Cytokinetics, Incorporated

and welcome to the Cytokinetics Q3 2025 Earnings Conference Call. This call is being recorded and all participants are in a listen-only mode. After the speaker's remarks, we will open the call to questions. We will allow for one question per participant. If you would like to ask a question during that time, simply press the star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again once more. I would now like to turn the call over to Diane Wiser, Cytokinetics Senior Vice President of Corporate Affairs. Please go ahead.

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Andrew Kalos, EVP and Chief Commercial Officer, will address commercial readiness activities for Affy Campton. Fatty Malik, EVP of R&D, will provide updates related to the clinical development program and medical affairs activities for Affy Campton. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates on the clinical development program for Omicampton McCarble and Eula Campton. 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 8K 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 thanks to 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 advanced towards the end of the year, when we hoped to achieve our first potential FDA approval of Affy-Campden 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 Affy-Campden. And based on our exchanges and discussions with FDA to date, we continue to expect a differentiated label and risk mitigation profile for afecamtin 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 Affie-Campden. We presented the positive primary results from Maple HCM, which demonstrated superiority of afecamcin to metoprolol in patients with OHCM, challenging the long-held status quo of treatment in this disease. Our intention is to file a supplemental MDA 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 Afikampton, as may result in increased commercial launch velocity. Following closely behind the potential approval and launch of Afikampton in the United States is the expected potential approval of Afikampton 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 afecamptin in Europe. We also continue to work closely with Sanofi to support the potential approval of afecamptin 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 helped 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 toward the potential FDA approval of AfriCanton 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 SALS 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 SALS team has already been in the field since early September, introducing cytokinetics to key OHCM HCPs and providing disease education. Forward 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 AfriCanton. Our approach is designed to be simple and integrated across all touchpoints 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 ACP campaign that highlights the differentiating characters of africantin and key attributes of our REMS program. We believe this campaign will clearly communicate the clinical value of africantin 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 HCN. We remain confident in our ability to keep parity access by the second half of 2026. Importantly, our strategy is comparable access with focus to differentiate based on the clinical profile of Afikanton, 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 AFICANSON 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, ACP PRESCRIBING BREATH AS MEASURED BY THE NUMBER OF ACPs WHO ARE ACTIVELY WRITING PRESCRIPTIONS. SECOND, PRESCRIBING DEATH AS MEASURED BY THE VOLUME OF PRESCRIPTIONS IN ACP WRITES FOR AFICANSON. 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 specialist was to reach nearly all the estimated 650 HCPs, or approximately 80% of the HCMI prescribing to date, within the first few weeks of January. And third metric is the volume of patrons on Affecantin. 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, its rate of change, and overall strength of our commercial execution, focused on category growth and overall preference share in an expanding market. Finally, our attention is not only on the U.S., but also in the E.U., where we've made meaningful progress in preparing for a potential commercial launch of AfriCanton in that geography. We recently hired a general manager for Italy alongside colleagues that are already on board in the UK, 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 HTA 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 2026 and 2027. With that, I'll turn the call over to Fatih.

