which show superiority of aficamten to metoprolol represent a watershed moment in treatment of oHCM. While patients treated with aficamten experienced a significant improvement in exercise capacity, those on metoprolol showed a decline, challenging the long-standing rationale for beta blocker used as the standard-of-care therapy in this disease. This finding has resonated strongly across the cardiology community as we heard firsthand from many healthcare professionals and key opinion leaders on site at ESC. In addition to improving exercise capacity, aficamten also produced larger improvements in symptoms, gradients and cardiac biomarkers as compared to metoprolol. Improvements were consistent across all prespecified subgroups and confidence of the robustness of the findings. Importantly, adverse events were similar in the 2 groups and the safety of aficamten observed in MAPLE-HCM was consistent with previous studies. To that end, as the evidence of aficamten expands, so too does our confidence in its consistent safety profile. An updated integrated safety analysis representing nearly 700 patient years of exposure from REDWOOD-HCM, SEQUOIA-HCM, FOREST-HCM and now MAPLE-HCM as well, aficamten was shown to be well tolerated with a low incidence of LVEF less than 50% over extended periods of exposure, with no occurrences associated with a serious event of heart failure. Long-term treatment with aficamten has also been shown to not be associated with an increased risk for atrial fibrillation. Looking ahead and coming up this month at the AHA scientific session, pleased to have 3 late-breaker presentations with additional data from MAPLE-HCM providing new insights into these results. With respect to the ongoing clinical trial program for aficamten, the next major data milestone for us will be the readout of ACACIA-HCM, the pivotal Phase 3 trial in nHCM. We completed enrollment of the primary cohort, excluding Japan, in the first quarter of 2025, and we now expect to report the top line results from this cohort of ACACIA-HCM in the second quarter of 2026. During the third quarter, we completed enrollment of patients in the Japan cohort, closing enrollment of ACACIA-HCM worldwide. If the results of ACACIA-HCM are positive, it represents an opportunity to address the needs of a highly underserved patient population and an important opportunity to expand the therapeutic impact of aficamten. Our belief in the therapeutic potential of aficamten in nHCM is founded in the existing body of evidence from the nHCM cohort of REDWOOD-HCM and strengthened by their longer term follow-up in the FOREST-HCM trial as recently reported. At the Heart Failure Society of America meeting in late September, we presented new data covering at least 96 weeks of treatment in these nHCM patients. What you saw, albeit in an open-label setting was that 79% of the patients treated with aficamten improved by at least 1 NYHA functional class. Patients also had a mean increase in their KCCQ Clinical Summary Score of 11.2 points as well as improvements in cardiac biomarkers. Few patients experienced LVEF less than 50 and all instances were reversible after down titration or short treatment interruption. We are hopeful that these data may be replicated in the results of ACACIA-HCM given the similarity in patient populations and dosing scheme involved. Alongside our clinical research, our Medical Affairs organization has been very active, engaging the HCM community broadly as we prepare for launches in both the U.S. and Europe. They conducted recent advisory board meetings in the U.S. and Europe and met with the HCM community of physicians at ESC and HFSA alongside institutional visits in their territories. Our team of therapeutic medical scientists in Germany is in place, and we now have medical directors located in Germany, the U.K. and France, supported by our regional group located in Switzerland. Our field team in the U.S. have now also partnered with their newly hired sales colleagues to compliantly conduct introductory meetings with key opinion leaders and healthcare professionals. Now I'll turn it over to Stuart to provide updates on our ongoing clinical trials in heart failure.

