Good morning, welcome, ladies and gentlemen, to Cytokinetics ACC.23 conference call. At this time, I would like to inform you that this call is being recorded and that all participants are in a listen-only mode. For those of you joining us in the room, please silence your cell phones and computers. For those of you joining by webcast, you can download a PDF of the presentation slides. At the company's request, we will open the call for questions and answers after the presentation. We will begin with participants here in the room and then take questions from participants on the call. I will now turn the call over to Diane Weiser, Senior Vice President of Corporate Communications and Investor Relations. Please go ahead.
Good morning, thanks for joining us here in New Orleans and on the call today to discuss both the data from cohort 4 of REDWOOD-HCM, the phase II clinical trial of aficamten, and the 48-week data from FOREST-HCM label extension study of patients being treated with aficamten. Aficamten is our next in-class myosin for the potential treatment of hypertrophic cardiomyopathy. Here with me today are Robert I. Blum, President and Chief Executive Officer, who will make opening remarks. Dr. Fady Malik, EVP, Research & Development, who will lead a moderation following the presentation. We are honored to have Dr. Ahmad Masri, Director, Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, and Dr. Sara Saberi, Assistant Professor of Internal Medicine at the University of Michigan Health Frankel Cardiovascular Center, here with us to present the data.
Please note the following discussion, including our responses to questions, contains that relate to future performance rather than historical facts and could forward-looking statements. Our actual results may differ materially from those projected in these forward-looking statements. Additional information concerning factors cause our actual results to differ materially those in these forward-looking statements and additional risk factors are contained in our SEC filings. In particular, the report on Form 8-K was filed today in our annual report on Form 10-K. We undertake no obligation to update any forward-looking statements after this call. Now I will turn the call over to Robert.
Thank you, Diane. Thanks everyone for joining us this morning. We're pleased to be here in New Orleans with all of you and appreciate those participating by phone. HCM remains a challenging disease for the patients who suffer from debilitating symptoms, including chest pain, dizziness, shortness of breath or fainting during physical activity, and also for the physicians who treat these patients every day. That said, we're encouraged by the emerging data from our expanding clinical development program for aficamten, our next in-class cardiac myosin inhibitor being developed for the potential treatment of obstructive and non-obstructive HCM.
As you may have seen in the press release that we issued Saturday, as you will hear from Doctors Masri and Saberi in REDWOOD-HCM, our phase II clinical trial treatment with aficamten is showing to be well tolerated and associated with significant improvements in heart failure symptoms and cardiac biomarkers among patients with both non-obstructive disease and obstructive disease. Demonstrates sustained hemodynamic and biomarker improvement after nearly a year of treatment among patients with obstructive disease. In fact, in this study, the majority of patients with non-obstructive HCM, those patients became asymptomatic or mildly symptomatic following the length of treatment with aficamten. As we continue to follow patients over the longer term treatment for HCM and proceed with conduct of SEQUOIA-HCM, our phase III pivotal trial of aficamten in patients with obstructive HCM. We also look forward to beginning two additional phase III trials this year.
MAPLE-HCM, evaluating the effectiveness of aficamten versus metoprolol in patients with obstructive HCM. As well as an additional phase III clinical trial of aficamten in patients with non-obstructive HCM expected to occur later this year. Given the positive results from cohort 4 in REDWOOD-HCM. Together, this program, as will comprise three phase III clinical trials across various patient populations, aims to elaborate on the promise of aficamten as a potential treatment that may improve exercise capacity and relieve burdensome symptoms in patients with HCM, as well as potential long term effects on cardiac structure and function. With that, I'll turn it over to Dr. Masri to present the findings from cohort 4 of REDWOOD-HCM.
Thank you, Robert. Thank you for having me here today. I'll present to you on the results of aficamten in REDWOOD-HCM cohort 4. This is the first evaluation of aficamten in patients with non-obstructive HCM. We presented the data yesterday at ACC. Next slide please. Non-obstructive HCM constitutes a large proportion of patients with hypertrophic cardiomyopathy. At the time of presentation, for clinical evaluation, about a third of patients with HCM have non-obstructive HCM. This prevalence of non-obstructive HCM among the population increases over the lifetime of patients because of the interventions that we perform. Other than cardiac transplantation, when there is burnt out end-stage disease, there are no proven therapies for non-obstructive hypertrophic cardiomyopathy.
We tried beta blockers, calcium channel blockers, and diuretics to manage symptoms. None of these were evaluated or studied in large randomized clinical trials. From clinical experience, their effectiveness is minimum. In terms of aficamten, it's a small molecule cardiac myosin inhibitor that counteracts the hypercontractility that underlies the pathophysiology of hypertrophic cardiomyopathy. REDWOOD-HCM, as you are all aware, is a phase II clinical trial that is dose-finding safety and efficacy that started with cohorts 1 and 2 as well as cohort 3 in obstructive hypertrophic cardiomyopathy. Today we'll talk about cohort 4, which is a non-obstructive cohort. Next slide, please. These are the key eligibility criteria we're presenting to you. Patients had to have symptoms, NYHA Class II or III.
Their left ventricular ejection fraction was 60% or above, the NT-proBNP was 300 and above. The patients had to have no history of URSA-MAJOR in the past, and the cut-off is 45%. We did safety assessment as well as we looked at NYHA class, left ventricular ejection fraction, cardiac biomarkers as well as safety evaluation. We're presenting the data. This is all fresh data. Study was still ongoing as of a couple of weeks ago. We're presenting the data on 40 patients up to week 10, which is the on treatment duration study. There were two week washouts, and we're presenting data on 35 patients and usually, for the full completed of the data at a later report. Next slide. This is the schema of our study.
Again, you know, you can see in the box up there that they were symptomatic and obstructive HCM patients. A very important point to point out that the left ventricular outflow tract obstruction or lack of obstruction, we defined it as resting and Valsalva is greater than 30. These are patients with true non-obstructive HCM, and there are no gradient. There is no gradient even with Valsalva. Physically sometimes you get cut-offs like 50, for example, which you can see the skin sometimes, there's increased flow velocity. Those were excluded if they had Valsalva between 30 and 50. Again, 14-week study, 10 week on treatment, and four week washout. We did a couple of assessments, mainly echo, biomarkers, KCCQ, and safety assessment. Next slide.