Thanks, Andrew. During the quarter, we were pleased to have presented new data that further reinforces the differentiation of apicanthin 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 showed superiority of apicanthin to metoprolol, represent a watershed moment in treatment of OATM. While patients treated with africansin experienced a significant improvement in exercise capacity, those on metoprolol showed a decline, challenging the longstanding rationale for beta blocker use 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 onsite at ESC. In addition to improving exercise capacity, Abcanton also produced large improvements in symptoms, gradients, and cardiac biomarkers as compared to metoprolol. Improvements were consistent across all pre-specified subgroups and confidence Importantly, adverse events were similar in the two groups, and the safety of Aftecampton observed in Maple ACM was consistent with previous studies. To that end, as the evidence of Aftecampton expands, so too does our confidence in its consistent safety profile. An updated integrated safety analysis representing nearly 700 patient years of exposure to from Redwood HCM, Sequoia HCM, Forest HCM, and now Maple HCM as well, africantin 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 apicanthin has also been shown to not be associated with an increased risk for atrial fibrillation. Looking ahead, coming up this month at the HA Scientific Sessions, we're pleased to have three late-breaker presentations with additional data from Maple ACM providing new insights into these results. clinical trials program for Appycampton. The next major data milestone for us will be the readout of Acacia HCM, the pivotal Phase III trial in NACM. 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 an 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 aspirin to cancer. Our belief in the therapeutic potential of apikemptin in NACM is founded in the existing body of evidence from the NACM cohort of Redwood HCM and strengthened by their longer-term follow-up in the Forrest 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 NACM patients. What you saw, albeit in an open-label setting, was that 79% of the patients treated with apicanthin improved by at least one 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 a short treatment interruption. We are hopeful that these data may be replicated in the results of ACACM, given the similarity in patient populations and the dosing scheme involved. Alongside our clinical research, our medical affairs organization has been very active, engaging the ACM 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 ACM 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 health care professionals. I'll turn it over to Stuart to provide updates on our ongoing clinical trials in heart failure. Thanks, Paddy. During the quarter, we continued conduct of COMET-HF, 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. Common HF is designed to confirm the findings of the positive phase 3 clinical trial Galactic HF in a more severe FRAP 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 Omicantamacarbone. 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-HFPEP, the Phase II clinical trial of eulocampin in patients with symptomatic heart failure with preserved ejection fraction of at least 60%. By inhibiting cardiac myosin to attenuate hypercontractility, eulocampin 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-end need with limited treatment options. Enrollment in AmberHepTest is progressing, and we expect to complete cohorts one and two in 2026 to inform FDA interactions and the decision 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 continuing commitment to further advance innovative medicines within our specialty cardiology franchise. And with that, I'll pass it to Sam. 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 to 2031 and concurrent exchange of $399.5 million 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 Appy Camptons 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 investment. 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 toward 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 680 million to 700 million dollars from the previous range of 670 million to 710 million dollars. Stock-based compensation that is included in GAAP operating expense is expected to be between 110 million and 120 million dollars. Excluding stock-based compensation from GAAP 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 African-Americans 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, Son. 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 Affy Campton, 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 longstanding senior commercialization expertise from his time as Chief Commercial Officer at Insight 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 Appy Campton, We expect to advance NDA review activities with FDA to support the potential U.S. approval of Affy Campton by the end of the year. We expect to advance go-to-market strategies and continue launch preparations for Affy Campton 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 Afikampton by the EMA in the first half of 2026. We expect to continue to coordinate with Sanofi to support the potential approval of Afikampton in China, pending approval by the NMPA. And we expect to report top-line results from the primary cohort of Atatia HCM

in the second quarter of 2026 and continue patient for the granularity around the p-value here but fatty um so the acacia trial p-value is split so 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 in Odyssey with their Peak VO2 measure. And the trial only needed, again, specifically 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 two endpoints indication before unblinding the results? Thank you.

Again, I kind of go through what I said earlier is that Any positive result is not necessarily a meaningful result. You could, I think, you know, the Odyssey trial, it missed, and the KCCQ Delta was two or three, I can't remember the exact number, but pretty modest, and I doubt would magnitude of effect would be that compelling to regulators. So we proposed, you know, we powered this trial at 0.025 for each based on what we think is a solid clinical effect. It's KCCQ, that's five points, and with BPO2, it's improved by 1.0. 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 the alpha equally provides us an opportunity to win the best on each endpoint. And, you know, at this point, I don't anticipate us making any changes to that.

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

Akash? Hi, guys. This is actually for Akash. Thanks so much for the question. So, just again, I'm non-instructive. you've talked about how Bristol's Odyssey study had an outlier placebo, and thus, it almost seems like their standard deviation on KCCQ in particular came in higher than they expected in their protocol. So for Acacia, you've chosen to keep the trial actually at a similar size as the Odyssey with an even more aggressive alpha split. So I just want to know, in terms of what you're seeing on blinded variability, what gives you confidence that, one, you're not underpowered versus Odyssey, and two, that placebo is actually tracking it in line with your activity?

We do monitor the variability of the combined variability and for now the variability appears to be within our assumptions. So I think we're adequately powered based on the global variability. And, you know, again, I'll just say that the variability that we've observed in the KCCQ Several trials that we've run using that metric is generally about 15-point range, which, you know, is tracked with Sequoia. It's tracked with other trials we've done in that area. And I think in the case of it, it's not really any different at this point. So I think we're, you know, tracking along our assumptions for now. We'll just let things play out, see how they read out next year.