Thanks, Fady. During the quarter, we continued conduct of COMET-HF, the confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction less than 30%. These are patients who remain at high risk for frequent hospitalization and mortality despite receiving maximally tolerated guideline-directed therapies. COMET-HF is designed to confirm the findings of the positive Phase 3 clinical trial of GALACTIC-HF in a more severe HFrEF population in whom we believe this mechanism may be able to deliver greater cardiovascular risk reduction. In October, we conducted an investigator meeting in Europe, which revealed tremendous enthusiasm for COMET-HF. Many of the investigators had participated in GALACTIC-HF, and it was really wonderful to see their continued enthusiasm for the potential benefits of omecamtiv mecarbil. We now have over 75% of sites in North America and Europe activated and are continuing to activate sites around the world. We expect to continue patient enrollment in COMET-HF into 2026. We also continue to conduct AMBER-HFpEF, the Phase 2 clinical trial of ulacamten in patients with symptomatic heart failure with preserved ejection fraction of at least 60%. By inhibiting cardiac myosin to attenuate hypercontractility, ulacamten is uniquely positioned to address the underlying diastolic dysfunction in this subgroup of HFpEF patients. HFpEF represents approximately half of all heart failure cases and remains an area of high unmet need with limited treatment options. Enrollment in AMBER-HFpEF is progressing, and we expect to complete cohorts 1 and 2 in 2026 to inform FDA interactions and the decisions to proceed towards potential registrational studies. We're pleased with the continued execution of these ongoing clinical trials, each in a different form of heart failure, which reflects our continuing commitment to further advance innovative medicines within our specialty cardiology franchise. And with that, I'll pass it to Sung.

Thanks, Stuart. We're pleased to report our third quarter of 2025 financial results. Starting with the balance sheet. We finished the third quarter with approximately $1.25 billion in cash and investments compared to $1 billion at the end of the second quarter of 2025. Our cash and investments increased quarter-over-quarter due to the net proceeds of $327 million received from the issuance of $750 million aggregate principal amount of the convertible senior notes due 2031 and concurrent exchange of $399.5 million aggregate principal amount of our 2027 notes. These transactions together accomplish our goal of providing the company with financial flexibility ahead of the potential launch of aficamten for oHCM. Excluding the net proceeds received from this transaction, our cash would have declined by approximately $112 million quarter-over-quarter. In October, we received proceeds of $100 million from the Tranche 5 loan provided by Royalty Pharma, which will enable us to finish 2025 with approximately $1.2 billion in cash and investments. R&D expenses for the second quarter were $99.2 million compared to $84.6 million for the same period in 2024. The increase was primarily due to advancing our clinical trials and higher personnel-related costs, including stock-based compensation. G&A expenses for the third quarter of 2025 were $69.5 million compared to $56.7 million for the same period in 2024. The increase was primarily due to investments towards commercial readiness and higher personnel-related costs, including stock-based compensation. Net loss for the third quarter of 2025 was $306.2 million or $2.55 per share compared to a net loss of $160.5 million or $1.36 per share for the same period in 2024. The net loss for the third quarter of 2025 includes the debt conversion expense of $121.2 million due to the induced exchange of $399.5 million of aggregate principal amount of the 2027 notes. Turning to our financial guidance. We are narrowing our full year 2025 GAAP operating expense range to $680 million to $700 million from the previous range of $670 million to $710 million. Stock-based compensation that is included in GAAP operating expense is expected to be between $110 million and $120 million. Excluding stock-based compensation from GAAP operating expense results in a range of $560 million to $590 million. As we near the close of 2025, we have taken important steps to add flexibility and strength to our balance sheet. This positions us well ahead of the PDUFA date for aficamten in the U.S., potential approval in the EU in the first half of 2026 and the readout of results from ACACIA-HCM expected in the second quarter of 2026. With that, I'll hand it back to Robert.

