Cytokinetics, Incorporated (CYTK) Earnings Call Transcript & Summary

Good day, everyone. My name is Leila, and I will be your conference operator today. At this time, I would like to welcome you to Cytokinetics conference call for the FDA approval of MYQORZO. [Operator Instructions]. At this time, I would 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 today's call to discuss the FDA approval of MYQORZO for symptomatic obstructive HCM. Today, I'm joined by my colleagues, Robert Blum, President and CEO, who will provide introductory remarks; Fady Malik, EVP of R&D, who will review the label, the REMS and the data that support the approval; and Andrew Callos, EVP and Chief Commercial Officer, who will discuss our U.S. commercial launch plans. Today's presentation is accompanied by slides, which are available to download within the webcast. Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements. Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings. We undertake no obligation to update any forward-looking statements after this call. With that, I'll turn the call over to Rob.

Thank you, Diane. At Cytokinetics, our mission is to bring forward new medicines to improve the health span of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. With today's news, we've taken an important step forward towards successfully realizing that mission. Today, the U.S. Food and Drug Administration approved aficamten for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms. Aficamten will be available under the brand name MYQORZO. This is indeed an important milestone, first and foremost, for the oHCM community that we serve and for which there is still a high unmet need. It's also a major achievement for Cytokinetics as we celebrate the approval of our first medicine, fulfilling our promise to patients to transform our science into medicines to make a meaningful impact on their lives. Today's accomplishment reflects years of dedication to rigorous research and development as well as diligent commercial planning, all underscored by our unwavering commitment to patients and a belief that our innovative science can positively change lives. I'd like to express my gratitude to the many people who made this possible, our employees, clinical trial investigators and site staff, partners, investors, disease awareness advocates and most importantly, the patients who have supported and inspired us every day on this journey. As we celebrate this achievement, we remain focused on the future, ensuring access, deepening our engagement with the HCM communities and advancing the other programs in our pipeline with the same purpose and the same passion that brought us here today. I'm pleased that the approved label and REMS reflect the distinct characteristics of MYQORZO with a straightforward, flexible dosing regimen, no requirement for drug-drug interaction monitoring and a predictable safety profile. In designing and developing MYQORZO, we've been purposeful since the start. Our scientists pioneered cardiac myosin inhibition as a therapeutic strategy for HCM, and we designed MYQORZO around certain drug properties intended to maximize its benefit risk profile. Through an extensive preclinical program, we engineered MYQORZO to achieve a predictable exposure response as well as rapid onset of action and reversibility. And our clinical development program elaborated on how these properties contributed to the safety and efficacy of MYQORZO in patients with oHCM. We believe that today, with the FDA-approved label and REMS for MYQORZO, we have delivered an innovative medicine that advances treatment towards these objectives. Now we're eager to turn the page to bring this medicine to patients with a label that we believe is anchored in flexibility, ease of use and convenience for both physicians and patients and accompanied by a tailored and manageable REMS program based on the inherent characteristics of MYQORZO. Our years of planning and commercial preparations have readied us for this moment, and we're well positioned to bring MYQORZO to patients across the U.S. with oHCM. All of the work that led us to today and the work still to come has been inspired by people living with oHCM and their loved ones. Their courage in the face of uncertainty, their persistence through challenges and their unwavering hope fuels all that we do. They are our source of strength and our North Star, guiding us toward what matters the most, making a meaningful difference in their lives. Now I'll hand it over to Fady to speak about the FDA-approved label, the REMS and the clinical trial results that supported this approval.

