Cytokinetics, Incorporated (CYTK) Q3 2026 Earnings Report, Transcript and Summary

Thank you for standing by, and welcome to the Cytokinetics Q3 2026 Earnings Call. This call is being recorded. [Operator Instructions] I would now like to turn the call over to Diane Weiser, Cytokinetics Senior Vice President of Corporate Affairs. Please go ahead.

Good afternoon, and thanks for joining us on the call today. The slides accompanying today's webcast can be found on the Investors and Media section of our website at cytokinetics.com, along with today's press release. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Andrew Callos, EVP and Chief Commercial Officer, will discuss the commercial launch of MYQORZO in the U.S. and Europe. Fady Malik, EVP of R&D, will provide updates related to aficamten. Steve Heitner, SVP and Chief Medical Officer, will provide updates related to our ongoing clinical development programs. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview for the quarter. And finally, Robert will make closing remarks. As you can see on this slide, today's discussion will include forward-looking statements, which are subject to risks and uncertainties. Please refer to our SEC filings for a discussion of these factors. And now I will turn the call over to Robert.

Thank you, Diane. And thanks to all for joining us on the call today. The third quarter was another period of strong execution for Cytokinetics as we continue to build a leading muscle-focused specialty cardiology company. In Q3, we made progress on each of our priorities underlying that strategy. Nearly 9 months in, the launch of MYQORZO continues to exceed our expectations. In the third quarter, MYQORZO generated $44.5 million in net revenue, up 76% from Q2. As Andrew will describe, the number of prescribers prescribing per physician and patients dispensed all increased. We believe these trends reflect the differentiated profile of MYQORZO, and we see significant room for continued growth. Outside the United States, our launch in Germany is off to a strong start, and we continue to secure approvals in additional geographies, including recently in Canada and the United Kingdom. We expect to launch in the U.K. this quarter and in additional countries in 2027. We're also looking forward to the PDUFA date for data relating to MAPLE-HCM, which is November 14. Beyond oHCM, we're working diligently to bring aficamten to more patients living with HCM. In August, we presented the full results from ACACIA-HCM in a hotline session at ESC with simultaneous publication in the New England Journal of Medicine. In fact, the presentation was included in the opening plenary session for ESC, a clear sign of enthusiasm from the cardiology community, which today has no approved therapy that addresses the underlying disease for nHCM. We also presented additional results at ESC from prespecified analyses from ACACIA-HCM that further underscore the potential of aficamten in nHCM. These results bring us closer to the potential commercial availability of a treatment for the full spectrum of symptomatic HCM patients. Based on these results, we're on track to submit a supplemental NDA to FDA this quarter and an application to the EMA in early 2027. At the same time, pending regulatory approval, we're preparing for the potential launch in nHCM, building on the commercial foundation we've established with MYQORZO in oHCM. Andrew will share more on our commercial readiness in a moment. And beyond aficamten, we continue to advance our pipeline during the quarter. Our later-stage clinical trials for omecamtiv mecarbil and ulacamten continue to make progress. And earlier in our pipeline, we achieved a preclinical milestone in our collaboration with Accutar, which is focused on targeted protein degraders for muscle-related diseases. Taken all together, our third quarter results demonstrate the progress we're making towards our Vision 2030. Looking ahead, our priorities are clear: submit the sNDA in nHCM, prepare for a potential nHCM launch, expand MYQORZO into additional geographies and importantly, continue our commercial momentum in oHCM while advancing our pipeline, all while staying disciplined to how we deploy capital. And with that, I'll now turn the call over to Andrew, please.