Thank you, Sung. This quarter, we made substantial progress across the company. We reported additional data that continues to validate our pioneering and leading science, and reinforce the differentiated profile of aficamten, while also finalizing our commercial launch readiness and maintaining momentum across our pipeline. These accomplishments underscore the focus, rigor and dedication of our teams as we move closer to the most important milestone in our company's history. To help us prepare for this pivotal phase in the company's evolution, we were pleased to welcome James Daly to our Board of Directors during the quarter. Jim brings more than 30 years of global biopharma commercial leadership experience including long-standing senior commercialization expertise from his time as Chief Commercial Officer at Incyte and in senior commercial roles at Amgen, alongside now Board roles at leading commercial biopharma companies. We look forward to his guidance and oversight now as a Board member at Cytokinetics. As we approach our first potential FDA approval at Cytokinetics, I want to thank our employees, our partners and our shareholders for their continued trust and support. We're approaching a pivotal moment in our company's history, standing at an important threshold after many years of disciplined investment in our science, pipeline and infrastructure as well as capital structure, and that will enable our planned transition to a fully integrated commercial company. At this juncture, we are not spectators, but instead, we are active participants in shaping the next chapter for our company. Our near-term focus remains on potential regulatory approvals and commercial launch and velocity. I'm confident in the strength of our teams and the clarity of our shared vision now translating to execution. With that, I'll recap our upcoming milestones. For aficamten, we expect to advance NDA review activities with FDA to support the potential U.S. approval of aficamten by the end of the year. We expect to advance go-to-market strategies and continue launch preparations for aficamten in the United States. We expect to continue go-to-market planning in Germany and expand commercial readiness activities in Europe in 2025 and in preparation for potential approval of aficamten by the EMA in the first half of 2026. We expect to continue to coordinate with Sanofi to support the potential approval of aficamten in China, pending approval by the NMPA. And we expect to report top line results from the primary cohort of ACACIA-HCM in the second quarter of 2026 and continue patient enrollment and conduct of the adolescent cohort in CEDAR-HCM into 2026. For omecamtiv mecarbil, we expect to continue patient enrollment and conduct of COMET-HF through 2026. For ulacamten, we expect to continue patient enrollment and conduct of AMBER-HFpEF through 2026. And finally, for preclinical development and ongoing research, we expect to continue ongoing preclinical development and research activities directed to additional muscle biology-focused programs. And operator, with that, we can now open up the call to questions, please.

[Operator Instructions] We'll hear first from the line of Gena Wang at Barclays.

I have tons of questions on approval, but I will save that for my peers. So I will ask one question regarding ACACIA data. I think you did mention that the data will be coming out in 2Q '26. So as we remember that you added pVO2 as a dual primary endpoint for regulatory feedback from Europe and Japan. So technically, the drug should receive approval as long as you hit 1 of the 2 primary endpoints. So -- but in the case of missing pVO2, do you anticipate any issue of approval in Europe and Japan? I assume U.S. will be totally okay as long as you're hitting one endpoint.

I'll ask Fady to respond to that.

Gena, I think it's really difficult to know what will guarantee approval or not. Obviously, it depends on the magnitude of the other results. It depends on safety profile, depends on lots of things. But I think the trial will be considered positive based on our statistical analysis plan of either endpoint is positive, but you'd like to see them at least minimally moving in the same direction. You'd like to see magnitudes that we think are clinically meaningful. You like to see consistency across the other endpoints. So I think all of those things go into regulators' evaluation of whether a trial not only was statistically significant, but represents a clinically meaningful therapeutic in the field.

Our next question today will come from the line of Salim Syed at Mizuho.

I'll also ask one on ACACIA, just given the amount of attention this trial is receiving. And sorry for the granularity around the p-value here. But Fady, so the ACACIA trial p-value is split, as I understand it, between KCCQ and peak VO2, both at 0.025, so equal. And if one wanted to play devil's advocate for a second here, just curious why is that the better strategy at this point versus what ODYSSEY had, which was weighted to KCCQ at 0.04 and came in with a p-value of 0.06, which was close to hitting and also a better p-value than what we saw with ODYSSEY with the peak VO2 measure. And the trial only needing, again, statically one measure to hit to be successful. And to that point, while the study is still blinded, if you wanted to, could you change the weighting between the 2 endpoints in ACACIA before unblinding the results?

