Biotechnology firm Medley Therapeutics, Inc. (formerly YAP Therapeutics) announced that its lead investigational gene therapy, YAP101, has successfully cleared initial safety review in the Phase 1 SALVADOR‑HF trial targeting patients with advanced ischemic heart failure with reduced ejection fraction (HFrEF). According to the company, all three participants in the trial’s first dose cohort were dosed without safety concerns, and the study’s independent Safety Review Team recommended escalation to the next protocol‑defined dose level.
YAP101 is described as a first‑in‑class AAV‑based genetic medicine engineered to stimulate endogenous myocardial regeneration by using a cardiomyocyte‑specific promoter to express short hairpin RNAs (shRNAs) that transiently suppress the Hippo signalling pathway and activate the YAP pathway—mechanisms designed to enable controlled regeneration of heart muscle. The trial, conducted at Texas Heart Institute at Baylor College of Medicine (Houston) and Baylor St. Luke’s Medical Center, is enrolling 9–18 subjects in a dose‑escalation phase followed by an expansion cohort of up to six additional participants.
The company emphasised the clinical significance of the milestone, noting that inducing human heart muscle regeneration has long been considered elusive and that this step “brings the heart’s own repair mechanism closer to clinical reality.” While the data remain limited to the initial safety cohort and no efficacy outcomes have yet been disclosed, the advancement to the next dose level marks a meaningful step in Medley’s development path for treating heart failure through regenerative genetics.