I'd 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 AFI-CAMPT and has already been historic.

Good afternoon. Thanks for taking the question. 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?

Thank you. Andrew?

Those three metrics I talked about in terms of prescribing breath and death 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. You know, the revenue drives that as well. The specialty pharmacies, there's two of them, will not report data. We will report that on a quarterly basis. There are also pharmacies that will be qualified, you know, IVM 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, you know, maybe around 20 to 30 percent 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 is kind of like blinded safety data and maybe what the LDF 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. Thank you.

Yeah, I'm going to, you know, tread carefully here. I always say that, you know, 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 Corey Kasimov at Evercore.

Hey, Robert and guys. Good afternoon. Thanks for taking the question. So I want to go back to the pending launch. And I'm curious, do you anticipate the implementation of another program program at these HCM clinics that are already prescribing Mavacamptin 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 There are existing workflows that have already been adapted.

And as Andrew has already highlighted, it's our goal.

Yeah, it's a good question. You know, there was a lot of centers that physicians who weren't writing today. So part of the goal would be what a differentiated program alongside Maple, alongside Sequoia. Do these get more over the line to prescribing? So that would be new workflow for them. Those are that 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 much angst, especially among high users and high centers. So we are expecting that a differentiated REM, a differentiated label, and an overall profile will drive differentiated use when physicians certainly understand it. So that's the way we've been thinking about it.

Next, we'll hear from Tess Romero at J.P. Morgan.

Hey, good afternoon, team. This is Caroline Pocher on for Tess Romero at J.P. Morgan. Thanks for taking our question. Just one from us on Affecampton and OHCM. So acknowledging that the late cycle meeting took place on September 15th, can you just comment on if the REMS has been finalized yet at this point in the review process?

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 FTA to review this and hopefully approve it in time for the PDUTA date.

Moving forward, Maxwell Score with Morgan Stanley. Your line is open.

Great. Thank you for taking my question. 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? Thank you.

Hi, Max. I can't give you the exact overlap, but the overlap is not... Obviously, the sites were conducting two trials that were simultaneously in the same patients. It would be a bit problematic. Some trials had finished their commitment and obviously 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 had visited either our own prior experience or had clearly had experience in other ACM trials.

Yasmine Rahimi with Piper Sandler, you have our next question.

Thank you so much, team. Thank you. 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 Mavic Hampton. Obviously, given the product portfolio, you may have flexibility to go higher, so appreciate any color around that.

Sure. So we'll communicate our price when it's set. But I think you can think about when a second product comes out or a category that's already been priced, it's 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 Rowana Ruiz at Learing Partners.

Great, thanks, and good afternoon, everyone.

So a quick follow-up of the AFI-CAMPTN potential U.S. launch. Could you share more details about what you expect

In terms of conversion, in the beginning we'll have blocks as hires go through reviews. Medical acceptance is certainly the path that that will go through. Medical acceptance can be as fast as say two to three 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 timeframe 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 drugs for those that are appropriate for patient assistance. 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 every cardiovascular drug. I'm guessing likely because of the timeframe it takes to get on a drug, the commitment of going through ECHOs and the like that you're going to see compliance after two years probably still be above 50%. or so. And then your third question was, can you remind me?

Ms. Ruiz, if you would like to hit star one once more, I can reactivate your line. Thank you, ma'am.

Yes, the last part was about early adopter physicians prescribing Afikantin out of the gate.

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, you know, high use, if you will, relative to other physicians. In those physicians that were early adopters for CMIs, we should see the same for africans if it gets approved. So that's our expectation.

Thanks for the questions. And thank you for resigning, Mr. Ruiz. We'll go next to Mayank Mamtani at B. Reilly Securities.

Yes, good afternoon, Dean. Thanks for taking our questions, and congrats on a productive third quarter. I would love to hear your thoughts, maybe for Andrew, on what your latest thinking is on peak CMI drug test penetration. Maybe if you can also comment on where it stands now and your expectation of, you know, scenarios where, you know, it could land in the kind of near-term, one to two years. And like you said about your impact of the Maple HCM data, but also a lot of real-world data coming from your peer, including at AHA. You know, if you could maybe comment on that, that we have found. You know, some of the patient-navigated training that you're doing, you know, 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.