Again, I kind of go through the -- what I said earlier is that any positive result is not necessarily a meaningful result. You could -- I think the ODYSSEY trial missed and the KCCQ delta was 2 or 3, I can't remember the exact number, but pretty modest, and I doubt would -- if you consider the magnitude of effect would be that compelling to regulators. So we powered this trial of 0.025 for each based on what we think is a solid clinical effect at KCCQ that's 5 points and with peak VO2's improved by 1.0. Now that powering -- the trial is powered at 90% power for each of those magnitudes doesn't mean that the trial is positive only if we reach those magnitudes. The minimum, I guess, positive difference for those endpoints is substantially smaller and gets into the range of where it's probably debatable whether the size of the effect is meaningful or not. So we think we have adequately powered each endpoint. We think allocating alpha equally provides us an opportunity to win the best on each endpoint. And at this point, I don't anticipate us making any changes to that.

Our next question today will come from Akash Tewari at Jefferies.

This is actually

Well, I think your last point is impossible to answer because we're blinded, so we don't know what the placebo effect is in ACACIA. We do monitor the variability of the combined data set and for now, the variability appears to be within our assumptions. So I think we're adequately powered based on the global variability. And again, I'll just say that the variability that we've observed in the KCCQ and several trials that we run using that metric is generally about 15-point range, which tracked with SEQUOIA, it's tracked with other trials we've done in that area. And I think the indication, it's not really any different at this point. So I think we're tracking along our assumptions and for now, we'll just let things play out and see how they read out next year.

I might also underscore that variability is a function of a number of factors, including experience in the course of conduct of studies such as this. And please understand that we believe that one way to manage variability as we have done, is to go to centers with ample experience conducting clinical research using aficamten and as has already been historically validated in our prior studies. So we do believe that's something that serves to our favor.

Our next question will come from Carter Gould at Cantor Fitzgerald.

Maybe I'll give ACACIA a break for a minute. Andrew detailed a lot of metrics that you'll be watching. Which of those metrics are you likely to share with the investment community? And any of those I can get you to commit to today? And do you anticipate blocking third-party prescription data during the launch?

Andrew?

So those 3 metrics I talked about in terms of prescribing breadth and depth as well as volume of patients is what we plan on sharing. No, we're not going to give targets and share what those would be. Relative to data, this is a very limited distribution the REMS drives that as well. The specialty pharmacies or 2 of them will not report data. We will report that on a quarterly basis. There are also pharmacies that will be qualified IDN pharmacies through large healthcare systems. Many of those will be reported through syndicated data, but that will be a very small portion of our overall volume, maybe around 20% to 30% or so. So if you look at syndicated data from IQVIA or Symphony or one of those sources, you're not going to see anywhere near the complete picture, but we certainly will give that picture on a quarterly basis.

Our next question will come from the line of James Condulis at Stifel.

I'd like to ask one on back to ACACIA and again, on blinded data. I was curious how much of a line of sight do you have on kind of like blinded safety data and maybe what the LVF less than 50% rate looks like? Obviously, not anything specific, but like how it compares to, say, what you saw in SEQUOIA and Obstructive. Just curious if there's any color there.

Yes, I'm going to try carefully here. I'll just say that there's nothing out of the blinded data that are unexpected based on what we've seen so far.

Moving on, we'll hear from Cory Kasimov at Evercore.

So I want to go back to the pending launch. And I'm curious, do you anticipate the implementation of another REMS program at these HCM clinics where they're already prescribing mavacamten is going to be a barrier that we should expect to kind of slow down the cadence of launch in the early days? Or is the process of registering centers relatively straightforward at this point?

So I'll ask Andrew to comment. I might just start by saying we're respectful of the fact that there are existing workflows that have already been adapted. And as Andrew has already highlighted, it's our goal to be enabling a REMS program and implementation that should create for a more flexible and easy experience for physicians, patients and pharmacists within established workflows. Maybe Andrew can elaborate.

Yes, it's a good question. There's a lot of centers that physicians who are writing today. So part of the goal would be for a differentiated REMS program alongside MAPLE, alongside SEQUOIA to these get more over the line, so to speak, to prescribing. So that would be new workflow for them. Those who have existing workflow. The workflow in the office really is around echo for titration and monitoring. That is similar. So you're going to have echo monitoring potentially with, say, a different frequency or the ability to titrate up at each point of monitoring. So it's the same kind of workflow, if you will. So we're not anticipating that the workflow around monitoring or the window for monitoring will cause must act, especially among high users and high centers. So we are expecting that a differentiated REMS, the differentiated label and an overall profile will drive differentiated use when physicians certainly understand that. So that's the way we've been thinking about it.

