Cytokinetics (CYTK) Q3 2025 Earnings Transcript

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Date

Wednesday, Nov. 5, 2025 at 4:30 p.m. ET

Call participants

President & Chief Executive Officer — Robert I. Blum

Executive Vice President, Chief Commercial Officer — Andrew Callos

Executive Vice President, Research & Development — Fady I. Malik

Senior Vice President & Chief Medical Officer — Stuart Kupfer

Senior Vice President, Chief Financial Officer — Sung Lee

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Takeaways

Cash and investments -- $1.25 billion in cash and investments at the end of the third quarter of 2025, up from $1.00 billion at the end of 2024, reflecting $327 million in net proceeds from issuing $750 million in convertible senior notes and the concurrent exchange of $399.5 million in 2027 notes.

Expected year-end liquidity -- $1.2 billion in cash and investments projected at year-end 2025, following receipt of $100 million from the Tranche V Royalty Pharma loan in October 2025.

Net loss -- $306.2 million, or $2.55 per share, compared to $160.5 million, or $1.36 per share, in the prior year, primarily due to a $121.2 million debt conversion expense from the induced exchange of 2027 notes in the third quarter of 2025.

R&D expense -- $99.2 million, up from $84.6 million in the second quarter of 2024, with the increase mainly attributed to advancing clinical trials and higher personnel costs, including stock-based compensation.

G&A expense -- $69.5 million, compared to $56.7 million in 2024, driven by commercial readiness investments and higher personnel costs.

2025 GAAP operating expense guidance (revised) -- Narrowed to $680 million–$700 million from $670 million–$710 million for fiscal year 2025 (ending Dec. 31, 2025); stock-based compensation is anticipated at $110 million–$120 million for fiscal year 2025; excluding stock-based compensation, operating expense is forecast at $560 million–$590 million for fiscal 2025.

Aficamtan U.S. regulatory progress -- All Good Clinical Practice (GCP) and FDA inspections completed with no observations; finalization of REMS and label ongoing, with expectation for a "differentiated label and risk mitigation profile" if approved.

Commercial launch readiness -- U.S. sales force is in place and completing training, with sales representatives averaging over 20 years' industry experience and 14 years in cardiovascular markets; patient navigators staffed and trained for immediate launch post-anticipated December approval.

Key clinical milestone -- Maple HCM trial results presented, demonstrating the superiority of aficamtan over metoprolol in patients with obstructive hypertrophic cardiomyopathy (OHCM), as shown in the positive primary results from the Maple HCM study, including improved exercise capacity, symptom improvements, and favorable cardiac biomarker outcomes.

Maple HCM safety -- Adverse events between aficamtan and metoprolol groups were similar, and an integrated safety analysis (nearly 700 patient-years) confirmed a favorable safety profile, including a low incidence of left ventricular ejection fraction (LVEF) less than 50% and absence of serious heart failure events.

EU regulatory progress -- Day 120 European Medicines Agency (EMA) questions were received and addressed during the third quarter of 2025; Day 180 responses in preparation, with potential European Commission decision for aficamtan expected in the first half of 2026.

Ongoing global launch activities -- European commercial teams recruited across major markets (Italy, UK, France, Germany); China approval being pursued in collaboration with Sanofi.

Acacia HCM trial (NHCM) -- Enrollment completed in both primary and Japan cohorts, with top-line pivotal data expected in 2026; open-label data presented at the Heart Failure Society of America meeting showed that 79% of patients improved by at least one NYHA class and a mean KCCQ improvement of 11.2 points in the open-label data.

Omecamtiv mecarbil (COMMOD HF) -- 75% site activation was achieved in North America and Europe as of the third quarter of 2025; global site activation ongoing for Phase III confirmatory study in severe heart failure; enrollment to continue into 2026.

Ulicamten (AMBER HFpEF) -- Enrollment advancing in Phase II heart failure trial; completion of cohorts one and two targeted for 2026 to inform registrational plans.

Board expansion -- James Daly, with over 30 years' biopharmaceutical commercial experience, appointed to the Board of Directors during the quarter.

Summary

Cytokinetics (NASDAQ:CYTK) reported a strengthened balance sheet supported by recent convertible debt and royalty-based financing. Management also underscored the competitive clinical profile of aficamtan in OHCM as seen in the Maple HCM trial, and shared timelines for upcoming pivotal data and additional global regulatory actions.

