EDG-7500 / Edgewise Therap - LARVOL DELTA

CIRRUS­HCM: A multiple-dose phase 2 study of safety, tolerability, and effects on hemodynamics and functional capacity of the novel cardiac sarcomere modulator EDG-7500 in hypertrophic cardiomyopathy (HEART FAILURE 2025) - No abstract available

Clinical • Late-breaking abstract • P2 data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Study to Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C]-EDG-7500 (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Edgewise Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

Edgewise Therapeutics Announces Positive Top-Line Results from Phase 2 CIRRUS-HCM Four-Week Trial of EDG-7500 in Hypertrophic Cardiomyopathy (HCM) (PRNewswire) - P2 | N=75 | CIRRUS-HCM (NCT06347159) | Sponsor: Edgewise Therapeutics, Inc. | "Part B of CIRRUS-HCM included 17 participants with obstructive HCM and Part C included 12 participants with nonobstructive HCM....Treatment with 100 mg of EDG-7500 also demonstrated a 62% mean reduction from baseline in NT-proBNP, a key biomarker of heart failure. In addition, positive trends in echocardiographic parameters of diastolic function were observed following treatment with EDG-7500. Clinically meaningful improvements were also observed on the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), with a substantial mean increase of 23 points observed at the 100 mg dose. In addition, treatment with 100 mg of EDG-7500 over four weeks demonstrated improvements on the NYHA functional class score. Seventy-eight percent of participants improved by ≥ 1 NYHA Class, and 67% improved to NYHA Class I (i.e. asymptomatic)."

P2 data • Hypertrophic Cardiomyopathy

Edgewise Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (Businesswire) - "The Company plans to engage the U.S. FDA in the first half of 2025 to discuss marketing authorization filing strategies for sevasemten in Becker...The Company expects to report data from LYNX and FOX as well as its future clinical trial plans in the first half of 2025...The Company expects to report topline CIRRUS-HCM 28-day data in the first quarter of 2025. Further, the Company expects to report data from the 12-week CIRRUS-HCM trial in individuals with obstructive HCM and non-obstructive HCM in the second half of 2025...During 2025, the Company expects to file an investigational new drug application for a novel candidate for the treatment of heart failure, and select a proprietary cardiometabolic drug candidate based on preclinical proof-of-concept data."

FDA event • IND • P2 data • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Heart Failure • Hypertrophic Cardiomyopathy

A Study of EDG-7500 in Adults with Hypertrophic Cardiomyopathy (CIRRUS-HCM) (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Edgewise Therapeutics, Inc. | N=55 ➔ 75 | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Enrollment change • Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Study to Evaluate the Absorption, Metabolism, and Excretion of Orally Administered [14C]-EDG-7500 (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P1 trial

EDG-7500, a First-in-Class Cardiac Sarcomere Modulator, Demonstrates Favorable Tolerability, Safety, Pharmacokinetic and Hemodynamic Effects in Healthy Adults and Patients with Hypertrophic Cardiomyopathy (CVCT USA 2024) - No abstract available

Clinical • PK/PD data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Chronic administration of EDG-7500, a novel sarcomere modulator, prevents increases in cardiac mass, T1 relaxation time, and left ventricular end diastolic pressure in a Yucatan mini-pig model of genetic non-obstructive hypertrophic cardiomyopathy. (AHA 2024) - "In a mini-pig model of nHCM, chronic EDG-7500 therapy prevents pathologic cardiac remodeling, decreased LV compliance, and disease progression without impairing resting systolic function. These findings support clinical investigation of EDG-7500 in nHCM."

Preclinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Non-obstructive Hypertrophic Cardiomyopathy • MYH7

EDG-7500, A First-in-Class Cardiac Sarcomere Modulator, Demonstrates Favorable Tolerability, Safety, And Pharmacokinetics In Healthy Adults (HFSA 2024) - "EDG-7500 was well tolerated; adverse events were generally mild and comparable in frequency to those seen with placebo. The observed half-life supports once-daily dosing with rapid achievement of steady-state plasma concentrations. At plasma concentrations that exceed those demonstrating efficacy in nonclinical oHCM models, decreases in LVEF below normal were not observed in healthy subjects receiving a single dose of EDG-7500 over a 60-fold range."

Clinical • PK/PD data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

CIRRUS-HCM: An Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of EDG-7500 in Adults with Hypertrophic Cardiomyopathy (HFSA 2024) - "Dose and exposure response relationships of the resulting echocardiography parameters along with safety and tolerability will be used to select doses for subsequent HCM patient studies. It is anticipated that participants in CIRRUS-HCM will be eligible for chronic administration of EDG-7500 in an open-label extension study."

Clinical • PK/PD data • Cardiomyopathy • Cardiovascular • Fatigue • Fibrosis • Hypertrophic Cardiomyopathy • Immunology • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Pulmonary Disease

Data from EDG-7500 in #HCM (LinkedIn)

A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM) (clinicaltrials.gov) - P2 | N=55 | Recruiting | Sponsor: Edgewise Therapeutics, Inc. | N=30 ➔ 55

Enrollment change • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Study of EDG-7500 in Healthy Adults (clinicaltrials.gov) - P1 | N=84 | Completed | Sponsor: Edgewise Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion

CHRONIC TREATMENT WITH THE NOVEL SARCOMERE MODULATOR EDG-7500 IMPROVES LEFT VENTRICULAR DISTENSIBILITY AND CARDIAC OUTPUT RECRUITMENT UNDER STRESS IN A MINI-PIG GENETIC MODEL OF NON-OBSTRUCTED HYPERTROPHIC CARDIOMYOPATHY (ACC 2024) - "After 12 to 16 weeks of treatment, pigs underwent in vivo imaging and invasive hemodynamic assessment both at rest and under β-adrenergic (β-AR) cardiac stress (dobutamine, 2 ug/kg/min IV). Chronic EDG-7500 treatment was well tolerated and improved the diastolic dysfunction characteristics of this disease model. EDG-7500 treatment also improved cardiac output recruitment under β-AR stress, a surrogate of exercise capacity, thus supporting the clinical investigation of EDG-7500 in nHCM."