A dose-finding study, we wanted to understand the full range of the dose that we're offering from 5-15 mg and how patients do on the high dose if they are tolerating it well. The titration criteria, very simple. Ejection fraction above 55%, you increase and up titrate. If it's between 50%-55%, you maintain. If it's below, then you reduce and then discontinue if it's below 40%. This is important because in general, typically, you also try to look at symptoms. You try to look at sometimes biomarkers. In this scenario, again, in the dose-finding study, we wanted to see what happens to patients on the high dose, so we up titrated to the maximum dose tolerated according to LVEF. Next slide.
These are our baseline characteristics of the 41 patients that we're reporting on. Mean age was 56. 58% of them were women. Our trial has a diverse patient population. 20% or so were Black or African American, 5% were Asian. A little bit, about half of the patients were NYHA Class II, and the other half were NYHA Class III. As you can see, these patients have hypercontractility with elevated LVEF, and their BMI is 30, as well as their NT-proBNP was significantly elevated at 1,200. This is, in my recollection, the highest NT-proBNP you've seen in any of the hypertrophic cardiac trials of this, you know, contemporary trial. This is important because it's known that it tracks with disease and how patients are doing as well.
Also troponin, the high-sensitivity troponin I was elevated at 28.7. Next slide, please. I think we did a good job in the study. These are our doses. Remember we started at five, and we capped at 15. Day One is five, week two is 10, week four is 15, and then week six is a safety follow-up assessment. You don't have to get to 15 if the EF is below 55%, but we try to push patients there. As you can see, 85% of the patients achieved the maximum dose offered in the study, which is 15 mg . The rest of the patients were at 10 mg . One did not up titrate aficamten for personal reasons. These are not AEs, otherwise we'd have recorded it, but these were personal reasons.
No patient remained on 5 mg . Next slide, please. This is our left ventricular ejection fraction during the titration period. As you can see, the mean is going from 70 to 66, so modest effect with an average of four. There was no situation where during the up titration we had an LVEF less than 60%. We followed the rules, and we had patients continue to throughout the study until week 10 on treatment. Next slide. These are the summary numbers for our treatment-emergent adverse event. It's important to highlight that of the 66% of the patients reported 1 or more treatment-emergent adverse event. There were no discontinuation during the study itself initiated by PI or patient.
There was one interruption that a patient had an upper respiratory infection and had those for two days, then they were instructed to go back on that medication again after that. We'll talk more about some more events in the next slide. This is recapping some of the things that I already mentioned, so I'm not going to repeat them. There were no drug discontinuation related to AEs. One patient had a dose reduction to 10 mg at week nine due to a hip. One patient had dose interaction for two days due to an AE that we talked about. Three patients had an AE. These were non-related or unrelated to aficamten. These were bronchitis, new onset atrial fibrillation, as well as cardiac arrest.
The cardiac arrest patient who died had history of aborted sudden cardiac death or cardiac arrest was prescribed to the enrollment in the study. They had all of their assessments during the study and the trial period, there was no indication that this is related to aficamten by the further TI as well as the sponsored determination. Three patients had LVEF less than 50%, that's around 67% of the patients enrolled. This happened at the end of the study. This is a short study where you don't have a lot of times within the study that you can down titrate at a later time point. Remember, by week six, you have to make a decision. You either essentially staying at the same dose or you down titrate.
Two of these patients were intermittent AFib, and one of whom reported palpitations that required adjustment of their background medical therapy for rate control. There were no clinical heart failure events. This is very important for us because when we say that someone is on a certain dose, especially when you're pushing the dose in a dose-finding study to 15 mg , you can essentially look at also how they're doing and how they're feeling. There were no clinical events of heart failure with those patients. As you recall, by week 10, we stopped the drug, and by week 12, all these patients had returned to their baseline LVEF. Next slide. These are the changes in NYHA class. This is very encouraging for us.
We have the luxury of having many clinical trials now in HCM reporting on the placebo effect of NYHA class, which is typically about a third to 35% or so in those trials. You can see here from baseline, as we mentioned, half and half NYHA Class III and NYHA Class II. As you progress through the study, you can see an increase in the prevalence of patients who have NYHA Class I and II and a decrease in NYHA Class III. This translates to a 54% improvement in NYHA Class at this I class in these patients, which is again, you know, exciting for us and significant. The other point to highlight is that it's sometimes somewhat easier to move patients from NYHA Class III to II than moving from III to I or II to I.
We provide you here some numbers. They're small numbers, but they're very encouraging because when someone is in NYHA Class I, they present to you and say, "I have no symptoms regardless of what I do." That's not an easily achievable goal, typically, these patients who have been dealing with this disease and condition for many, many years without any treatment available for them. Next slide. NT-proBNP, which is important marker for us. It's a marker of increased wall stress, but more importantly, it's been associated also with symptom severity, with disease burden as and with outcome. As you can see, we're going from a high value of about 1,200 and over the study period and the visits, you can see how it decreased down by about 55%-56% by week 10. Then there is, of course, a rebound that you'd expect there. Next slide.
Similarly for high-sensitivity troponin I, your range here is tighter. For troponin, the elevation is not as much as NT-proBNP when it comes to patients with non-obstructive hypertrophic cardiomyopathy. Here, remember the baseline was about 28 or so for troponin. You can see a proportionate decrease in troponin over the study period, starting from as early as week two with a proportionate decrease all the way up to week 10, then you see the rebound. These were statistically significant as well. The summary final number at week 10 is about 21% proportionate decrease from baseline. Next slide. In conclusion, REDWOOD-HCM over 4 is the first study exploring dosing and tolerability of aficamten in patients with non-obstructive HCM. Aficamten was well-tolerated. We pushed the drug to 15 mg in the majority of the patients.
There were modest reductions in LVEF, and the response was significant in terms of improvement in NYHA Cl ass, reduction in cardiac biomarkers, and burden of the disease. In FOREST-HCM, we will have an opportunity to look at the 20 mg of these patients. That's important to mention. These results support our progression to a larger, longer-term phase III trial of aficamten in non-obstructive HCM. I'll turn it over to Dr. Saberi, who's joining us online, to present data on the FOREST-HCM study.
Thank you, Dr. Masri. Can everybody hear me okay?
Yes.
Okay, great. Thank you. I'm assuming that the slide that you see is the first one from the FOREST-HCM long-term efficacy and safety of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy. Is that correct?
Correct.