Thank you, Robert. MYQORZO delivered another quarter of strong growth, and the launch continues to exceed our expectations. In Q3, we are pleased to see growth across prescribing, patient demand and market access, all while the CMI category itself continued to expand. These trends show that MYQORZO is on a strong trajectory in the first year, and we're focused on building that momentum into 2027. As we committed at launch, we continue to measure performance using 3 key metrics: breadth of prescribing, depth of prescribing and patient volume. In the third quarter, we saw continued growth across all 3, driven by an expanding prescriber base. By the end of the third quarter, nearly 1,100 unique health care providers in the U.S. have prescribed MYQORZO, up from more than 700 at the end of Q2. On average, these HCPs have prescribed MYQORZO to nearly 4 of their patients, up from 3 last quarter. Among high-volume CMI writers, the figure is 7 patients, up from 5 in the second quarter. We believe this increase in prescribing reflects growing physician confidence in MYQORZO. Turning to patient demand by the end of the third quarter, MYQORZO had been dispensed to more than 2,800 patients, up approximately 86% from 1,500 at the end of Q2. While syndicated data has limitations, our internal analysis suggests that new-to-brand exit share for MYQORZO in the CMI category is continuing to grow and approaching [ 45% ] in the third quarter, up from approximately 40% in the second quarter. Our launch strategy was to focus on high-volume CMI prescribers, and our NBRx share is highest among these HCPs approaching 50%, a leading indicator of future growth. We remain committed to our goal of achieving greater than 50% new-to-brand exit share by year-end, which would represent a strong result for the second entrant in less than a year of launch. Beyond capturing new-to-brand share, MYQORZO is also helping to expand the CMI category. Q3 '26 versus Q3 '25 new-to-brand prescription grew 56%. When comparing year-to-date growth for the same period in '25, the CMI market has grown 45% since the introduction of MYQORZO, and there is still significant room to grow. Of approximately 120,000 eligible oHCM patients in the U.S., only about 28,000 are treated with the CMI today. That leaves over 75 of CMI-eligible patients who could benefit from therapy, and that's where our launch continues to be focused. As we said, prior to our launch, prescribing was concentrated among high-volume CMI prescribers who historically accounted for approximately 80% of CMI volume. By the end of Q3, our sales team had reached more than 95% of these HCPs. Since launch, as we continue to grow share among high-volume prescribers, adoption has also broadened beyond this core group. Specifically, low-volume CMI prescribers now represent 30% of all MYQORZO prescribers, while prescribers naive to CMI represents another 35%. Importantly, in Q3, we estimate that the CMI naive prescriber segment accounted for approximately 70% of total CMI growth since Q2. We continue to expand access and ended the third quarter with over 60% of commercial lives covered, up from 50% of lives covered at the end of Q2, while continuing to maintain a consistent level of Medicare coverage throughout 2026. In Q3, we continued to achieve over 80% of paid prescriptions, showing continued success in access and our ability to manage payer appeal process. Outside the United States, our launch in Germany is continuing to gain traction. By the end of August, MYQORZO had already captured more than 50% of new CMI patient starts. We also recently received approval in Canada, and we expect to launch in the U.K. this quarter and in additional countries in 2027. As a result, we expect MYQORZO to be available in all key European markets in 2027. At the same time, as we move towards our planned sNDA submission for nHCM this quarter, we're preparing for a potential commercial launch in that indication in 2027. Our field force was designed from the start to reach the physicians who treat both obstructive and nonobstructive patients. So the infrastructure is already in place. We're also building disease awareness to run branded education, and our payer account teams are preparing to engage payers in compliant pre-approval information exchange in preparation for coverage discussions. In the U.S., we estimate that over 200,000 patients have been diagnosed with nHCM and over 120,000 are symptomatic and eligible for treatment. Recent market research reacting to ACACIA-HCM suggests that if MYQORZO is approved for the treatment of symptomatic patients with nHCM, physicians see a meaningful role for their therapy, particularly among patients with greater symptom burden or persistent functional limitations where unmet need is highest. Importantly, physicians indicated that patients with the greatest symptom burden may be the most likely to receive treatment, potentially driving higher utilization within this segment. Moreover, a dual indication label could further strengthen MYQORZO's position in oHCM as physicians gain broader experience and confidence with MYQORZO across both obstructive and nonobstructive HCM. Ultimately, we hope MYQORZO will be approved to address this important unmet need. Overall, we are very encouraged by the performance in our launch markets. It reflects the differentiated profile of MYQORZO and the execution of our colleagues across the U.S. and Europe. Together, this progress is building a strong foundation for continued growth. And with that, I'll turn the call over to Fady.

Thanks, Andrew. The third quarter was an important period for further differentiating the clinical profile of aficamten. In August, we presented the full results from ACACIA-HCM, our pivotal Phase III clinical trial of aficamten in patients with symptomatic nHCM in a hotline session at the European Society of Cardiology. These results were published at the same time in the New England Journal of Medicine. As we previously reported, aficamten met both dual primary endpoints with statistically significant improvements versus placebo in patient-reported health status as measured by KCCQ and in exercise capacity as measured by peak VO2. Aficamten also achieved significance on 3 of 5 key secondary endpoints, including NYHA class and NT-proBNP. Importantly, the treatment effect was consistent across all prespecified subgroups, including patients on beta blockers, those with intracavitary obstruction and across genotype positive and negative patients. The response from the cardiology community at ESC was quite positive. Leading HCM experts called the results a transformative moment for patients with nonobstructive HCM, a population where there are currently no approved treatments. Since ESC, we've seen strong engagement from the HCM community, including centers of excellence, patient advocacy groups and physicians who treat these patients every day. With no approved therapies that address the underlying disease in nHCM, we believe these results have the potential to meaningfully change how HCM is treated. We also presented additional analyses from ACACIA-HCM at ESC and HFSA that further characterize the treatment effect and safety of aficamten in nHCM. At ESC, we presented data showing that aficamten significantly improved diastolic function, meaning how well the heart relaxes and fills and reduced left ventricular wall thickness, effects that strengthen with longer treatment. These findings related to the mechanism of aficamten help elucidate the underlying effects on the heart that lead to improvements in symptoms and exercise capacity. At the Heart Failure Society of America meeting in October, we presented data showing that aficamten improved global exercise performance across multiple domains of the cardiopulmonary exercise test in addition to peak VO2. In a second presentation of a responder analysis, 53% of patients on aficamten achieved a clinical meaningful response in 3 or more domains compared with 13% on placebo, which puts the mean treatment effect in the clinical context. With respect to safety, an analysis from ACACIA-HCM showed that heart failure events occurred early during titration, often after a triggering event such as atrial fibrillation or infection and generally resolved with standard therapy. Importantly, in an open-label extension FOREST-HCM, where patient judgment guides dose titration and more closely reflects clinical practice, these events have been rare. The view of leading HCM experts see these events as manageable in clinical practice, and it gives us confidence in how aficamten can be used in the real world. On the regulatory front, our supplemental NDA based on ACACIA-HCM remains on track for submission to FDA this quarter. As Robert mentioned, we're also preparing to submit to the European Medicines Agency in early 2027. In oHCM, our sNDA based on MAPLE-HCM remains under review with a PDUFA date of November 14. We continue to engage constructively with FDA and look forward to its decision. Taken together, this progress reinforces our conviction in the potential of aficamten to become the first cardiac myosin inhibitor to treat the full spectrum of HCM. With MYQORZO available for adults with symptomatic oHCM and ACACIA-HCM supporting a potential expansion into nHCM, we see a substantial opportunity to reach a broader population of patients in the U.S. and around the world. And with that, I'll hand it over to Steve.

