Executives from Edgewise Therapeutics (NASDAQ:EWTX) highlighted recent clinical updates and upcoming milestones across the company’s neuromuscular and cardiovascular pipeline during a discussion hosted by Leerink Partners’ Joseph Schwartz, with CEO Kevin Koch and COO Behrad Derakhshan providing commentary.
Becker muscular dystrophy: posters and a Phase III timeline
Koch said the company recently presented two posters at the Muscular Dystrophy Association meeting. One poster included early observations from the GRAND CANYON study that referenced cardiovascular-related endpoints. Koch said that among patients with a low ejection fraction, the company observed increases in ejection fraction, and discussed NT-proBNP as a heart failure-associated biomarker. He added that patients who were normal did not show changes in NT-proBNP, while patients who were not on sevasemten showed increases in that biomarker.
EDG-7500 in hypertrophic cardiomyopathy: what the company is emphasizing
The executives spent much of the discussion on EDG-7500 for hypertrophic cardiomyopathy (HCM). Koch said the company has shared a “short high level summary” from Part D of its study (a 12-week dataset) in both obstructive and non-obstructive HCM. He emphasized what he called a differentiating feature: no changes in ejection fraction with increasing dose and concentration, alongside a tolerable safety profile.
On timing, Koch said Edgewise stopped screening patients in December and that the last patient initiated dosing in January. He said the company expects to release Part D data toward the end of the second quarter, describing the expected dataset as “about 50–60 patients’ data,” with “probably a few extra in non-obstructive.” Koch added that Edgewise plans to move EDG-7500 into Phase III and is in discussions with the FDA, with the intent to hold an end-of-Phase II meeting to finalize Phase III protocols. He also stated the company remains committed to initiating the first patient in Phase III by the end of this year.
When asked what would constitute a clear Phase II win, Koch said the company needs to continue to show: (1) no changes in ejection fraction, (2) efficacy consistent with what it previously observed, and (3) no safety signals that would prevent advancing the program.
Dosing strategy and “normalization” goals in HCM
Derakhshan contrasted Part D with earlier fixed-dose portions of the program, describing Part D as providing physician discretion to adjust dose based on multiple measures. He discussed a responder framework aimed at getting patients “as close to normal as you can,” referencing multiple targets that could be evaluated together, including NT-proBNP, NYHA class, Kansas City Cardiomyopathy Questionnaire (KCCQ), and (for obstructive patients) gradient thresholds.
Derakhshan also described a potential strategy intended to make dosing easier in community cardiology settings. He outlined a “base case” approach using an echocardiogram at baseline and at end of study, while relying on “feel and function” measures in between—citing guideline concepts of dosing based on how patients feel rather than titrating solely to gradient or other metrics. Both executives argued that removing ejection fraction declines from the decision-making calculus could change how physicians dose and monitor sarcomere modulators, particularly in non-obstructive HCM where gradients are not available to guide response.
Safety considerations: LVEF, REMS, and atrial fibrillation monitoring
On whether the data could support avoiding a risk evaluation and mitigation strategy (REMS), Koch said the company has reported a wide concentration range without ejection fraction changes, while noting inherent variability in ejection fraction measurement. He said Edgewise had not seen cases below 50% in the dataset described and that, as sample sizes grow, confidence increases. Koch also said the company had spoken with former FDA administrators and advisors who reviewed the dataset and commented that it was sufficient to de-risk the potential for a REMS, given the novel mechanism and lack of ejection fraction changes.
Addressing atrial fibrillation (AFib), Koch said the company is using Zio Patch monitoring to quantify arrhythmias and described screening observations indicating AFib is pervasive in the HCM population. He referenced AFib rates seen in placebo groups across prior Phase III studies and said Edgewise has consistently guided to a 2%–8% background rate, which he expects to remain the backdrop for Part D. Koch also contrasted AFib with reduced ejection fraction, arguing that clinicians regularly manage AFib in practice and that symptomatic AFib is easier to detect than silent declines in ejection fraction.
Other pipeline programs: EDG-15400 and sevasemten clinical relevance
On EDG-15400 in HFpEF, Koch said the company expects Phase I healthy volunteer data “soon” and described looking for pharmacokinetic and pharmacodynamic signals informed by preclinical work and learnings from EDG-7500. He also said Edgewise believes EDG-15400 may have a metabolic profile more amenable to an older HFpEF population and that the company wants to confirm this clinically and with additional preclinical data.
Returning to sevasemten and GRAND CANYON, Schwartz noted the study is powered for a 1.7-point change on the North Star Ambulatory Assessment (NSAA) and asked about clinical meaningfulness. Koch said physicians have been consistent that a 1-point NSAA change matters, offering practical examples of functional tasks that can be impacted. He also discussed longer-term implications, saying that stabilization over multiple years could equate to several NSAA points relative to expected decline and described open-label observations as showing no progression where natural history would suggest decline.
About Edgewise Therapeutics (NASDAQ:EWTX)
Edgewise Therapeutics, Inc (NASDAQ: EWTX) is a clinical-stage biopharmaceutical company headquartered in Cambridge, Massachusetts, focused on the discovery and development of precision medicines for the treatment of rare diseases. The company leverages its expertise in small-molecule chemistry and ion channel biology to address severe, unmet medical needs, particularly in the areas of kidney disorders and neuromuscular diseases.
At the core of Edgewise’s pipeline is EWTX-101, a novel, orally available inhibitor of TRPC5, a calcium channel implicated in nephrotic syndromes such as focal segmental glomerulosclerosis (FSGS) and other proteinuric kidney diseases.