Great. Next slide, please. The disclosures that I have to report are that I have received consultant fees from Bristol Myers Squibb, as well as research grants from BMS, Cytokinetics, Novartis, and Actelion for clinical trials that we are participating in. Next slide, please. Dr. Masri has already spoken a bit about hypertrophic cardiomyopathy, and everybody in this room is certainly familiar. Just as a reminder, our understanding of hypertrophic cardiomyopathy as a disease process is really expanded in the last 15 years. Where we used to think that this was really just a disease of hypertrophy, what our understanding now is that it's really a disease of hypercontractility, and that the hypertrophy that we see is just a byproduct of that hypercontractility.
It's also noted to be associated with abnormal relaxation, myocardial fibrosis, and about 2/3 of patients have left ventricular outflow obstruction. Current standard of care, first-line therapies for obstructive hypertrophic cardiomyopathy have included beta blockers, calcium channel blockers, and disopyramide, none of which actually address the underlying pathophysiology of the disease. Next slide, please. Aficamten is a next-in-class cardiac myosin inhibitor that's in development for treatment of hypertrophic cardiomyopathy, and it does address the underlying pathophysiology. It reduces the hypercontractility that underlies hypertrophic cardiomyopathy. It's been shown to be safe and effective in lowering resting and Valsalva outflow tract gradients, improving heart failure symptoms, improving patient-reported outcomes through the Kansas City Cardiomyopathy Questionnaire, as well as biomarkers of wall stress and myocardial injury.
FOREST-HCM, which was the former REDWOOD-HCM OLE, is an ongoing open-label extension study for eligible patients with obstructive or non-obstructive hypertrophic cardiomyopathy who had completed the parent study of aficamten. Here we're going to report the interim safety and efficacy data of aficamten in patients with obstructive HCM in the FOREST-HCM trial over a 48-week period of time. Next slide, please. This is the study schema. So patients, like I said, who had completed the parent study of aficamten and whose baseline ejection fraction was at least 55%, were eligible to continue on to screening for the FOREST study.
At Day One, patients were started on aficamten and had an opportunity to have dose changes at weeks two, four, and six based on echo-guided titration that's managed by the site PIs. That titration is dependent on left ventricular ejection fraction assessments, as well as assessments of outflow gradients. Patients underwent cardiac MRI at enrollment and undergo cardiac MRI again at weeks 48, 144, and 240. We do not have that data to share with you at this time, are excited to find this data in the future. They also underwent cardiac rhythm monitoring at baseline, that also occurs at weeks 48, 96, 144, 192, and 240. Next slide, please.
The patients were initiated on aficamten 5 mg a day. The dose was adjusted between 5 and 20 mg at 5 mg increments, like I said, based on the site read echo, assessments of ejection fraction and Valsalva gradients. The dose could be increased if the ejection fraction was maintained at least 55%, and Valsalva gradients were at least 30 mL of mercury. The dose was decreased if the ejection fraction was less than 50%, regardless of the Valsalva gradients, and the medication was either discontinued or the dose interrupted if ejection fraction is less than 40%.
We'll be talking a bit about septal reduction therapy later, so I just want to let you know that the septal reduction therapy eligibility criteria were what is recommended by the ACC/AHA guidelines, and that is the presence of New York Heart Association Class III symptoms, along with a peak gradient in the outflow tract of at least 50 mL of mercury, and that is either resting or dynamic. Next slide, please. From May of 2021 through September of 2022, 45 patients with obstructive HCM were enrolled. These are some of their baseline characteristics. Mean age is 59. 60% of the participants are women. It is an overwhelmingly Caucasian study population, with 93% white. They are symptomatic and pretty well split between New York Heart Association Class II and Class III.
The average time since the initial HCM diagnosis is about five years, and the vast majority are treated with what we consider at this point to be standard of care therapies, with the majority being treated with beta blockers and then an a smaller proportion that are treated with calcium channel blockers and disopyramide. As expected, they are quite hyperdynamic, with a mean ejection fraction of 69% at baseline, and they have obstruction. Their resting gradients are about 50 mL of mercury in Valsalva, about 80 mL of mercury. 19 of the 45 patients, so 42%, met eligibility criteria for septal reduction therapy at baseline. Next slide, please.
This is a presentation of the range of aficamten doses that have been achieved at various times throughout the study so far. I'd like to just also say that the 20 mg dose of aficamten was introduced with a protocol amendment that was finalized in December of 2021, about 9 months prior to this data cut. That was not really available in the first couple of assessments here. You can see that the majority of patients were already at a 15 mg dose by week six. As that 20 mg dose became more and more available at sites, we start to see a creep down of the 15 mg dose and a creep up of the 20 mg dose.
By week 48, about a quarter of patients are on the 20 mg dose. Another, roughly quarter of patients are on the smaller doses at five and 10 mg a day, and then, about just under half are on the 15 mg dose. Next slide, please. This is a representation of the effect of aficamten on the outflow gradients. Panel A shows you the resting gradients, and panel B shows you the Valsalva gradients. The green line here is the core lab interpretation of the gradients, and the black line is the site interpretation. I would just like to point out that these two lines pretty much overlap or mirror each other. There's not a lot of differences between the site read interpretations and the core lab interpretations.
If you focus just first on panel A, you'll see that there's a rapid decline in resting gradients, from the initiation of aficamten by two weeks and down below 30 mL of mercury by four weeks of medication initiation. Why that 30 mL r of mercury dashed line is important is because that is the cutoff for defining somebody as having obstructive hypertrophic cardiomyopathy or not. By about six weeks of treatment, the resting gradients are well below 20 mL of mercury on average. You can see that this reduction in resting outflow obstruction is maintained and actually even declines a little bit more through week 48. From baseline, we see about a 32 mL mercury reduction in resting gradients, which is huge.
If we turn our attention over to panel B, we're looking at the Valsalva gradients and the same thing. We see that the site read and core lab interpretations of the outflow peak pressure gradients are really the same. Again, we see a dramatic fall in the Valsalva gradients by the second week of treatment. This dashed line of 50 indicates what that cutoff is for being eligible for septal reduction therapy. You can see that the mean gradients really fall down below that 50 mL of mercury mark within a month of treatment. Those reduced gradients are actually maintained throughout the entirety of the next 40 weeks. There's nearly 50 mL of mercury reduction in Valsalva gradients, which again is really dramatic.