Next, we'll hear from Tess Romero at JPMorgan.

This is Caroline Poacher on for Tess Romero with JPMorgan. Just one from us on aficamten and oHCM. So acknowledging that the late cycle meeting took place on September 15, can you just comment on if the REMS has been finalized yet at this point in the review process? And if not, what are the remaining items of the REMS that need to be finalized? And when would you expect this to be completed?

So we're continuing with interactions with FDA, and we have not finalized those matters. We do anticipate that we're making progress towards enablement of finalization of those in order to meet the PDUFA date. With that said, we've had exchanges and interactions -- and as I've indicated previously, we don't believe that we're engaging around framework, but rather some operational details, things that speak more to things like web pages and that which is administrative. Those are things that we think should come together to be enabling of FDA to review this and hopefully approve it in time for the PDUFA date.

Moving forward, Maxwell Skor with Morgan Stanley.

One more on ACACIA. Could you just confirm whether there are any shared trial sites between ODYSSEY and ACACIA, approximately how many -- the percentage overlap? And if so, what potential impact that might have on, let's say, a placebo response or other factors relevant to interpreting ACACIA results?

Max, I can't give you the exact overlap, but the overlap is not very large. Obviously, sites were conducting 2 trials that were simultaneously in the same patients, it would be a bit problematic. Some trials have finished their commitment and obviously and then became a case of sites later and things. But the overlap, I don't think is very large. We ended up generally going to sites that we already had experience with or have visited ourselves, either our HCM team or clinical operations group. And so we ended up choosing a cadre of sites in South America, Europe, North America, Australia, China, Israel that represented either our own prior experience or had -- clearly had experience in other HCM trials.

Yasmeen Rahimi with Piper Sandler. You have our next question.

Maybe a question for Andrew. You did such a nice job outlining your commercial strategy. How are you thinking about pricing? It sounded like you're thinking about pricing and parity to mavacamten. Obviously, given the product profile, you may have flexibility to go higher. So I appreciate any color around that.

Sure. So we'll communicate our price what it's set. But I think you can think about when a second product comes out or a category that's already been priced is typically priced in proximity to the initial product. So I would think we're going to be in that same kind of ballpark, plus or minus maybe a small percentage, but we're certainly going to be in that range.

Our next question today will come from Roanna Ruiz at Leerink Partners.

So a quick follow-up of the aficamten potential U.S. launch. Could you share more details about what you expect in terms of time to conversion to commercial drug, patient compliance over time? And anything you're hearing or learning about the possible rate in which early adopters could prescribe aficamten?

Sure. So thanks for the question. So in terms of conversion, in the beginning, we'll have blocks as payers go through reviews, medical exception is certainly the path that, that will go through. Medical exception can be as fast as, say, 2 to 3 weeks or it could take 90 days. So it depends on the plan, depends on the doctor's office, the documentation and if it's in compliance with what the plan wants. But I think you can think in that time frame, we're going to have the patient support programs where we can have them for commercial patients to bridge them through that process. Medicare patients, of course, we can't do that. We'll provide free drug for those that are appropriate for patient assistance. And so that's how I would think about time to conversion until we have more broader access. In terms of compliance, we are seeing that at least in this category, compliance and persistency is higher than you see for other cardiovascular drug. I'm guessing likely because of the time frame it takes to get our drug, the commitment of going through echos and the like that you're going to see compliance after 2 years probably still be above 50% or so. And then your third question was, can you remind me?

Yes. The last part was about early adopter physicians prescribing aficamten out of the gate.

Yes. So this is a very, very focused market, 650 prescribers or so, about 80% of the market. Those prescribers, we know well. We've actually been interacting with many of them already. We will call on the vast majority, if not all of them in the first few weeks of launch. When you think about those high users, if you will, when we've done even most -- market research even in the last month or so, MAPLE with SEQUOIA increases their urgency to treat. So we're expecting to get high use, if you will, relative to other physicians in those physicians that were early adopters for CMIs, we should see the same for aficamten if it gets approved. So that's our expectation.

