Cytokinetics, Incorporated (CYTK) Q2 2025 Earnings Call Transcript

Cytokinetics, Incorporated (NASDAQ: CYTK) Q2 2025 Earnings Call dated Aug. 07, 2025

Corporate Participants:

Diane Weiser — Senior Vice President, Corporate Aairs

Robert I. Blum — President and Chief Executive Officer

Andrew Callos — Executive Vice President, Chief Commercial Officer

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

Stuart Kupfer — Senior Vice President, Chief Medical Officer

Sung Lee — Executive Vice President, Chief Financial Officer

Analysts:

Gena Wang — Analyst

Akash Tewari — Analyst

Tessa Romero — Analyst

Salim Syed — Analyst

Cory Kasimov — Analyst

Unidentified Participant

Jason Butler — Analyst

James Condulis — Analyst

Leonid Timashev — Analyst

Joseph Pantginis — Analyst

Ashwani Verma — Analyst

Presentation:

Operator

Thank you for standing by. My name is Prilla, and I will be your conference operator today. Welcome to the Cytokinetics Q2 2025 Earnings Conference Call. This call is being recorded, and all participants are in the listen-only mode. After the speaker’s remarks, we will open the call to questions. [Operator Instructions] I would now like to turn the call over to Diane Weiser, Cytokinetics, Senior Vice President of Corporate Affairs. Please go ahead.

Diane Weiser — Senior Vice President, Corporate Aairs

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter, and recent development. Andrew Callos, EVP and Chief Commercial Officer, will address commercial readiness activities for Aficamten. Fady Malik, EVP of R&D, will provide updates related to the clinical development program and medical affairs activities for Aficamten. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates on the clinical development program for Omecamtiv Mecarbil and CK-586, which is now called Ulacamten. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the past quarter. And finally, Robert will provide closing comments, and review our expected key milestones for the remainder of 2025.

Please note that portions of the following discussion including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statement. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statement is contained in our SEC filings, including our current report regarding our second quarter 2025 financial results, filed on Form 8-K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call.

And now I will turn the call over to Robert.

Robert I. Blum — President and Chief Executive Officer

Thank you, Diane, and thanks to all for joining us on the call today. The first half of this year has been defined by solid progress, as we continue to deliver on key milestones that bring us closer to realizing our vision. A vision of being the leading muscle focused specialty biopharma company intent on meaningfully improving the lives of patients through global access to our innovative medicines. During the second quarter, we announced that the FDA extended our PDUFA date for the NDA for Aficamten for the treatment of patients with oHCM to December 26, 2025. Our late cycle review meeting has since been moved to September, consistent with the three-month PDUFA extension. We believe this timing should have no bearing on the approvability of Aficamten, and we look forward to that meeting with FDA as we expect will occur soon, and inform our next steps.

In the meantime, all activities expected alongside the FDA’s ongoing review process continue to timeline. For example, GCP inspections of clinical trial sites and also of Cytokinetics by FDA are now completed with no observations recorded. In addition, we’re maintaining a productive dialogue with FDA, and we’re answering questions to support their review of the NDA. Also during the quarter, we had a collaborative meeting with FDA on our submitted REMS program following their initial review.

Subsequent to the meeting, we promptly submitted an updated REMS package, and during or rather despite the extension to the PDUFA date, we remain confident in the US regulatory position of Aficamten, given the quality of our clinical data, perceived alignment on a REMS program, and ongoing collaborative dialogue with FDA. We also maintain strong conviction that the data behind Aficamten support its potential FDA approval, its distinct benefit, risk, and pharmaceutic profile, and potentially differentiated label, and risk mitigation profile as a potential new treatment option for patients with oHCM. At the same time, regulatory reviews for Aficamten continued during the second quarter in both Europe and in China.

In April, we received the day 120 list of questions from EMA regarding the MAA for Aficamten in Europe, and we’re on track to submit responses soon in accordance with the timeline agreed with the EMA. EMA inspections of clinical sites and of Cytokinetics have also been completed with the overall conclusion that the conduct of the Phase 3 trial was compliant with regulations and guidelines, and data are acceptable and reliable. We remain on track for potential approval by EMA in the first half of 2026, and we’re targeting Germany for our first potential launch following approval. We have also been working closely with Sanofi, our partner in China, to support the NDA review of Aficamten with the NMPA, and that’s on accelerated regulatory pathway for innovative therapies.

We look forward to the prospect of bringing Aficamten to patients in additional geographies, and we continue to expect potential approval in China in the second half of this year. Moreover, in the past few months our commercial launch readiness activities have advanced with increased intensity and focus, and we’re taking advantage of the extra time to further strengthen our commercial launch and our operational strategies in the US. As Andrew will elaborate, key progress areas in the second quarter include recruiting a world class US sales force, fine tuning out patient centric treatment experience, and engaging key payers, and also other important stakeholders.

During the quarter we also made important progress in our ongoing clinical trials program for Aficamten. Notably, we announced positive topline results from MAPLE-HCM. We look forward to expanding on these results and their implications for what standard of care treatment may look like in oHCM following the presentation of the primary results at the upcoming European Society of Cardiology Congress to occur later this month.

We also continued conducting ACACIA-HCM, the pivotal phase 3 clinical trial in nHCM, which is now fully enrolled, and towards our expected topline readout in the first half of next year. nHCM represents an area of significant unmet need, and it’s growing within the overall HCM population, with no approved treatment options that address the underlying disease. Following the first potential approval in oHCM, nHCM represents a clear opportunity for Aficamten and innovation. Beyond Aficamten in Q2, we continue to advance patient enrollment in COMET-HF and also in AMBER-HFpEF. Our two later stage clinical trials evaluating Omecamtiv Mecarbil and CK-586, now called Ulacamten respectively.

Each trial addresses a different form of advanced heart failure, and these programs are central to our mission of delivering new medicines to patients suffering from diseases of cardiac muscle dysfunction, and also addressing the high unmet needs in heart failure, as we progress our specialty cardiology franchise forward. In summary, in the past quarter we made important progress across regulatory, commercial readiness, and also clinical development priorities, and we’re building momentum as we approach important milestones expected to occur in the second half of 2025.

With that, I’ll turn the call over to Andrew please.

Andrew Callos — Executive Vice President, Chief Commercial Officer

Thanks Robert. With the PDUFA data extension we adjusted our plans and are leveraging the extra time to finalize US commercial launch readiness activities, as well as refine the implementation of our promotional campaign and patient support program. Recently a key focus has been the hiring of our US sales force. After our highly successful virtual recruiting event in April, we received over 8,800 applications, and proceeded to hire a very experienced cardiovascular sales team with nearly all territories now filled. This exceptional level of interest in joining Cytokinetics has provided a deep and experienced talent pool enabling us to be highly selective in assembling a best-in-class sales team.