Next slide, please. This is a presentation of the effects of aficamten on the left ventricular ejection fraction. Again, at what we're seeing is the green line is the core lab interpretation. The black line is the site read interpretation. There's a small difference between the two. Interestingly, the site read interpretations are a bit more conservative in terms of the ejection fraction assessments than the core lab interpretations. It's kind of consistently about 5% less in the site read interpretations as compared with the core lab interpretations. Again, at baseline, the patients were quite hyperdynamic with ejection fractions right about 70%.
You can see that there is a small reduction in the ejection fraction by about four weeks, from a mean of about 70 down to about 65%, which is still well within normal limits, and that that mean is pretty much maintained through the rest of the study period. Next slide, please. There's a significant improvement in New York Heart Association class through the 48 weeks of study. So you can see that at baseline, like we had said before, that the patients are pretty evenly split between New York Heart Association Class II and Class III symptoms. By 12 weeks of treatment, 45% of patients were New York Heart Association Class I. By 48 weeks of treatment, 60% of patients were New York Heart Association Class III.
Importantly, there were no patients that reported New York Heart Association Class III symptoms by 48 weeks of treatment. 88% of patients by 48 weeks experienced at least a one class functional, sorry, a one functional class New York Heart Association improvement, and none that had worsening symptoms over that time. Next slide, please. Nineteen of our patients, 42%, had been eligible for septal reduction therapy per the guideline criteria. That was despite receiving optimal medical therapy. By 48 weeks, none of the patients that had reached that time point actually met that criteria. Next slide, please. NT-proBNP decreased significantly, 70% reduction from baseline to week 48, going from a mean of 651 to a mean of 111 during that time.
Next slide, please. Aficamten was well tolerated. There were no treatment-related serious adverse events reported through week 48 of treatment. One patient underwent a temporary dose reduction, and this was a site error related to QTC that was interpreted as being prolonged by at the site. The core lab interpretation of that EKG actually revealed normal QTC, and the patient was resumed on the aficamten. The other was a temporary dose interruption in a patient who had recurrent alcohol-induced atrial fibrillation, which he had had a history of prior to initiation of the study. His ejection fraction in the setting of this clinical instability was 47%, and then normalized after dose interruption. He was able to restart on aficamten. Next slide, please.
In conclusion, this is a long-term study that shows that treatment with aficamten in patients with obstructive hypertrophic cardiomyopathy could be actually appropriately managed by investigators and was shown to be safe and well tolerated through week 48. Treatment was associated with rapid and sustained improvements in echocardiographic hemodynamics, paralleled by significant improvements in New York Heart Association class. Aficamten was shown to be able to eliminate SRT eligibility in patients who had previously been guideline eligible at baseline. There were no instances of systolic dysfunction with ejection fraction less than 50% that we could attribute to aficamten. These data really do support the continued development of aficamten, which is currently being investigated in the phase III clinical trial SEQUOIA-HCM , and planned as a head-to-head comparison of aficamten against metoprolol in the future. Thank you for your attention.
Thank you, Dr. Saberi. We'll begin the Q&A session now with the participants in the room. Afterwards we'll take questions from those on the call associated by the operator. I'll ask the first question, though. I know you have a couple of questions you'd like to ask, and I'll direct it to Dr. Masri. You enrolled, you know, a reasonable number of patients in the NHCM study. I wonder if you can give people a sense of what your experience was in this space and what they also felt that are, you know, perhaps a little harder to discern from NYHA Classes and other things like that are more quantitative.
Excellent question. We've enrolled 11 patients in the study out of the 41 patients total enrolled. You know, it's interesting that in non-obstructive HCM, the phenotypes and severity of symptoms are more consistent over time with students since we have no intervention. These patients are seen over and over in the clinic over the years. There is consistency on the report and what you find and your exercise testing and everything. You take these patients with significant burden of symptoms, and you enroll them in a trial, and they feel fairly well.
They report how good they feel on the drug during the study, and that that's particularly affirmed to them during the washout period that they ask, "Can this be actually shortened or skipped?" Because they want essentially to go back on the drug or aficamten as soon as possible. I think this is important because in a lot of scenarios, we don't actually have that luxury of knowledge. In many trials we enroll in, patients present new diagnosis, new patients. You meet them for the first time, and then you offer them the study, and you enroll them. Here it is different where we have a longitudinal relationship with these patients, understood their natural history, and then we enrolled them. That's why we're excited about aficamten in obstructive HCM, and we're excited about the effect that we have seen.
Despite the fact that it's a short study with many visits, we actually have not had any complaints about that. We still do the patients' positive on internet.
Great. Thank you, Dr. Masri. Questions in the room?
Hi, Justin Kim from Oppenheimer. Thanks for the presentations and graphs and updates. Maybe for Dr. Masri, as we think about the rollover of those NHCM patients in SEQUOIA-HCM , do you anticipate that patients could experience added benefits from a higher available dose? How much of a role do you think, based on some of the experience in symptomatic oHCM, that the removal of beta blockers might also help in sort of getting patients maybe to that dose or just receiving greater clinical benefits?
Excellent question. For your first question about higher dose, we will find out. That's why I really like the design of FOREST that allows us as investigators to push the drug to a higher maximum level of 20 mg. That would be allowed also for non-obstructive HCM. In general, if you think about it, while in this cohort for phase II, it's a dose finding study. We're going to push the drug to 20 mg and see what happens. In FOREST, there's more flexibility. You're gonna incorporate how the patient is doing, what is going on, and how the LVEF and biomarkers and whatnot. I already have patients on 20 mg in FOREST-HCM with non-obstructive HCM because they already were over, you know, either titrating therapy for that nitrate.
Again, this is important because if the patient is still symptomatic, you wanna push the dose higher. I can tell you again from the experience in the trial, and you saw the NYHA Class graph as well. Patients do start deriving benefits early. Again, this is important because it in a way pushes against some of our assumptions that in non-obstructive HCM, you need to do very long treatment periods before you see any effect. We didn't see that in the trial. We've actually seen a gradual improvement in symptoms early and more improvement in symptoms with a nitrate medication. The short answer is yes, I think that 20 mg will be helpful in some patients, not necessarily everyone. Your second question was about beta blockers. Again, as I mentioned, there is no evidence that they actually work in non-obstructive HCM.
