Hello, and welcome to Edgewise Therapeutics' investor event. My name is John, and I will be the operator for today's call. I would now like to pass the call over to Edgewise Chief Financial Officer, Mike Carruthers. Please go ahead when you're ready.
Thank you, and good morning, everyone. Welcome to the Edgewise Therapeutics conference call to discuss our top-line data of EDG-7500 from the phase II series HCM 28-day trial in individuals with hypertrophic cardiomyopathy. This morning, we issued a press release which outlines these results. You can access the press release, as well as the slides that we will be presenting today, by going to the Investors and News section of our website at edgewisetx.com. A replay of the event will also be available as a webcast on our website. Joining me today are Dr. Kevin Koch, CEO, Dr. Robert Blaustein, Chief Development Officer, Dr. Behrad Derakhshan , Chief Operating Officer, and Dr. Alan Russel l, our Chief Scientific Officer.
As special guests, we have two serious HCM clinical investigators joining us: Dr. Ahmad Masri, Director of Hypertrophic Cardiomyopathy Center at the Oregon Health and Science University, and Dr. Anjali Owens, Medical Director at the Center for Inherited Cardiac Disease and Associate Professor of Medicine at the University of Pennsylvania. Before we begin, I'd like to remind you that some of our statements made during this call today are forward-looking statements and are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, including those described in our reports filed with the SEC. Your caution not to place any undue reliance on these forward-looking statements, and Edgewise disclaims any obligation to update statements. I'll now turn the call over to Kevin.
Thanks, Mike, and thanks to all of you today for joining us. I'm Kevin Koch, President and CEO of Edgewise Therapeutics. I'll introduce the company and provide a broad overview of our programs. Ahmad Masri, the Director of the Hypertrophic Cardiomyopathy Center at Oregon School of Medicine , will then present an overview of the imminent needs in hypertrophic cardiomyopathy. Anjali Owens, a cardiovascular fellow at the Hospital of the University of Pennsylvania, will then go over new data describing EDG-7500 in the 28-day study of CIRRUS. Rob Blaustein, Edgewise's Chief Development Officer, will speak to the design of our part D study for CIRRUS, and I'll finish up with closing comments and questions. Edgewise Therapeutics is a leading muscle disease pharmaceutical company. Our deep expertise in muscle physiology is driving a new generation of novel therapeutics for the treatment of muscular dystrophies and serious cardiac conditions.
I think we've got some really compelling data to provide you today on EDG-7500 for the treatment of obstructive and non-obstructive hypertrophic cardiomyopathy. We anticipate filing an IND in the second quarter for a second-generation 7500 analog targeting heart failure and other diseases of diastolic dysfunction. We have also a research program on a novel muscle-targeted mechanism for the treatment of obesity and cardiometabolic disease. Our second major asset, sevasemten, is a first-in-class, first type 2 myosin inhibitor for the treatment of Becker and Duchenne muscular dystrophy. We reported in December that we had positive results in our CANYON study. CANYON is the largest placebo-controlled study in a targeted Becker population ever completed. We had positive, statistically significant top-line results regarding muscle damage biomarker endpoints and showed strong positive trends regarding functional endpoints.
Overall, we showed disease stabilization in the treated group, with the placebo group declining, as predicted by multiple recent natural history studies. We also reported that the GRAND CANYON pivotal study for Becker completed enrollment with 175 patients. We are meeting with the FDA this quarter to discuss options and timing for the approval of this agent in a population with no approved therapies or treatment options. Now let's turn to HCM. HCM is the most common genetic cardiovascular disease. While the diagnosis can be made at any age, especially now with familial genetic testing, HCM is most commonly identified when patients are in their 30s and 40s. HCM patients display both hypercontractility coupled with pathologic diastolic dysfunction characterized by the inability to relax the ventricle to fully fill with blood.
Current treatments for HCM, including surgical and pharmacologic approaches, have key limitations that leave substantial gaps in the treatment of HCM patients. These include the limited efficacy of drug therapies, including beta-blockers, calcium channel blockers, and most recently, cardiac myosin inhibitors, or CMIs. There are no approved therapies for the treatment of non-obstructive HCM. Cardiac myosin inhibitor efficacy is limited by the mechanism of action, which is associated with reductions in left ventricular ejection fraction, requiring monitoring and dose adjustment, driving a black box warning for Mavacamten, the first-generation CMI. This limits a clinician's ability to easily and safely prescribe Mavacamten because of concerns about the risk of development of heart failure in patients. Additionally, the black box warning mandates multiple echo measures to ensure that patients do not go below a threshold ejection fraction of 50%. EDG-7500 is a novel sarcomere modulator for both obstructive and non-obstructive HCM.
Preclinical and early clinical studies in both normal healthy volunteers and obstructive HCM patients demonstrate that EDG-7500 can potently reduce gradients, a measure of cardiac obstruction, and uncouple these reductions from changes in left ventricular ejection fraction. No drug concentration relationship was observed on ejection fraction reduction with EDG- 7500. Additionally, NT-proBNP, a potential measure of diastolic dysfunction and heart failure, was rapidly decreased in a dose-responsive manner. I'll turn the presentation to Dr. Masri to discuss in greater depth the unmet medical need in HCM.
Thank you, Kevin. Happy to be here to discuss the unmet need in hypertrophic cardiomyopathy. When we talk about the unmet need, one has to realize what the continuum in HCM is. Myocyte hypertrophy, interstitial fibrosis, and atherosclerotic dysfunction do underlie the continuum of HCM. We sometimes think of purely obstructive patients and purely non-obstructive patients, but the reality is that the majority of the patients are somewhere in the middle because they have shared characteristics of both of these in a way distinct but interconnected pathophysiology at the same time. As such, we really shouldn't continue in the future to think about these as distinct entities. They do have a lot of shared characteristics, and that's what underlies a lot of the unmet need in hypertrophic cardiomyopathy. When we think of HCM disease complexity, it really requires thorough and thoughtful evaluation.
That's why it's still a complicated disease, even though it's been described and it's been around for many, many decades. Despite our mature understanding of the disease, it still does present a complex problem to many of our physicians and many of the individuals who evaluate this disease. We do have numerous tools at our hand that allow us to evaluate and phenotype patients, but ultimately, the most important thing to think about is how is the patient feeling, how is the condition affecting the patient's life, and how is it affecting their quality of life. When we think about the burden of hypertrophic cardiomyopathy, it is substantial. If you look at different studies, you do have some controversial findings here and there in terms of some studies telling us that patients are doing great and the unmet need is small.