We have now hired sales professionals who have existing relationships with cardiologists, and possess deep therapeutic and industry expertise, positioning us to execute a highly impactful launch. Overall, our new sales colleagues have over 21 years of industry experience and an average of 14 years of cardiovascular experience. We expect to have the sales force on board and trained in Q4 so they’re ready for an early Q1 2026 US launch of Aficamten. Additionally, during the quarter we also made progress in optimizing our distribution network of specialty pharmacies and distributors. This infrastructure will be key in delivering a high-quality patient centric experience for both patients and providers alike.

We also advanced the development of our bespoke patient support program. Taken together, we have a goal to create an integrated, simple, and patient centric treatment and assistance experience across all touch point both for HCPs and their patients. As we approach potential approval later this year and commercialization, we remain focused and driven by the compelling unmet need. We believe that approximately 80% of eligible obstructive HCM patients will be treatment naive relative to a cardiac myosin inhibitor, so symptomatic oHCM patients naive to CMIs and primarily in specialty centers for HCM represent an entry point for Aficamten.

Our launch strategy is to expand the market, ensure more cardiologists are comfortable with Aficamten and more patients can potentially benefit from this new therapy. Importantly, according to our market research, nearly 80% of HCPs polled in ACM specialized centers are familiar with Aficamten on a native basis, giving us a strong starting point for initial engagements from which we expect to grow market adoption and to expand to community cardiology. Recently, market research findings that incorporated a target product profile based on MAPLE-HCM resulted in further support, likely expanding prescribing beyond HCM specialized centers. Our promotional launch campaign for both HCP and patients, which are currently in final market research testing, and refinement, are designed to evolve in step with our market positioning in key areas of differentiation.

We believe that given the differentiated profile of Aficamten, these messages will resonate and contribute both to commercial launch as well as category preference. Payer engagement also remains a priority, and in the second quarter we continue to educate payers on the results from SEQUOIA-HCM along with the clinical and economic burden of HCM. We also began building foundational health economics and outcomes research models around budget impact, cost effectiveness, and cost comparisons to support both US and ex US payer requirements as we approach potential regulatory approval in key US and EU geographies. Specifically in Europe, we were making meaningful progress for commercial readiness.

In the second quarter we added to our EU commercial team, our leadership team, and continued dossiers preparation for 2026 submissions to multiple HTAs and progress launch readiness across multiple countries, with a focus on our first potential commercial launch in Germany during the first half of 2026. Overall, I am pleased with where we position relative to the potential upcoming approval of Aficamten.

With that, I’ll turn the call over to Fady to share updates on our ongoing clinical trials program, and medical affair activities for Aficamten.

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

Thanks Andrew. During the second quarter we were pleased to report positive topline results from MAPLE-HCM which demonstrated a statistically significant improvement in peak oxygen uptake from baseline to week 24 Aficamten compared to the standard of care beta-blocker Metoprolol. Safety and tolerability profile of Aficamten was also favorable in comparison to Metoprolol. MAPLE-HCM is the only trial comparing a cardiac myosin inhibitor head-to-head with a long-standing standard of care therapeutic approach of beta-adrenergic receptor blockade. As we recently announced, the full results from MAPLE-HCM will be presented in a hotline session on Saturday, August 30th at the European Society of Cardiology Congress in Madrid later this month.

A prespecified analysis from the trial on the effect of Aficamten versus Metoprolol on cardiac structure and function will also be presented on Sunday, August 31st. Until then, we can’t elaborate on the topline results, but we look forward to sharing much more detail in a few weeks. Why are these data important? MAPLE-HCM reads not only on the treatment effect and safety of Aficamten compared to Metoprolol, but also on the impact of Metoprolol itself on exercise performance gradients, symptoms, and biomarkers. As you’ll see when the results are presented at ESC, we believe these results may lead to their incorporation into treatment guidelines, and may lead to changes in standard of care treatment algorithms and obstructive HCM.

We also plan to share other data and analyses of interest at ESC, including a late breaking clinical trial presentation on the incidence, and impact of atrial fibrillation in patients with oHCM via an integrated analysis of REDWOOD-HCM, SEQUOIA-HCM, and FOREST-HCM. Atrial fibrillation has been an emerging topic of conversation around the safety of cardiac myosin inhibitors, but speculation as to whether adverse events of atrial fibrillation are disease specific, or treatment dependent. As we’ve previously shared, in completed studies of Aficamten, we’ve observed no difference in the rates of atrial fibrillation between placebo and Aficamten and in the open label extension trial FOREST-HCM, the incidents remain similar to historical data.

We’re looking forward to sharing these data, that we believe reinforce a consistent safety profile for Aficamten in patients with oHCM. NEFC[Phonetic]

Will also have an oral presentation on longer term follow up of patients treated with Aficamten and FOREST-HCM with up to three years of data combined together into an updated integrated safety analysis of the clinical trials program for Aficamten and oHCM inclusive of MAPLE-HCM. In totality, we expect the data presented at ESC will importantly expand on the safety and longer-term effects of Aficamten in patients with oHCM.

Moving on to non-obstructive HCM. During the quarter we continued conduct of ACACIA-HCM pivotal phase 3 clinical trial of Aficamten in non-obstructive HCM. As we previously communicated, ACACIA completed patient enrollment ahead of schedule earlier this year, and in fact exceeded our original target to randomize and randomize a total of 516 patient — participants. During the second quarter we reviewed the emerging safety data from ACACIA-HCM with the Data Monitoring Committee which recommended continuing the trial without any changes to the protocol or study conduct. We expect to be able to share topline results of the primary cohort from ACACIA-HCM excluding Japan in the first half of 2026. Speaking of Japan, we recently dosed the first patient in the Japan cohort of ACACIA-HCM, and our partner buyer opened to enrollment CAMELLIA-HCM, a phase 3 clinical trial in Japanese patients with obstructive HCM, a trial which is intended to support potential marketing authorization in Japan.

Such a ongoing clinical trials of Aficamten during the second quarter, we made progress enrolling CEDAR-HCM which is evaluating Aficamten pediatric obstructive HCM. The trial remains on track to complete enrollment of its adolescent cohort in the second half of this year. Finally, in addition to progress in our clinical development programs during the quarter our field medical affairs teams engaged in nearly 600 USHCP interactions including over 200 HCM KOL, as well as over 50 European KOLs. Team also attended key payer conferences including Asembia, AMCP, and regional AMCP meetings to actively engage with national and regional payers.

And I’ll turn it over to Stuart to provide updates on our other late-stage development programs.

