EDG-7500 / Edgewise Therap - LARVOL DELTA

REDUCED CARDIAC STRESS AND INFLAMMATORY PROTEOMIC SIGNATURES IN OBSTRUCTIVE AND NONOBSTRUCTIVE HCM FOLLOWING EDG‑7500 TREATMENT IN CIRRUS‑HCM (ACC 2026) - P2 | "This analysis showed that EDG-7500 not only reduced NT-proBNP but also downregulated inflammatory and high-risk cardiac pathways in both oHCM and nHCM. Proteomic changes reflected improvements in cardiac function, reductions in LVOT gradients in oHCM, and decreased enrichment of proteins associated with atrial fibrillation risk across both subtypes."

Atrial Fibrillation • Fibrosis • Hematological Disorders • Immunology • Non-obstructive Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

A Study to Evaluate EDG-7500 in People With Renal Impairment (clinicaltrials.gov) - P1 | N=37 | Completed | Sponsor: Edgewise Therapeutics, Inc. | Recruiting ➔ Completed

Trial completion • Renal Disease

A Study to Evaluate EDG-7500 in Adults With Hepatic Impairment (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Edgewise Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Study to Evaluate EDG-7500 in Caucasian and Japanese Adults (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P1 trial

A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM) (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Edgewise Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Study to Evaluate EDG-7500 in Adults With Hepatic Impairment (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P1 trial • Hepatology

A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Edgewise Therapeutics, Inc. | N=75 ➔ 100 | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Jun 2026

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

Emerging Pharmacological and Invasive Therapies for Hypertrophic Cardiomyopathy with Obstructive Physiology. (PubMed, Card Fail Rev) - "Emerging pharmacological approaches, including EDG-7500 and gene therapies, aim to refine treatment strategies...Innovations such as radiofrequency ablation and septal scoring along the midline endocardium (SESAME) offer promising, minimally invasive alternatives. As treatment options expand, optimising patient selection, monitoring protocols and long-term outcomes remain essential to advancing care for patients with obstructive hypertrophic cardiomyopathy."

Journal • Review • Cardiomyopathy • Cardiovascular • Gene Therapies • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

A Study to Evaluate EDG-7500 in People With Renal Impairment (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Edgewise Therapeutics, Inc.

New P1 trial • Renal Disease

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