Sure. So, a lot of questions there, so I'll try to address those.

TMI penetration, I think, was your first question.

The market to be available, meaning... patients who are eligible but not currently on a CMI. You know, the expectation is that that probably penetration probably increases in the around five 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, you know, 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 penetration, but that's where it is now. In terms of training, you know, we did provide a label to the FDA. We've had a few rounds of feedback, I think, that we've alluded to that 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 range.

Thank you.

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

Hey, everybody. Good afternoon. Thanks. Hey, there. So, curious, just totally switching gears here to Omicamp to McCarvel.

Right now, the guidance is, you know, 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 2020? And, you know, we're seeing screening picking up, randomization picking up, and we're sort of not at a point where we can sort of start providing visibility those numbers, because I think we're going to roll off on that until we have all the sites activated and we have a good trajectory. But so far, so good. Steady conduct is going well, and so is site interaction and screening.

Thank you. 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.

Hi. Good afternoon. Thank you for taking the question. 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

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 hopefully approval there. So I can't really give you specifics yet in terms of of where it is, but the community is moving along within the line of that expectation. And then Amber, you know, I think it's still 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.

Hi, good afternoon. This is John Gianco on for Serge today. Thanks for taking our question. So, with the results of Maple now in the public domain, I'm curious what your timelines look like in terms of how quickly you'd like to file the SNDA to incorporate that data into Appy's label, and whether you think having it in the... 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.

I believe 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 brain share for Affy Canton, 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 and 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. 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 You know, a larger market, a larger share, and, you know, we're certainly seeing this as one of the expansion strategies we've talked about in terms of the bigger market. Thanks for the question.

DARYL FOX- Next we'll hear from-is there anything we should be aware of to indicate that the rents requirement could possibly be meaningly different from the U.S. and the 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 Afti Campton, if approved in the U.S. and in the EU, will be addressed similarly in terms of risk mitigation.

All right. Thank you. Our next question will come from Ash Verma at UBS. Your line is open. Hello, Ash. You may have us on mute. Your line is open. Hearing no response, we'll move forward.

Ash, please try to re-signal with star and one. We'll hear instead from Jason Zemanski at Bank of America.

Good evening, Jason.

Afternoon. Congrats on the progress, and thanks for taking our question. 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. I mean, do you foresee any need for additional capital launch?

Thanks. Jason, this is Tom. Thanks for the question. You know, we can't rule out future financing, but with that said, we expect to finish the year with $2.2 billion in cash investments. I'm sorry, 1.2. Thank you. I got a little excited there. So that puts us in a very strong position not only to launch AppyCamp in the U.S., but so we'll continuously weigh our options in terms of capital requirements and capital structure. Thanks, Ben.

And now we'll move into Ash Verma with UBS once again. Please go ahead. Your line is open. Hello, Ash. We have you connected, and I do see you're open. We're not hearing anything. If you are speaking to us, please check your mute.

Hi there, can you hear me?

There you are, thank you.

Hi there, can everyone hear me? Natalie, I'm fresh.

We can hear you.

Hey there, this is Natalie, I'm fresh. Can you hear me?

We can hear you.

Sorry about that. This is Natalie on for ASHFIRM at UCS. So we just had a quick question on NHCM. Now, I know there's a lot of discussion about the heterogeneity.

Unanswered, maybe, perhaps, and we'll 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, a classic HCM phenotype as evident on echocardiography that has, you know, certain biomarker increases. I think all of those things talk about symptomatic, highly symptomatic and functionally limited patient population. And based on our prior experience and Redwood, we think that population should be responsive to africansin. So I think we'll have more to say when we see the Acacia data next year. I think I would add that, you know, we've been following a cohort of non-astrophysic patients for over two years now. And the large majority of them are responding well symptomatically and based on cardiac biomarker improvements. So I think what we're observing so far, at least in this cohort and for us, 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 closing remarks you have.

Thank you. I want to thank all of our participants and a product arising out of our longstanding 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.

Thank you. And ladies and gentlemen, thank you for joining today's Cytokinetics Q3 2025 earnings call.