If you look at bigger studies, which included many patients from many centers and tried to look at the lifetime burden of hypertrophic cardiomyopathy, as well as when the disease onset started and how people did over time, the burden is really substantial. These are data from the shared registry, thousands of patients, and these were curated outcomes. If you look at an overall composite of serious outcomes, such as ventricular arrhythmias, heart failure, and atrial fibrillation, you can see how burdensome the disease is. Take an example of heart failure composite. If you develop hypertrophic cardiomyopathy below 40 years of age, 40-60 or so, your risk of having cumulative incidence from birth for heart failure goes all the way up to 60%, 70%. The same thing applies for atrial fibrillation, and much less so for ventricular arrhythmias, but still very burdensome.
If you try to compare that to how the U.S. population is, even though these comparisons are limited, patients with HCM do suffer from increased incidence and rate of mortality compared to age-matched populations as well. When we think about the unmet need, we also should think about what are the goals of therapy in hypertrophic cardiomyopathy. We do want rapid and consistent relief of symptoms. We want improvement in quality of life for our patients, improvement in their exercise capacity, and we do want to achieve favorable remodeling because we think if we achieve favorable remodeling, we will in turn have less complications and overall better outcomes. It's hard to study hard outcomes in hypertrophic cardiomyopathy, but this is a chronic, morbid, disabling disease, and that is why we really focus on how patients are feeling and our ability to improve their exercise capacity.
When we think about the unmet need, when it comes in line with these goals of therapies, one is non-obstructive HCM. There are no approved therapies for non-obstructive HCM, and right now, if I meet a patient in the clinic, really what we offer them is clinical trials because the different therapies that are recommended in this space are not very effective at this stage. In obstructive HCM, there still remains significant unmet need as well. You do have patients who do not respond to our current therapies. You have patients who have mild obstruction but severe symptoms, and those typically are driven not by the obstruction. They are typically driven by diastolic dysfunction, by LV stiffness, by other factors that require to be addressed, not just the obstruction itself. Diastolic dysfunction underlies a lot of the disease pathophysiology, as we spoke about before.
Finally, the monitoring burden. While a lot of the medications and a lot of the procedures that we have done over the years allow you to treat patients and achieve a reasonable response, you are still with newer therapies such as CMIs and commercially available Mavacamten, for example, to us, is that you do have a monitoring burden, and you have to continue to monitor for systolic dysfunction. This is not just related to initiation of a drug. You have to continue to do that throughout the follow-up for the patient as well. In terms of the ultimate principles of therapy here, it is to improve quality of life based on the ACC/AHA guidelines.
We always want to have objective data to support that we are achieving other objective markers that support that the quality of life improvement is related to what we are doing in terms of an intervention, but that's the ultimate goal. When you have patients come back in the clinic, the ultimate goal is how are you feeling now compared to where you were feeling before you were started on the therapy. KCCQ, for example, is an important metric and measure now becoming a very standardized measure in our different clinical trials. It's a validated tool in heart failure patients and in hypertrophic cardiomyopathy nowadays. It's also a prognostic tool. The degree of reduction in KCCQ is associated with outcomes in heart failure with reduced ejection fraction as well as with preserved ejection fraction.
Beyond the directionality of how KCCQ essentially is, it is a robust measure of the magnitude of benefit, and we have seen this being reproducible across many different disease areas, not just hypertrophic cardiomyopathy. Now I am happy to hand it over to Dr. Owens.
Hello, and thank you for the introduction, Dr. Masri. I'm looking forward to sharing the results of the CIRRUS-HCM trial, part B in obstructive HCM and part C in non-obstructive HCM patients with you today. As a reminder, we previously reported results of the single-dose study in obstructive HCM patients, which showed a 67% reduction in LVOT gradients at rest, 55% reduction in LVOT gradients with Valsalva, without a reduction in LV ejection fraction. We also observed a dose-dependent reduction in NT-proBNP starting as early as eight hours after a single dose, with a 30%-60% reduction after 24 hours in the 100 ml and 200 ml dose cohorts, respectively. The focus of today's call will be the results of the 28-day fixed daily dosing in patients with obstructive HCM in part B and patients with non-obstructive HCM in part C.
This study included adults with HCM identified by the site PI who had LVEF greater than 60% at baseline by site read echo. For this study, doses of 50 ml and 100 ml once daily were tested. Let's move on to the baseline patient characteristics. As you can see from the table here, the non-obstructive HCM patients were slightly younger than the obstructive patients. Both parts B and C enrolled a majority of female patients, and between 35% and 50% of patients were NYHA class III, so severely affected. Baseline gradients in the obstructive group were severe, and Valsalva gradients were even higher than what we have seen in trials of cardiac myosin inhibitors. There were 6%-17% of patients at baseline who had a history of atrial fibrillation.
Now that we've entered the era of cardiac myosin inhibition being used as part of standard of care for obstructive HCM with FDA-approved Mavacamten and a number of patients on the next-in-class agent aficamten as part of long-term open label studies, we are starting to see a shift in the baseline characteristics of patients who choose to enroll in clinical trials of novel agents such as EDG-7500. It's certainly a bit more challenging to enroll patients when there is an option to go straight to an FDA-approved targeted therapy. As a reminder, we pre-specify the efficacy evaluable population for an LVOT gradient as patients in part B who received at least one dose of 7500 and had a baseline LVOT gradient greater than or equal to 30 mmHg measured at rest and greater than or equal to 50 mmHg measured during Valsalva.
This is determined by echo with adequate acoustic windows that were necessary for inclusion. Let's start with the part B data. When we looked at gradient data to determine the efficacy of valuable population, we found that two patients on the 50 ml dose and three patients on the 100 ml dose were removed because they didn't meet the gradient criteria. This results in a total of 17 patients who were counted in the safety population and 12 patients in the efficacy population. The next slide breaks down the gradient changes seen in patients at rest and with Valsalva. The patients who received 50 ml are represented by the lighter blue line and those who received 100 ml by the darker blue. Resting gradients are on the top panel and Valsalva gradients on the bottom.
The resting gradient in this efficacy evaluable group was in the 70s at baseline, which is quite severe, and greater than 100 mmHg with Valsalva. These are core lab reads, and they are higher than the three phase III trials of cardiac myosin inhibitors that we have seen published thus far. Despite these very high gradients, we observed robust reductions, including a 71% decrease from baseline in the 100 ml dose cohort, with over 80% of patients achieving a resting gradient less than 30 mmHg and a Valsalva gradient less than 50 mmHg . Of note, we also saw gradient reduction at the 50 ml dose. As this was a phase II dose-finding study, we did not optimize individual patient dosing. This will be studied in part D and phase III.
