Edgewise Therapeutics (NASDAQ:EWTX) highlighted multiple upcoming milestones across its cardiac and neuromuscular programs during a presentation at Guggenheim’s 2026 Healthcare Innovations Conference. Chief Operating Officer Behrad Derakhshan said the company is approaching a “remarkable year” as it heads toward a Phase 3 readout for sevasemten in Becker muscular dystrophy, while also advancing its hypertrophic cardiomyopathy (HCM) franchise and a second cardiac candidate slated to enter the clinic later in the year.
Edgewise outlines changes to address earlier atrial fibrillation observations in HCM program
Discussion centered early on CIRRUS Part D, the company’s ongoing work with EDG-7500 in both obstructive and non-obstructive HCM. Derakhshan was asked whether earlier atrial fibrillation (AFib) observations are now “firmly behind” the program. He described several protocol and screening changes implemented in Part D after reviewing approaches used by peers in the cardiac myosin inhibitor (CMI) space.
He added that the company implemented continuous cardiac monitoring using a patch worn during four weeks of screening and for two weeks during each dose escalation. Derakhshan said Edgewise conducted extensive screening—citing “over 2,000 measures”—and reported no AFib burden during that monitoring period. He also said the company has not seen a relationship between plasma concentration and dose and the incidence of AFib in this setting.
Timing and disclosure approach for CIRRUS Part D data
When asked how the company is thinking about cadence relative to other readouts in the space, Derakhshan said Edgewise is not guided by competitor timing. Instead, he said the company intends to provide a rigorous, high-quality data package, noting that the update is expected to cover both obstructive and non-obstructive HCM results. He also emphasized that Part D is designed to dose-optimize patients to their “max efficacious dose,” which he said is supported by the company’s view that EDG-7500 does not show a relationship between plasma concentration and left ventricular ejection fraction (LVEF).
REMS and monitoring: focus on LVEF and physician workflow
Derakhshan addressed the possibility of FDA-required monitoring and any potential risk evaluation and mitigation strategy (REMS). He said the company has generated data across healthy volunteers and multiple HCM study parts and believes it has increasingly supported a dissociation between LVEF and plasma concentration for EDG-7500.
He said Edgewise consulted with the former head of the FDA’s cardiorenal division and received feedback that EDG-7500’s mechanism differs from the CMI class. Derakhshan said the company’s view is that, with a continued lack of relationship between plasma concentration and LVEF, it would be difficult for the FDA to require intensive echocardiographic monitoring. He described a potential approach of an echocardiogram at baseline and end of study as a framework for discussion.
Derakhshan also argued that reduced echo burden could expand adoption outside centers of excellence, particularly among community physicians who often rely on “feel and function,” such as NYHA class, to evaluate therapy in heart failure. He contrasted routine echoes performed every six to 12 months in typical HCM management with more frequent requirements associated with therapies that carry concerns about LVEF reduction.
How Edgewise describes EDG-7500 positioning in obstructive and non-obstructive HCM
In non-obstructive HCM, Derakhshan characterized EDG-7500 as a “positive lusitrope” with a mechanism he said preferentially acts during early relaxation (diastole), improving ventricular filling and cardiac output. He pointed to previously shared fixed-dose data: at 50 mg over four weeks, the company observed a 16-point improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. He said Part D is designed to allow physician-directed titration using biomarkers and symptoms, including thresholds based on NT-proBNP reduction (at least 50%) or achieving 200 pg/mL, which he described as the threshold for “normal” in these individuals.
In obstructive HCM, Derakhshan said there remains room to improve outcomes despite advances with CMIs. He referenced EDG-7500 fixed-dose data presented previously, including results at 100 mg over four weeks:
- 89% of patients achieved gradient responses below 30 at rest and below 50 with Valsalva
- Approximately 60% had NT-proBNP reductions into the normal range
- KCCQ improvements of 23 points
- 78% had at least a one-class improvement in NYHA
He added that these results were coupled with no observed drops in LVEF in those data. On potential combination use with CMIs, Derakhshan suggested a “switch dynamic” may be more likely than add-on use, given his view that EDG-7500 could provide efficacy without the LVEF limitation that can constrain dose optimization.
On Phase 3 planning, Derakhshan said an end-of-Phase 2 FDA meeting would come after public disclosure of Part D data. He stated the company remains on track to initiate a Phase 3 program in the fourth quarter of the year and is considering options that include parallel obstructive and non-obstructive trials, or potentially a single study approach, depending on FDA feedback.
Pipeline updates: EDG-15400 and sevasemten in Becker muscular dystrophy
Derakhshan said EDG-15400 is in a single-ascending dose and multiple-ascending dose healthy volunteer study, with data expected in the second quarter. He said the company will also outline how EDG-15400 differs from EDG-7500 despite sharing a target, and will disclose plans for a HFpEF study expected to begin in the third to fourth quarter. He described a “bogey” for HFpEF Phase 2 as a 25% to 30% reduction in NT-proBNP, based on discussions with experts and the company’s scientific advisory board, with the aim of translating into a Phase 3 feel-and-function endpoint such as KCCQ.
On sevasemten, Derakhshan said the FDA previously provided guidance—during a meeting in the second quarter of the prior year—that the pivotal GRAND CANYON study in Becker muscular dystrophy would be a single registrational study, and that the agency accepted the North Star measure as the primary endpoint. He said GRAND CANYON remains on track for the fourth quarter and noted what he called a low dropout rate.
Derakhshan also pointed to enrollment exceeding the original 120-patient target, ending at 175 patients, which he said increased the study’s statistical power. He said the study is powered at 98% to show a 1.8-point improvement at 18 months, and noted the statistical significance “tipping point” is 0.8.
He highlighted high continuation into open-label follow-on dosing, stating that 99% of eligible patients rolled over into the MESA open-label and continue to receive sevasemten. Derakhshan said this “stickiness” supports a commercial narrative around perceived patient benefit and the payer argument for continued treatment. He also said the company has begun building commercial infrastructure and, if data are positive, expects to be positioned to launch, while noting a hoped-for approval timeframe of the end of the fourth quarter of 2027 and first full year of revenue in 2028, “if everything goes well.”
In Duchenne muscular dystrophy, Derakhshan said Edgewise is evaluating next steps based on additional data from a 10 mg cohort and future discussions with the FDA regarding endpoints and study duration. He said a go/no-go decision would likely come after the GRAND CANYON readout, while sites are being readied in case a Phase 3 program is pursued.
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.