Stuart Kupfer — Senior Vice President, Chief Medical Officer

Thanks, Fady. First, we continued start-up activities and enrollment of COMET-HF, the confirmatory phase 3 clinical trial of Omecamtiv Mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction less than 30%. During the quarter, our first sites in Europe came online, and we continued expanding site activations in the US, both of which are driving progress in enrollment. We expect to continue enrolling COMET-HF through this year, and to complete enrollment in 2026. Second, as we announced in today’s press release, we received approval from the INN Program of the World Health Organization for Ulacamten to be used as a Nonproprietary Name for CK-586.

During the second quarter, we continued conduct of AMBER-HFpEF, the phase 2 clinical trial of Ulacamten in patients with symptomatic heart failure with preserved ejection fraction of at least 60%. Enrollment in the first cohort is progressing, and we’re pleased by the progress we’ve made in activating new clinical trial sites, and in engaging investigators in this important trial. Overall, we’re encouraged by the clinical trials progress of both of these later stage pipeline programs, which represent the next strategic pillars in advancing our specialty cardiology franchise. Despite the advances in heart failure care over the years, a substantial unmet need persists across the spectrum of the disease, and one that we believe our potential medicine may impact.

With that, I’ll pass it to Sung.

Sung Lee — Executive Vice President, Chief Financial Officer

Thanks Stuart. We’re pleased to report our second quarter of 2025 financial results. Starting with the balance sheet, we finished the second quarter with approximately $1.04 billion in cash, cash equivalents, and investments compared to $1.09 billion at the end of the first quarter of 2025. In the second quarter, we exercised our option on the Tranche 4 loan provided by Royalty Pharma and received proceeds of $75 million. We have an option to draw $100 million on the Tranche 5 loan prior to November 25th of this year. R&D expenses for the second quarter were $112.6 million compared to $79.6 million for the same period in 2024.

The increase was primarily due to advancing our clinical trials, higher personnel-related costs, and medical affairs related activities. G&A expenses for the second quarter of 2025 were $65.7 million compared to $50.8 million for the same period in 2024. The increase was primarily due to investments toward commercial readiness, and higher personnel-related costs. Net loss for the second quarter of 2025 was $134.4 million, or $1.12 per share, compared to a net loss of $143.3 million or $1.31 per share for the same period in 2024.

Turning to our financial guidance, we are maintaining our full year 2025 financial guidance with GAAP operating expense expected to be between $670 million and $710 million. Stock based compensation that is included in GAAP operating expense is expected to be between $110 million and $120 million. Excluding stock-based compensation from GAAP operating expense, results in a range of $550 million to $600 million. We continue to monitor the pace of our commercial readiness investments as we move closer to the PDUFA date for Aficamten, and we will update you accordingly. With our current balance sheet and access to additional capital, we are well positioned to fund the potential launch of Aficamten in the US later this year and continue to advance our pipeline.

With that, I’ll hand it back to. Robert

Robert I. Blum — President and Chief Executive Officer

Thank you Sung. So midway through 2025 I’m pleased with the progress we’ve made in the position we are in, ahead of a very important second half of the year. As we approach a significant inflection point, one that has been more than 25 years in the making, our company stands at the cusp of transformative growth. This moment reflects the culmination of decades of scientific innovation, strategic investment in R&D, and a steadfast commitment to delivering potentially meaningful therapies to patients in need. None of this would be possible without the dedication of our teams across the organization whose tireless work is propelling us towards these long-anticipated milestones.

With a strong foundation, a clear vision, and the right people in place, we’re poised to unlock substantial value for patients and shareholders, ushering in the next chapter of maturation as a fully integrated, high impact leader in specialty biopharma. Now, I’ll recap our upcoming milestones. For Aficamten, we expect to advance NDA review activities with FDA to support the potential US approval of Aficamten in the second half of this year. We expect to advance go to market strategies and to continue launch preparations for Aficamten in the United States in the second half of this year.

We expect to continue go to market planning in Germany, and expand commercial readiness activities throughout Europe in 2025 in preparation for the potential approval by the EMA in the first half of 2026. We expect to coordinate with Sanofi to support the potential approval of Aficamten in China pending approval by the NMPA, and we expect to present primary results from MAPLE-HCM later this month at ESC. We expect to report topline results from the primary cohort of ACACIA-HCM in the first half of 2026, while we continue enrolling the Japan cohort of ACACIA-HCM in 2025, and we expect to complete enrollment of the adolescent cohort in CEDAR-HCM in the second half of this year.

Omecamtiv Mecarbil, we expect to continue patient enrollment in COMET-HF throughout 2025 to enable completion of enrollment in 2026. For Ulacamten, we expect to complete enrollment of the first two patient cohorts in AMBER-HFpEF in the second half of this year, and finally for preclinical development and our ongoing research we expect to continue ongoing preclinical development and research activities directed to additional muscle biology focused programs.

Operator with that we can now open up the call to questions, please.

Questions and Answers:

Operator

Thank you. We will now begin the question-and-answer session. [Operator Instructions] With that our first question comes from the line of Gena Wang with Barclays, please go ahead.

Robert I. Blum

Hello Gena.

Gena Wang

Hey, thank you for taking my question. So, I have so many. Okay. But I will limit my question to one that’s regarding the ESC update. So, you did mention the MAPLE data could be potentially guideline change. Can you elaborate a little bit? Like what kind of magnitude of benefit like you are looking for? What are the key data points we should be focusing on, and what kind of a magnitude benefit the payer or physician are willing to use first line or switch those patients on beta-blockers to Aficamten.

Robert I. Blum

So obviously it’s difficult to answer your question until you have the data that we have, but I’ll ask Fady to do his best.

Fady I. Malik

I see it. Yeah. I think the data this is really one of the few comparative efficacy trials that’s conducted in cardiology and when the data themselves will present a picture not only of the difference between the two, but what is the absolute benefit of each of the two drugs themselves compared to baseline when these patients start the drug? Right now, cardiac myosin inhibitors are thought of as last line of treatment after you fail everything else. And I think when we see the data from MAPLE-HCM, that conversation will be revisited and hopefully Its guidelines as well will be updated to reflect, what we have already announced the superiority of Aficamten versus the Metoprolol and exercise tolerance. But I think we’ll just have to wait to be able to expand on that once the data are out.

Gena Wang

Thank you.

Robert I. Blum

Thank you, Gena.

Operator

And your next question comes from the line of Akash Tewari with Jefferies. Please go ahead.

Akash Tewari

Hey, thanks so much[Speech Overlap]. So, hey. Hey, how’s it going? So, look, it looks increasingly likely that you’re going to get the Camzyos[Phonetic] ODYSSEY data at ESC. What are the two or three things’ investors should be looking at in that data that would support, the team’s hypothesis that ACACIA will be successful where Camzyos wasn’t, and also would support a clear exposure response relationship in this population. Thank you.