Thank you, Fady. In the third quarter, we made meaningful progress across our clinical development programs. Starting with aficamten, we continue to strengthen its evidence base. We recently began ASPEN-HCM, a real-world study of MYQORZO in obstructive HCM. We believe that this data will help us better understand real-world safety, clinical effectiveness and health care resource impact of MYQORZO in routine clinical practice and will help inform future discussions with regulators, particularly with respect to the REMS. We also completed the adolescent cohort of CEDAR-HCM, a Phase III clinical trial evaluating the efficacy, pharmacokinetics and safety of aficamten in the pediatric population with symptomatic obstructive hypertrophic cardiomyopathy, and we expect to share the top line results in early 2027. Additionally, our partner, Bayer, completed the main study treatment period of CAMELLIA-HCM, a Phase III clinical trial of aficamten in Japanese patients with obstructive HCM. And we recently completed the conduct of the Japan cohort of ACACIA-HCM. Beyond aficamten, we continue to advance our late-stage cardiovascular pipeline. For omecamtiv mecarbil, enrollment continued in COMET-HCM, our confirmatory Phase III clinical trial in patients with heart failure with severely reduced ejection fraction. Enrollment has now accelerated as expected now that all sites are active, and we expect enrollment to continue through 2027. Even on standard of care, these patients remain poorly served with about 35% re-hospitalized rate within a year. In GALACTIC-HF, the benefit of omecamtiv mecarbil was greatest in patients with the most severely reduced ejection fraction. And COMET-HF is specifically designed to enroll exactly those patients. The baseline characteristics we've collected so far indicate that we are matching the patient population we intended to enroll. This gives us confidence in the trial and the potential to address the significant unmet need with omecamtiv mecarbil. For ulacamten, enrollment continued in Cohort 1 of AMBER-HFpEF, our Phase II study in patients with heart failure with preserved ejection fraction. We remain on track to complete enrollment this quarter. With this trial's focus, we're generating data to help define the potential role of a cardiac myosin inhibitor in HFpEF. We're pleased with our execution across a promising later-stage pipeline, and we look forward to several important milestones ahead. With that, I'll turn it over to Sung.

Thanks, Steve. Beginning with revenue, total revenues for the third quarter were $47.6 million compared with $1.9 million in the same period in 2025. Net product revenues for MYQORZO were $44.5 million, representing 76% growth quarter-over-quarter. U.S. net product revenues were $43.1 million, driven by robust demand. Europe contributed $1.4 million to net product revenues in the third quarter following the launch in the second quarter, which was comprised of initial inventory build in Germany. Collaboration revenue was $3.1 million in the third quarter compared with $1.9 million in the same period in 2025. Turning to operating expenses. R&D expenses for the third quarter were $99.3 million compared with $97.3 million in the same period in 2025. The increase was primarily driven by higher clinical trial activity and personnel-related costs. SG&A expenses for the third quarter were $113.1 million compared with $69.5 million in the same period in 2025. The increase was primarily driven by external costs associated with the commercial launch of MYQORZO as well as higher personnel-related costs, including stock-based compensation. Cost of goods sold for MYQORZO in the third quarter was a credit of $0.5 million, primarily reflecting a credit related to drug supply optimization activities. Collaboration cost of revenues, which primarily reflects partner costs for which the company is reimbursed was $2.7 million in the third quarter compared with $1.9 million in the same period in 2025. Net loss for the third quarter was $190.1 million or $1.37 per share compared with a net loss of $306.2 million or $2.55 per share in the same period in 2025. Turning to the balance sheet. We ended the third quarter with approximately $1.6 billion in cash and investments compared with $1.7 billion at the end of the second quarter of 2026. Turning to financial guidance. We are reaffirming our full year 2026 GAAP combined R&D and SG&A expense guidance of $860 million to $890 million. Our expectation for stock-based compensation, which is included in our GAAP combined R&D and SG&A expense guidance is also unchanged at $130 million to $140 million. With that, I'll turn the call back over to Robert.

Thank you, Sung. Before we open up the call to questions, I'd like to highlight how far we've come this year and what's ahead. Since launching MYQORZO, we've built a strong commercial foundation with nearly 1,100 U.S. prescribers, a growing presence in Europe and approvals across 4 additional regions. ACACIA-HCM became the first positive Phase III clinical trial in nonobstructive HCM, and we continue to advance our later-stage pipeline, which we expect to drive longer-term growth beyond aficamten. Now we're focused on finishing the year strong with several significant milestones ahead. Next week, we expect an FDA decision relating to MAPLE-HCM. Before year-end, we plan to submit our sNDA relating to results from ACACIA-HCM. We expect to launch MYQORZO in the U.K. in this quarter and complete enrollment in Cohort 1 of AMBER-HFpEF. And in early 2027, we expect to submit our application relating to the results of ACACIA-HCM in the EU and launch in additional countries in 2027 as well as share top line results from the adolescent cohort of CEDAR-HCM. We're pursuing all of this from a position of financial strength with a strong balance sheet that supports our launch activities as well as our pipeline advancement and our longer-term value creation. We believe we're well positioned to drive continued growth and to execute on our priorities as guided by our Vision 2030. And with that, operator, we'd like to now open up the call to questions, please.

We will now begin the Question-and-Answer Session. [Operator Instructions] Your first question comes from the line of Carter Gould with Cantor Fitzgerald.