Management described its commercial approach as designed to deliver "a differentiated patient-centric treatment experience" according to Andrew Callos for aficamtan by coordinating specialized sales teams, patient navigators, and tailored REMS support.

The company indicated its intention for rapid market reach, stating a goal to engage "nearly all the estimated 650 HCPs or approximately 80% of the ACMI prescribing base," according to Andrew Callos, within the first few weeks of January.

Regarding European launch sequence, preparatory activities include medical education, market access, and key account hires, with Germany anticipated as the first launch market contingent on EMA approval.

Chief Commercial Officer Callos described pricing plans as likely to be "in that same kind of ballpark or minus maybe a small percentage" relative to existing market benchmarks, pending final determination at launch.

The company expects continued progress in ongoing clinical trials for omecamtiv mecarbil and ulicamten, maintaining pipeline momentum independent of aficamtan launch outcomes.

Sung Lee noted availability of an additional $175 million from a Royalty Pharma loan, if needed, further bolstering liquidity for near-term strategic initiatives.

Management confirmed no REMS requirement in the EU, with risk mitigation expected to be managed via product labeling.

Pending FDA decisions on REMS framework and label content remain the final regulatory gating items for the initial aficamtan U.S. approval.

Industry glossary

REMS (Risk Evaluation and Mitigation Strategies): FDA-mandated programs to manage known or potential risks associated with a drug, often involving restricted distribution and monitoring requirements.

OHCM (Obstructive Hypertrophic Cardiomyopathy): A form of hypertrophic cardiomyopathy characterized by obstruction of blood flow from the left ventricle.

NHCM (Nonobstructive Hypertrophic Cardiomyopathy): A subtype of hypertrophic cardiomyopathy without significant left ventricular outflow tract obstruction.

KCCQ (Kansas City Cardiomyopathy Questionnaire): A validated, patient-reported outcome tool measuring symptoms and quality of life in heart failure.

LVEF (Left Ventricular Ejection Fraction): A measurement of the percentage of blood leaving the left ventricle each time it contracts, used to assess cardiac function.

PDUFA date: The date by which the FDA must respond to a drug New Drug Application under the Prescription Drug User Fee Act.

sNDA (Supplemental New Drug Application): An application to the FDA seeking approval of a labeling update or new indication for an already approved drug.

CMI (Cardiac Myosin Inhibitor): A class of small molecule drugs targeting cardiac myosin to reduce hypercontractility in heart muscle disorders.

Maple HCM, Sequoia HCM, Redwood HCM, Forest HCM, Acacia HCM: Cytokinetics-sponsored clinical trials evaluating aficamtan in various forms or subtypes of hypertrophic cardiomyopathy.

Full Conference Call Transcript

Robert Blum 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-Ks 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 Blum. Thank you, Diane.

Robert Blum: 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 advance towards the end of the year. When we hope to achieve our first potential FDA approval of abacamten for patients with OHCM. Our major accomplishments this past quarter were dedicated to preparing for that milestone, including 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 Itasu as well as anticipated post-marketing requirements.

Prior to the meeting, we had received FDA's responses to our proposed REMS and label for aficamtan. And based on our exchanges and discussions with FDA to date, we continue to expect a differentiated label and risk mitigation profile for aficamtan if approved by the FDA. We've completed all GCP and inspections by the FDA with no observations noted. Moreover, to date, we have not been notified of the intention of FDA to conduct preapproval 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 aficamtan, we presented the positive primary results from Maple HCM which demonstrated superiority of aficamtiv 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 aficamtan as may result in increased commercial launch velocity.

Following closely behind the potential approval and launch of aficamtiv in The United States, is the expected potential approval of aficamtan 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 aficamtan in Europe. We also continue to work closely with Sanofi, to support the potential approval of aficamtan 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. As Sung will elaborate, this transaction helped not only to provide additional capital reflecting our ongoing commitment to sustained innovation and longer-term growth. With that, I'll turn the call over now to Andrew Callos, please.

Andrew Callos: We continue to make strong progress with commercial readiness activities toward the potential FDA approval of Aficansen 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. 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 health care 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 twenty years of industry experience and fourteen 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 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 in our vision of a differentiated patient-centric treatment experience, one that has been built from the ground up specifically for aficamtan. Our approach is designed to be simple and integrated across all types 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 ACP campaign that highlights a differentiated character of aficamtan and key attributes of our REMS program. We believe this campaign will clearly communicate the clinical value of aficamtan 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 ACN.

