Biohaven has announced the completion of patient enrollment in its Phase II Proof-of-Concept (PoC) trial evaluating taldefgrobep alfa, an investigational therapy for obesity designed to improve body composition by reducing fat mass while increasing muscle mass.

The study is assessing taldefgrobep, a myostatin-activin pathway inhibitor (MAPI), which represents a novel approach to weight management by targeting both adipose tissue and lean muscle. Topline results from the trial are expected in the second half of 2026.

The Phase II trial is a randomised, double-blind, placebo-controlled, dose-ranging study involving approximately 150 participants across 20 clinical sites in the United States. It is evaluating once-weekly and once-monthly dosing of taldefgrobep as a monotherapy, administered via a self-injectable device.

The primary endpoint is the percentage change in total body weight over a 24-week period, while secondary endpoints include changes in body fat mass and lean muscle mass. The study also includes a 24-week open-label extension phase to further assess safety and efficacy.

The development comes amid growing interest in next-generation obesity therapies that go beyond weight loss alone to address overall metabolic health and body composition. While existing treatments such as GLP-1 receptor agonists have demonstrated significant weight reduction, maintaining muscle mass remains a key challenge in long-term obesity management.

Earlier clinical studies of taldefgrobep have shown promising results. In a Phase I trial, participants experienced significant reductions in total body fat mass alongside increases in lean muscle mass after short-term dosing. Additional data from studies in other indications have also demonstrated improvements in fat accumulation, muscle mass and bone density.

The therapy has been evaluated in more than 700 participants to date, with a safety profile characterised by low rates of serious adverse events and tolerability comparable to placebo in most cases.

Preclinical studies further support the drug’s mechanism of action, showing its ability to inhibit activin receptor signalling, which plays a key role in regulating muscle growth and fat accumulation. Combination studies with GLP-1 therapies have also indicated potential additive benefits in weight and metabolic outcomes.

Biohaven believes taldefgrobep could emerge as a differentiated treatment option, either as a standalone therapy or in combination with existing obesity treatments, to deliver more ‘high-quality’ weight loss by preserving or increasing muscle mass.

The completion of enrollment marks a key milestone in the clinical development of taldefgrobep, as the company continues to expand its pipeline of therapies targeting complex metabolic and chronic diseases.