Great. Good afternoon. Thanks. Hey Robert, good afternoon. Thanks for taking the question. Robert and Andrew, I appreciate all the metrics. Trying to square some of the implied sequential growth at the market level with some of your commentary there, it seems to sort of indicate a step-up of around 400 to 500 incremental patients at the CMI level quarter-on-quarter. I guess, to some extent, I'm asking you to bless that math, but also maybe comment if you think that sort of is a sustainable step-up as we think about the quarters going forward? Or are there governors at the site level that may tamp down the ability for that to step up sequentially?

Sure. I'll ask Andrew to comment, please.

Sure, Carter. So yes, we are seeing sequential growth, to your point. The number is probably more like the 300 range in terms of prescriptions. If you factor in free drug, you might get up to a higher number. But I think the math is probably closer to a little over 3,000 patients for the category, which is up around 300 from the second quarter. In terms of sustained growth, certainly, as we mentioned in the call in the remarks earlier nearly 80% of the market is still available. If we continue to see these, what we call naive, meaning they didn't prescribe a CMI before our launch, if we continue to see the good growth of new prescribers for the category, that certainly is what fueled most of the growth, as I mentioned, in Q3. And our expectation is we will continue to see that. So you'll continue to see growth in the category.

Carter, I might add a comment. What's especially encouraging is where that growth is coming from. It's coming not just simply from the velocity accounts, but also from a broader foundation of new to the category prescribing. So not only should we expect sequentially sustained growth, but at some point, that may hopefully translate into a higher velocity growth as well.

Your next question comes from the line of Tessa Romero with JPMorgan.

Hi Robert and team. Will you be providing longer-term guidance for MYQORZO at our small conference in January? Or is that something that will be further out for Cytokinetics? And then just to double-click on Carter's question, Andrew, is north of 3,000 adds the right way to think about the run rate for this category?

So regarding your first question, I'll mention, we're still discussing how we're going to approach 2027 and what we're going to speak to in the way of guidance. And certainly, over the longer term, you can expect that we'll speak to where we see this ultimately going for the benefit of the company. But it's premature, I think, to comment on that today. Andrew, do you want to address the comment about 3,000?

Sure. So if you look at kind of year-to-date factoring in an estimate for free drug, we're close to around 9,000 patients in our estimate for the category through the end of the third quarter. With that growth factored in. So yes, I certainly feel that 3,000 plus per quarter moving on. And obviously, when nHCM comes on board, the HCM categories should certainly grow even more than that.

To put that in context of where we were a year ago, substantial growth in the category year-over-year.

Thank you, Robert.

Your next question comes from the line of Akash Tewari with Jefferies.

Hey, thanks so much. So I wonder if you could just comment on Edgewise is proposing kind of a Phase III design without echo-guided dose adjustments, more of a kind of symptomatic paradigm. How much have you engaged with the FDA on improving the REMS you have with your titration with MYQORZO? Could we get into a symptomatic paradigm for your drug? I know only about, I think, 1.3% of your patients even had a LVEF-mandated change in your titration during SEQUOIA. So it seems like it's at least possible to do. And what long-term data do you have to submit to the FDA to get that done?

So before I turn it over to Fady, I'll just make the following comment. There's nothing that any fast follower is contemplating that we haven't been discussing here at Cytokinetics already for quite some time. And we do believe that it will be incumbent upon us with real-world evidence to demonstrate where we can go with a potentially relaxed or even removed REMS over time. But that does require based on our intuitions and communications with regulatory authorities, some evidence of real-world evidence that will come with what will ultimately be thousands of patients, but certainly within line of sight to what we expect to be able to accomplish here over a period of time. I'll ask Fady to comment on where we could go with these potential strategies.

Thanks, Robert. I think, first of all, there's certainly the ability to simplify the titration protocol and there are things that we can do. I'm not going to lay out any specifics at the moment that can enable more flexible use of echoes during titration or different starting doses, things like that. I think Robert's point is a strong one, which is that any new drug in the market is not likely going to have a safety profile informed by a few hundred patients treated for a couple of dozen weeks. In fact, it's clear the FDA wants to see real-world data from thousands of patients treated over many, many months or years even. But I would anticipate in the 2- to 3-year time frame as we see data coming out of the REMS, out of our real-world evidence experiences that we will reinforce the safety we've already observed with aficamten and enable us strategies by which to simplify the REMS. I might also add that even our real-world experience now suggests that majority of patients are entering the maintenance phase with a treatment of 5 or 10 milligrams of aficamten. That suggests that patients feel those doses are effective in reducing their symptoms. That's for them to judge as they integrate both symptom assessment as well as biomarkers and LVOT assessments and ultimately, the question of simplifying dose titration may frankly take care of itself if patients are doing fine on the starting dose or one dose later.

And hopefully, to underscore, Cytokinetics believes very strongly in the credibility and integrity of how we engage around these matters, and we believe the best way to enable achieving those outcomes, including a relaxed or removal of the REMS is to do what we've already been doing, pioneer and lead in this space, and that speaks to what will come from real-world evidence as we already have a strategy in place.

Your next question comes from the line of Cory Kasimov with Evercore ISI.

Hi this is [ Josh ] on for Cory. Can you help characterize the size of the EU opportunity in relation to the U.S.? And when do you expect to see a significant step up here?

Sure. So I'm going to ask both Andrew and Sung to speak to that question, starting with Andrew, please?

Sure. So thanks for the question. I mentioned, we've launched in Germany. Germany is the largest market. Overall, we're expecting Europe to be around 15% of revenue when Europe is mature, when the U.S. is mature. Europe does take a little longer to get going. Germany, you can launch at approval while you're negotiating price. The other major markets, you need to -- after you get regulatory approval, submit to a health technology assessment body to get reimbursement, which generally takes, say, 12 to 18 months after the approval. So you'll see more meaningful revenue probably in the 2028, 2029 time frame. And I'll turn it over to Sung if he has any additional comments.