We remain confident in our ability to keep parity access by the second half of to differentiate based on the clinical profile of aficamtan, 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 aficansen 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 breadth as measured by the number of ACP who are actively writing prescriptions.

Second, prescribing depth as measured by the volume of prescriptions in HAP rights for aficamtan. 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 our field-based cardiology account specialists was to reach nearly all the estimated six fifty HCPs or approximately 80% of the ACMI prescribing to date. Within the first few weeks of January. And third metric is the volume of patrons 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 speed and trajectory of our launch, its 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 Aficamtiv 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. In addition, we are preparing dossiers for upcoming discussions with H.

Bodies across key EU countries with potential EMA approval expected in the 2026, we remain on track launching Germany in the 2026 with other geographies to follow in 2026 and 2027. With that, I'll turn the call over to Fady Malik. Thanks, Andrew.

Fady Malik: During the quarter, we were pleased to have presented new data that further reinforces the differentiation of aficamtan 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 aficamtiv to metoprolol, represent a watershed moment in treatment of OHCM. While patients treated with aficanserin 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 on-site at ESC. In addition to improving exercise capacity, epicanthin also produced larger improvements in symptoms, gradients, and cardiac biomarkers as compared to metoprolol. Improvements were consistent across all pre-specified subgroups and confidence in the robustness of the findings. Importantly, adverse events were similar in the two groups, and the safety of aficamtan observed in Maple HCM was consistent with previous studies. To that end, the evidence of aficamtin expands so too does our confidence in its consistent safety profile.

An updated integrated safety analysis representing nearly seven hundred patient years of exposure from REDWOOD HCM, SEQUOIA HCM, Forest HCM, and now Maple HCM as well. Apicanthin was shown to be well tolerated with a low incidence of LVF less than fifty percent over extended periods of exposure. With no occurrences associated with a serious event of heart failure. Long-term treatment with abecamtin has also been shown to not be associated with an increased risk for atrial fibrillation. Looking ahead, coming up this month at the Science Scientific Sessions, please have three late breaker presentations with additional data from Maple HCM providing new insights into these results.

With respect to the ongoing clinical trials program for aficamtan, the next major data milestone for us will be the readout of Acacia HCM the pivotal Phase III trial in NHCM, we completed enrollment to the primary cohort excluding Japan in the 2025. And we now expect to report the top line results from this cohort of Acacia HCM in the 2026. During the third quarter, we completed enrollment of patients 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 avacamtiv.

Our belief in the therapeutic potential of camptan in NATM 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 forest ACM trial is recently reported. At the Heart Failure Society of America meeting in late September, we presented new data covering at least ninety-six weeks of treatment in these NHCM patients. What you saw, albeit in an open label setting, was that seventy-nine percent 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 in or reversible after down titration or a short treatment interruption. We are hopeful that these data may be replicated in the results of Acacia Centimeters 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 ACM community of physicians at ES 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 UK, 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 compliantly conduct introductory meetings with key opinion leaders, and health care professionals. Now I'll turn it over to Stuart Kupfer to provide updates on our ongoing clinical trials in heart failure.

Stuart Kupfer: Thanks, Fady. During the quarter, we continued conduct of COMMOD HF. The confirmatory Phase III 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. COMMID HF is designed to confirm the findings of the positive Phase III clinical trial 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 COMMOD 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 seventy-five percent of site in North America and Europe activated, and are continuing to activate sites around the world. We expect to continue patient enrollment in COMMOD HS into 2026. We also continued to conduct AMBER HFpETS. The Phase II clinical trial of ulicamten in patients with symptomatic heart failure with preserved ejection fraction of at least sixty percent. By inhibiting cardiac myosin to attenuate hypercontractility, ulicamten is uniquely positioned to address the underlying diastolic dysfunction in this subgroup of HFpEp 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, 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 our continuing commitment to further advance innovative medicines within our specialty cardiology franchise. And with that, I'll pass it to Sung Lee. Thanks Stuart.

Sung Lee: We're pleased to report our 2025 financial results. Starting with the balance sheet. We finished the third quarter with approximately $1,250,000,000 in cash and investments compared to $1,000,000,000 at the end of the 2025. Our cash and investments increased quarter over quarter due to the net proceeds of $327,000,000 received from the issuance of $750,000,000 aggregate principal amount of the convertible senior notes due 2031 and a concurrent exchange of $399,500,000 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 apocamtiv for OHCM. Excluding the net proceeds received from this transaction, our cash would have declined by approximately $112,000,000 quarter over quarter.

