Edgewise Therapeutics, Inc. announced positive topline results from the BMD, or Phase 1b, portion of a first-in-human Phase 1 clinical trial assessing the safety, tolerability, PK and pharmacodynamics (PD) of EDG-5506, an orally administered small molecule myosin inhibitor designed to protect injury-susceptible fast skeletal muscle fibers in dystrophinopathies such as Duchenne muscular dystrophy (DMD) and BMD. The seven adults with BMD enrolled in the Phase 1b clinical trial were administered 20 mg oral doses of EDG-5506 (n=5) or placebo (n=2). EDG-5506 was shown to be well-tolerated with no discontinuations or dose reductions.

The most common adverse event, observed in all Phase 1b participants, was dizziness which was mild, transient and self-resolving. In addition to safety, a key goal in the Phase 1b BMD clinical trial was to understand the relationship between dose, muscle exposure and biomarkers of muscle damage on a dystrophic background. PK data were consistent with robust target engagement, with plasma and muscle exposures exceeding pharmacologically active levels observed in multiple preclinical models of DMD.

Similar to observations in the healthy volunteer portion of the clinical trial, dosing with EDG-5506 was not found to affect voluntary grip, shoulder, or hip strength. Treatment with EDG-5506 led to a significant and time-dependent decrease in key biomarkers of muscle damage when assessed by both standard laboratory assays and proteomic analysis using the SOMAscan 7,000 analyte set. Importantly, creatine kinase (CK) and fast skeletal muscle troponin (TNNI2) were reduced by 71% and 83%, respectively, to levels near those observed in healthy volunteers when evaluated by SOMAscan.

This reduction in muscle damage biomarkers supports the hypothesis that EDG-5506 meaningfully reduces damage from the excessive stress present in dystrophic muscle, thus potentially preserving muscle function and preventing disease progression in dystrophinopathies.