Yes, [ Josh ], I'll just simply add. When you look at Europe, it's not just for us, but across our industry, it's generally characterized with long, gradual steady launches, right, especially as you go through the HTA process for each country, you have staggered launches. So I think you have to keep that in perspective. And in the end, this is a long game for us, and we expect meaningful contributions from Europe. As Andrew said, it could be 15% of our total MYQORZO net product sales.

Thank you.

Your next question comes from the line of Maxwell Skor with Morgan Stanley.

Great thank you very much for taking my question. Could you expand a bit more on the profile of potentially eligible nHCM patients? For example, what share of those diagnosed would meet ACACIA's entry criteria? And is that kind of the right starting point for sizing the market?

I'll ask Steve to comment on that, please.

So the criteria that we implemented in ACACIA really simply put our patients with symptomatic nonobstructive HCM. And the data that we presented at the ESC, with particular reference to that forest plot, did not show any heterogeneity of the treatment effect according to the prespecified subgroups that we looked at, so age and sex and whether they had particular ejection fraction or preexisting atrial fibrillation, none of those seem to impact. The way we would foresee this being implemented should we achieve regulatory approval would be that patients would come in and if they had any symptoms and a diagnosis of nonobstructive HCM and an ejection fraction above 55% or 60%, those patients would be eligible for treatment trial, at least of aficamten.

Great. Thank you.

Your next question comes from the line of Salim Syed with Mizuho.

Congrats on the progress, guys. One from us actually on omecamtiv mecarbil. So I think the commentary in the call, you mentioned you've accelerated enrollment, but the press release now lists continuing enrollment through 2027, if I'm not mistaken, versus in the 2Q, it was through 2026. So I'm just wondering if you could just square those dynamics. What exactly is happening with enrollment for you to change the language on when you expect enrollment to go through in 2027 versus 2026?

Sure. I'm going to ask Fady to comment on that, please.

The language in the prior releases just referred to what was happening in 2026. As you look through our milestones, it basically says what is we're planning for 2026 and enrollment was continuing through 2027 rather through 2026. We didn't expect enrollment to conclude in 2026. Otherwise, we would have said that in that guidance. Obviously, enrollment won't conclude in 2026. It will conclude sometime in 2027. And we'll give guidance to that matter when we give guidance for the rest of 2027.

Okay. Got it. Thanks so much.

Your next question comes from the line of Roanna Ruiz Leerink Partners.

Hey everyone. Good afternoon. I was curious about the MYQORZO naive prescribers. Are they more in the community hospitals rather than large academic centers or more of a mix? And in terms of greater penetration into that group, how are you thinking about driving breadth and depth and maybe converting some of them to high-volume prescribers?

Andrew, can you take that, please?

Sure. So thanks for the question. Yes, the vast majority of those are community cardiologists the depth of those prescribers right now, it's one to 2 scripts generally we see with each. I think one, they do have less patients that they see as compared to the academic centers. So we're not expecting that same level of demand driven. But as they get more experience, and what we're learning is when a physician is treating 3 or 4 patients, they've got experience with the REM, they've got experience with MYQORZO, they have experience with the market access that they generally then get on board. But it does take a little bit of time, and we are expecting depth of prescribing in that group and continued expansion. One of the things that I mentioned around nHCM, on average, you're really doubling the patient population for every one of those prescribers if nHCM is approved. And there's certainly the ability to leverage oHCM and nHCM as kind of the dual indication to give you even more opportunity for that experience to increase depth.

Got it. Thanks.

Sure. Thanks for the question.

Your next question comes from the line of Eric Joseph with Citi.

Good evening. Thanks for taking the questions. Just from your discussions with the cardiology community with the full ACACIA data, can you talk about a little bit about the feedback you may have received regarding the titration scheme in the study? I'm just wondering kind of going into your planned sNDA submission, whether you might be proposing a scheme that varies a bit from the protocol focused more on positive symptom or symptom improvement rather than safety-driven stopping rules?

Sure. As you know, we're both looking at the data from ACACIA-HCM as well as FOREST-HCM, and I'll ask both Fady and Steve to comment, please.

So as Robert kind of alluded, if you think back to how we approach the obstructive HCM titration schedule, we used data from both the randomized clinical trial SEQUOIA and complemented that with the experience from FOREST-HCM. And that's part of the plan that we're implementing for the sNDA for nonobstructive cohorts. The feedback that we've gotten so far, and it's more than feedback, it's evidence that has been generated. And actually, we showed this at the investor meeting that we had after the presentation, of the data in Munich was that the implementation of the dosing schedule that was designed in FOREST appeared to be easier, firstly, for physicians and patients due to the flexibility and also associated with fewer adverse events that have been seen in the clinical trial. So I think the feedback that we're getting is, please, can we do our very best to get that sort of titration regimen implemented in the real world, which also would actually harmonize nicely with what's already in the real world for obstructive HCM. I hope that answers your question.

That was great. Thanks for taking it. Congrats on a good quarter.

Your next question comes from the line of Ashwani Verma with UBS.

Great. Yeah, thanks for taking the question. So maybe just wanted to get your thoughts on the competitive assertions here that not having an echo monitoring requirement during titration can create a significant advantage in oHCM. And it seems like Edgewise has talked about this publicly that they proposed one baseline and one end-of-study echo. Just curious to hear your perspective if you think that this can actually change favorably when we see the finalized Phase 3 trial design in the near term.