Thank you, Robert. Today is indeed a historic moment for patients and for our company. I'd also like to extend my gratitude to the patients who participated in our clinical trials as well as the investigators, clinical trial staff, partners and of course, my colleagues who contributed to the discovery and development of MYQORZO. HCM is the most common inherited heart disease. In HCM, the heart muscle abnormally thickens, which causes the inside of the left ventricle to become smaller, stiffer and less able to relax and fill with blood. In oHCM, the thickened heart muscle and mitral valve narrow the left ventricular outflow tract, limiting the heart's pumping function. Patients experience reduced exercise capacity and symptoms, including chest pain, dizziness, shortness of breath or fainting during physical activity. MYQORZO is an allosteric and reversible inhibitor of the cardiac myosin motor activity. MYQORZO reduces the force generated by myosin at the cardiac sarcomere, which contributes to the pathophysiology of HCM. In patients with oHCM, myosin inhibition with MYQORZO reduces cardiac contractility and left ventricular outflow tract obstruction. MYQORZO is now approved for symptomatic adults with oHCM to improve functional capacity and symptoms and is available at 5-, 10-, 15- and 20-milligram tablets. This FDA approval is based on the results of SEQUOIA-HCM, and those results are reflected in our medicines' label. The Phase III clinical trial showed that adults with oHCM treated with MYQORZO for 24 weeks significantly improved exercise capacity, increased peak VO2 by 1.7 mls per kilo per minute compared to placebo with a p-value of 0.000002. This treatment effect was consistent across all prespecified subgroups, including patients receiving beta blockers. Significant improvements, all less than -- p less than 0.001 were observed in each of the 10 secondary endpoints. Patients treated with MYQORZO also had substantial reductions in symptom burden, including a 7-point improvement in KCCQ, and 34% more patients improving by at least 1 NYHA functional class compared to placebo. MYQORZO was also associated with substantial improvements in post-Valsalva left ventricular outflow tract gradient with 49% of patients achieving an LVOT gradient of less than 30 millimeters of mercury compared to 4% on placebo as well as an 80% reduction in NT-proBNP, a biomarker of cardiac wall stress. MYQORZO was well tolerated with no instances of clinical heart failure or treatment interruptions due to low ejection fraction. Treatment-emergent serious events -- adverse events occurred in 5.6% of patients on MYQORZO and 9.3% of patients on placebo. Core laboratory echocardiographic LVEF was observed to be less than 50% in 5 patients or 3.5% on MYQORZO compared to 1 patient or 0.7% on placebo. Hypertension was the only adverse reaction occurring in more than 5% of patients and more commonly on MYQORZO than on placebo, occurring in 8% of patients on MYQORZO compared to 2% of patients on placebo. As described in the label, MYQORZO-associated increases in blood pressure are consistent with the relief of LVOT obstruction and improved cardiac output. The label for MYQORZO is reflective of the clinical data as well as the intrinsic properties in pharmacokinetics engineered in its development. The label includes a boxed warning for the risk of heart failure. This is consistent with our expectations and aligns with the mechanism of the drug. The risk of heart failure can be mitigated through echo monitoring, which I'll speak to in a minute. Before that, I want to note what the label does not include. There are no drug interactions included in the boxed warning. The label carries a single contraindication for rifampin, an antibiotic used to treat tuberculosis, and a strong inducer of CYP P450 enzymes known to interact with many commonly used drugs. There's no warning around embryo-fetal toxicity nor are there warnings regarding the use of MYQORZO alongside oral contraceptives. Dose adjustment of MYQORZO is explained with one straightforward table that's based on our experience with dosing in both SEQUOIA-HCM and the open-label extension, FOREST-HCM. All patients will initiate MYQORZO on the lowest dose, 5 milligrams. Following treatment initiation, patients may titrate dose with an echo assessment within 2 to 8 weeks of initiation or subsequent increase in dose until the patient reaches their target dose. Depending on a patient's individualized maintenance dose, the number of titration phase echo assessments could range from 1 to 4 following initiation of therapy for a maintenance dose of 5 milligrams or 20 milligrams, respectively. Once the patient reaches their target dose and enters the maintenance phase, echoes are required approximately every 6 months for patients with an LVEF of 55% or above and every 3 months for patients with LVEF between 50% and 55%. We anticipate that the majority of patients will require echo assessments every 6 months after the establishment of their maintenance dose. Notably, treatment interruption for LVEF less than 50% is not required unless EF falls below 40%, when treatment is interrupted for at least 7 days and can be resumed at 5 milligrams, when LVEF is greater than or equal to 55%. This approach mirrors the protocol in SEQUOIA-HCM and reflects the wide therapeutic window and rapid reversibility of MYQORZO. As Robert mentioned, the FDA required a REMS to mitigate the risk of heart failure due to systolic dysfunction. The REMS is designed to ensure adequate education, safe use and monitoring for risk of left ventricular systolic dysfunction and heart failure with MYQORZO. The REMS is tailored to the label dosing and administration of MYQORZO and does not include the need to monitor for drug-drug interactions. Within the REMS for MYQORZO, there are 4 elements to assure safe use, also referred to as ETASU. They are: that prescribers become REMS certified; that patients enroll in the program and comply with echo monitoring requirements; that pharmacies become REMS certified and dispense only authorized patients; and that wholesalers and distributors only distribute to certified pharmacies. As the REMS is intended to implement labeling, the REMS for MYQORZO follows the dosing and administration instructions in the label, allowing for echoes in the titration phase to occur in a 2- to 8-week window following the initiation or titration of MYQORZO, providing flexibility in scheduling for both patients and their care teams. There's no screening for drug-drug interactions required. As MYQORZO reflects the latest innovation in this market, its FDA-approved label and accompanying REMS will offer a new treatment experience for physicians and patients. Physicians can escalate dose of MYQORZO with confidence to reduce the LVOT gradient and treat patient symptoms, and every echo informs either a change in dose or entry into the maintenance phase. The only contraindication is to a rarely used drug, rifampin, and there are no clinically common drug interactions complicating the use of MYQORZO. Overall, we're very pleased with this FDA-approved label as it reflects the bespoke design properties we've carefully engineered when developing MYQORZO, and the REMS has been designed such that it can be incorporated into clinical practice with minimal burden. Now I'll turn it over to Andrew to review our U.S. commercial launch plans.

