Medley Doses First Cohort in AAV Gene Therapy Trial for Heart Regeneration

LAGUNA HILLS, Calif. & HOUSTON, November 11, 2025 — Medley Therapeutics, Inc. (formerly YAP Therapeutics), a company focused on regenerative genetic medicines, today announced a major clinical milestone: completion of dosing in the first cohort (n=3) of the Phase 1 SALVADOR-HF clinical trial. This trial is evaluating YAP101, an investigational, first-in-class AAV genetic medicine, in patients with advanced ischemic heart failure with reduced ejection fraction (HFrEF).

Following a review of safety findings, the independent Safety Review Team recommended escalating to the next protocol-defined dose level, signaling a favorable safety profile in the initial recipients.

The Holy Grail: Endogenous Heart Regeneration via AAV

This trial represents the first clinical investigation of a genetic medicine designed to induce endogenous regeneration—the holy grail of modern cardiology—by stimulating the heart’s own repair mechanism.

YAP101 is an AAV-based genetic medicine specifically engineered to stimulate new heart muscle growth. It utilizes an AAV vector equipped with a cardiomyocyte-specific promoter to express short hairpin RNAs (shRNAs). This mechanism transiently suppresses the Hippo signaling pathway and activates the YAP protein within heart muscle cells (cardiomyocytes), with the goal of enabling self-limiting myocardial regeneration.

Dr. James F. Martin, Founder of Medley Therapeutics and Director of the Cardiomyocyte Renewal Laboratory at Baylor College of Medicine (BCM), highlighted the transformative approach: “YAP101 is designed to unlock the heart’s own repair mechanism by transiently lifting the Hippo pathway ‘brake’ and activating YAP via shRNAs delivered directly to cardiomyocytes using this sophisticated AAV genetic medicine.”

The core technology behind the AAV genetic medicine was developed in the Martin Laboratories at The Texas Heart Institute (THI) at BCM.

Trial Progress and Patient Hope

The dosing was conducted at The Texas Heart Institute at Baylor College of Medicine and Baylor St. Luke’s Medical Center in Houston. The SALVADOR-HF trial includes three planned dose levels in a dose-escalation phase (targeting 9-18 subjects), followed by a dose-level expansion.

Dr. Emerson Perin, Medical Director for Medley Therapeutics and Director of the Center for Clinical Research at THI, noted the clinical significance: “Until now, there has not been a way to regenerate human heart tissue. YAP101, an AAV-delivered therapy, offers new hope for patients with heart failure. Our aim is to enable the heart to repair itself and reverse heart failure through a brief cardiac catheterization procedure.”

For the tens of millions of people living with heart failure, successful completion of the first cohort and advancement to the next dose level represents a decisive milestone toward a potentially transformative treatment option, driven by this pioneering AAV technology.