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • MYH7

A Study of EDG-7500 in Adult Patients With Obstructive Hypertrophic Cardiomyopathy (CIRRUS-HCM) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P2 trial • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

EDG-7500, a Novel Cardiac Sarcomere Regulator That Preserves Intrinsic Myosin-Motor Function, Improves Cardiac Function and Reserve in a Minipig Model of Hypertrophic Cardiomyopathy (AHA 2023) - "EDG-7500, a novel cardiac sarcomere regulator, improved diastolic function in EHT and animals with the HCM-pathogenic MYH7 R403Q mutation, improving ß-AR dependent cardiac output reserve. This novel profile could be valuable for the treatment of patients with HCM and diseases of diastolic dysfunction."

Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • MYH7

Cardiac Effects of EDG-7500, a Novel Cardiac Sarcomere Regulator: In vitro and in vivo Evidence for Slowing Isovolumic Contraction and Improved Ventricular Compliance (AHA 2023) - "Cardiac sarcomere regulation with EDG-7500 has a unique cardiovascular profile characterized by the overall preservation of the myosin motor-head population and a slowing of early cardiac contraction and improved LV distensibility. This cardiovascular profile could have salutary effects in patients with HCM or patients with impaired diastolic function."

Compliance • Preclinical • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

Trial Name: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single And Multiple Ascending Dose Study Of The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Edg-7500 In Healthy Adults (HFSA 2023) - "Echocardiography at rest, and in some MAD cohorts after exercise, will be used to assess the effects of EDG-7500 on myocardial systolic and diastolic function. Dose and exposure response relationships with the resulting echocardiography parameters along with safety and tolerability will be used to select doses in subsequent HCM patient studies."

Clinical • P1 data • PK/PD data • Cardiomyopathy • Cardiovascular • Fatigue • Fibrosis • Hypertrophic Cardiomyopathy • Immunology • Pulmonary Disease

Edgewise Therapeutics Begins Dosing First-in-Human Phase 1 Trial of EDG-7500, its Lead Clinical Candidate for Hypertrophic Cardiomyopathy (HCM) and Other Serious Diseases of Cardiac Diastolic Dysfunction (Businesswire) - "Edgewise Therapeutics...today announced initial dosing in a Phase 1 trial of EDG-7500. EDG-7500 is a first-in-class oral, selective, cardiac sarcomere modulator, specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with HCM and other diseases of diastolic dysfunction....The Company is also planning to begin a Phase 1b study of EDG-7500 in individuals with obstructive HCM in the first half of 2024."

New P1 trial • Trial status • Cardiomyopathy • Cardiovascular • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

A Study of EDG-7500 in Healthy Adults (clinicaltrials.gov) - P1 | N=126 | Recruiting | Sponsor: Edgewise Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of EDG-7500 in Healthy Adults (clinicaltrials.gov) - P1 | N=126 | Not yet recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P1 trial

EDG-002, A NOVEL TARGETED SARCOMERE REGULATOR PRESERVES INTRINSIC MYOSIN-MOTOR FUNCTION, BLUNTS HYPERCONTRACTILITY AND ELIMINATES LVOT OBSTRUCTION IN CATS WITH HYPERTROPHIC CARDIOMYOPATHY: IN VITRO AND IN VIVO EVIDENCE (ACC-WCC 2023) - "Here, this hypothesis was tested in vivo in a translationally relevant feline model of oHCM. Five cats (A31P MYBPC3 mutants) with HCM were used; LVOT obstruction was present at baseline (1/5 cats) or induced (4/5) with dobutamine (<20 µg/kg/min IV). EDG-002, a targeted sarcomere regulator designed to preserve cardiac myosin activity, normalized systolic function and eliminated LVOT obstruction in a model of oHCM, while being tolerated over a wide range of exposures. This novel profile could be valuable for the treatment of patients with HCM."

Preclinical • Cardiomyopathy • Cardiovascular • CNS Disorders • Depression • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy • Psychiatry

Edgewise Therapeutics Reports First Quarter 2022 Financial Results (Businesswire) - "The Company is advancing the EDG-002 program, which is focused on identifying cardiac muscle modulators with a novel mechanism of action, initially targeting inherited hypertrophic cardiomyopathy (HCM)....We plan to initiate IND-enabling studies in 2022."

IND • Cardiovascular

Edgewise Therapeutics Reports First Quarter 2021 Financial Results and Recent Highlights (Businesswire) - "As part of our EDG-002 program, Edgewise is also advancing a novel mechanism cardiac modulator for inherited hypertrophic cardiomyopathy (HCM). Preliminary preclinical studies offer evidence that the EDG-002 program has the potential to yield molecules that could become a new standard of care for the treatment of HCM."

Preclinical • Hypertrophic Cardiomyopathy