Thanks, Fady. I'm excited to review the U.S. commercial launch plans for MYQORZO. As Robert said, this is a major milestone moment for the company and one for which we have been planning over many years. I echo both Fady and Robert in the gratitude for the tremendous contributions and collaborations amongst many stakeholders that enabled us to reach this day. For me, this moment is personal and speaks to mission and purpose. I joined Cytokinetics nearly 5 years ago to build our commercial organization, capabilities and launch our specialty cardiology franchise led by MYQORZO for many reasons. But one important reason is that I lost a close family member to HCM in 1989. It is extremely meaningful to have the opportunity to bring MYQORZO to patients living with obstructive HCM today, to raise greater awareness, to honor the legacy of my deceased family member and to make a difference in the lives of patients with obstructive HCM. In the U.S., there's approximately 0.7 million to 1.1 million patients living with HCM. Among those diagnosed with HCM, obstructive HCM, or oHCM, has historically represented over 50% of cases. As diagnosis of non-obstructive HCM or nHCM has increased in recent years, overall prevalence rates for nHCM are now up to 60% with figures varying by region and study design, leading to our current estimate of a roughly even split of diagnosed HCM patients between oHCM and nHCM. Within the oHCM population, about 200,000 people have been diagnosed, of which 110,000 to 130,000 are symptomatic. HCM diagnosis continues to increase over time, driven by a better awareness, approved CMI products and genetic testing. Our market research supports our belief that MYQORZO is likely to achieve greater than 50% CMI preference share and grow the cardiac myosin inhibitor category based on 3 launch drivers: clinical evidence; our bespoke patient services and support; and the REMS. First, the clinical evidence from SEQUOIA-HCM, the pivotal Phase III clinical trial, and FOREST-HCM, the open-label extension showed that treatment with MYQORZO led to rapid and sustained reduction in obstruction and improvement in symptoms, allow for dose titration as early as 2 weeks with an adaptable monitoring schedule and did not lead to treatment interruptions or clinical heart failure events. Second is our approach to patient support services. Our patient support services program is designed to help patients through their treatment journey. Our program is built on compassion and integrity, and that means striving for equitable access so that no one is left behind when it comes to care. Our patient support program called MYQORZO & You provides a single point of contact for patients, delivering a consistent but tailored user experience. The program also enables seamless integration with our systems for data analysis. The program is designed to build empathetic connections with patients and providers. In doing so, we believe we will create a positive ecosystem of care to help patients get and stay on treatment. In a moment, I'll speak more about this specific offerings within MYQORZO & You. The third driver is the REMS. The MYQORZO REMS allows for the flexibility to titrate as early as 2 weeks with echo assessment within the 2 to 8 weeks following dose initiation and any subsequent dose change. Importantly, a patient's dosing may be titrated after each echo with no delay. What this means is that for a patient on 10 or 15 milligrams, they can expect to reach their target dose as quickly as 4 or 6 weeks, respectively. Once the patient is in the maintenance phase, echoes are required every 6 months for patients with LVEF greater than or equal to 55% and no monthly DDI screening calls with pharmacies before dispensing. Each of these drivers have been extensively researched and designed to help propel our launch and encourage uptake, not only towards motivating the existing oHCM specialists and prescribers, but also in expanding the prescriber base and market penetration of the category. Our commercial launch strategy is designed with all this in mind, and we feel confident in our ability to translate this potential into strong uptake and long-term growth. As I mentioned, with the approval, we are launching MYQORZO & You, a personalized support program for patients prescribed MYQORZO. The program will offer the following: support with insurance coverage and reimbursement; a free trial offering for government -- for eligible government-insured patients; a bridge program providing up to 12 months of free drug for eligible commercial-insured patients who are facing delays in insurance coverage; a co-pay savings program to provide financial assistance to eligible commercial-insured patients to reduce out-of-pocket costs; and the patient assistance program offering a free supply of MYQORZO for eligible patients meeting certain financial criteria. In providing this bespoke and comprehensive support program, we hope to ease the burden on patients and help them to get the care they deserve. Another key work stream we began pre-approval, and that continues as our engagement with payers. As we've shared, we've been engaging with payers for quite some time, ahead of this FDA approval, to educate them on the evidence from our clinical trial as well as the clinical and economic burden of obstructive HCM. In fact, through the past few years, we've interacted with every major payer ahead of this approval. Now post approval, we plan to meet again with all targeted payers within the first quarter of the year to discuss the value proposition for MYQORZO. As we work to secure access, MYQORZO & You will provide support for prior authorizations and medical exceptions for both commercial- and government-insured patients. Our goal is to reach parity access with criteria coverage consistent with our clinical evidence, which we believe we will achieve by the second half of 2026. Of course, to fuel this launch, we rely on our sales team. We are pleased to have a very experienced team of roughly 125 people. They have an average of over 20 years of industry experience, 14 years of cardiovascular experience. They have brought a great expertise in existing relationships that we're confident will create strong launch momentum and velocity, and they will be fully trained and ready to hit the ground running. We are pleased to share that MYQORZO will be available in the second half of January. Immediately in the new year, ahead of that date, our cardiovascular account specialists and field-based medical colleagues will be deployed with around 100,000 accounts and initial hire emphasis -- with initial hire emphasis on centers of excellence and existing CMI writers. In advance of product availability in January, we will announce price, which we have previously discussed will roughly be in line with current pricing of the category. We are excited and very well prepared to launch MYQORZO in the United States and redefine the future for people living with obstructive HCM. Now I'll hand the call back to Robert to close.