Also of note, the gradient measurements were taken at trough for this study and not at Cmax, which is distinct from what other development programs have done. With regard to the gradient reduction in the safety evaluable population, we saw greater than 80% of patients at the 100 ml dose achieve an LVOT gradient less than 30 at rest and less than 50 with Valsalva. In this population, some patients had lower gradients to start with. Next, I'm showing results of NT-proBNP changes. NT-proBNP is a key marker of myocardial stretch and heart failure in HCM patients, and it is associated with poor outcomes long term. The magnitude of response that we saw was similar to what we observed with a single dose, which was measured at trough in that single-dose study.
The response that we observed was dose-dependent with a robust reduction of 62% in the 100 ml cohort, with over half of patients on that dose achieving a completely normalized NT-proBNP within just four weeks of treatment. We know from prior published data from the CMI trials that improvements in NT-proBNP strongly correlate to improvements in PCO2, a measure of functional status objectively, so this is very encouraging data. Interestingly, when you couple with the marked improvement in biomarkers, we also observed an increase in e' velocity that was dose responsive. E' improved by approximately 20% from baseline in the 100 ml dose cohort, suggesting improved diastolic function potentially as a reason for the improved biomarkers. To expand upon this improvement in e' , we looked at other markers of diastolic function, including e/e' and left atrial volume index.
In particular, the e’ Septal velocity improved in a significant percentage of patients who had abnormal baseline values, with almost half of patients normalizing e' after four weeks of treatment. This improvement, to me, ties into EDG-7500's mechanism of action and selectively improving diastolic function without effects on systolic function. Next, I'm showing changes in quality of life as measured by the KCCQ score. For the overall summary score, 89% of patients receiving the 100 ml dose had improvement in KCCQ- OSS with a mean increase of 23 points. This is very encouraging data, even with the limitation of an open label trial, and the response was dose-dependent from 50-1 00 ml. If you take the mean change in KCCQ- OSS in the context of changes that we've seen in CMI trials, this remains an impressive change.
In the RCTs that I have shown on this slide, the placebo groups tended to have a change of five to seven points, and the placebo-adjusted change in KCCQ was typically in the range of seven to 10 points. We are seeing with EDG-7500 data at 28 days a significantly larger change, which, of course, is a good first step, albeit in an open label design. If you dive deeper into the breakdown of the 89% of patients on the 100 ml dose who said they felt better, this is driven by 78% of patients who reported a very large improvement in KCCQ defined as greater than or equal to 20 points. Given that in our HCM patients, hard cardiovascular outcomes are fortunately relatively rare, we are really focused on improving feel and function for both clinical and regulatory endpoints, so this KCCQ data is quite important.
Next, we looked at NYHA functional class, where we saw that 78% of patients who received the 100 ml dose had greater than or equal to one functional class improvement, with approximately 67% of patients achieving class I. This data, again, is in the context of an open label study design, but is encouraging as we move into phase III. Next, let's discuss data from part C, the patients with non-obstructive HCM. This is a breakdown of the non-obstructive cohort, which was comprised of 12 patients who were evaluated as the safety population and eight patients who completed all four weeks of treatment, six patients at the 50 ml dose and two at the 100 ml dose. These eight patients were evaluated for LVEF, e' , KCCQ, and NT-proBNP.
Similar to the obstructive HCM patients, we observed a robust reduction in NT-proBNP in the non-obstructive group, on the order of a 50% decrease from baseline values. Notably, this change occurs early. It is present by the first set of follow-up labs at just one week of treatment, and that benefit is sustained in those who completed the four weeks. Changes in e' as a marker of improved diastolic function were also observed. This, again, was a small number of patients, but an encouraging signal after only four weeks of treatment. In some of the trials of cardiac myosin inhibitors, we had to wait a longer duration to see benefits in diastolic function. I want to spend a little bit of time on this next slide, which shows changes in KCCQ- OSS and CSS in the non-obstructive patients who received 50 and 100 ml.
The magnitude of change was quite large and encouraging. It ranged from nine to 22 point improvement, and we saw that even at the 50 ml dose level, albeit in an open label design. By comparison with prior CMI trials, we did not see a change in KCCQ in the double-blind placebo-controlled phase II MAVERICK trial of Mavacamten, and we saw an approximately 10-point improvement in the REDWOOD cohort IV study of open label Aficamten. Again, in this patient population of non-obstructive HCM, where we do not have a biomarker of elevated LVOT gradient to target as a marker of efficacy, it's really important to find other measures of efficacy, including patient-reported outcomes and also measures of function. Now that we have discussed efficacy, which looks quite promising, let's turn our attention to safety, starting with ejection fraction.
On the left side of this slide is the change in LVEF in the obstructive HCM cohort, and you can see that there is a negligible change in LVEF on the order of approximately 2% from baseline to week four by core lab read. Importantly, there was no correlation seen between plasma concentration and LVEF change. Baseline LVEF in this obstructive HCM cohort was more similar to the VALOR patients who had LVEF in the high 60s as opposed to the EXPLORER and SEQUOIA patients who had LVEF in the low 70s at baseline. On the right side is the change in LVEF in the non-obstructive HCM cohort, and you can see there was really no change at all.
In fact, I'll call your attention to the table at the bottom of the slide where there were four patients who, by core lab read, had LVEF less than the 60% threshold that was required for site read inclusion. Even in those patients who had a lower starting EF, some as low as the low 50s, there was no change in systolic function after dosing with EDG-7500. There were also no patients in the study who experienced an LVEF less than 50%, and this was at doses that show promising efficacy. These are still small numbers, but very encouraging results. If we are able to have an agent where we can uncouple the risk of dropping LVEF with the desire or need to increase dose, we can perhaps focus on titrating dose based on feel and function without needing serial echoes for safety.
Here's a slide with a table summarizing the treatment-emergent adverse events that occurred during the study. Of special interest are any cardiac-related TEAEs. We saw approximately 28% of patients who reported transient dizziness. We've also seen dizziness in trials of patients on cardiac myosin inhibitors, where it's typically transient after starting the dose or dose increase. Four patients in the study had atrial fibrillation, and three patients had palpitations. Atrial fibrillation, we know, is part of the disease of HCM. We see in population-based studies anywhere from 25%-30% of patients who have AFib, and certainly those percentages grow as the patients are sicker and more symptomatic. A deeper examination of the four patients who had newly diagnosed AFib was conducted post hoc. Three were in the obstructive group and one in the non-obstructive group.
One obstructive patient who received the 100 ml dose was found to have significant mitral regurgitation and an enlarged left atrium, typical of obstructive HCM. One patient who received the 50 ml dose was found to have severe mitral annular calcification with intrinsic valve disease, mild to moderate mitral stenosis, and did not meet wall thickness criteria diagnostic of HCM by an external independent echo reviewer. Another patient who received the 100 ml dose also had hypertension, thyroid disease, COPD, and diabetes, and did not meet wall thickness criteria diagnostic of HCM by an external independent echo reviewer. The final patient who had non-obstructive HCM received the 100 ml dose and had, at baseline, left atrial volume index greater than 50 and left atrial size of 6 cm. None of the patients who developed AFib had an LVEF of less than 50%.