Robert I. Blum

Yeah. So, I’ll take a stab at that and maybe ask Fady to add. I think it’s very important to distinguish between that which is related to clinical trial conduct and that which is related to potential mechanism of action as translates to that patient population. Clearly, with ACACIA, we took what we believe to be an optimized dosing regimen that was verified in a Phase 2 study and took that into a Phase 3 trial where we elected to proceed without altering a lot of other things. We took a dose optimization regimen, we took a population, we focus to centers where we already had experience. And obviously here at Cytokinetics we have an expert team of HCM experts that have been both academic and industry trained in order to be able to ensure that patients met the criteria.

The kinds of things that we’ll be focused on is related to from a study conduct standpoint and operations. How much might there have been a change between the Phase 2 and the Phase 3 study for mavacamten, and how much might that have read on the outcome in Phase 3 versus where we think we’ve been quite linear in focus one to the next.

Fady, anything you want to add?

Fady I. Malik

I just might add that, when you look see the ODYSSEY data and we see the ODYSSEY data, we haven’t seen them yet. The question will be whether the trial didn’t meet its primary endpoint because of specific features of mavacamten or trial conduct versus, mechanism of action and I think ultimately that is what will provide some confidence in terms of ACACIA’s potential success. But I think as Robert mentioned, we believe strongly in ACACIA success just based on the strength of the Phase 2 data we generated and the fact that, ACACIA is being conducted in a manner that was very consistent with the way we conducted Phase 2.

Robert I. Blum

Thank you, Akash.

Operator

And your next question comes from the line of Tessa Romero with J P Morgan. Please go ahead.

Tessa Romero

Hi, good afternoon, Robert and team, thanks so much for taking our question. So, what does an ideal label look like for Aficamten and obstructive HCM here? And Robert, can you just double click on any specifics you can give us on the updated REMS that it sounds like you submitted, versus the original one and how these updates track to your expectations for a differentiated REMs? Thank you.

Robert I. Blum

Yes. So, there’s a lot in that question that I cannot unpack, given that we are in ongoing conversations with FDA. But I think what I can say is that an ideal label for Aficamten is one that tracks with its engineered properties and the way it’s been studied. And both are, we believe, enabling of differentiation as could be supportive of our expected profile. We designed into Aficamten features that Fady has spoken of often, and we’ve studied Aficamten in ways that we believe elaborate on how those features read on benefit risk.

And, the data from our Phase 2 and Phase 3 studies and also as further substantiated in the open label extension are supportive of what we’ve argued would be a potential differentiated program in the clinical setting for patients, but also for physicians. I might ask Andrew, our Chief Commercial Officer, to speak to how his market research has been pointing to the unmet need, and where we believe a differentiated label could support our expectations and aspirations.

Andrew Callos

Sure, Robert. So, I think you addressed well that, differentiated label really would reflect the results of the clinical trial and the properties of Aficamten in terms of market research. I think what we’ve seen in our research is if the REMS and the label do reflect the properties and the study, that we would be expecting good uptake at the centers of excellence where most of the prescribing is occurring now. There’s already, as I mentioned in my remarks earlier, there’s a lot of 80% plus of physicians in those centers who are aware of Aficamten. So very, very high awareness, even before we come to market, that expansion into community cardiology and general cardiology supported by that differentiation, further supported by MAPLE.

That’s what we’re finding in our market research, leading to a preference here, even adjusted for overstatement in our market research. So ultimately, we have to wait to see what that label and REMs look like from the FDA. But we’re pretty bullish given those comments.

Robert I. Blum

Thank You, Andrew. Thank you, Tessa.

Operator

And your next question comes from the line of Salim Syed with Mizuho. Please go ahead.

Salim Syed

Hey guys. Good afternoon. Thanks for the question. I guess one for us on the oHCM late cycle meeting. So, Robert, what exactly are you planning to learn or discuss in that September late cycle meeting? And just can you remind us how much of the REMS negotiation here actually happens post the late cycle meeting? Actually, during the label negotiations themselves. Thank you.

Robert I. Blum

Salim, very good questions. I’m not sure I can answer them to your full satisfaction simply because. So much has already been discussed between Cytokinetics and FDA. I would hope that come the late cycle meeting we’re learning that everything we are assuming continues to be tracking towards potential approval, and that there’s nothing new that gets introduced. But as far as the activities that have occurred, we believe we’ve addressed them without a lot of difference or distance between what FDA might be interested in and what we could provide with supportive evidence. Case in point, the REMS, FDA and Cytokinetics convened a meeting to discuss the REMS promptly after we submitted one. And the conversation was a very fruitful one.

We were able to turn around very quickly, revisions that we believe were responsive to FDA’s interest. And as such, I would hope that at a late cycle meeting we get validation that we’re all good to go. But this is somewhat unchartered territory with regard to a REMS conversation. And it may be that we learn something new. I hope not. But we’re very much in a position where we think we’re aligned together with FDA on what it’s interested in. And to that point it was anticipated very nicely by Cytokinetics, our colleagues here, such that when we heard from FDA that they did in fact want a REMS, we were ready to submit one right afterwards.

So, I guess in that regard, to answer your question at the late cycle meeting, I’d like to learn that we’re proceeding to final label conversations and that we’re expecting no other new news.

Salim Syed

Okay, got it. Thank you very much.

Robert I. Blum

Thank you.

Operator

And your next question comes from the line of Cory Kasimov with Evercore ISI, please go ahead.

Robert I. Blum

Hello, Cory.

Cory Kasimov

Hey, Robert. Good afternoon. So, I wanted to ask go back to ACACIA and wondering if you could walk us through how drug interruptions and discontinuation protocols differ versus ODYSSEY. I guess I’m particularly curious about how ACACIA differs from the four-week dose Interruption that is necessary if LVEF drops below 50%, as was the case in ODYSSEY, and maybe you can point out any other significant design differences you would. Maybe call out between the two studies. Thank you.

Robert I. Blum

Yeah. So, the design differences are significant, it would appear, much like there are design differences in other studies. And again, how ACACIA is conducted in accordance with that design may ultimately prove to matter. So I’ll ask Fady to comment. Now that we have ODYSSEY as published in terms of the design, and we know what we’re doing with ACACIA, I think it’s good to highlight some of those distinctions.

Fady I. Malik

Yeah. Hi, Cory, I think, with regards to what happens when LVEF falls below 50%, in the non-obstructive, you don’t have a left ventricular outflow tract gradient to buffer you, for that you really. I think of what we do in oHCM is we’re tolerating a minimum effective dose, whereas in nHCM we’re tolerating the maximum tolerated dose, which is quite a different concept. And so, with EFs less than 50%, it’s nice that with ACACIA, primarily, as long as the EF is above 40%, patients can just down titrate drug there is no treatment interruption.