Thank you, Andrew. Today, we've demonstrated that we've been able to translate our legacy of innovative science into an FDA-approved medicine for patients. And now we're entering a new era of care for patients with oHCM. With this approval, Cytokinetics is also beginning a new chapter in our own journey. MYQORZO represents our first approved medicine in our emerging specialty cardiology franchise. However, today is not the finish line. It defines a new starting point as we seek to build an enduring global franchise of cardiac muscle modulators, not only within HCM, but in adjacent and synergistic indications. As we announced early this week, MYQORZO was also approved in China for the treatment of oHCM. And last week, the CHMP of the EMA adopted a positive opinion recommending marketing authorization in the EU for MYQORZO, and a final decision is anticipated from the European Commission in the first quarter of 2026. As such, we've dialed up our commercial readiness activities in Europe and to enable launch in the second quarter of next year. All of this is guided by our Vision 2030, which outlines our ambitious goals to become the leading muscle-focused specialty biopharma company intent on meaningfully improving the lives of patients through global access to our innovative medicines. The FDA approval of MYQORZO today marks important progress towards realizing that vision. With this forward momentum, we intend to positively impact patients with oHCM while creating a prosperous future for our company and our shareholders. Before we open up the call to questions, I'd like to again share my gratitude to those who made today possible, including our investors. I'm deeply appreciative of the dedication that has led us to today and for your continued support as we move forward from here. Operator, with that, we can now open up the call to questions, please.

[Operator Instructions] First question will come from Akash Tewari with Jefferies.

This is Zaki on for Akash. Congrats so much on the approval. Just a question on the echo window and the flexibility around that. So it looks like 2- to 8-week flexibility. What have you seen or heard from docs who are prescribing Camzyos and the flexibility around that window? And how much is it cutting into adherence for patients when they can't meet their scheduled echo timing?

So thank you for the question. We'll be careful not to make comparative statements as it relates to MYQORZO and Camzyos, but we can speak to market research and where we think there could be an enablement with aficamten now called MYQORZO. Maybe I'll ask Andrew to comment on the market research and Fady to add any color if he likes.

Thanks for the question. So from a -- I'll go backwards. From an adherence point of view, we don't have specific data that fine around adherence rates. I can only say that adherence in this category is much higher than other cardiovascular categories, and we're expecting the same. And relative to the window, we do know that from our market research that uptake across a broad prescriber base, one of the reasons that it has been somewhat limited, is because of ETASU REMS. The second thing we know of the window is that those that prescribe, especially those that prescribe high volumes, need to create workflow around a more precise schedule, and having a more adaptability will allow easier scheduling ultimately. I think we'll see what that translates to in the real world as compared to market research. I think much of that is intuitive, but that's what we've been hearing. I don't know, Fady, if you want to add anything?

Yes. I'll just add that scheduling echoes is always something that is resource limiting, and we think this is advantageous that patients essentially have a 6-week window. It not only helps the sites fit patients into their schedule, but also helps patients fit these echoes into their lives. And I think that's something that will be very appealing to patients and physician practices.

Our next question will come from Gena Wang with Barclays.

This is [indiscernible] on behalf of Gena Wang from Barclays. Congrats on the early approval and the strong label. So for the questions. I want to ask about the drug-drug interactions -- highlighted that there's no -- that drug-drug interaction in the warning box and no monthly screening. So could you further elaborate especially in the initiation phase when physicians first prescribe this drug, is there a required pharmacy drug interaction counseling? So could you just give us more color for the differentiation in this part?

Sure. I can do that. When the physician introduces a patient to a new drug, they should obviously educate them on the label aspects that are relevant to them. And so -- but there's no formal requirement per se, if you will. The pharmacy doesn't need to counsel the patients. It's not a required element of the REMS to either initiation or during maintenance dosing to counsel patients on drug interactions. But it is obviously -- it's important for anybody taking any medicine to be counseled on any relevant drug interactions. We just find -- in the case of aficamten, there are very few drug interactions and really none to common clinically used medicines.

Your next question will come from Tess Romero with JPMorgan.

Congrats, Robert, Fady and to the whole team on this approval and all the work it took to get to here. Can you give us a little bit of a preview of what's in store for us at our JPMorgan Healthcare Conference next month from Cytokinetics? Congratulations.