This next slide has detailed data on AFib rates across phase II and III studies from the cardiac myosin inhibitor class of medication. This is a lot of data on this slide, and you may want to take some time after to review it, but we see varying rates by study design, including dosing algorithm, time of follow-up, and by agent. In the CIRRUS study, as a phase II dose-finding study, we do not have a placebo comparator arm. In addition, a dosing strategy typical of a phase II trial design was employed, with fixed dosing for 28 days and dose escalation by cohort. In general, we have seen a trend towards lower AFib rates when moving from phase II to phase III trials in the CMI class.
Perhaps this is due to refining inclusion criteria or due to a slower individualized dose escalation strategy, which may minimize the acute hemodynamic effects of drugs that we know can modulate sarcomere function and are rather potent. Certainly, we will gather more data in this regard as development plans for EDG-7500 progress. In summary, EDG-7500 is emerging as a potentially exciting therapeutic option for both obstructive and non-obstructive HCM patients. The potential for EDG-7500 to improve LVOT gradients, NT-proBNP, markers of diastolic function, KCCQ, and NYHA, importantly, without reduction in LVEF, could allow treatment of a broader population of HCM patients without the need for serial safety echoes.
EDG-7500 appears to be generally well tolerated across a broad exposure range, and refinement of patient selection criteria, slower dose escalation strategy, and individualized dose optimization may serve to minimize risk of adverse events and deepen clinical benefits heading into a larger placebo-controlled trial. I'd now like to turn it over to Dr. Blaustein to walk through the future development plans.
Thank you, Dr. Owens. part D of our phase II CIRRUS study will build on the prior encouraging data from parts B and C that you've just seen. The goal of part D is to optimize the safety and efficacy of EDG-7500 using an interpatient dose escalation strategy.
During the trial, we will be acquiring a comprehensive data set that includes echocardiography indices, feel and function measures, and biomarkers that we will carefully analyze at the end of the study to help determine the dose optimization strategy that we will eventually employ in phase III. As illustrated in the slide, our approach for part D for both non-obstructive HCM patients and obstructive HCM patients is to further explore the minimally effective dose by having all participants start at 25 ml a day. After two weeks, the dose will be increased in all participants to 50 ml for another two weeks. At this point, they will undergo testing by echocardiography, measurement of NT-proBNP, and assessment of feel and function by KCCQ and New York Heart Association class. This is represented by the arrow at week four in the figure.
Based on the extent of reduction in their left ventricular outflow tract gradient and potentially taking into account improvements in NT-proBNP and KCCQ score, a decision will be made for those with obstructive HCM to either increase their dose to 100 ml for four weeks, or if they have achieved sufficient benefit from the 50 ml dose, they can remain on that dose for the remainder of the study. Those with non-obstructive HCM will advance to the 100 ml dose unless they have clearly benefited from the 50 ml dose based on their reduction in NT-proBNP and improvement in KCCQ score. After four weeks, participants will again undergo the above testing as indicated by the arrow at week eight. For those currently on 100 ml a day, a determination will be made regarding the need to increase their dose to up to 200 ml a day.
Now, we feel confident that we can evaluate doses as high as 200 ml if needed, given our observation that achieving substantial efficacy does not come at the expense of any meaningful reduction in left ventricular ejection fraction. We plan to leverage learnings from the CMI trials and will modify the inclusion and exclusion criteria for part D accordingly. Prior to entry into the study, all participants will undergo careful screening by the investigator and sponsor to ensure that they meet these entry criteria and are appropriate for inclusion in the trial. I will conclude by pointing out that we remain committed to providing continued access to EDG-7500 after 12 weeks of treatment. Therefore, all participants will have the opportunity to remain on their optimized dose by enrolling in a long-term extension. I will now han d it back over to Kevin for some concluding remarks.
Thanks, Rob.
That was a great presentation. I'd like to summarize our differentiated profile of EDG-7500 for the treatment of hypertrophic cardiomyopathy. Based on our observations to date, we've identified a molecule that does not require the reduction of ejection fraction to provide disease amelioration as measured by gradient reduction and biomarkers such as NT-proBNP. As shown in this slide, we saw no meaningful relationship between concentration of the drug relative to ejection fraction changes, no patients dropping their ejection fraction outside of the range defined by the placebo group in gray dots on the left portion of the slide of plus or minus 12%. Additionally, no patients dropped below the 50% ejection fraction threshold for heart failure. Turning to the comparison with Mavacamten in phase II data, we believe our data clearly differentiates our mechanism from the cardiac myosin inhibitors, which requires drops in ejection fraction to demonstrate clinical benefit.
As you can see on this slide, Mavacamten has multiple measures falling below 20% on ejection fraction outside of the placebo range. Even more impressive, we were pleased to see significant benefit on feel and function measure change in New York Heart Association scores, where several patients became asymptomatic and outsized improvements in the KCCQ scores. Just to level set you on how strong these KCCQ scores increases are, we aggregated results from several heart failure studies from recent years and determined that the magnitude of benefit appeared superior to all pharmacologic interventions, including CMIs, and that our activity was approaching invasive surgical interventions like septal reduction therapy or aortic valve replacement.
On the next slide, you can see that we achieved these broad positive results in a patient population that was arguably more medically complex than previous CMI trials with higher levels of baseline comorbidities like prior septal reduction therapy, higher hypertension, a greater percentage of class III patients. Additionally, we had lower levels of baseline ejection fraction, increasing the risk of going below 50% threshold and higher baseline levels of gradient. What is our hypothesis of why we're seeing these large changes in feel and function? Since I'm not a cardiologist, from a simple sense, a mechanism that requires the ambition of systolic function, as with the cardiac myosin inhibitors, may have some benefit in relieving gradient and decreasing wall stress, but at the expense of lowering ejection fraction.
While ejection fraction measures have been recognized as a marker of safety and a predictor of heart failure, by definition, decreasing total blood pumped by the ventricle after contraction would be expected to blunt how a patient feels. In contrast, EDG-7500 was designed to be more potent on diastolic relaxation of the ventricle. It does not cause decreases in ejection fraction, thus affording the full potential of a sarcomere modulator with the resulting large improvements in measures of feel and function. It should be noted that AHA guidelines that state gradient should not be used to select dose for obstructive HCM patients, as it is too variable, and that dosing should be optimized based on feel and function measures.