So I don't want to spend too much time talking about speculation relating to another company's development program. But what I will say is that FDA can be permitting you to do any sort of thing in a clinical trial. And ultimately, it will be post availability of data and upon review of an NDA that the FDA may consider what ultimately it wants to see in a potential approval and labeling. We've experienced that firsthand. As you may recall, in SEQUOIA-HCM, we saw no dose terminations relating to EF excursions and it would not have been thought necessary to even have the kinds of regulatory restrictions on dose titration and echos based on those data, but for the fact that FDA upon review thought it prudent until such time as it had real-world evidence to put in place the REMS requirements we complied, and that's what we have now for MYQORZO. I might ask Fady to comment on in the course of a regulatory review, who gets involved in making these decisions because it may not always be obvious to those on this call.

Yes. In assessing these things, there are more than one division of the FDA that's involved, not just the cardiorenal division, which generally reviews protocols and efficacy and safety of clinical trials. But also if a question about whether REMS are or are not necessary the division of risk management gets involved, they can often have a very different view than the division of cardiology. In fact, you can read our publicly released documents around the approval of aficamten and see such a discussion between the division and the division risk management. So it's hard to know what you'll see from a protocol and how that ultimately translates into REMS or not a REMS and what the structure of it will be. And I think we probably should wait until we see data before we have that discussion again.

Yes. I might ask Steve also to weigh in here.

I just wanted to add from a clinician's perspective, it's not that echoes are in themselves necessarily burdensome or not indicated in these patients. In fact, in the setting of obstructive HCM, if you speak to cardiologists, that's the tool that they go to in order to evaluate the effectiveness of any treatment. So I think that it is presumptuous to assume that you're going to take a patient with obstructive HCM and never get another echo on. It's the ability to be flexible as to when you need that echo and ultimately how many echoes that patient is going to require. And as Fady alluded to earlier on, what we're seeing in the clinic is that many patients are seeing their providers and exiting the titration phase with just 5 or 10 milligrams being sufficient. That's in the real world. And that's a similar story to what was seen with the EXPLORER-HCM clinical trial and what subsequently occurred with CAMZYOS in the real world, where lower doses were actually seen as being the required ultimate dose for patients. So you might imagine that patients in the current environment only need one or 2 echoes on an annual basis with MYQORZO. And it's hard to beat that, especially when you put in context the fact that those echos are already flexible in their requirement based on the REMS program that we have.

Hopefully, that helps. I think put succinctly, we do believe, again, as a pioneer and a leader in this space, as we will leverage real-world evidence, we're in a good position to ensure we continue to be the innovator in this space even as it may relate to frequency of echoes.

Your next question comes from the line of James Condulis with Stifel.

It's [ Mark ] on for James. A quick one from us on the nHCM launch. So do you think the kinetics or cadence of the nHCM rollout will follow the obstructive launch? Basically, is oHCM the right analog here for how we should be thinking about the overall nHCM uptake or trajectory? And then in general, do you expect anything with respect to the REMS or monitoring to change with the label expansion?

So before I turn it over to Andrew, I'll just underscore, if approved in nHCM, MYQORZO will be the first and only. And in that regard, there needs to be some education awareness, market development and other activities to occur even as we will be building on the base of already a strong business and launch momentum in oHCM. But then, Andrew, do you want to add anything to that?

Sure. So we've actually thought about this a good bit, done some research. And I guess the key finding is we do expect faster uptake for existing MYQORZO writers because they're familiar with MYQORZO, they've used it, they're familiar with the REMS, they're familiar with the dosing and the echo requirements. So we will expect faster uptake with a subset, and that subset is those that are kind of experienced CMI users.

You also asked about REMS, and maybe I'll ask Fady to comment on how we may be approaching REMS for the sNDA relating to nHCM.

Right. The things that you monitor in nHCM are the same things that you monitor for in oHCM. And as the patients have gone into FOREST, they essentially follow the same timing, the same cutoffs for whether they down titrate or they have to interrupt drug and things like that. So we would hope that there would be minimum changes to the way the REMS is currently implemented. But of course, that will require some discussion and negotiation with FDA.

Thanks.

Your next question comes from the line of Kripa Devarakonda with Truist Securities.

Hi. Thanks for taking the questions. This is Alex on for Kripa. We wanted to know ahead of the launches in the additional ex-U.S. markets next year, can you provide any color on the discussions that you've had with prescribers? And how would you classify the physician appetite for MYQORZO versus how much additional physician education may be needed to drive growth in the market?

Your question relates to Europe specifically?

Yes, specific to Europe.

Okay. Andrew, do you want to take that on as we are approaching launches sequentially country by country?

Certainly. So we've submitted every dossier in all the major countries in Europe. We're expecting, as we said, to launch in every major market. We spent more time on the major markets, think Italy, Spain, France, U.K., Germany, although we've certainly spent time on the Western European markets. We have teams in place in Europe, medical colleagues that are field-based. We have our general management teams, our marketing teams, we've done market research. So we're expecting uptake similar to what we see in Germany. Germany in 5 or 6 months for new-to-brand are market leaders and doing very well. You have to also remember that in Europe, there is not a REMS program associated with launch. There's not patient support. Once you get payer access, there generally isn't that much of a barrier from an access point of view. That's why you do negotiations. So it is a country-by-country launch. The price is lower, but we are expecting good uptake, and we are seeing from our research, physicians seeing a clear differentiator like we're seeing in Germany.

Thanks for the additional color.

Your next question comes from the line of Alethia Young with William Blair.