I can tell you from clinical experience, in at least my patients, for patients, they won't. We have a large cohort of patients. When you initially try them, you keep the patients on them when they're feeling okay. Some people don't feel or don't realize they actually are slowed down by the beta blockers. That's why exactly we are attempting to withdraw beta blockers and background beta-blockade in FOREST-HCM. Again, the FOREST-HCM design empowers the PI to decide what they wanna do for a patient within the protocol, of course. There are some rules there. Typically, once you're stable on mavacamten, we do withdraw the background beta-blocker. We are already deciding, and it's actually done it in some patients with non-obstructive HCM as well already.
That by the time they cross week 12 and they're on a stable dose in FOREST, we do withdraw their background beta-blockade. We have done this also in obstructive HCM cohorts that you've seen some data on this previously. I do believe that it's important to attempt to do that and see how patients feel improved because they would like to feel better.
Just maybe one more for Sara Saberi. You know, you provided some presentations on the longer-term benefits from cardiac myosin inhibition at the conference and, you know, a duration longer than the sort of RCTs that have been studied. When you noted how you didn't expect normalization of the heart with these sort of treatments, how should we then think about cardiac myosin inhibition as a tool of prevention of hypertrophy? You know, what sort of evidence would motivate you to want to explore this in maybe an asymptomatic patient or even earlier stage disease patient?
Thank you for that question. Yeah, I mean, I'll point out again that the mean age of the participants here is 60. While the time since initial HCM diagnosis was about five years, we know that HCM is very under-recognized, and that there is a significant delay from the time of symptom onset to the time of actual diagnosis. My own kind of observations, and I think it's supported by the literature, is that patients who are diagnosed younger have a more advanced or more severe phenotype, and that's really related to the penetrance. I think the fact that at least the data that we have seen with mavacamten shows that there are structural changes that occur with mavacamten through the cardiac MR sub study.
Even with just a 30-week, you know, treatment course, again, in a patient population that already has kind of well-defined left ventricular hypertrophy, other structural changes such as left atrial dilation. I don't think that we're going to be able to take, you know, a 20 mL septum and make it 10. I don't think. That doesn't mean that it's not gonna happen. We were already surprised by the effects of mavacamten just with, you know, a few months of treatment that we even saw the structural changes that we did. The fact that we see those structural changes with mavacamten is what's the most, hope filling kind of promise for me and for the future, is that, you know, again, it harps back to this understanding of HCM now as a disease of hypercontractility.
I will say that in my patients who are genotype positive, quote, "phenotype negative," meaning that I don't actually detect left ventricular hypertrophy either by echo or by cardiac MRI. A lot of them already have hypercontractility. Their ejection fractions are hovering 70% and above. While that finding is not within the current definition of hypertrophic cardiomyopathy, my personal belief is that it should be, and that these patients are already seeing the effects of the genetic change. That the hypertrophy is a later development than the hypercontractility.
If cardiac myosin inhibitors can be actually implemented far earlier in the disease process. If we can extrapolate the findings from the CMR sub-study of mavacamten, then it leads me to believe that we may be actually able to prevent and significantly delay the progression of the hypertrophy and all of the other consequences that happen thereafter in terms of myocardial stiffness, diastolic dysfunction, relaxation abnormalities, left atrial dilation. I actually think it makes the most sense the way that these studies have been laid out. Meaning we have been investigating the effects of these agents in patients who clearly have disease and oftentimes have had disease for a decade plus. Where in my opinion, the likely biggest impact for patients themselves will be in thinking about how this disease affects them and their families.
My hope is actually that these medications can really be implemented in way younger patients and hopefully pediatric age patients in order to prevent everything that I see as an adult cardiologist.
I might just add, I think, as Dr. Saberi noted, the earlier recognition of disease provides an opportunity for earlier intervention. It ultimately will be up to us to show that that's meaningful. There is precedent if you think about treatment of hypertension and either the regression of left ventricular hypertrophy seen with certain treatments that lower blood pressure in patients that have established LVH or, the goal really is to prevent the development of left ventricular hypertrophy by treating the underlying seamless of it, which in the case of hypertension is high blood pressure. You know, the heart clearly has some capacity to model and that's very good.
We've seen that where longer term data are available, with mavacamten and, I think it will be an important objective of this program to establish that down the road. Other questions in the room?
Hi, Cameron Molineux on for Jason Zemansky. My question is, can you talk some about the design characteristics of MAPLE-HCM? What's your commercial strategy here? What you're looking at your primary market?
Yeah. I'll take that question. MAPLE-HCM, for those of you that don't know, is a study that we plan to start in the first half of this year that will look at aficamten as monotherapy against beta blocker as monotherapy, beta blocker being metoprolol. It gets to the question, many patients are on monotherapy with beta blocker. SEQUOIA-HCM and REDWOOD-HCM, FOREST-HCM, and for many of them are studying on top of the beta blocker. Beta blockers have, you know, a number of symptomatic adverse consequences to patients, as well as they blunt heart rate increase, and so they actually reduce the ability for patients to exercise to a greater extent.
What we wanted to do is establish quantitative randomized data that will look at the magnitude of the treatment effect of a cardiac myosin inhibitor like aficamten versus metoprolol. We haven't given a lot of details of this study, but in general it will be a look at that randomization, 24 weeks of treatment, using pVO2 as a primary outcome. You know, other symptomatic measures that are fairly similar to what you see in SEQUOIA-HCM . What we hope is that should the results be supportive of it provides the basis for thinking of cardiac myosin inhibition as first line therapy. Superior results, superior adverse event profile, superior symptom improvement.
Ultimately, you know, with that evidence and perhaps also looking at modeling over time, whether you see that with beta blockers and or whether you only see it with myosin inhibition, you know, may provide the impetus for deciding where to position or to position myosin inhibition as first line therapy.
Just to follow on, you asked a question about that as it might pertain to commercial readiness strategy. After we close here, I'll introduce you to our Chief Commercial Officer sitting in the back of the room. Just to highlight, we see this as consistent with an expectation that aficamten may ultimately contribute to an expanding of what could be deemed the category and ultimately where this class of medications may be used by experts in the specialty cardiovascular region. Not necessarily primary care, as I think you alluded, but perhaps where other cardiologists, even outside of HCM centers of excellence, may ultimately get comfortable with the use of a myosin inhibitor, in particular aficamten, for patients who might present with these symptoms.
Other questions? Okay. Well, not no questions in the room. We'll turn to see if there are any questions on the call. Operator?
Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question will come from Ash Verma from UBS. Your line is open.