In summary, EDG-7500 has a strong safety profile with no drops in ejection fraction outside of the noise in the measure with substantial improvement in function, symptoms, and quality of life measures in HCM patients. Since we have not observed any patients go below the threshold of 50% in ejection fraction, we may not need echo measurements for safety, which would expand the utilization of our therapeutic mechanism into community cardiologists outside the centers of excellence. We observe rapid effects on multiple diastolic parameters, broadly an important driver of pathology in heart failure. We will utilize interpatient dose optimization to drive maximal benefit for each patient using a combination of biomarkers, feel and function, and echo measures as utilized in cardiac standard of care strategies. Moving on to our major company milestones for 2025.
For our cardiovascular programs, we will continue with our CIRRUS- HCM data release at the end of the year with top line from the 12-week portions of the study in obstructive and non-obstructive HCM. Also, we expect to file an IND for a second-generation 7500-like molecule for the treatment of heart failure, including HFpEF. For our muscular dystrophy program, we expect feedback from the FDA regarding a potential accelerated approval path for the use of sevasemten for the treatment of patients with Becker. Also, in the first half of this year, we will disclose dose-ranging data in patients with Duchenne, evaluating functional measures and biomarker responses, which will guide our phase III design. Turning to our financial position, this morning we announced that we raised $200 million from top-tier healthcare investors, bringing our cash position to $660 million with no debt and runway through 2028.
This will support the potential U.S. commercial launch of sevasemten in patients with Becker, advancement of phase III trials in sevasemten in Duchenne, complete phase III trials of EDG-7500 in patients with obstructive and non-obstructive hypertrophic cardiomyopathy, advance our second-generation cardiovascular asset into heart failure trials, and support our other ongoing research programs. In conclusion, I'd like to personally thank everyone who's chosen to support our mission, particularly our dedicated employees and their families, as well as our shareholders. Most importantly, I'd also like to thank our patient community, trial participants, their families, and clinical investigators, especially Dr. Masri and Dr. Owens, who have all been integral in our success.
It's been an exciting time here at Edgewise, and I truly believe we are on the cusp of demonstrating the potential of our therapeutic agents that could help to improve the lives of patients in need of more effective treatments. Thank you all for joining the call. We'll be happy to take any questions, and I'll hand it over to the operator.
Thank you. We will begin our question and answer session. If you have dialed in and would like to ask a question, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, simply press star one again. If you are called upon to ask a question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question.
We kindly ask each person to limit themselves to one question only. Our first question today comes from the line of Joe Schwartz from Leerink Partners. Please go ahead. Your line is now open.
Thanks, and congrats on the continued strong progress in data. I have a question on efficacy and another on safety. First, on efficacy, it looks like you're seeing really encouraging signs in terms of biomarkers like NT-proBNP and clinical measures like NYHA and KCCQ. How much of this is being driven by changes or lack of changes on diastolic versus systolic function, do you think? What do you think it could translate into in terms of peak VO2 in phase III?
Yeah, it's interesting. We're the first true leucotropic molecule that has seen these kinds of rapid diastolic responses within a week.
The easiest thing to say is that that direct diastolic effect on the relaxation of the ventricle is driving the outsized efficacy signals we're seeing. I guess from another standpoint, you can look at the CMIs in general and say, you know, lowering ejection fraction from, say, 70 to 55, why would one expect that to provide benefit to a patient? Certainly, if you take a patient from, say, 55 to 40, you would observe patients having fatigue during exertion, shortness of breath, and other measures of feel and function would go down. I think from my perspective, we're seeing both the absolute benefit of a sarcomere modulator coupled with our diastolic effect, and with the CMIs, you're seeing a blunting of the effect because they lower ejection fraction. We have intrinsically a competitive advantage over the CMIs on feel and function measures.
As has been described by multiple folks on this call today, feel and function is what drives community physicians to prescribe a drug for hypertrophic cardiomyopathy. I am quite confident that we will have a truly beneficial drug to a wide range of patients in this space.
Great, thanks. On safety, this might be for the KOLs or the company. In terms of the AF, which has been seen here, how does the AF incidence here strike you relative to what you are seeing in HCM patients who receive the current standard of care? How much do you think this can be managed by patient selection and dosing optimization in phase III?
I think we will start with Anjali and then Dr. Masri can address this point as well.
Great, thank you.
In terms of what we see in the population of patients with HCM, in general, we see about 25%-30% of patients with atrial fibrillation. That increases based on risk factors, including age, left atrial size, and the more symptomatic you are, we see higher rates of AFib. On our current CMI, which is FDA-approved Mavacamten, we published work showing about 11% of patients with either new onset or worsening of AFib after starting commercial Mavacamten. Importantly, those patients were able to be managed, and they did not have to stop their CMI therapy. You do have to manage AFib when it occurs. That includes the use of antiarrhythmic agents and/or cardioversion to bring patients back into sinus rhythm. It is part of this disease, but it is manageable.
Dr. Masri, perhaps you could describe—you actually reviewed the echoes associated with our AFib patients.
Maybe you might describe the extent of the disease and the complex medical nature of their background comorbidities.
Sure. I think ultimately, when you look at HCM patients, as I've shown, it's a pretty wide spectrum. It's a continuum. Depending on where you fall on the continuum, that dictates your comorbidities, that dictates what your outcomes are and what complications you could develop. Ultimately, AFib is an important piece of the HCM story, and you have to look for it, monitor it, and see what's going on with these patients. Now, from a phenotype perspective, typically, the more restrictive a heart looks like, and the less left ventricular hypertrophy you have, and the more valvular disease you have, the more likely you're going to develop atrial fibrillation, as well as the more metabolic risk factors you have. That typically would be taken into account.
When we see patients in the clinic, you do classify patients as patients who are likely to have arrhythmias and atrial fibrillation and patients who are less likely to have that. I do not think it is kind of a one-size-fits-all that it is just a number and everybody is at the same risk. I fully agree that there is a spectrum there. Some of the cases that I have reviewed are falling on the spectrum of being very high risk for developing AFib as well.
Thank you, Dr. Masri.
Very helpful. Thank you.
T he next question for today comes from the line of Laura Chico with Wedbush . Please go ahead. Your line is now open.
Hi, thank you very much for taking the question. This is Dylan on for Laura Chico.
We're just wondering, could you talk about the part D study in terms of the expectations for it to inform more on the durability of effects? In the initial 28-day study, you're seeing a rapid reversal of effects after drug removal. With longer administration, we're wondering what would be the potential for remodeling of the heart and greater durability of effects? Would this be something that part D results can inform o n?
I'll take the first part of that, but Dr. Blaustein will take perhaps discussion of the trial itself. We've seen remodeling in the preclinical studies in non-obstructive HCM. We would expect to see the same in the obstructive HCM. We don't have an intermediate time point. Originally, in the preclinical models, we saw—or at a five-month time point.