Congrats on all the progress with MYQORZO. I just wanted to dig a little bit more into how -- when we're thinking about kind of the opportunity, how broad it can be perhaps in the second half of the year, the benefit of potential first-line use and having that label. Just talk a little bit about how you think that will frame for doctors and also just ultimately then get to a broader label potentially nonobstructive. I mean do you think that's kind of what doctors are looking for as a one-stop shop answer perhaps?

Yes. So Andrew can comment on some of the market research that he has done in and around this area and what the addition of nHCM may mean both across o and nHCM. Andrew, please?

Sure. So you're saying the second half, are you referring to the fourth quarter? Or are you talking about next year? I just want to make sure I'm clear on your question.

Next year on nonobstructive, fourth quarter for first line.

I see. Okay. So for nonobstructive, as I mentioned, it's the same size of market overall as oHCM, although obviously, there's 2 players in the market today for a nonobstructive if we're approved, we would be the first and only. And from our research, yes, especially in the community, physicians are looking for more of a one-stop shop. They did talk about faster uptake. They did talk about having experience and with a dual indication, both for o and n to drive share. On the MAPLE side of things, we're not looking for a monotherapy or a first-line therapy. We're really looking to generate evidence from what is in the guidelines today and which most community cardiologists consider that metoprolol specific beta blocker really had been the standard of care and showing them the difference in data as well as educating patients that are taking metoprolol that there's potentially something better, assuming we get our -- that in the label and everything this year. So I think both of those are going to be a lift. Obviously, the nHCM is a much broader lift from a revenue opportunity. MAPLE, really just extends our differentiation, and I think gives us some good data to educate community cardiologists on. Thanks for the question.

Thank you.

Your next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Hi team. Thank you very much for all the updates. Maybe I would love to understand with MAPLE coming on to the label, how soon it could actually change the payers' views on actually removing the requirement of being on a beta blocker and making MYQORZO as the first choice and therefore, could increase the potential TAM of patients and uptake. We appreciate your color.

Sure. So certainly, as we hope the MAPLE data will be reflected in an expanded label, that's one step towards the objective that you mentioned. But payers may have their own agenda. And I'll ask Andrew to comment on what may factor into payer decisions, including as ultimately may be enabled by changes in guidelines.

Sure. We're not expecting nor are we pushing first line. Beta blockers are going to have a place. I think every prior auth criteria I'm aware of from a payer point of view, beta blocker use or prior beta blocker use is required. So we're not looking to change that. We're really looking to accelerate use of MYQORZO, we're looking to help inform guidelines. I think that will have a bigger influence both on community cardiology and perhaps payers over time. But it really just adds to the body of evidence. It really adds to a rationale for a community cardiologist to better understand the use of the CMI as compared to something they've been doing a long time. It helps inform guidelines, which then creates this greater demand. And that's really what we're after from a MAPLE point of view. MAPLE also allows us to then communicate to patients, which we don't do today about maybe what they're taking as a beta blocker today and there could be something better for them. So I think they are the kinds of things we think about strategically from a commercial point of view, but looking at first-line therapy is probably not a realistic thing in the next couple of years.

Still have meaningful voice in this conversation, of course. But what it may translate into is faster step edits time through beta blockers that's perhaps more practical in the near term.

Your next question comes from the line of Josh Brewer with RBC Capital Markets.

Joshua on for Leo Timashev here. I was wondering, how should we think about expectations for the HFpEF data for ulacamten in '27? And how do you plan to share those data across the cohorts?

Certainly. So obviously, this is early in the development program for ulacamten and HFpEF, and we're very interested in understanding in this first Phase II study, what that might look like from a PK and PD standpoint. Maybe I'll turn it over to Fady to speak about Cohort 1 and what we may be communicating.

Yes. I think in 2027, we will have data from Cohort 1. Cohort 1 is really a dose-finding exercise and understanding safety and tolerability. So the data from that may just be summarized in one of our calls as we describe progress. Ultimately, we always try to get those data out into the public domain, but we don't have a specific time line or plan for that.

Your next question comes from the line of Yanan Zhu with Wells Fargo.

The oHCM launch, now that you are getting close to the 50% goal for year-end in terms of new-to-brand share. I was wondering, looking into 2027, is there any expectations for this metric? And is there any reason why this couldn't be further increased substantially? So that's on the new-to-brand side of things. In terms of switching, could you give any color in terms of the percentage of prescriptions this quarter that are switching patients?

Sure. So I'll start and turn it over to Andrew. Obviously, it was already very bold statement we made earlier this year that we would be committing to a goal of north of 50% of new-to-brand share and at the same time, experiencing such significant category growth. Andrew, do you want to comment on what may be our objectives from this point forward?

Sure. So I mean we're very focused on the new-to-brand share of greater than 50%. I think a good leading indicator. If you look at the different segments, our share among the highest writers, what we call velocity accounts that was historically 80% of the business. We're pretty close to 50% already with that group. So I think that's a good leading indicator given that's the majority of the volume. So when you look into 2027, I think we're really going to be looking at establishing a stronger foothold, growing that 50 to beyond 50. But at the same time, that expanded prescriber base, leveraging MAPLE before ACACIA would come on, assuming ACACIA gets approved, that's really what we'll be focusing. We'll focus on continuing to build share in that core velocity accounts while expanding the markets to these naive prescribers, those that have started to prescribe increased depth, those that haven't, leverage MAPLE, leverage SEQUOIA to start to get experience. And then assuming ACACIA gets on board, then as I mentioned earlier, that kind of doubles the patient base for each one of these groups, and we will continue to look to expand prescribing there. So that's really kind of how we're thinking about 2027 beyond the successful launch we've had to date.