For an EF below 40 they do interrupt drug for about a week, and they would resume drug after that at a lower dose. So that’s a substantial difference, I think, from ODYSSEY, where patients have to interrupt drug for four weeks and restart and leads to a lot of disruption, if you will, in treatment. Another aspect of this is that we tested all the doses, if you will, in Phase 2, 5, 10, 15 and 20. And primarily the 15 and 20 milligram doses were the ones that were most commonly used. We know that In ODYSSEY the VMS introduced doses of 1 milligram and 2.5 milligrams.

Patients could down titrate to those doses. And ultimately, we don’t know if the dose density, if you will, is in the range that is known to be is potentially effective. And in ACACIA, we are testing doses where at least we believe we saw meaningful clinical benefit in the Phase 2 and as we’re trying now to replicate in Phase 3. So, I think, with regard to dosing, those are an ES of less than 50%. Those are the major differences. There are some differences in the entry criteria with regards to thresholds, upper limit for peak VO2 or NT-proBNP.

We, have a group here that is highly knowledgeable about HCM and really look at every patient echo that came into the study and so, trying to maximize, if you will, the appropriateness of the patient population. So, I think there is a number of differences there. And ultimately when we see the ODYSSEY data, we can ask ourselves how, which of them might be impactful in terms of of ACACIA’s success down the road.

Cory Kasimov

That’s very helpful. Appreciate it.

Fady I. Malik

Thanks, Cory.

Operator

And your next question comes from the line of Yasmeen Rahimi with Piper Sandler. Please go ahead.

Unidentified Participant

Hi, this is Emma on for Yas. Thank you for taking our question. I guess mine is what are your expectations in regards to potential REM differences between the US and EU and implications of that. Thank you.

Robert I. Blum

So, understanding that in the EU there is not the same sort of mechanism for a REMS, it would otherwise be addressed in other means. I don’t think there’s going to be altogether so many differences taken collectively in light of the fact that we conducted an international study, and the conversations we’re having with FDA and EMA are tracking very similarly. So, while there’s not a formal REMS in Europe, we should expect, and we are anticipating labels that are encompassing from a risk mitigation drug, drug interaction, pharmacology, and otherwise dosing an indication that there’s going to be so much more in common than necessarily would be different.

Unidentified Participant

Thank you.

Robert I. Blum

Thank you.

Operator

And your next question comes from the line of David Lebowitz with Citi. Please go ahead.

Robert I. Blum

Hello, David.

Unidentified Participant

Hi there. Thanks for taking our question. This is Ikely[Phonetic] on for David Lebowitz, wanted to ask about the larger market opportunity and non-obstructive HCM which we all know is there. Presumably you will need to reach more community doctors is our understanding upon that launch. So, thinking about that, how much larger do you think your sales force is going to be if and when that time comes? Thank you.

Robert I. Blum

Perhaps I’ll ask Fady and maybe Stuart if he wants to add with regard to how nHCM is treated and where. And then maybe ask Andrew also to add his perspective to that, especially as it might ultimately read on the size of our commercial group.

Fady I. Malik

Yeah. nHCM is really like the tip of the iceberg. I think we’re seeing, we see nHCM cases and clinics that are more severe, more obvious on echocardiograms and things. But it’s a disease that is difficult to diagnose. And maybe Stuart, I’ll ask you to comment on, what are the challenges with recognizing it and why, it might be far more prevalent throughout the community than we recognize.

Stuart Kupfer

Well, I think as you commented previously, of course, the non-obstructive patients don’t have gradients. And, so that’s one sort of key criterion that makes it more difficult to diagnose. And there are a number of features that make the sort of the HCM patients sort of appear like patients with heart failure with preserved ejection fraction. And so, it does take some discrimination, to identify these patients without sort of assuming they’re patients with heart failure with preserved ejection fraction.

I think another important factor is unlike obstructive HCM, where there are some more specific guidelines referring to available treatments and we can debate about the evidence base to support those treatments, but there’s sort of even more, less guidance around treatments in non-obstructive HCM. So, clear the medical need is even higher. And I think that maybe Andrew can address that.

Andrew Callos

Sure. So, when you look at nHCM versus oHCM, the initial physician target list won’t be any different. So, we’re not expecting to increase our sales[Phonetic] force at the launch of nHCM if a case is positive and it gets approved by regulatory authorities. The way we target and look at the cardiologists who are engaged in HCM, both diagnosis and treatment is through claims data and ICD-10 codes. And the physicians we’re calling on for oHCM treat both nHCM and oHCM. And there’s a really large overlap with those subspecialties who are advanced heart failure cardiologists as well who treat HCM.

So around 10,000 who are 80% of the HCM, diagnosis and treatment is where we’re focused. If we learn more about nHCM, which right now it’s about a 50%, 50% split between the size of the oHCM patient population and the nHCM population, then we’ll certainly expand sales force as needed. But at launch, we’re not expecting it.

Operator

Thank you. And your next question comes from the line of Paul Choi with Goldman Sachs. Please go ahead.

Unidentified Participant

Hi, this is Kahlil[Indecipherable] calling in for Paul. Thank you so much for taking our question since there’s been a lot of questions about regulatory interactions. So, I guess we’ll ask about Aficamten and commercial. I suppose, given some other launches in cardiology recently, there’s been this focus on patient access. So, we’re just curious whether you had any strategies in place to differentiate against perhaps chemxios on patient access, whether that be, Camzyos age patients or Medicare patients. That’ll be helpful for us. Thank you so much.

Robert I. Blum

Yeah. This is an area where I think Cytokinetics has been laser focused already for quite some time, and Andrew and his expert team have been very diligently attending to this from a market development standpoint and what we’ll read on Aficamten. So, I’ll ask him to comment.

Andrew Callos

Yeah. Sure. So, as Robert had mentioned, we’ve had our account manager, field personnel, talking to payers for quite some time. We’ve hit or have interacted with every major payer. When we look at commercial, we expect to have kind of parity of access in commercial. When we look at Medicare, we expect to have parity and access in Medicare. So, the really, the strategy really is to have the same access and really have differentiation and support, be the differentiators. And when you look at patient support, we are designing our patient support program around this patient population and the journey they go through and the support that’s needed, including REMs.

When you look at the kinds of programs we’ll support, we certainly will have for eligible patients. commercial patients will have co pay assistance. What patient assistance programs for those who are uninsured or underinsured. So, I think you’ll find that the patient support programs, the access, the affordability are really targeted to be at par, if not slightly differentiated positively from where market[Phonetic] is. The differentiation again is really going to be focused on the clinical data, the REMs and the patient experience.

Unidentified Participant

Got it. Thank you very much.

Operator

And your next question comes from the line of Jason Butler with Citizens JMP. Please go ahead.

Jason Butler

Hi. Thanks for taking the question. Just I guess an extension of that. When you think about the expansion into Europe and the commercial work that you’re doing there, can you maybe speak, to some of the similarities and differences of what needs to be done to get ready for the European launch.