We'll go next to Mayank Mamtani at B. Riley Securities.

Productive third quarter. Would love to hear your thoughts maybe for Andrew on what your latest thinking is on peak CMI drug penetration. Maybe if you can also comment on where it stands now and your expectation of scenarios where it could land in the kind of near-term, 1 to 2 years. And like you said about your impact of the MAPLE-HCM data, but also a lot of real-world data coming from your peers, including at AHA. If you could maybe comment on that, that would be helpful. And a subpart question was around some of the patient navigator training that you're doing that happens around when you have a label in hand. I was just curious if any key FAQs or pushbacks you're preparing for would also be helpful to get color on.

So a lot of questions there, so I'll try to address those. CMI penetration, I think, was your first question. Right now, the penetration is probably in the 15% to 20% range of oHCM, and I'm defining that as the number of eligible patients, those that are Class II, Class III, those that are treated with the CMI. So we are expecting, as we said all along, around 80% or so of the market to be available, meaning patients who are eligible, but not currently on a CMI. The expectation is that, that probably penetration probably increases in the -- around 5 percentage points each year. So when you look at real-world evidence when you look at additional trials, that certainly will increase penetration. If guidelines are impacted, if MAPLE helps influence guidelines in '26 or '27, that certainly will accelerate penetration. So I think there's things that can change the trajectory of penetration, but that's where it is now. In terms of training, we did provide the label to the FDA. We've had a few rounds of feedback. I think that we've alluded to. I think we can certainly train on a draft label and then we'll train again on the final. That's pretty typical around how you would train relative to a label and relative to a REMS.

Moving forward, we'll take our next question from Joe Pantginis at H.C. Wainwright.

So curious, just totally switching gears here to omecamtiv mecarbil. Right now, the guidance is moving enrollment continuing into 2026. When do you anticipate providing more visibility as to sites, enrollment numbers? And what levels of clarity can we get, do you think, starting in '26?

We'll ask Stuart maybe to take that, please.

As I mentioned, we are making good progress in terms of site activation. We have 75% of sites activated in North America and Europe. And we're seeing screening picking up, randomization picking up. And I mean we're sort of not at a point where we can sort of start providing those numbers because I think we're going to hold off on that until we have all the sites activated and we have a good trajectory. But so far, so good. Study conduct is going well and so with site interaction and screening.

So Joe, I think as we roll into the new year and have a better sense of how these new sites that have been activated are enrolling, we should be able to tighten some of that guidance to the expectation of when we might complete enrollment. And then from there, as you know, this is a study that's accruing events. It's event-driven, and we can maybe point more generally to when we might expect data.

Our next question will come from the line of Paul Choi with Goldman Sachs.

I want to ask on your partnered CAMELLIA trial and just if you can provide any updates on timing on that and just sort of maybe help us think about when your partner might be able to launch in Japan and just sort of what would be a reasonable assumption there? And then on the AMBER trial study for HFpEF, would you be in a position to potentially present some initial data on that in 2026?

I'll ask Fady to tackle those, please.

Yes. I mean with regards to the progress of the oHCM trial in Japan, I mean, the strategy in Japan will be a little bit tied more to completion both of ACACIA and CAMELLIA. We expect them really to kind of complete in a similar time frame and both leading to regulatory interactions and ultimately approval there. So I can't really give you specifics yet in terms of where it is, but CAMELLIA is moving along within line of that expectation. And then AMBER, I think we're still a little too early for us to commit to data in 2026. We should be able to say more about that probably at our next earnings call.

Next, we'll hear from Serge Belanger at Needham.

This is John Gionco on for Serge today. So with the results of MAPLE now in the public domain, curious what your time lines look like in terms of how quickly you'd like to file the sNDA to incorporate that data into API label and whether you think having it in the label will alter in any way prescribing habits for treating physicians?