Thank you. Yes, indeed, it's going to be, I think, a very important conference for us. We're very pleased with already what appears to be our best schedule ever. And what I can say is that we intend at that conference to be showcasing and highlighting a lot of important developments and announcements associated with this approval. We're going to go into some meaningful details that will shine a light on operationally how we expect to go to market, included amongst which will be matters associated with pricing and other activities around building for the patient experience and timing with regard to product availability. So we do believe that we're going to be asking folks to be mindful in paying attention to those communications at the conference. We think it will be showcasing why we think aficamten now called MYQORZO will make a big dent in the universe for patients with oHCM.

Okay. We'll move on to Roanna Ruiz with Leerink.

So for me, I was just curious, could you elaborate on some of the remaining steps that are left for payer engagement now that you have MYQORZO's label in hand? And how quickly could payers update their formularies and decisions to offer coverage of MYQORZO?

Thank you. We'll ask Andrew to comment on that, please.

Thanks for the question. So we will get to the most critical payers in the month of January. As I mentioned, we'll get to all target payers in the first quarter. For the first several months, we will primarily be getting access through medical exception. There will be some payers who will cover immediately, but that will be the minority. And that -- the answer to that, I think, varies based on payer and how quickly they take to review that category. So I think we can give a good update on where we are with that probably in our February earnings call.

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

Robert, congratulations to you and the team. As we look at the indication statement on the label, there's no specific requirement for prior therapies. And so I'm just curious, as you've engaged in your pre-approval conversations with payers, just sort of what the receptivity to potential frontline utilization is for MYQORZO.

So do you want me to answer that, Robert?

Yes, please.

So the label in the clinical trial section does describe SEQUOIA and beta blocker. Most payers are going to restrict label relative to study design. So it does -- although the indication statement doesn't show that the study itself did include beta blockers, our expectation is that beta blockers will be required, either a patient has tried a beta blocker or can't use a beta blocker, and the physician has attested to that. So that would be our expectation relative to beta blockers for now.

Our next question will come from Salim Syed with Mizuho.

Great. Congratulations, guys. Label looks great. Andrew, one from us on the commercial side. Did I hear you correct? You said a 50% preference. Was that the correct number?

What I said was we believe that we will have over a 50% preference share over time in the CMI category.

Okay. Got it. Just curious, what was that -- when was that market share data calculated? What was it calculated on? Was it based on -- like did the physicians putting in that data have access to a profile that's similar to this label? And just the other piece here that would not be preferred to go to AbbVie, what was the color that you got from there that maybe you can now counter detail? Like, why wouldn't anybody prefer Minerva here?

So the market research actually was done several times with an evolving label. We did do research very specific to this label as well. And in each instance, we were getting a very similar answer of a preference share. I won't give a specific number, but it was a good bit over 50%. And we do show a profile, i.e., like a summary label, if you will, based on -- but blinded relative to products. And that's what we did. I think in terms of what we heard in the research for Minerva is I think physicians are telling us they're happy with Minerva. They're happy with the clinical profile, the efficacy, et cetera. So I think we'll have to see over time what happens in the real world once physicians truly understand the differentiation. And we were out there with our field sales organization as well as our medical organization. But I certainly expect that Minerva will continue to get -- physicians prescribing patients is certainly a good drug that works well.

Congrats again.

Thank you, Salim.

Our next question will come from Cory Kasimov with Evercore.

This is Josh Chazaro on for Cory. Congrats on getting this over the finish line. The question is, what kind of launch metrics do you expect to give investors with the second half of 2026 -- or second half of January 2026 launch?

Yes. So we're going to echo some things we shared on our last earnings call. And obviously, things evolve more over time. But I'll ask Andrew to reaffirm those things that we're going to be pointing to initially.

So we will certainly share the prescribing breadth, meaning the number of HCPs who are active prescribing and depth, meaning the volume of prescribing as well. Our goal would be to do well in those that are currently writing CMIs, but also to expand prescribing, and that's essentially what we mean by breadth and depth. We'll also talk about the volume of patients or the number of patients on MYQORZO, and we'll share that kind of longitudinally through the year. We'll probably share some metrics as we go quarter-to-quarter, but those 3 metrics, breadth, depth of prescribing, and volume of patients, is what we'll share continuously through 2026.

Our next question will come from Jason Butler with Citizens JMP.

Congrats. Just wondering if you could speak to your plans to now submit the MAPLE data to expand the label and ultimately, what you think that can do to the launch over the midterm?

Thanks, Jason. So we're now with this approval announced today, going to move very swiftly to submit for what could be an expanded label, inclusive of the MAPLE data, a supplemental NDA submission promptly early in 2026. I'll ask Andrew to comment on how he thinks it may factor into commercial adoption.