I would suspect we would see some deepening of response at 12 weeks, but the magnitude of that, I think, really depends on getting that data. Maybe, Dr. Blaustein, maybe speak to the trial design and aspects of the other parts of the question.
Sure, thank you. I think Dr. Owens teed it up pretty nicely when she talked about our data and the fact that a dose optimization strategy of the sort that we're proposing for part D is likely to improve both efficacy and the safety profile. The durations of treatment at each of these dose escalation epics should certainly be enough for us to really get a sense of what efficacy is like at that dose level. Four weeks at each dose level, that's probably early to see remodeling. We've seen changes, obviously, as early as a few days to a few weeks.
I think having a longer-term extension and the ability to see changes over the course of, say, about a year will let us understand the potential for remodeling even better.
I think maybe just one more comment is that from the 50 ml and 100 ml data, we've noticed that there are some patients who benefit from the 50 ml dose. This dose optimization strategy optimizes the dose and efficacy for each individual patient. I suspect that we will get to a place where 20% of the patients will be quite well treated at 50 ml, perhaps 60% at 100 ml, and some smaller percentage at a slightly higher dose. As you saw with our data set, we saw robust efficacy at 100 ml. I would estimate many of the patients will ultimately be at that state.
Now, in the non-obstructive patients, we saw virtually or no change in ejection fraction, which is quite different from the CMIs, so that we anticipate that we can go up higher in the non-obstructive patients. Since KCCQ is the primary endpoint for the phase III trials in non-obstructive, I think really bodes well to the potential of this drug in non-obstructive, where there's no need for a gradient, and you're looking at feel and function measure as a way of titration.
Thank you.
The next question today comes from the line of Tessa Romero from JPMorgan. Please go ahead. Your line is now open.
Hi, team. Thanks so much for taking our questions. For the doctors, can you contextualize the risk-benefit profile for EDG-7500 in this population and also contextualize the risk-benefit profile to that of the CMIs based on the known data?
For the company, given you know the target of EDG-7500 specifically on the sarcomere, how comfortable are you that the drug is not causing the AFib that you are seeing? Thanks so much.
Why do we not start with Dr. Masri on the first question? Which is the risk-benefit relative to the CMIs, I guess?
Yeah, I think it is too early, really, to do these comparisons. You are looking here at a small sample size and short-term follow-up. I think what you are looking for is that you are seeing efficacy, and you are seeing efficacy on multiple domains, and you are seeing patients who had atrial fibrillation. As you continue to go through your phase II and potentially also phase III, you want to keep that in mind.
You want to continue to focus on the efficacy that you want to achieve while monitoring for safety, monitoring for atrial fibrillation, which would develop in the patients or not. You can really get to that. I do think it's quite early to look into this. I think the principle is when you ask me, for example, when we're using commercial Mavacamten, I think the principle is that monitoring burden for the use of commercial Mavacamten is substantial. That's one. The second thing, which is data we showed at ACC, what's emerging for us, also what's emerging is not just the monitoring burden. What's emerging is there is the risk of heart failure with the commercial real-world data set. There is the risk of also atrial fibrillation. The data we've shown was 5% of patients had new onset AFib.
I think it's difficult this early on to do a detailed comparative analysis. I would say that we would want to generate more data. While you're generating data here, you are also looking at what's going on with the commercial Mavacamten use at the same time as well.
Dr. Owens, any additional comments?
I agree. It's small patient numbers. I think if you compare, for example, I was an investigator of the PIONEER study, which was the phase II trial for Mavacamten. We saw about 20%-25% AFib in that dose-finding phase II study of Mavacamten. Of course, we're using doses of 10, 15 ml of Mavacamten. These trials are used to learn about the molecule. We frequently see that there is a change in the risk side effect profile once we optimize those selection patient selection.
I do think that it is early. If comparisons are to be made, it should be with other phase II trials.
In regards to the target, we have not described the target of this drug. There's been no preclinical work or clinical work to actually ascribe any risk of AFib associated with it. We've never seen that in any of the preclinical models. I would also point out that we ran normal healthy volunteers for 14 days. We saw in normal healthy volunteers, we saw over 14 days, we saw no effect on and no AEs. We had ECG monitoring within the 100 ml dose. That 100 ml dose produced CK that was as high or higher than what we observed from the HCM patients. There's no signal.
From our perspective, this is entirely driven by individual patients with high levels of comorbidities and not dose-related and not mechanism-related.
Thanks so much. Congratulations on the progress.
The next question today comes from the line of Yasmeen Rahimi with Piper Sandler. Please go ahead. Your line is now open.
Good morning, team. And congrats to the outstanding data. I think as the call is going in the direction of AFib, I feel like we really need to kind of come back to what the thesis of the molecule was, which is to show diastolic improvement. And you just did that with your data sets on obstructive and non-obstructive. And you both of our thoughts, KOL, highlighted that. Would love to ask two questions in that relation.
One, obviously, that not only unlocks the opportunity in non-obstructive population as well as obstructive, but it could also work in diastolic heart failure. Given the diastolic properties that you see, how do you think about development further? That is question one. Question two is the profound change that you are seeing at four weeks with KCCQ, which makes you wonder that at six months, it could get better. Therefore, you could run a registrational study based on KCCQ as a primary endpoint and have it on their label to truly make function and feel patients better. Could you maybe talk about those aspects? I think the whole AFib thing, you are going to work it out through patient selection and dosing. The bigger picture is maybe something we need your help on that I think is more important. Sorry for the long-winded commentary here, but if you could tackle that.
Thanks, Yasmeen. I think the diastolic effects are unprecedented. I do not know if there are any other examples where within seven days, you see these kinds of robust changes on e' . Of course, it is early here, but it is the underlying pathology of heart failure and disease. It does appear to be at least contributing to the tremendous efficacy we are seeing on the KCCQ scores. I think I noted that the primary endpoint of KCCQ is the primary endpoint most liked by the FDA for things like non-obstructive HCM. For Dr. Blaustein, though, it would be useful to talk about how a drug with a true diastolic effect might be used in cases of HFpEF and other in heart failure and how that would fit within the therapeutic regimen in the heart failure space.
Sure. Yeah, thank you.
Certainly, diastolic improvement would play a key role in the treatment of really any form of heart failure, be it heart failure with preserved ejection fraction or even heart failure with reduced ejection fraction. I think a more attractive population to study would be the HFpEF population. Obviously, for many years, we did not have any drugs approved for HFpEF. Now, we do have a couple. It is becoming a little trickier in terms of development. I think having that key diastolic improvement puts us in a really nice position to leverage this mechanism. We could, of course, think about HFref, but I think heart failure with reduced ejection fraction perhaps is a bit more challenging given the large number of currently approved therapies. I think going after the preserved population probably would fit most closely with the mechanism and is something we are very excited about leveraging.