In October, we received proceeds of $100,000,000 from the Tranche V loan provided by Royalty Pharma which will enable us to finish 2025 with approximately $1,200,000,000 in cash and investments. R and D expenses for the second quarter were $99,200,000 compared to $84,600,000 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 and A expenses for the 2025 were $69,500,000 compared to $56,700,000 for 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 2025 was $306,200,000 or $2.55 per share compared to a net loss of $160,500,000 or $1.36 per share for the same period in 2024. The net loss for the 2025 includes the debt conversion expense of $121,200,000 due to the induced exchange of $399,500,000 of aggregate principal amount of the 2027 notes.

We are narrowing our full year 2025 GAAP operating expense range to $680,000,000 to $700,000,000 from the previous range of $670,000,000 to $710,000,000 Stock based compensation that is included in GAAP operating expense is expected to be between 110,000,000 and $120,000,000 Excluding stock based compensation from GAAP operating expense, results in a range of $560,000,000 to $590,000,000 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 aficamtan in The U. S. Potential approval in The EU in the 2026 and the readout of results from Acacia HCM expected in the 2026.

With that, I'll hand it back to Robert Blum. Thank you, Sung.

Robert Blum: 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 aficamtan 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 thirty 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 aficamtan by the end of the year.

We expect to advance go to market strategies and continue launch preparations for aficamtan 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 avacamten by the EMA in the 2026. We expect to continue to coordinate with Sanofi to support the potential approval of aficamtan in China pending approval by the NMPA. And we expect to report top line results from the primary cohort of Acacia HCM in the 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 common HCF through 2026 For ulicamptin, we expect to continue patient enrollment and conduct of Amber Hefpef. 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: Certainly, and thank you. You. Repeat the steps of star and one, and that will also remove you from our queue. Once again, ladies and gentlemen, that is star and one. And we ask today that you please. We'll hear first from the line of Gena Wang at Barclays.

Gena Wang: Thanks. Good afternoon, Gena. Hi. Good afternoon. I have tons of a question on you know, 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 twenty-six. So you know, as like, we remember that you add a p v o two as a dual primary endpoint per regulatory feedback from Europe and Japan. So technically the drug should receive approval as long as you hit one of two primary endpoints. So but in the case of a missing p v o two, 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.

Robert Blum: I'll ask Fady to respond to that.

Fady Malik: Yeah. Hi, Gena. I think it's really difficult to know what will guarantee approval or not. Obviously, it depends on magnitude of the other results. It depends on safety profile. It depends on lots of things. But the trial will be considered positive 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'd like to see consistency across the other endpoints. So, you know, 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. Thank you.

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

Salim Syed: Great. Good afternoon. Hey, good afternoon, Robert. Thanks for the question. 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 Fadi, so the Acacia trial p value is split. So as I understand it, between kccq and peak VO2, both at point zero two five, so equal.

And 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 point zero four, and came in with a p value of point zero six, which was close to hitting and also a better p value than what we saw with an 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 in Acacia 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 OHDSI trial it missed and the KCCQ delta was two to two or three. 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've 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 the peak VO two, it's improved by one point o.

Now that power powering the trials 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 either 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 the 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.

Operator: Next question today will come from Akash Tewari at Jefferies.

Akash Tewari: Hi, guys. This is actually Zaki on for Akash. Thanks so much. For the question. So just again on non obstructive, talked about how Bristol's OHDIESY 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 AUDIT with an even more aggressive alpha split. So I just wanna know in terms of what you're seeing on blinded variability, gives you confidence that one, you're not underpowered versus Odyssey?

And two, that placebo is actually tracking in line with your expectations around that five point placebo adjusted delta on KCQ. Thank you.

Fady Malik: Well, think your last point is to answer because we're blinded, so we don't know what the placebo effect is. In Acacia You know, we do monitor the variability of the combined dataset and the 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've run using that metric is generally, in about 15 range, which you know, is tracked with Sequoia. It's tracked with other trials we've done in that area. And I think in Acacia, it's not really any different at this point.

So I think we're tracking along our assumptions and for now, you know, we'll just let things play out, see how they 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 aphicamtin and as has already been historically validated in our prior studies, So we do believe that's something that serves to our favor.