So MAPLE and the commercial adoption. One is MAPLE, is in the public domain. Our medical colleagues will have MAPLE and be able to answer questions and describe MAPLE to physicians. But essentially, what we learned in our research has been confirmed by kind of anecdotal conversations is that MAPLE really highlights the lack of efficacy of beta blockers if you -- if one looks at biomarkers or relief of obstruction, and MAPLE should -- our expectation is MAPLE will also influence guidelines, if not in '26, then in '27. And the combination of a second trial, confirming efficacy, safety, showing data that's from a clinical trial that beta blockers are impacting gradients, and if our expectation is correct and that MAPLE or beta -- is added -- or at least the results are added in influencing guidelines, I think the combination of those things, it would increase prescribing beyond the current prescribing base. The current prescribing base from the data we have is about 700 physicians or about 80% of the prescribing today as compared to the over 30,000 cardiologists in the market and 10,000 cardiologists who actively treat and -- existing patients. When you look at claims data, that's about 80% of the market is those 10,000.

Your next question will come from Kripa Devarakonda with Truist.

Congratulations on the approval. In the initial launch, I was wondering if you can help us understand a little bit about what your plan for the distribution footprint is expected to be. [indiscernible] you have at launch, what percent of HCM centers of excellence, for instance, would you expect to cover within the first quarter of launch?

Sure. So you referenced distribution, but I think maybe you're asking more about promotion, coverage, reach and frequency.

One was distribution footprint and the other one was HCM centers of excellence covering -- coverage of centers of excellence. Yes.

So we'll elaborate more on these activities in January. But maybe, Andrew, you can talk about how we're creating a more bespoke distribution channel for the benefit of patients and how we're thinking about coverage.

So associated with the REMS is that pharmacies need to be certified. We have 2 specialty pharmacies that will be certified and able to distribute. We will have a hub to support patients and then large hospital systems or IDNs, integrated delivery networks. Once they have an agreement in place, they'll also have access to distribute product over time. Our expectation is that those 2 specialty pharmacies will be right away, and we'll have well over 20 IDNs probably by second quarter that can also distribute drug. In terms of HCM centers, we will get to every HCM center in the first quarter.

Your next question will come from Joe Pantginis with H.C. Wainwright.

Huge congratulations. So my question is, besides the payers, what do you consider to be the rate-limiting steps with regard to the launch, for example, the rapidity of getting docs certified? Or anything else you'd like to add? Congrats again.

Yes. I think given this label, given this REMS, we believe that this should be enabling of a rapid adoption for aficamten enabled by which we engineered into the product from the beginning, things like we mentioned pertaining to convenience, ease of use and flexibility. But to your specific question, maybe Andrew can comment on those things that ultimately have to be processed and what may be cycle time associated with that.

Yes, Joe, thanks for the question. So one is payer and you -- besides payer, likely, aficamten is differentiated. We have to make sure physicians and their offices understand the differentiation. The workflows associated with the REMS has to be administered as well. So that's probably going to be the biggest rate limiter. I don't think it's going to be a very big rate limiter, but following payers, making sure physicians understand the difference and then putting that workflow in the REMS, giving that adaptability, et cetera, that will probably take a little bit of time. But when I say, "a little bit of time," I'm talking weeks or maybe a month or 2, not much longer than that.

Our next question will come from Martin Auster with Raymond James.

My question has been asked and answered. Congratulations to you.

Our next question will come from Yasmeen Rahimi with Piper Sandler.

Congrats on that accomplishment. Have you guys -- maybe this question is for Andrew. What is the distribution of HCM patients, obstructive [ blockage ], patients that are under cardiology centers versus centers of excellence? And maybe also your color around this really flexibility and echoes, how that could actually be very helpful when we think about general cardiology practices?

Sure. Thanks, Yas, for the question. So are you asking how many patients are in centers of excellence versus outside of centers of excellence?

Yes, that's exactly right. Yes.

Your first question?

Yes.

Yes. So I don't know that we have that level of precise data. I can say that those patients that are currently treated with a CMI is probably right around 50-50 at this point, maybe slightly higher for non-centers of excellence, but -- and that number has been kind of growing outside that non-center of excellence. In terms of the flexibility of echo, our market research would tell us. And I think it's fairly intuitive, if you can increase dose at every echo, if they have a little more adaptability of when you can perform an echo relative to a patient scheduling, that should allow for patients to get on the proper level of drug, from an efficacy point of view, very quickly and that very straightforward. Every time you increase dose, you do an echo. Once you're at the maintenance dose, you do an echo in the maintenance phase and for most patients, it's every 6 months. So I think what we heard in our research again is that's very straightforward and easy to understand.

Your next question will come from James Condulis with Stifel, Nicolaus.

Congrats on the approval. Just wanted to clarify something really quick on these echo windows and specifically in the maintenance setting. As I understand it with Camzyos, these echoes need to be done within sort of a 5-day window. For aficamten, including in the maintenance setting, it sounds like it's a 6-week window to get these echoes in. Is that right? Just wanted to clarify that. Congrats again.

Yes. In the maintenance space, the window is not 2- to 6-week thing, plus or minus a month at 6 months. So it gives you latitude on either side to generate some flexibility.