So I'll take the first part and ask Andrew to address the second part. But our goal is if we see aficamten approved based on the SEQUOIA results by the end of this year that we're moving very swiftly to submitting a supplemental NDA based on MAPLE data promptly in early 2026 to be enabling of a potential expanded label even possibly by the end of 2026. Andrew can comment on how that may factor into expanded use.

We've tested this several times, including most recently this quarter. Each time we get a top line increased use of CMI, so CMI penetration goes up and increased brand share for aficamten or preferential share, if you will. So a larger market, larger share of that market. When you segment it, those that are kind of the core users, they're basically saying it's confirmatory of safety and efficacy, and that gives them even more reason in belief. When you look at those that are heavy beta blocker, it really challenges their belief in the efficacy of beta blockers. It increases their urgency to treat or urgency to refer I think that second group is going to take a little longer, some of them and guidelines as well as continued education and promotion will certainly continue to move those. So at a high level, we're expecting a larger market, a larger share, and we're certainly seeing this as one of the expansion strategies we've talked about in terms of a bigger market.

Next, we'll hear from Kripa Devarakonda at Truist Securities.

Alex on for Kripa. Based on your updated late cycle meeting with the FDA and the nature of the day 120 List of Questions for the CHMP, is there anything we should be aware of to indicate that the REMS requirement could possibly be meaningfully different from the U.S. and EU?

Well, there is no REMS requirement in the EU. That's all handled through labeling, as you know. But I do think that to your question, we're expecting that aficamten, if approved in the U.S. and in the EU will be addressed similarly in terms of risk mitigation.

Our next question will come from Ash Verma at UBS. Hearing no response, we'll move forward. We'll hear instead from Jason

Congrats on the progress. Maybe just to switch gears, but in light of your recent balance sheet updates, where do you stand in terms of your ability to support both the U.S. and EU launches? I mean, do you foresee any need for additional capital, especially given your expectations for the launch?

Jason, this is Sung. Thanks for the question. We can't rule out future financing. But with that said, we expect to finish the year with $2.2 billion in cash and investments I'm sorry. $1.2 billion Thank you. I got a little excited there. So that puts us in a very strong position, not only to launch aficamten in the U.S., but also to continue to build out in the EU and importantly, to continue to advance our pipeline. Keep in mind that we do have access to further capital potentially up to $175 million. This is from the Tranche 7 loan from Royalty Pharma. So we'll continuously weigh our options in terms of capital requirements and capital structure.

And now we'll move to Ash Verma with UBS.

This is Natalie on for Ash. This is Natalie on for Ash Verma at UBS. So we just had a quick question on nHCM. Now I know there's a lot of discussion about the heterogeneity of this patient population. Have you guys been able to identify if there is a specific set of patients that see the most benefit from CMI?

Well, I would say that, that question remains unanswered, maybe perhaps we will require both analyses of the ODYSSEY data, the ACACIA data when they come out. We think enrolling patients that are symptomatic, that have classic HCM -- classic HCM phenotype as evident on echocardiography that have certain biomarker increases. I think all of those things talk about a symptomatic, highly symptomatic and functionally limited patient population. And based on our prior experience in REDWOOD, we think that population should be responsive to aficamten. So I think we'll have more to say when we see the ACACIA data in next year.

I think I would add that we've been following a cohort of Nonobstructive patients for over 2 years now. And the large majority of them are responding well symptomatically and based on cardiac biomarker improvement. So I think what we're observing so far, at least in this cohort in FOREST is a pretty general improvement in response to treatment.

And thank you, ladies and gentlemen. That was our final question from our audience today. Mr. Blum, I'm happy to turn it back to you for any additional or closing remarks you have.

Thank you. I want to thank all of our participants on the call today. I want to thank you for your continued support as well as your interest in Cytokinetics. This will conclude our Q3 earnings call. And my hope is that next time we convene in one of these earnings calls, we'll talk about what could be the first potential approval for aficamten and a product arising out of our long-standing research and development, a very important milestone for our company and all of our stakeholders, including our shareholders. With that, operator, we can now conclude the call.