Dr. Owens, maybe weigh in on the potential of a diastolic agent for the treatment of heart failure as well?
Absolutely. Heart failure specialists, we are searching for agents that can affect dysentropy and improve diastolic function because it's a driver of disease in many heart failure states. I think seeing that robust change in NT-proBNP is quite promising as a potential mechanism of providing benefit in a larger population of patients who suffer from the underlying problem of diastolic dysfunction and stiff ventricles. That comes along the spectrum of systolic function. I think it is encouraging data, albeit small numbers, and the potential may be there for additional popul ations.
Thanks, Dr. Owens.
Thank you. If I may just squeeze one question in. Are you modifying your sort of selection of patients as you're continuing to go up in higher doses?
Is there any stratifications or modifications that are going to be made in terms of the protocol for series? Or is it just to learn from series and make those changes in phase III?
No. Actually, the part D has extensive changes. We'll move to a core lab read instead of a site lab read of the echoes for inclusion into the trial, which would include a clinical steering committee to evaluate patients in a more rigorous way before they enter into the trial. This was exactly the approach taken by the CMIs going from phase II to phase III. We also would increase the looking back in the medical records, go back further than 90 days, go back to at least 180 days to look for asymptomatic and symptomatic AFib in these patients.
We would add to the exclusion criteria mitral valve stenosis and calcification, which were in both of the CMI inclusion exclusion criteria. Of course, we would look at total comorbidities on individual patients just simply from the standpoint of making sure that they should enter the trial because of their overall safety profile. A number of different measures will be changed in the part D to optimize for both safety and efficacy.
Thank you so much.
The next question today comes from the line of Leonid Timashev with RBC Capital Markets. Please go ahead. Your line is now open.
Yeah. Thanks, guys. Wanted to stay with the AFib topic for a minute.
I guess I was curious if the KOLs could compare how they would be monitoring or treating or sort of the weight of monitoring and treating for AFib versus for LVF reductions that could be seen with CMIs, how that would impact their clinical practice, and then sort of what the clinical course of AFib typically is in these patients. Is it normal for new-onset AFib to sometimes be moderate to severe? Lastly, just keeping in mind some of the changes that you mentioned to the trial. I know one of the physicians had mentioned that there's now some potential for enrollment challenges because there's commercially approved agents. I guess, how are you thinking about how enrollment would go and ultimately the patient population you would target? I mean, would you be willing to enroll CMI non-responsive patients? Thanks.
Thanks, Leonid. Dr. Masri, why don't you take a quick crack at that?
Definitely. Ultimately, AFib is an important event. It is manageable, but it's an important event. You need to work with the patient. You institute anticoagulation, and you treat them. The standard of treatment for AFib in HCM is rhythm control because these patients are symptomatic typically. It is very unusual for patients with HCM to have asymptomatic AFib when it's new onset or early on in their disease course. As such, what you would do is not necessarily proactively go and implant devices or whatever to monitor for AFib. The patients will come and tell you that, "I felt something," and you investigate it. Also, clinical trials here and in other clinical trials, you have rigorous monitoring when patients come back every visit. You have EKGs. You have echoes. You examine the patient. You look into things.
It is much more likely that you're going to pick up on these things by the patient's reporting as well as by the evaluations you're doing. That's one of them. The second thing is that, as I think we talked about already, you need longer exposure to understand what is the potential incidence and what's going on with AFib in patients. Dr. Owens referred nicely to the PIONEER versus EXPLORER experience. Now, later on, look at the VALOR experience versus commercial experience. These things are dynamic, and they do change over time. Ultimately, we want to see improvement in symptoms. We want to see improvement in exercise capacity without necessarily having major issues that are related to the use of our therapy. I mean, that's ultimately the goal in any HCM patient. There was another part to the question, but I forgot it.
I think recruitment.
Oh, yeah. From a recruitment perspective, this is not something that is necessarily new to physicians and others taking care of patients with HCM. The trial was ongoing when Mavacamten was or is commercially available. There is not necessarily a change here in terms of your background approach. It's not like if you're tightening your review of the patients being enrolled that you're going to make the trial harder to recruit. Not necessarily. We have many patients with HCM, and I think it's not difficult to enroll in trials with HCM.
Dr. Owens, could you maybe address the complexity of monitoring for ejection fraction versus AFib? What are you more worried about in your practice?
It's a good question. We monitor for ejection fraction with a standard echocardiogram, at least at this point.
We do not have other non-invasive, less invasive ways, although they are being developed to assess for systolic function or EF. In our standard patients, they get echoes. If they are not on commercial Mavacamten, they typically get an echo once a year if they are stable. On Mavacamten with the current REMS program, we are doing echoes every three months on otherwise stable patients. They come into the office, they are seen, they get an EKG, they get an exam, they get an echocardiogram. For AFib, as Dr. Masri highlighted, anytime a patient reports a symptom like palpitations, dizziness, irregular heartbeat, any other symptom that is concerning, we do a rhythm assessment. We would do an EKG, and we have ambulatory monitors that are sent to the patient, patch monitors and others that can assess for cardiac rhythm in an ongoing fashion.
The latest 2024 HCM guidelines suggest that we should be doing increased monitoring for AFib in patients who are at high risk for AFib, and that includes age, left atrial volume size, symptomatic status. We do monitor for AFib pretty much every year in a standard patient with HCM with an ambulatory monitor. How that might or might not change with the therapy, I think, is too early to say. For Mavacamten, for example, I referenced our publication. There were about 10%-11% of patients who either had new onset or worsening of paroxysmal AFib. We did not change our standard monitoring practice. Those patients presented due to symptoms, and we took care of their symptoms and their AFib when it was found.
Thanks, Dr. Owens. Maybe speak to the next analyst, or are we done?
The next question for today comes from the line of Srikripa Devarakonda with Truist Securities. Please go ahead. Your line is now open.
Hey, guys. Thank you so much for taking my question, and congratulations on the data. I want to open Gavin's question. For nHCM patients in particular, very early on, you were seeing 50% reduction in NT-proBNP, and our core rate goes down, I should say, 42%. Just wondering if you expect stabilized at these levels, do you expect to see a differentiation with the CMIs based on this particular biomarker? And maybe one quick question on AF. The cardioversion, just wondering if the patients where you had to do cardioversion, were they the same people who would be excluded from phase III, or they're different? Thank you.
Okay.