Hi, Good morning. Thanks for taking our questions. I have two, first one, in the cohort 4 data for these three patients that you saw the ejection fraction go below 50%, at the week 10, like, how low did it go? Just curious to understand the dynamic there. Just like broadly about this non-obstructive side of things, like what percentage of these patients are symptomatic? Symptomatic percentage kind of below where what we see in obstructive? Is this a market segment that can lend itself to expanding diagnosis over time, like you've described the obstructive market?
Okay. Like I get 3 questions. Maybe I'll ask Dr. Masri to answer the first one. It had to do with resolution of EF less than 50% with the NAC.
Sure. As we mentioned that there were three patients with LVEF less than 50. They were obviously in the forties range. They were on the end of the study or treatment period. These patients were not symptomatic. Which means they were not more symptomatic than they already been. They just showed up for an echocardiogram. Had the echocardiogram, they stopped the treatment because it was week 10, and then it was reported on the echo that they had an EF in the forties. This is a numerical read, not clinical presentation of heart failure or systematic presentation. As we mentioned, by week 12, everybody's EF went back to where it was at baseline, or at least what we consider an acceptable or normal range. One has to realize the variability in ejection fraction quantification, especially in patients with atrial fibrillation.
Two of these patients were in atrial fibrillation. That essentially changes your length of cardiac cycle. We're doing a single assessment at time point. It depends on where you choose in the cardiac cycle to see your ejection fraction. All of this needs to be taken into account. The way I think about this personally is if the patients are symptom, do they complain? Do they have an adverse event because of that low numerical number? You saw something on an echo. Then you adjusted your treatment accordingly. They continue to be doing well and asymptomatic or might be asymptomatic.
I believe we had really no treatment interruption due to low ejection fraction. It's really as Dr. Masri said, an adjustment of dose or in the case of these patients, they're at the end of study, so they just continue drug. Your second question, if I can paraphrase this, correct me if I'm wrong, had to do with really comparing symptom burden in the non-obstructive patients versus the obstructive patients. Maybe I can ask Dr. Masri to comment on that as well.
Sure. When you think about non-obstructive HCM, it's a largely underdiagnosed disease, even much more than obstructive HCM, because you don't have the hallmark that essentially tells the practitioner or the clinician that there's actually a problem. When someone listens to someone's chest with a stethoscope or do an echo, when you have obstruction, it's easier to pick up that there is an obstruction there or this could be HCM. Non-obstructive, you have left ventricular hypertrophy without obstruction. You can blame anything you want from hypertension to obesity to all other things. That leads to patients presenting typically after multiple rounds of, you know, contact with persistent complaints. They come and go. You have no treatment necessarily for this condition, and there is typically delayed diagnosis.
In terms of symptoms, there are some patients who are asymptomatic, and there are patients who are chronically symptomatic and debilitated by the condition. The difference from obstructive HCM is the acuity of the presentation. In obstructive HCM, typically patients who are found to have the obstruction with the disease burden or the symptom, you find them fairly quickly within months to maybe one to two years on average, by which one they present until they come to you. Patients with non-obstructive HCM have more of a chronic stage of having symptoms, and they are typically limited. If you look at an outcome of death, obviously it's not very common in non-obstructive HCM or obstructive HCM for them. These patients are limited. They have limited exercise capacity, and they have a lot of symptoms that they adapt and adjust how they live accordingly.
That's actually a forward follow reflective of the data that you see as the patients were NYHA class B for example.
Just maybe in the interest of time, operator, I'll see if there are other questions on the line.
Thank you. As a reminder, we do ask that you please limit yourself to one question at this time. We'll take our next question from Rohit Bansal from Needham & Co. Your line is open.
Hi. Good morning. This is Rohit on for Serge. Thanks for taking our questions. The cohort four results appear compelling. How should we think about potential placebo rates for NYHA improvements based on other studies? Thanks.
Well, you know, prior to this study, now that in prior studies, we've seen placebo rates of one class improvement of about 30%-35%. In fact, in the FOREST data, the poster, we calculated the P values assuming a placebo event rate of about 30%. These statistics are calculated against the, you know, the background placebo rate that we've seen, you know, in more than one study now that's in about that range.
Thank you.
Thank you.
Our next question comes from Jeff Hung from Morgan Stanley. Your line is open.
Thanks for taking my question. For Dr. Saberi and Jad Majzoub if you want to comment, where does the 100% of patients becoming ineligible for septal reduction therapy rank in importance relative to other aspects of this weekend's FOREST HCM data? Thanks.
Dr. Saberi, do you want to comment on the resolution, if you will, of these patients meeting criteria for septal reduction therapy in FOREST?
Sure. I think that it's actually very important. If you think about from a patient perspective what the, you know, effect of undergoing an open heart surgery would mean for them in their lives, that's not a small bit. We're talking about two months of being out of work. We're talking about patients being able to afford the cost of the surgery. We actually already know that just because a patient undergoes septal reduction therapy does not mean that they're going to be a one and done, essentially situation. Meaning that there are a significant proportion of patients, and I can attest to this just being in the clinic, that undergo septal reduction therapies with or without mitral valve repairs, who years later will develop recurrence of obstruction.
Oftentimes, in my experience, it's not necessarily in the outflow tract. It's deeper into the ventricle, and it relates to the underlying hypercontractility of the ventricle. That surgery does not actually affect the hypercontractility, the underlying pathophysiology of the disease. If we can use medications that actually address the underlying pathophysiology of the disease, they may actually be more effective in the long haul for patients than the mechanical dealing with just one section of the heart causing a problem, but leaving the entire heart still diseased.
Thanks.
Thank you.
Thank you. Our next question come from Carter Gould from Barclays. Your line is open.
Great. Good morning. Thank you for taking the question. Maybe one for Dr. Saberi. Just going back to your commentary on the structural changes, you've seen with the class, and you highlighted the CMR data. You did not see really an impact in fibrosis in that study. Is that more a reflection of the amount of fibrosis, the small sample size? I mean, I guess even to the bigger question around, you know, the class effect on reversing fibrosis in this, you know, in this setting. Maybe Cytokinetics can just comment on, you know, the imaging component of SEQUOIA-HCM , and it sounds like there's Maple as well, based on Fady's comments. Thank you.
Yeah.
Dr. Saberi, You heard the question.
Go ahead.
Go ahead.
