Edgewise Therapeutics (NASDAQ:EWTX) executives used an RBC Capital Markets session to highlight what they view as key differentiators for EDG-7500, the company’s investigational therapy for hypertrophic cardiomyopathy, and to discuss expectations for upcoming clinical data in both cardiomyopathy and muscular dystrophy.
Kevin Koch, Edgewise’s CEO, president and director, said EDG-7500 is differentiated because it targets a different protein within the sarcomere than competing cardiac myosin inhibitors, or CMIs. He described the drug as a “partial modulator” of contraction, arguing that this could avoid some of the challenges associated with fully blocking contraction.
“Our mechanism, we are more potent on the relaxation of the ventricle, which allows the ventricle to increase its capacity for oxygenated blood,” Koch said.
Company Points to Lack of Ejection Fraction Changes
Koch said Edgewise has observed “no changes in ejection fraction” as EDG-7500 dose and concentration increased, referring to data disclosed in December and earlier results released around the same time last year. He contrasted that with CMIs, saying reductions in ejection fraction can lead to a black box warning and a Risk Evaluation and Mitigation Strategy, or REMS, requiring multiple echocardiograms to titrate patients to an effective dose.
According to Koch, avoiding ejection fraction reductions could make EDG-7500 easier for physicians and patients to use if approved. He said the company believes the drug could be used beyond centers of excellence and across broader treating-physician settings.
Koch also addressed investor concerns about atrial fibrillation signals, saying atrial fibrillation, tachycardias and irregular heartbeats are common in the background of hypertrophic cardiomyopathy. He said trial monitoring can increase detection compared with real-world practice.
“We expect to see nothing different within our next study, because that’s the background patients,” Koch said.
Phase 3 Design Could Emphasize Symptom-Based Titration
Koch said Edgewise has proposed to the U.S. Food and Drug Administration a Phase 3 design in which echocardiography would not be required to titrate EDG-7500. Under that proposal, the trial would include an echocardiogram at the beginning and end of the study, and possibly another echo in the middle that would not be tied to dose changes.
He said physicians would start patients at a lower dose and titrate upward based on how patients feel and tolerate the treatment. The goal, Koch said, would be to move patients from New York Heart Association Class 2 or 3 to Class 1.
Behrad Derakhshan, Edgewise’s chief operating officer, said the company expects FDA feedback after its end-of-Phase 2 data to help clarify the level of monitoring required in Phase 3 and potentially inform how regulators may view a REMS in the future.
Derakhshan said the company is not suggesting physicians would stop using echocardiograms, but rather that physicians could use them at their discretion instead of being required to perform an echo before dose escalation.
Executives Discuss Obstructive and Non-Obstructive HCM
Asked about obstructive and non-obstructive hypertrophic cardiomyopathy, Koch said obstructive disease involves changing the flow obstruction caused by the mitral valve and cardiac contraction dynamics. In non-obstructive disease, he said, the focus is on the thickened and stiff ventricular wall, which he characterized as more difficult to affect.
Koch said Edgewise believes EDG-7500’s mechanism directly affects relaxation and the non-obstructive disease phenotype. Derakhshan pointed to data from an obstructive cohort at a 25-milligram dose, saying NT-proBNP dropped by more than 30% within a week while gradients were initially flat and later caught up by week two.
Derakhshan said that pattern supports the company’s view that EDG-7500 works preferentially during diastole before hemodynamic measures change.
Koch added that maintaining ejection fraction may be important for patient function, saying that lowering the amount of oxygenated blood being ejected could limit how much better a patient feels.
Upcoming Data and Becker Muscular Dystrophy Program
Koch said Edgewise expects upcoming 12-week data for EDG-7500 to be “equivalent or better” than earlier disclosures and relative to CMIs, while noting he was not providing specific numbers. He said longer treatment could show a deepening response across biomarkers and echo parameters.
The executives also discussed the company’s Grand Canyon study in Becker muscular dystrophy. Derakhshan said Edgewise has already shown functional improvements relative to placebo and natural history in Phase 2, though the study was not powered for that endpoint. Koch described those findings as directionally positive.
Derakhshan said physicians reviewing the data have told the company they see treated patients stabilizing in a way that differs from the decline they typically observe in practice. Koch pointed investors to a poster from the Muscular Dystrophy Association, saying patients treated across the study appeared stable over multiple years while placebo patients initially followed natural history before flattening or improving after switching.
“Every physician who looked at it said, ‘I’ve never seen that before,’” Koch said.
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.
