Biohaven Ltd. announced the presentation of preclinical data demonstrating the ability of taldefgrobep alfa to significantly reduce fat mass while increasing lean mass in an obese mouse model. Separately, data supporting the correlation between change in waist circumference and change in total body weight among adults living with overweight and obesity treated with approved anti-obesity medications were reported. Both sets of data were presented on October 15, 2023 at The Obesity Society's annual ObesityWeek conference held in Dallas, TX.

Poster 210: Correlation Between Reduction in Total Body Weight and Change in Waist Circumference, Poster 211: Taldefgrobep Alfa Reduces Fat and Increases Muscle in an Obese Mouse Model, The poster presentations highlight the potential benefit of taldefgrobep in the treatment of adults living with overweight and obesity and suggest anthropometric measures of central obesity, such as waist circumference or waist-to-height ratio, may be considered as effective alternative estimations of therapeutic effect. In a mouse model of diet-induced obesity, untreated mice exhibited an increase in fat mass of 31%, while the taldefgrobep-treated mice demonstrated increases in lean mass of 25% from baseline (p=0.001) and lost 11% of their baseline fat (p=0.001) compared to vehicle (placebo) treated mice. Insulin and leptin levels were consistently lower in taldefgrobep-treated mice compared to untreated.

There was no difference in food intake over time across the taldefgrobep and untreated mice, counter to what has been observed with incretin mimetics (e.g., semaglutide) which are consistently associated with a reduction in energy intake. A Phase 2 obesity study with taldefgrobep is planned for 2024. Taldefgrobep alfa (BHV-2000) is a fully human recombinant protein designed to specifically designed to bind to myostatin (GDF-8) and inhibit the signaling of both myostatin and activin A, both key regulators of muscle and adipose tissue.

Taldefgrobep binds myostatin. The myostatin-taldefgrobep complex then acts as an Activin 2a/2b receptor antagonist. Anti-myostatin therapy has a novel mechanism of action that may reduce fat mass, increase lean mass, and improve other metabolic parameters.