On the first question in regard to NT-proBNP, I think the response was quite large initially, even within the first seven days. I think probably 90% of the effect on BNP will occur and probably be driven by the dose. Over time, I think 12 weeks and longer, some level of remodeling might deepen that response. We do not know at this point. In regards to the exclusion criteria, I think I would suspect that none of the patients who had the AF events would end up being in a typical phase III study given the level of background comorbidities those patients had. As I said, as we said, two of the patients were not HCM patients. That seems obvious they would not be included simply on wall thickness.
The other thing to add, Srikripa, particularly in non-obstructive, what's really novel here and what's going to be really exciting is we know that non-obstructive is making up a high proportion of diagnosed HCM patients. This is well- known. Overall, non-obstructive patients start with a lower baseline LVEF. If you look at our baseline criteria, the average LVEF at baseline was 61%. The fact that we're not seeing any changes in LVEF and we're able to push the dose to drive benefit, whereas what we've seen with the CMIs is their benefit comes at the cost of ejection fraction drops in HCM. That is going to be ultimately the limitation with that mechanism where you're impacting systolic function, whereas we're able to drive that benefit without dropping ejection fraction.
Great. If I can say something about the KCCQ. Than k you.
Excuse me?
Before we take the next question, I would like to give a reminder to all the analysts to please leave it yourself to one question. The next question comes from the line of Cory Kasimov with Evercore. Please go ahead. Your line is now open.
Hey, good morning, guys. Thanks for taking the question. Hi, guys. Yeah. Hey. Yeah. Sorry to pile on to the AFib discussion, but I'd like to follow up on the KOL color here. I guess the bottom line and what I think investors are trying to understand is how much of a risk is AFib for the future outlook of EDG-7500? Investors are acting this morning as if there is no future for this product. I would really like to better understand where the KOLs think the disconnect is here. Thank you.
Dr. Owens?
Sure.
Perhaps.
I think you need a placebo control trial.
That's what we've done in prior programs. I mentioned the PIONEER data, which was phase II Mavacamten. If that drug would have stopped development based on a 23% risk in their phase II study, we would not have the opportunity to use a great drug that we're using now in 200+ patients. I think you really need a placebo-controlled trial so that you can understand if there are differences. The population of patients with HCM is complex. It is not one-size-fits-all. There are patients with really thick walls. There are patients with thinner walls. There are patients with very large atria. There are patients with normal-sized atria. I think it's too early to say what the effect is going to be. I enrolled nine patients in part B and C of this study, and zero of the nine had AFib.
Dr. Masri, maybe your thoughts?
Yeah.
I think not much to add with Dr. Owens sharing her own experience with this. Ultimately, you really have to take the data with the size of the population that you're dealing with. I think even though we're talking about a small study here, the phase II is still ongoing. The part D portion of it, as Rob has shown, essentially is going to be looking into this further. The patients, more patients will be treated. That's going to give you a lot of ideas. Ultimately, I fully agree that you need phase III trials with placebo control to essentially really walk away with these ideas and concepts. That's ultimately what you need.
All right. Great. That's helpful. I'll stick to the one question. Thank you.
The next question comes from the line of Paul Choi with Goldman Sachs. Please go ahead. Your line is now open.
Hi. Thanks. Good morning. Thank you for taking—hi. Thank you for taking our question. My question is for the two KOLs, Dr. Masri and Dr. Owens. As you think about the future here in 2026, there will likely be two approved therapies for obstructive HCM. As you think about your typical obstructive HCM patient in your practice, I guess the question is, what would you sort of recommend to them in 2026? Would you recommend, I guess, at that point, going on one of the commercially available ones or enrolling in a clinical trial? If enrolling in a clinical trial, is there a particular population or subpopulation you would focus on? Thank you very much.
Dr. Masri, want to take that?
Yeah. Again, we're not new to this. Correct.
When we were enrolling in many different clinical trials for HCM, we've had commercial Mavacamten. Even before commercial Mavacamten, you always had the competition of other things going on in the space. We simply offer patients these opportunities, and we let them choose. I think ultimately, that's where you want to think about. It's such a specialty space that this is not a disease where you go to 1,000 sites and you just try your best. This is a disease where you focus on your sites that have patients, and they know essentially how to approach this. Ultimately, you offer patients the options and help work with them to select one option. I personally, at least, have not experienced major challenges in terms of recruitment for trials when you actually are honest, forthcoming, and offer patients all the options.
Dr. Owens just mentioned that in the study, she recruited nine patients, and that's when you would have other commercially available options. I'm not so sure that this is an issue on its own, honestly. You just offer patients the options available. We've had experience from another disease that is somewhat similar in a way, amyloidosis, transthyretin amyloidosis. You've had many options on the market, and you've had newer options coming and clinical trials, and there weren't issues there either.
Dr. Owens, maybe how do you select patients to go on either a trial or one of the commercial agents, perhaps, is an interesting question.
Sure. As Dr. Masri said, our prime edict in HCM is shared decision-making, and that is what we do. We have a multidisciplinary team. We offer the patients all of the options.
We do this for other standard of care therapies for HCM, including septal myectomy, alcohol ablation, other therapies that are available for the obstructive patients, for example. We talk with them about what the options are. The other thing I would add is now that there are targeted therapies, at least one available and one under FDA review, there is now more focus on identifying and diagnosing new patients with HCM. We know this condition occurs in at least one in 500 individuals, and the vast majority of them are currently undiagnosed. We are seeing an increase in the number of patients being diagnosed and ultimately making it to our center for evaluation. We are seeing new patients. Those patients, of course, afford the opportunity to be presented with all of the options. I think we will be able to enroll.
Whether the baseline characteristics of those patients differ from the early EPLORER patients, for example, I think is yet to be seen. In this small cohort, we did see higher gradients than what we saw in EXPLORER and even VALOR and SEQUOIA. I think we'll watch to see if the demographics are changing. There are absolutely patients with HCM who are candidates for trials. Many of them come to academic centers because they're interested in research, and they want to be in a trial.
Okay. Are there any other questions? Thank you.
If there are no further questions at this time, I would like to pass the call back over to Kevin Koch for closing remarks. Please go ahead.
Thank you all for joining today.
I think we have really an exciting mechanism where we've seen robust changes in gradient, BNP, major markers of disease, and really outsized increases in the KCCQ scores and decreases in New York Heart Association moving patients to asymptomatic. This is really where this drug is going to show its most benefit, all with no changes in left ventricular ejection fraction, which is exciting with a manageable AE profile. We plan to continue to move forward in part D, and I anticipate that we will move to phase III with this drug sometime in the first half of 2026. Look forward to any additional questions in the future and talking to you all. Thank you for joining. Bye.
That concludes today's webinar and conference call. Thank you all for your participation. You may now disconnect.