Veru (VERU) investor relations material

Clinical development strategy

• Focus on muscle preservation in older patients with obesity, targeting those over 65 and BMI >35, a group at high risk for muscle loss and functional decline.

• Enobosarm, an oral SARM, is being developed for obesity in combination with GLP-1 RA to preserve muscle and enhance fat loss, with a focus on older, sarcopenic patients at high risk.

• Phase II-B QUALITY trial demonstrated that combining enobosarm with semaglutide preserved muscle mass and function, with 3 mg enobosarm maintaining 100% lean mass and reducing stair climb decline by up to 60%.

• The ongoing PLATEAU trial is fully enrolled (239 patients), extends treatment to 68 weeks, and focuses on the same high-risk population to amplify differences in muscle and function outcomes, with interim analysis expected Q1 2027 and topline data in Q4 2027.

• Interim analysis at 32 weeks will assess lean and fat mass changes, guiding phase III design, which will require 4,500 patients.

Regulatory and clinical endpoints

• FDA prefers functional endpoints like stair climb over cosmetic or strength measures; stair climb is sensitive to anabolic interventions and predictive of adverse outcomes.

• FDA has provided regulatory clarity, accepting incremental weight loss and preservation of physical function as approvable endpoints for enobosarm/GLP-1 RA combinations.

• Quality of life is measured using SF-36 PF-10 and IWQOL-Lite questionnaires, linking functional changes to patient-reported outcomes.

• Statistical significance alone is insufficient; endpoints must demonstrate meaningful functional benefit to patients.

• The PLATEAU trial incorporates expanded functional and quality of life endpoints based on learnings from QUALITY.

Mechanism of action and combination rationale

• Enobosarm is a selective androgen receptor modulator (SARM) that is anabolic on muscle, catabolic on fat, and anti-resorptive on bone, with minimal masculinizing effects.

• Oral dosing allows for combination with oral semaglutide, maximizing market and patent opportunities.

• Combination with semaglutide targets incremental fat loss while preserving muscle, addressing the plateau in weight loss seen with GLP-1s alone.

• No significant drug-drug interaction is expected due to different molecular classes.