Robert I. Blum

Yeah. So, understand our focus is on the US launch, but we’re taking measured and deliberate steps in Europe to prepare for what would hopefully be a launch in the first half of the year with focus to Germany and then from there. So, Andrew, in leading those activities with colleagues already domiciled in Europe, are looking at this country by country and where reimbursement is going to be ungating of some significant investment. But I’ll ask him to describe more in detail how we’re thinking about this.

Andrew Callos

Sure. I think the key thing is obvious is it’s a country-by-country launch in Europe. You get EMA for most of Europe, excludes Switzerland in the UK for now, but you get EMA approval. So, you get uniform approval across the majority of the European countries and then you have to get reimbursement on a country-by-country basis, you have free pricing in Germany for six months while you’re negotiating price. So, that is a key difference in terms of launch by launch and the government is the main payer. You have to go through health technology assessments and assign pricing and reimbursement and then you launch.

So, beyond the regulatory gate, then you have a reimbursement gate. I think the other key difference is, once that reimbursement occurs, they’re usually occurring in focus centers of excellence, hospitals, specific cardiology. So, it’s more narrow, and focused prescribing generally in Europe than in the US and as Robert alluded to, Europe does not have a REMS program. Risk management is typically handled as part of labeling. So, I think they’re the key differences. But fundamentally in terms of the differentiation in Aficamten from the clinical trial and how we communicate that, once we get that access is that’s going to be very similar.

But again, on a country-by-country basis, most of our spend does not occur on a country-by-country basis until reimbursement occurs. So, we have gated and we’re building Europe slowly where the US will launch all at once, hopefully. And end of this year, early next year, Europe will launch really over about two to two and a half years based on that reimbursement timing.

Robert I. Blum

Hopefully we’re being good students of how companies have gone to Europe, some who have done it more successfully, most who have not, frankly. And that’s where Sung, working with Andrew, working with others of our executives, are taking a very disciplined, deliberate approach to how we think about Europe, and doing so as is informed by de risking milestones.

Operator

Thank you. And your next question comes from the line of James Condulis with Stifel. Please go ahead.

James Condulis

Hey, thanks so much for taking my question, and congrats on all the progress. Maybe just a quick one on HFpEF. Curious. We’ll get those data like early next year and wondering if you can kind of frame out what a win looks like and kind of in that context wondering how important you think success in Phase 3 within non-obstructive is to kind of confirm any initial signals there just kind of given both are driven by diastolic dysfunction. Thanks so much.

Robert I. Blum

Yeah. Good questions, especially the linkage between what we’re doing in nHCM. As could read on HFpEF. I’ll ask Fady and Stuart both to comment please.

Fady I. Malik

Yeah. I mean I think the discussions we’ve had around ACACIA earlier are a good read on what we think will we hope to see in the AMBER. And I’ll ask Stuart maybe to draw the parallels between the two conditions, and how we think each one will be reinforcing of the other.

Stuart Kupfer

Yeah. Thank you for the question. And as Fady mentioned, the non-obstructive HCM patients do inform potential benefit, and these patients with HFpEF and hyper contractility. And the endpoints that we’re evaluating, our Phase 2 AMBER HFpEF trial will read on the potential benefit. We’re — we evaluating for symptomatic improvement looking at endpoints like KCCQ, NYHA class looking for improved, so improvements in symptoms, cardiac biomarkers like NT-proBNP and Troponin and of course evaluating echocardiographic parameters, looking for potential benefit in terms of diastolic function. These will all contribute to the profile of potential benefit that will inform whether we progress to Phase 3, and identifying dose or doses that will result in a favorable benefit risk profile.

So, again we’re encouraged by what we observe with non-obstructive HCM, and the benefit with benefits with Aficamten and the Phase 2 REDWOOD trial and the ongoing cohort that’s been evaluated in FOREST or open label extension. So those are some of the key findings that we’ll be looking for as well, as well as safety and tolerability.

James Condulis

Thanks.

Operator

And your next question, comes from the line of Leonid Timashev with RBC Capital Markets. Please go ahead.

Leonid Timashev

Hey, thanks for taking my question. I just wanted to ask as you approach commercialization how you’re thinking about the message that you’re going to lead with in HCM. I guess what I’m getting at is what do you think really drives physician and patient enthusiasm to use the drug? and Is it gradient which is readily checkable? Is it the symptomatic benefits? Is it cardiac function? You have a lot of data across a lot of these endpoints and obviously potential convenience advantages. I guess. What’s the messaging that you’re going to lead with to try to drive use? Thanks.

Robert I. Blum

Yeah. I think you probably can appreciate it. Not on an earnings call where we’re going to be communicating our messaging and our positioning with any kind of specifics, rather instead you should expect us to want to see the label and ultimately, we’ll be promoting to label in ways that we think will be to the advantage of adoption of Aficamten. But, as we’ve discussed in the way that we’ve designed Aficamten and the way we’ve studied it, we do believe there’s high levels of differentiation, and it would be reasonable for this being a next cardiac myosin inhibitor for us to want to be focused on how might we be able to grow the category and grow preferential share of the category for the benefit of more patients, more physicians, comfortable with cardiac myosin inhibitors.

So maybe with that as a bit of a backdrop, I’ll ask Andrew if there’s anything further, he might want to add.

Andrew Callos

Yeah. I mean to your point, we’re not going to get into what there are our messaging is, but generally once a product’s approved by the FDA, the physicians really want to understand and lead with the efficacy component, the balance of safety relative to that efficacy, and then in this instance then the REMs. So, we’ll communicate clearly the differentiation. We believe we have differentiation in each of those areas, as well as very, very differentiated positioning. But you’ll have to wait until we get our launch and approval and our label until that kind of gets unveiled. Thanks for the question.

Operator

All right, thank you. And your next question comes from the line Srikripa Devarakonda with Truist Securities. Please go ahead.

Unidentified Participant

Hi, this is Alex on for Kripa. Given that we might see approval in China as the first market, can you remind us of dynamics of the China market, and what type of cadence of revenue we can expect in the upcoming quarters? Thanks.

Robert I. Blum

Yeah. So, this is somewhat of an uncommon situation, isn’t it, that we might could expect an approval in China even before an approval in the United States. It’s not without precedent, but they are few and far between. With that said, we are working with Sanofi, our partner and maybe I’ll ask Andrew, he’s one of the leaders of that collaboration to speak to your question.

Andrew Callos

You asking about market sizing, and revenue. So, is that right?

Unidentified Participant

Yes. And the rate that we can expect adoption in the market.

Andrew Callos

So, like the US, China would be Aficamten would be second to market, like kind of like Europe, you need to get NRDL listing, National Reimbursed Drug Listing in China that use that it occurs on an annual basis, and you have to file by the end of June of a given year to have reimbursement the following January. So, likely the first period of time reimbursement would be through cash paying market versus say Mava having NRDL. So, I would imagine that the uptake would be slow at start. But it’s a large market as you can imagine.