Your next question will come from Serge Belanger with Needham & Company.

Congratulations on the early Christmas present. I guess a question for Fady. I believe in the SEQUOIA trial, about 80% of patients were on the top 2 doses and maybe 50% were on the top dose. Just curious if you expect a similar distribution outside of the clinical trial setting.

Sure. What you commonly see in the clinical setting is that dosing is not as aggressive as is done in the clinical trial. I think we might see somewhat lower doses utilized in the real world. That's, I think, a likely scenario. It doesn't necessarily -- there's no reason not to push the dose as we did in the trials because those high doses -- the highest -- the highest doses were extremely well tolerated and also quite safe, and some patients are necessary to maximize efficacy. So in the clinical setting, physicians can take more variables into consideration than they can in our clinical trial. I mean the clinical trial was driven primarily by gradient and ejection fraction. But in the clinical setting, physicians will probably take symptoms into account. And so patients that may be just above the thresholds for titration but are completely asymptomatic, they, for instance, may choose not to titrate them because you can't make somebody that's asymptomatic feel better. So I think there are rationale to believe that lower doses will be probably more common in the clinical setting.

Got it. Congrats again.

Thank you.

Thank you.

Your next question will come from Maxwell Skor with Morgan Stanley.

Congratulations, team, on the approval. So based on your conversations with physicians, I was just wondering, do you anticipate that the flexibility in monitoring and the risk mitigation strategy could facilitate broader use or able streamline REM requirement, basically unlock a certain group of patients that maybe physicians were hesitant to put on Camzyos? Are there any qualities or specifics within the label or REMS you'd like to call out?

So yes, most definitely, we believe that aficamten now called MYQORZO is -- with associated label and REMS going to drive not only category penetration more widely for more physicians to be prescribing for more patients, but we also expect that it should be enabling of preferential share. We've highlighted already today where we think those differences lie in attributes of MYQORZO, originally engineered into its design and development. Maybe we could repeat those for you. Would that be helpful?

Yes. Or if there's any you would call out that you think physicians are really focused on or you're excited about it being included.

Sure. So maybe I'll just ask Fady to highlight them again.

I mean I think, again, the label provides use cases for aficamten that will make it easier for physicians to implement. So maybe I'll just pick one in terms of women of child-bearing age. And in the case of women of child-bearing age, there's no contra -- or rather no warning with regards to embryo-fetal toxicity. Aficamten doesn't have to be discontinued prior to pregnancy. There's no pregnancy test prior to administering aficamten. Those kinds of things, if you are practicing and taking care of those patients, should hopefully broaden access of those patients to aficamten, on a cardiac myosin inhibitor as opposed to where people might have stayed on the beta blocker or something that's clearly less effective. So we think there are -- and there are other things as well, some of this -- DDI, lack of DDIs that are common in terms of clinical importance. Those things, I think, all make aficamten something that can be implemented in patients where perhaps physicians were reticent before.

Maybe I'll just add -- maybe I can just add, rapid and sustained symptom improvement is one we hear a lot from physicians as well as very straightforward and easy-to-understand dosing.

Congratulations again.

Thank you.

Your next question will come from Leonid Timashev with RBC Capital Markets.

Yes. Congratulations again on the approval. I had a similar follow-up question to a few of the others. I guess on the maintenance echoes, patients over -- with an LVEF over 55%, every 6 months but between 50% and 55%, every 3 months. I guess based on your experience in SEQUOIA and FOREST, what percentage of patients fall in that 50% to 55% LVEF category? And then as you move into the real world, you mentioned already maybe less aggressive dosing. I guess, what do you think that percentage might be?

Yes. I mean, in our experience, it's very few patients. I can't give you an exact number in the 50% to 55% range, but probably single-digit percentage of the total number of patients. And so I don't expect it to be a burden, and it's not a requirement that they continue to be monitored at infinitum in that frequency. It's just that you just need to establish that they're stable there, and then you can move on to 6 months. The other piece of it in terms of -- I'm not going to speculate what range of doses we'll see clinically. I just think that it's -- you see that with almost every medicine that's deployed that the doses tend to be a little less aggressive in the real world than they are in clinical trials. And that may be okay if there are patients who feel perfectly adequately treated. But I think we'll just need to wait to see what the real-world data looks like to be able to speak to that.

Your next question will come from Mayank Mamtani with B. Riley Securities.

Many congrats on the approval in U.S. and China and also the positive CHMP opinion. Sorry if I missed this, could you touch on how the label grant informs sort of your thinking on pricing and your expectation of proportion of patients getting on the patient assistance program within the initial few months? And Andrew, I know this has been discussed before. Anything you can comment on your expectation for 2026, 2027 market penetration you're sort of working to get to relative to where we are today at the end of 2025?