Any comments on the switching?

The switching, sorry. Yes, switching is mid-single digit. So it's not a major factor. It's not something we promote. It's not something we discuss. That's really between a physician and a patient. And it's not a major driver for us. It's, again, mid-single-digit percent of our overall patients came from switches.

Yes. And in terms of growing the category, you can expect more publications from more patients longer in the open-label extension study, FOREST. And as it relates to switching, there is a study underway that is an investigator-initiated study that may inform switching down the road.

Okay. Thanks for the color.

Your next question comes from the line of Jason Zemansky with Bank of America.

Congrats on a strong quarter. Maybe to connect a few dots here. You framed category growth at 3,000 new patients a quarter-to-date. I guess what do you see as the main hurdle to expanding the patient funnel before nHCM? Is it primarily expanding the prescriber base? Is it access? Is it patient activation? And when could we see the run rate inflect? Is this a 2027 event? Or is it nHCM the real catalyst?

Sure. So this is 4 years into this category. As you know, CAMZYOS preceded us and now with MYQORZO in this market, it's a reasonable ask when might we see an exponential inflection in that growth. So Andrew, do you want to comment on those things?

Sure. So I think in terms of uptake, I don't really see an impediment at launch. There's a pretty good prescriber base now. There are several thousand prescribers in the CMI category. We have over 1,000 prescribers and growing. We grow about 400 or so quarter-to-quarter. I think those groups were telling us, especially the centers of excellence, what we call these velocity accounts that they are kind of "warehousing patients" and there's patients that they have in mind. So I think you'll see several months of growth from that group. When you think about an inflection point, the inflection point is really going to be driven by this prescriber base. I think we've said this even before we launched where if you have -- I think historically, there were 700 physicians who are 80% of the market, and you're not going to get to a multibillion-dollar market because that few physicians can't treat enough patients to get to those levels of revenue. So we really need to continue as a category to expand those prescribers. ACACIA, again, as I mentioned, doubled their patient population. So I don't want to put a date on it, but I think that is the inflection point where you get enough of these expanded prescribers that have 3 or 4 patient seats, they've gained enough experience and they're at the point now where they feel comfortable having that conversation sooner with the patient and having that conversation and getting and treating themselves as compared to referring, the referring slows things down as well. So I think we'll do more work on when we see a change in the inflection point. But as Robert mentioned, the category has been in the market for 4-plus years. And it's been, as cardiology launches often go for several years, linear, but I do think we will see an inflection point. Hopefully, that answers your question.

But also to your question, in terms of headwinds and impediments, we've come a long way from the types of conversations we would have on these calls relating to REMS and differentiated REMS and whether that would itself be a major impediment. And what we're seeing already just in these relatively short few quarters since MYQORZO has been available is a significant expansion of the prescriber base both those that were low-volume prescribers as well as those that were never prescribers. And I do think that's underscoring how our positioning in this category has driven category growth and movement towards what could be preferential share of new scripts. So we're very encouraged by that, and that should hopefully continue.

Your next question comes from the line of Amine Chaherli with B. Riley Securities.

Congratulations on the quarter. This is Amine on for Mayank Mamtani. I had a question for Fady. ACACIA showed the strongest effect in patients with, I guess, higher NT-proBNP and preserved filling pressure physiology. You also put some real numbers behind that on the diastolic side. I guess how has that informed patient selection and dosing in AMBER-HFpEF? And with Cohort 1 completing enrollment this quarter, how should we think about what you would need to move ulacamten into a pivotal?

Yes. I guess when you look at the forest plot for ACACIA-HCM, the I wouldn't say there's any strong driver. I have to go back and look specifically at the NT-pro difference, but I don't think it's maybe as strong as you're stating. Of course, we know that higher NT-proBNPs generally imply greater filling pressures and larger left atrial size. Those things are positively impacted by cardiac myosin inhibitors in nHCM and certainly inform our patient selection for a trial like AMBER. So we've had NT-proBNP criteria in AMBER that we have [indiscernible]. So I think figuring out the right patient population in HFpEF is one of our goals. And you may see the Cohort 1 data pointing us in the same or a different direction. We'll adapt as we begin to hone in on where we think the MoA may be useful. But it is to a competitive advantage as we think about how best to design a study in HFpEF that we have the benefit of the ACACIA results given where there is a blurring of the lines in some respects between some of the patients who have an nHCM and where we're pointing to with ulacamten in HFpEF.

Your next question comes from the line of Serge Belanger with Needham.

Hi good evening. Maybe a question for Andrew. I may have missed this in your prepared comments, but just the level of switching that you saw this quarter from CAMZYOS to MYQORZO, whether it was stable and whether it's behind the downtick that they reported in CAMZYOS sales in the third quarter for -- in the U.S. last week.

Sure. The switching was not a significant part of the overall growth. It's mid-single digits. So for every 1,000 patients or so, maybe we're getting 40, 50, 60 switches that range. So it's not very many. It's not something we're going after strategically. We're not messaging it completely between a physician and a doctor. I can't comment, obviously, on BMS' earnings.

We have reached the end of the Q&A Session. I will now turn the call back to Robert Blum, CEO, for closing remarks.

Thank you, operator. And many thanks to all the participants on our call today. We thank you for your continued support and your interest in what we're doing. Obviously, we feel very strongly about a good quarter, Q3, and we're encouraged as to where this points us in the future. Operator, with that, we can now conclude the call.

This concludes today's call. Thank you for attending. You may now disconnect.