There’s over 350,000 patients who are very concentrated into about 1,300 hospitals. Obviously, we have a very sophisticated multinational partner who knows that market extremely well. So, I won’t comment on the phasing, but I would only say that once reimbursement occurs, I would expect an acceleration, follow that National Drug Reimbursement. Hopefully that answers your question.

Unidentified Participant

Yeah. Thanks. And congrats on the progress.

Andrew Callos

Thank you.

Operator

And your next question comes from the line of Joe Pantginis with H.C. Wainwright. Please go ahead.

Joseph Pantginis

Hey everybody, Good afternoon.

Robert I. Blum

Hey Joe.

Joseph Pantginis

Thanks for taking the question. First, I guess maybe for Andrew, as you’re preparing with all your broad commercial preparations, what do you feel are some of the components that you’re required to do, but won’t necessarily need, but needed to go through the motions depending on how a potential REMS may or may not play out? And secondly for Stuart, as you’re looking at comment with the Company’s broad, very broad experience with Omecamtiv long term, how would you characterize the site excitement with regard to enrollment versus all the other Omecamtiv studies? Thanks.

Robert I. Blum

So the first question was a complicated one. I’m trying to make sure I understand it. Joe, your question is the kinds of things we prepared for that we might not need to do. Is that what I heard?

Joseph Pantginis

Correct. Based on how REMs may or may not play out?

Robert I. Blum

Yeah. So, we’re pretty clear minded on how this is evolving, and in frankly it’s quite aligned to the three meetings we had with FDA even before we submitted the NDA. Although you’ll remember we did not submit originally with a REMS. We had already anticipated what we thought mattered to FDA and we incorporated that into label and then FDA indicated it would in fact like to see a REMS. So, we were already prepared to execute on that in the form of a REMS. So, I don’t know that there’s much in the way of distance between what we expected and where we’re at, such that we had to prepare something that may not be relevant. I think we’ve got a pretty good idea as to where this is going.

With respect to your next question, maybe I’ll ask Stuart to comment on the level of investigator interest in comment.

Stuart Kupfer

Yeah. Thank you. Bottom line is there’s a lot of interest in COMET, and we’re very pleased to see that and for several reasons. One is recognition of very high need in these patients with heart failure and severely reduced ejection fraction. They really don’t have medical options before, on the road to end stage heart failure. So, they recognize that Omecamtiv Mecarbil is potential medical option to save off that outcome. Second, they’re very well aware of the results of GALACTIC, which of course was a positive trial. And in the subgroup of patients we’re targeting now in COMET, the treatment benefit was of large magnitude, risk reduction for, the heart failure outcome.

So, there’s appreciation that, because of the large sample size of the subgroup of patients and the results we observed in GALACTIC, there’s a high probability of success. And third, I think they’re very pleased to see we’re running a very streamlined trial without much burden on investigators and their staff. And so operationally it’s going to be an easier trial to conduct. So overall, a lot of enthusiasm for COMET.

Joseph Pantginis

Great. Appreciate the clarification and color, guys.

Stuart Kupfer

Thank you.

Operator

And your next question comes from the line of Jason Zemansky with Bank of America. Please go ahead.

Unidentified Participant

Hi, good afternoon, this is Jackie on for Jason. Thanks for taking your question, and congrats on the progress. So now that you’ve seen more of the MAPLE data, can you comment on your expectations for first line use? How receptive do you think prescribers and payers are likely to be, and how long do you think it’ll take before there can be appreciable uptake in this part of the market?

Robert I. Blum

Sure. So, I’ll start and I think Fady and Andrew can both respond from their respective viewpoints. What I will say is that. We conducted a study head-to-head of Aficamten versus Metoprolol. And I do believe it’ll raise some eyebrows as to what is currently guideline directed first line therapy. But maybe that shouldn’t be too surprising in retrospect because those guidelines were written absent, a randomized controlled study of Metoprolol in this population. So, this is building of a body of evidence that didn’t exist before. And for having done that, we do believe that Aficamten, and you’ll understand maybe why we believe this after you see the results, should be part of the conversation about what medicines to reach for in what order for the treatment of these patients.

Now granted, Metoprolol is a generic drug, and there’s ample experience with beta-blockers. But I do believe in Cytokinetics. Fashion. We’re doing rigorous clinical research to inform guidelines and the guidelines will hopefully take into consideration the way in which the study was robustly conducted and the fidelity of the results.

With that, I’ll ask Fady to speak to that, and maybe Andrew, if he wants to also comment on how that might ultimately get reflected and over what time frame and guidelines and how that may afform a adoption.

Fady I. Malik

Yeah. I mean, I think, it’s going to take a while before beta-blockers are displaced as first line treatment given the cost differential. But I think study like MAPLE-HCM will facilitate earlier movement and hopefully elevate Aficamten in the guidelines. So, it’s not seen as the last, line of therapy before surgery potentially, but instead is, seen on par with the other therapies that physicians can consider. And so, if patients are only modestly improved, they know that they have an alternative that they can move to more quickly, and with longer time we hope to be able to develop evidence that there are things beyond just symptom and function relief that Aficamten addresses that other therapies don’t given Aficamten targets, the underlying path of disease.

So, with that we someday may be able to show that, we reduce the progression of disease, and then it becomes, I think a much more important question as to which therapy to start. So, this is the beginning, I think of a sort of a longer run in terms of changing the standard of care in this.

Andrew Callos

Yeah. I would think. I mean our expectation is launch in the first several years after launch that first line therapy is likely not going to occur mainly because of payers. And Robert mentioned beta-blockers obviously are generic. But what we do expect to occur is, more patients being on an Aficamten than would have been otherwise without MAPLE. We expect the acceleration of an add on of Aficamten to a beta-blocker and maybe weaning off a beta-blocker after the start over time. So, I think those are the kinds of things you’ll see for the first several years.

If guidelines are updated and Aficamten is part of first line therapy then with broader use we could see a first line therapy. But again, I think that’s several years out. Thanks for the question.

Operator

Your next question comes from the line of Mayank Mamtani with B. Riley Securities. Please go ahead.

Unidentified Participant

Thanks for taking our question. This is William on for Mayank. I just wanted to circle back to ACACIA. Today you mainly focus on sort of the ODYSSEY and the Phase 2 to Phase 3 transition on how that supports potential positive results when that reads out next year. But I was also curious how new data from the MAPLE study also, from past SEQUOIA, how those may, that new data may support ACACIA and what specifically, specific endpoints you may, specifically can highlight that may support those claims and then also just in terms of REMs, how should we think about the REMs in oHCM, sort of to read through to non-obstructive HCM.