Yes. So maybe I'll just start and ask Andrew then to elaborate. This label and also this REMS, we believe, are very reflective of what we set out when we designed and developed aficamten, enabling of what we see as an innovation in this marketplace. As such, when we think about our commercial strategy, it's incumbent upon us to be thinking about how we can drive broader adoption and be enabling of more physicians to be comfortable prescribing this cardiac myosin inhibitor for more patients. So I'm not going to reveal our pricing on this call. You'll hear about that in January. But you should expect everything we're doing reflects that same level of innovation in connection with how we go to market, how we engage physicians and patients ultimately for the benefit of wider adoption. Andrew, anything you want to comment on specifically?

No. I mean I think you answered the pricing. It's going to be in proximity to the market, and we'll reveal that in January. Penetration, we believe penetration is probably right, in the range of, say, 15% to 20%. Our expectation is, by the end of '26, penetration will be in the mid- to high 20% range. And -- did you have a third question? Maybe I'm misremembering one or not remembering one of the three you asked.

No, no, you answered it all. Congrats again.

Yes. Thank you.

Your next question will come from Ashwani Verma with UBS.

Congratulations on this big milestone for the company. I had a commercial question. Maybe, Andrew, if you can comment on this. As you're launching the drug, do you have a sense of like how many naive patients are there in play for a CMI every quarter? And how quickly can you penetrate that group?

Did you -- the number of naive in total, you're asking?

Yes, yes. So naive patients in play for either of the CMI every quarter.

Sure. So I mean currently, there's probably in the range of, say, high teens up to, say, 20,000 on a CMI. The market in the U.S. in terms of when you look at claims data longitudinally, there's probably in the range of 110,000, maybe 120,000 patients who are symptomatic and eligible for treatment. So doing the math, the number is probably in the 80% to 85% range that are still available. Now how many of them are actually in the market and seeing physicians, I think that's a tougher number to get to, but my expectation, that's probably about 1/3 to 1/2 of them.

Your final question will come from Jason Zemansky with Bank of America.

Congrats on the approval. You've talked about broadening the market both here and in the past, including moving into the community setting. So when you look at the 4 components of the ETASU, based on your market research, can you speak to how easy this transition is going to be? I mean, how quickly can your average prescriber outside of the center of excellence meet these criteria?

Andrew, do you want to take that?

Sure. So when you look at the components, I think one of the key drivers is that from a REMS system point of view, that -- much of that will be automated, meaning that physicians will be able to put in patient status forms. And when they put that status form in, every status form can correspond to an echo and can correspond to a dose increase until you get to the proper gradient based on the grid that Fady showed. When you consider the dosing, when you consider MAPLE on top of that dosing and what we hear in our market research is ease of use, so to speak. That's, I think, what speaks to broader utilization, that as well as the class is really well understood or at least well known by cardiologists. So when you look at those that are aware of CMIs, those that are aware of aficamten, the number is very high, much higher than you would typically go into a launch. So I think the combination of awareness, the combination of the multiple publications that this is more of a focus at meetings when we go to professional medical meetings that there's a second trial of if a case is positive, that's certainly going to accelerate, if guidelines get updated with MAPLE. So I think all these things in combination as well as the REMS that -- it's very straightforward, when you increase your dose, you do an echo. You start at the lowest dose and you have an adaptable window, you can get 2 prescriptions filled without having to get an echo. You don't have to worry about disrupting existing therapies with the exception of a very rifampin, which is not really used all that much. So I think when you put all these things together, that's what gives us the confidence that the market will expand, and that's what physicians tell us. So I think the time will tell in terms of how long that will take. Probably that will also correspond when we get broader access. So when these things all come together, my expectation, you'll start to see that for the third or fourth quarter of this year -- '26, sorry.

Jason, put another way, I think we're going to resist the temptation to rank order those elements of REMS that might in hierarchy point to enabling a broader category penetration and preferential share. Rather instead, what I would say is it's a collective experience that we're going to be hopefully enabled to create with MYQORZO for physicians and patients. And it may vary depending on the physician or the patient as to which one might ultimately be the most important advantage. But I do believe that MYQORZO represents an innovation rooted in the attributes that are differentiated and were intentional in its design. And if we are executing properly, then we should be in a good position based on label, based on REMS and based on efficacy, including things like speed of onset to addressing treatment and disease burden that we're in a good position to drive the ambitions of this commercial business. So I hope that answers your question well enough.

It does.

There are no more questions at this time. I'd now like to turn the call back over to Robert Blum for closing remarks.

Thank you, operator, and thanks very much to everybody who participated in the call today. Today, we've entered a new era for Cytokinetics. Again, it's not the end, it's instead a new beginning. And we're going to focus on commercializing MYQORZO alongside of continuing to prosecute our specialty cardiology pipeline, always with a focus to our continued convictions, our innovative science and for the benefit of patients. With patients as our North Star, [indiscernible] continue to grow shareholder value, and now as a fully integrated biopharmaceutical company, hopefully now deliver on the promise of muscle biology and pharmacology for more and more patients. Thank you for your continued support. Thank you for your interest in Cytokinetics. Operator, with that, we can now conclude the call, please.