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

Carter Gould: Hi, Robert and team. Good afternoon. Thanks for taking the question. Maybe I'll give a case 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 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 Callos: Thank you. Andrew? Sure. So those three 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, we're this is a very limited distribution The REMS drives that as well. The specialty pharmacies, there's two of them that will not report data. We will that on a quarterly basis. There are so pharmacies that will be qualified, IDN pharmacies through large health care 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 looked 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.

Operator: Next question today comes from will come from the line of James Condulis at Stifel.

James Condulis: Hey, thanks for taking my question. How's it going? Like to ask one on back to Acacia and again on blinded data. I was curious how much of a line of sight you have on kind of like blinded safety data and maybe what the LVF less than fifty percent rate looks like. Obviously not anything specific, but like how it compares to say what you saw in SEQUOIA and obstructive. Curious if there's any color there. Thank you.

Fady Malik: Yes. I'm going tread carefully here. I don't I'll just say that you know, there's nothing out of the blinded data that are unexpected. Based on what we've seen so far.

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

Cory Kasimov: Hey, Cory. Hey. Good hey, Robert and guys. Good afternoon. Thanks for taking the question. So I want to go back to the pending launch. 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?

Andrew Callos: 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 of 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. Yeah. It's a good question.

You know, there was a lot of centers that physicians who aren't writing today So part of the goal would be what a differentiated REMS program alongside Maple, alongside Sequoia, Do 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 much angst, especially among high users and high centers. So we are expecting that a differentiated REMS, 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.

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

Tessa Romero: Hey, Tess. Hey, good afternoon, team. This is Caroline Poacher on for Tessa Romero with JPMorgan. Thanks for taking our question. Just one from us on aficamtan 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?

Robert Blum: 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.

Operator: Moving forward, Maxwell Skor with Morgan Stanley. Your line is open.

Maxwell Skor: Great. Thank you for taking my question. One more on Acacia. Could you just confirm whether there are any shared trial sites between OHDICEY 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.

Fady Malik: Yeah. Hi, Max. I can't give you the exact overlap, but the overlap's not very large. You know, obviously, if sites were conducting two trials that were simultaneously in the same patients and be a bit problematic. Some trials have finished their commitment and, obviously, and then, you know, 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, you know, 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.

Operator: Yasmeen Rahimi with Piper Sandler, you have our next question.

Yasmeen Rahimi: 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, sounded like you're thinking about pricing in parity to mavacamten, obviously, given the product portfolio may have flexibility to go higher. So appreciate any color around that.

Andrew Callos: Sure. So we're we'll 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 that's typically priced in proximity, to the initial product. So would think, you know, we're gonna be in that same kind of ballpark or minus maybe a small percentage we're certainly going to be in that range.

Operator: Our next question today will come Roana Ruiz at Leerink Partners.

Roanna Ruiz: Great. Thanks and good afternoon everyone. So a quick follow-up of the aficamtan potential U. S. Launch. Could you share more details about what you're 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.

Andrew Callos: Sure. 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 will go through. Medical exception can be as fast as, say, two to three weeks or it could take you know, ninety 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 on a drug the commitment of going through echoes 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?

Operator: Mister Eaves, if you would like to hit star one once more, I can reactivate your line. Thank you, ma'am.

Roanna Ruiz: Yes. The last part was about early adopter physicians. Prescribing Afucanthin out of the gate.

Andrew Callos: Thank you. Yes. So there's this is a very, very focused market, six fifty prescribers or so, about 80% of the market. Those prescribers we know well. We've actually been interacting with many of them already. We're 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 Aficans and if it gets approved. So that's our expectation. Thanks for the questions.

Operator: And thank you for resigning Ms. Ruiz. We'll go next to Mayank Mamtani at B. Riley Securities.

Mayank Mamtani: Yes. Good afternoon, team. Thanks for taking our questions and congrats on a productive third quarter. Would love to hear your thoughts maybe for Andrew on your latest thinking is on peak CMI drug class 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, 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 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.

Andrew Callos: Sure. So a lot of questions there. So I'll try to address those PMI penetration, I think, was your first question. Right now, the penetration is probably in the 15% to 20% range. Of OATM, and I'm defining that as the number of eligible patients those that are class two, class three. Those that are treated with a CMI. So we are expecting, as we've said all along, around eighty percent or so of the 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 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, if Maple helps influence guidelines and 'twenty-six or 'twenty-seven, 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 a label to the FDA. We've had a 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. Thank you.

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

Joe Pantginis: Hey, everybody. Good afternoon. Thanks. Hey, there. 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 you can we get do you think starting in 2026?