Should we think that those would be relatively the same or potentially differentiating just based on profiles? Thank you.

Robert I. Blum

Yeah. So, you’re asking us to speculate on some things that are pretty far down the road and obviously we can’t be considering claims. But the MAPLE study was conducted in a population of oHCM where echoes are very informative to how one approaches dose titration. ACACIA is conducted, absent that, in a very different population. So, I’ll ask Fady and Stuart to comment, but I can already suggest that we don’t think that there’s going to be a lot of translation from one to the other. Fady?

Fady I. Malik

Yeah. I think, you asked whether there’s anything we’ve learned in MAPLE or SEQUOIA that might inform ACACIA, and we’ve already published data from SEQUOIA that look at how Aficamten improves diastolic function. Relaxation of the heart, which is probably the primary mode by which patients with nHCM will receive treatment benefit since they don’t have a gradient to reduce. And, similarly you’ll see data presented on diastolic function in MAPLE at the ESC. That’s part of the late breaker that I described earlier. And so, I think both of these data sets will inform the fact that there is a meaningful pharmacologic effect that, we believe impacts the functioning of the heart in nHCM.

I think both of those studies are supportive. Then those analyses are supportive of ACACIA’s potential success. And as to the other questions, I agree it’s kind of a little too early to speculate on those, labeling or REMs, things like that. I don’t know if there’s anything you’d like to add, Stuart.

Stuart Kupfer

Well, the only thing I’ll add is the safety and tolerability profile we’ve observed in obstructive HCM, in SEQUOIA and the fact that Aficamten is a drug with a shallow exposure response profile, relatively short half life and, very quite stable PK profile. I think all that contributes to what we observed in obstructive HCM in terms of its tolerability and, expectation that will carry through to non-obstructive HCM.

Robert I. Blum

You didn’t ask this, but I’ll add in our Phase 2 REDWOOD Cohort 4, we saw very large magnitude effect changes that give us confidence that if that translates in Phase 3, we should anticipate a good outcome for ACACIA HCM. But also, and please don’t lose sight of the fact that those patients roll over into FOREST. And FOREST is an open label study. And later this year you’ll have a chance to see what we’re already seeing in patients who rolled into FOREST with nHCM. And that gives us confidence in what we can expect from ACACIA next year. So, we remain quite optimistic about ACACIA.

Unidentified Participant

Appreciate that. Thank you

Operator

All right, thank you. And your next question comes from the line of Serge Belanger with Needham and Company. Please go ahead.

Unidentified Participant

Hi, good afternoon. This is John on for Serge today. Thanks for squeezing in my question. Just want to touch back on with Omecamtiv and the common trial. It seems like you guys have been getting some positive feedback from investor — investigators and KOLs. Just wanted to gauge kind of how enrollment’s tracking relative to your internal expectations as you’re on your way to completing enrollment next year. Thanks.

Robert I. Blum

Stuart. You want to take that?

Stuart Kupfer

Sure, yeah. As we sort of indicated in our, in the call today in a press release, the common HF trial enrollment is on track. We plan to, this is an 1,800 patient trial, less than a fourth of the size of GALACTIC’s. So that’s certainly makes it easier in terms of the operational scope. However, this is a more severe patient population, so, we are targeting a smaller subgroup of patients with HFpEF. Having said that, the plan is still to complete enrollment by the end of next year. We have site activations, most of them complete in the US, and we’re on track for site activations in Europe as well. So, things are going according to plan.

Robert I. Blum

It’s important to note with this study is it’s not competing with a bunch of other studies for the same population. This is a population that we don’t believe is well served by existing standard of care or other investigational treatments. And instead, we’re building off a body of evidence where we’ve already seen in GALACTIC a profound treatment effect in these patients. And we just want to confirm that in this next trial. So that’s contributing, we believe, to momentum for the study.

Operator

All right, thank you. And your next question comes from the line of Roanna Ruiz with Leerink Partners. Please go ahead.

Unidentified Participant

Yep, thank you. This is Mazy on for Roanna. Just one from answer, obviously. So, from a cardiac myosin biology perspective, as you advance Aficamten and more of the HCM phenotypes and develop Ulacamten for HFpEF. With this distinct mechanism can you discuss the key differentiating factors in how these myosin inhibitors differ, and how they interact with sarcomere function?

Robert I. Blum

Sure. Nobody better than Fady Malik to answer that question.

Fady I. Malik

Well, so it’s really interesting, when we look at the myosin motor protein after 20 plus years, we’ve now identified three distinct binding sites for small molecule modulators of the protein. Aficamten binds in one place, Omecamtiv Mecarbil and mavacamten bind in another place and lastly the CK-586 or Ulacamten bind and even a third place. And each of them has distinct facts on how they impact motor function in the sarcomere. You can describe. I won’t really go into the details and specifics here, but those differences I think as we may be seeing in the clinic, lead to differences in their profiles.

And I think it’s still a little early to know exactly how they differ and which one may be preferred. But there are, I think differences that are emerging. Ulacamten we see potentially a more shallow decrease in ejection fraction, a more shallow PKPD curve than even Aficamten. And we think the reversibility of both compounds is not just a feature of the compound itself but also potentially, the mechanism where they bind. So, I’d say stay tuned. I hope to someday write a paper that describes all the various different biology and how it links to clinical.

Unidentified Participant

Thank you so much.

Robert I. Blum

Good question.

Operator

And your next question comes from the line of Ash Verma with UBS. Please go ahead.

Ashwani Verma

Oh hi. Thanks for taking my question. I wanted to ask like this late cycle meeting push out from June to September, is it as a result of your prior three-month PDUFA extension or is this a separate development which can now have a cascading effect on the PDUFA date? What I’m trying to understand is like does the September late cycle meeting give FDA enough of a runway to now finish up the wrap up activities on the review before the deadline? Thanks.

Robert I. Blum

Yes. So, as we said in the scripted comments, we believe that the shift in the late cycle meeting is consistent with the PDUFA date extension, and we don’t have any reason to think that there’s anything else here, and we believe that based on interactions we’ve been having in the meantime with FDA, that we should consider still this as a hopeful approval consistent with PDUFA date. No reason to believe otherwise.

Ashwani Verma

Great. Good to hear that, thanks.

Robert I. Blum

Thank you.

Operator

And I’m showing no further questions at this time, I would like to turn it back to the President and CEO, Robert Blum, for closing remarks.

Robert I. Blum

Thank you, operator, and thanks to all the participants on our call today. We appreciate your continued support. We appreciate your continued interest in Cytokinetics. Lots going on. And we think this mid-year check in is indicative of why we continue to be quite ambitious and hopeful, and planning for success with what we hope will be our first medicine to be potentially approved later this year and all that goes with it.

With that, operator, we can conclude the call. Thanks very much.

Operator

[Operator Closing Remarks]