Yeah. No, we'll definitely have cardiac MRI data to share with aficamten in the future as well. What I can say is we do not have the capability of turning scar fibrotic tissue back to muscle. I don't actually expect that we're gonna see any regression of fibrosis with these medications. The hope is that with correcting some of the underlying pathophysiology that we would see a decline in the progression of fibrosis. In the mavacamten assessments so far, we have seen in the 96 week cohort data that I presented a small increase in absolute mass of fibrosis of 0.2 grams over the 96 week period. I will say that, you know, again, that's a single arm study.
We're losing you.
Is that okay?
We're losing your sound stream there a little bit, Dr. Saberi.
I don't know why. Sometimes true. Other times. I just illustrated that with, you know, we've seen a small progression in fibrosis in the 96-week cohort of from that CMR endpoint study of mavacamten. I think that, you know, that's a single arm study and therefore we cannot make any conclusions about the effect of mavacamten itself on the fibrosis. We could absolutely well just represent the natural history and course of the HCM in those kinds of patients. I do think that in the long haul, we are likely to see a decline in the progression of fibrosis, which I would anticipate to be a manifestation very soon what that data will do for aficamten.
Thanks.
For those here in the room, apologies for the Wi-Fi challenges. I don't think that people on the line are hearing what we're here.
Thank you.
Thank you. Thank you, Dr. Saberi. We'll take the next question.
Thank you. Our next question will come from Charles Duncan from Cantor Fitzgerald. Your line is open.
Hey, good morning. Thank you, Robert and Fady, for hosting this call. I was going to address this question to Dr. Saberi, but I think I'll actually do it for Dr. Masri. Relative to Dr. Saberi's presentation, I'm thinking slides 26 to 29, really the data slides. I'm kind of a picture tells a 1,000 words guy. When you consider the LVOT, NYHA class change and SRT eligibility change, I'm kind of wondering if you can tell us what stands out most to you. Is it really just the ease of use of aficamten in this cohort versus, you know, perhaps other candidates or other drugs that are have been developed for this indication? Thank you.
Charles, I guess maybe I'll ask Dr. Masri to comment on magnet effects that were observed in the black patients meeting eligibility SRT, impressions of that.
Sure. Thank you for the question. I think when you think about SRT, you think about someone with more and the fact that patients eligible just means that they're feeling better, and you don't have significant obstruction anymore. Obviously, it's very that the drug was doing so using it, which is being shown over and over here, but you can't. The second point is, as you mentioned, ease of use. This comes into play when the patients are thinking about it. It doesn't just mean that you're no longer eligible for SRT, that you don't want to start. You could still decide to go to SRT, and you can have both the drugs. The fact that the patients still continue and want to continue means, one, they are essentially enjoying how they're feeling.
Two, they don't feel a burden that they would want to withdraw back and change their mind. To your point, again, when a drug becomes commercially available, this comes into play when patients are making their decisions and deciding on undergoing SRT versus not. It is not only what ACC and AHA guidelines recommend, it's also how the patients are doing and feeling and also the ease of use and days of follow-up. Data is very important to us.
Thanks, Dr. Masri. Operator, can we take the next question, please?
Thank you. Our next question will come from Jason Butler from JMP. Your line is open.
Hi. Thanks for taking the question. Robert, you mentioned the fact that, you know, you had studied echoes in the study. Can you talk about the importance of those data and when we might see them? Thank you.
I'm guessing you're referring to cohort 4 in NHCM.
Yeah. Sure. Yeah.
I'll turn that over to Fady. These are the initial datasets from cohort 4. He can speak to when we might have additional data coming.
Yeah. I think as Dr. Masri noted in his presentation, we really have just finished these patients through the study. EF is something that's set to the safety metric very quickly, but the rest of the metrics takes more time and analysis. We'll have more detailed echo information, you know, presented, I think, in the first half of this year at another medical conference. There's also KCCQ data that was collected in this study that will also be included in a later presentation. I think you'll see an evolution of the data over the next few weeks to a couple of months.
In parallel with that, we're already, as we noted, proceeding towards readying to start a phase III study. You'll get more details on the design and conduct of that phase III study as we move into the middle part of the year.
Thanks.
Operator, next question.
Thank you. Our next question comes from Salim Syed from Mizuho. Your line is open.
Hey, guys. Thanks for the question. I guess one for me on phase III dynamics here, Fady. You know, when we look at this NT-proBNP chart that's in the cohort 4 poster, it looks like you may actually have a faster onset of action on NT-proBNP versus mavacamten, and that's in line with what we saw in gradient in oHCM. Just curious if you're thinking about 52 weeks being a relevant time marker on Peak VO2 as Bristol's ODYSSEY-HCM study is designed, or do you think perhaps you'd be able to see something quicker on Peak VO2? Thank you.
Thanks for the question, Salim. I think at this time, probably I'm not gonna comment on what we're thinking in terms of duration of study for phase III. Your point is an important one in that there is a rapid resolution of biomarkers and also, these patients reach their steady state dose, if you will, you know, approximately six weeks. I think that current for me.
Thanks so much, Fady. Congrats on the data, guys.
Thanks.
Thank you.
Operator, next question.
Our next question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.
Good morning, team, and congrats on both presentations. My questions are directed to Ahmad Masri. I know this study measured KCCQ, but it was not reported. Maybe, what did that measure look like? We also didn't see any details on pVO2 cardiac structure and mechanics measurements such as lobby and lateral e' and septa l e '. Any comments there on those measures? Also it would be great if you could just put into context how this data compares to what we have seen in mavacamten in the non-obstructive population. Thank you, and I'll jump back into the queue.
Maybe I'll just clarify a couple things. First of all, we didn't measure pVO2 in this study, Yas. I mean, we focused on symptomatic changes in biomarkers, including KCCQ. As I said earlier, the KCCQ data are forthcoming. Maybe Dr. Masri, if you wanna comment on what you think the echo data might show.
Yeah. In terms of the echo data, in general, you know, this is a 10-week study, so you wanna keep that in mind as you start evaluating structural change. If you start seeing a variable structure change, welcome that. Over a 10-week period, you're not gonna be able to derive final conclusion from, you know, what would happen. However, these patients have elevated intracardiac pressures. As you are modulating contractility and improving their hemodynamics and symptoms, you might be able to see something of their of some indirect measures of this elevated intracardiac pressure. In terms of your other questions, I think, you know, it's always difficult to compare across different studies.