Robert Blum: Thank you, Joe. We'll ask Stuart maybe to take that please.

Stuart Kupfer: Yes. Thank you, Joe. 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 you know, the, the we were we're seeing screen picking up randomization picking up, and, I mean, we're 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 sides activated and we have a good trajectory. But so far, so good. Study conduct is going well, and so it was site interaction. And, screening. Thank you.

Robert Blum: 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. We can maybe point more generally to when we might expect data.

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

Paul Choi: Hey, Paul. Hi. Good Hi, good afternoon. Thank you for taking the question. I want to ask on your partnered CAMMELIA 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 would you be in a position to potentially present some initial data on that in 2026? Thanks for taking the questions.

Robert Blum: I'll ask Nadia to tackle those, please.

Fady Malik: Yes. Mean, with regards to the progress of the OA trial, in Japan, I mean, that's a strategy in Japan. Be a little bit tied to more new 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 where it is, but Camilli is moving along with within line of that expectation. And then Amber, I think it was 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. Okay. Thank you. Bye.

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

John Gionco: 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, curious what your timelines look like in terms of how quickly you'd like to file the sNDA, to incorporate that data into Appian's label? And whether you think having it in the label will alter in any way prescribing habits for treating physicians.

Robert Blum: So I'll take the first part and ask Andrew to address the second part. But Our goal is if we see afikamtan 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 twenty-six. To be enabling of a potential expanded label even possibly by the 2026. Andrew can comment on how that may factor into expanded use.

Andrew Callos: Yeah. And 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 aficamtan 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.

I see, you know, that second group is gonna take a little longer some of them. And guidelines as well as continued education and promotion we'll 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. Thanks for the question.

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

Kripa Devarakonda: Good afternoon. This is Alex on Hi. Alex on to Cripa. Based on your updated late cycle meeting with the FDA, and the nature of the day 120 listed questions for the CHMP, Is there anything we should be aware of to indicate that there's that the rents requirement could possibly be meaningfully different from The U. S. And the EU?

Robert Blum: 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, afdecamtiv, if approved in The U. S. And in the EU will be addressed similarly in terms of risk mitigation. All right. Thank you.

Operator: Our next question will come from Ash Verma at UBS. Your line is open. And hearing no response, we'll move forward. Ash please try to resignal with star and one. We'll hear instead from Jason Zamanski at Bank of America.

Jason Zamanski: Good evening. Afternoon, Afternoon. Congrats on the progress and thanks taking our question. Maybe just to switch gears but in light of your recent balance sheet updates, do you stand in terms of your ability to support both The U. S. And EU launches? I mean, you foresee any need for additional capital, especially given your expectations for the launch? Thanks.

Sung Lee: Jason, this is Tom. Thanks for the question. We can't rule out future financings. But with that said, we expect to finish the year with $2,200,000,000 in cash investments. I'm sorry, 1,200,000,000.0. Thank you. I got a little excited there. That puts us in a very strong position, not only to launch aficamtiv 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 $175,000,000 This is from the Tranche seven loan from Royalty Pharma. So we'll continuously weigh our options. In terms of capital requirements and capital structure. Got it.

Operator: And now we'll move to Ash Verma with UBS once again. 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.

Natalie: Hi there. Can you hear me?

Operator: There you are. Thank you.

Natalie: Hi there. Can everyone hear me?

Natalie: Natalie on for Ash?

Andrew Callos: We can hear you.

Natalie: There. This is Natalie on Fresh. Can you hear me? We can hear you.

Natalie: Sorry about that. This is Natalie on for Ash from UPS. 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 CMIs?

Fady Malik: Well, I would say that, you know, that question remains unanswered maybe perhaps, and we'll acquire both analyses of the OHDSI 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 have certain biomarker increases think all of those things talk about asymptomatic, highly symptomatic, and functionally limited patient population. And based on our prior experience and Redwood, we think that population should be responsive to Afrikaansson. 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 non obstructive patients for over two years now. And large majority of them are responding well symptomatically, based on cardiac biomarker improvement. So think what we're observing so far, at least in this cohort in forest, is pretty general improvement. In response to treatment.

Operator: 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.

Robert Blum: Thank you. 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 one of these earnings calls, we'll talk about, what could be the first potential approval for aficamtan 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.

Operator: Thank you. And ladies and gentlemen, thank you for joining today's Cytokinetics Q3 2025 earnings call. You may now disconnect your lines.

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