I think, you know, my focus is mainly related to cohort 4 showing, you know, early and continued improvement in NYHA class beyond what I would have expected personally, as being involved in all these studies. That's beyond what I had expected to see from a myosin inhibitor over a short period of time. This is why this is encouraging to me as well as, you know, the effect on the biomarkers as well as the safety profile of the drug is also encouraging that we're gonna be progressing to a.
Thank you.
Thank you.
Fady, Oh, sorry, Fady, just a clarification. Why is the KCCQ measurement not complete? Is it just because it takes time to get all the answers and analyzed, or it just didn't make it into the poster and therefore not? Like, maybe just color on why we didn't have it this morning?
Right. Yeah, on the KCCQ, it just requires more analysis. You know, it's a multi-question questionnaire or survey. There are lots of domains, so it takes a fair bit of analysis, whereas, you know, NYHA class is pretty simple. It's I, II, III or IV, and it's easy to sort of put together. Given the timing of the data, you know, KCCQ will come out a bit later, like the echo data, which also are more complicated to analyze. We want to get you something, which we did a little bit. Some of the more complicated data will come out a bit later.
Thank you. We're very grateful for the data.
Okay.
Thank you.
Thanks for asking.
Our next question will come from Srikripa Devarakonda from Truist Securities. Your line is open.
Hey, guys. Congrats on the presentations and thank you so much for taking my questions. Sara Saberi commented about starting earlier and that having the biggest impact in, you know, even younger patients in obstructive HCM. Ahmad Masri, I was just wondering, based on what you've seen with the non-obstructive patients, does this apply to those patients as well? What would it take for that to actually happen?
Thank you. I'll maybe I'll ask Sara Saberi to answer that question in terms of do you make a comment about potentially starting earlier in the course of disease of OHCM? Do you think it applies to NHCM? You know, what do you think we might need to do in order to do that?
Sure. I do think that it would apply to patients with non-obstructive HCM as well. The finding of obstruction versus not is not necessarily defining a different disease process. It's the same disease process. It's just really a matter of where is the majority of the hypertrophy and is it basal enough in within the ventricle that it's actually causing outflow obstruction. In my mind, it's the same exact disease no matter whether you have obstruction or not.
I expect that the same exact outcome would be seen with the patients with non-obstructive disease, that if we were to be able to implement the drug earlier in the disease process, we would see likely less of a hypertrophy burden, and less of left atrial dilation and some of the other kind of complications that occur from the diastolic dysfunction that's a function of the disease itself.
Great. Thank you. You know, in your presentation, you talked about not seeing any instances of LVEF less than 50%, especially in the longer-term 48-week data.
Yeah.
I was just wondering if, you know, this has changed perspective in terms of potential for REMS program, for aficamten in any way. It may be a tough question to answer at this point, but just wondering if you're seeing this as a safer drug.
Yeah, maybe I can just rephrase that because I think it's, you know, REMS program is really in the regulatory domain. I think the real question you're getting at is what, given you've seen in FOREST-HCM, do you think, you know, ongoing monitoring of ejection fraction, things like that, do you think they're necessary from a clinical point of view?
It's I guess to put it into context, the MAVA-LTE data presentation in, at the 2021 ACC, we don't have a manuscript to be able to kind of compare with. Dr. Rader had presented data through week 60 in, at ACC 2021, in patients with obstructive HCM that were treated with mavacamten. At that point, they had had four patients with an LVEF less than 50%, and that range had been 44%-48%. By contrast, with our data, we actually have seen zero patients with an ejection fraction less than 50%. You know, I can't influence regulators and their decision-making in terms of this, but I think this contrast actually is a step in the right direction.
If we continue to see this type of data come in terms of safety and a lack of significant decline in LV systolic function, that regulators will actually see that as a defining difference between aficamten and mavacamten, perhaps they'd be more open to a less stringent REMS. it's hard for me-
Great. Thank you so much.
For them.
Yes. Got it. Thank you so much.
Thank you. We'll take our last question from Madhu Kumar from Goldman Sachs. Your line is open.
Good morning. This is Omari on for Madhu. We just wanted to know what the correlation was between NT-proBNP and cardiac troponin declines in NYHA Class improvement. What dose for the three patients who had a left ventricular ejection fraction below 50% at week 10?
Okay. Yeah, two questions there. I think, correlations between NT-pro, troponin, NYHA Class improvements. Those analyses, formal analyses, haven't been done yet for this study. Maybe Dr. Masri, you want to comment on how you think those might be correlated?
Yeah. As you mentioned, you know, more analysis will be forthcoming from the dataset. In general, based on our experience, as you influence patient symptoms and they feel better, you see a reduction in NT-proBNP and you see a reduction in troponin. Where you started with these biomarkers is very important. I know everyone likes summary numbers, but the reality is you need to look at the individual patient data to try to view as well and think about how they're doing. These tend to correlate but also depend on what other comorbidities do the patients have. Sometimes patients have increased clearance of certain of these biomarkers. You are still doing this over time, but a lot of these things are dynamic, including kidney function can be dynamic, you know, stressful situations, exercise intensity.
Some of these patients, as they feel much better, they start exercising a lot more. When they exercise a lot more, some of these biomarkers can actually fluctuate up and down a little bit. In general, they do correlate fairly well, the range that you have with NT-proBNP correlating with NYHA Class is a more tight range in terms of correlation because of how wide some of these patients have in terms of the reductions of NT-proBNP. That's a lot more specific than troponin. I can tell you in most practices, people follow more NT-proBNP. Few practices follow troponin. We follow troponin because it helps us tremendously in avoiding unnecessary CT when patients present with chest pain or present in the community. Troponins are very important. They predict outcome in patients with HCM.
However, their correlation with symptoms is not as tight as the NT-proBNP.
Great. Thanks for the question.
Thank you.
Thanks a lot.
I'd like to turn the conference back over to Dr. Fady Malik for any closing remarks.
Great. Well, I'd just like to thank everyone for the dynamic discussion today and all the questions and all the interest. As Robert said at the outset, we're pleased with the data emerging from REDWOOD-HCM and FOREST-HCM, and we look forward to beginning additional phase III clinical trials in patients with obstructive and non-obstructive HCM as we continue to elucidate the potential of aficamten in patients who greatly need new treatment options to address their underlying hypercontractility that is present in this disease. With that, operator, we can conclude the call.
This concludes today's conference call. Thank you for your participation. You may now disconnect.