Harbour BioMed's LET003 shows breakthrough fat loss with muscle preservation in obesity studies

Harbour BioMed has released new preclinical data for LET003, a next-generation monoclonal antibody targeting ACVR2A/2B for obesity treatment. The compound demonstrated strong potential in reducing fat while preserving muscle mass in animal models. In studies involving human FcRn transgenic mice and cynomolgus monkeys, LET003 showed significantly slower clearance than other molecules. Its pharmacokinetic profile proved superior to multiple competitors.

When combined with semaglutide, LET003 achieved a 76.0% reduction in fat mass compared with a control group. This was also 34.7% lower than semaglutide alone. The fat-to-body weight ratio dropped by 17.5% versus the control and by 6.0% compared with semaglutide monotherapy.

Lean mass in the combination group decreased by 6.5% compared with the control but rose by 5.7% over semaglutide alone. The lean mass-to-body weight ratio improved by 15.2% versus the control and by 5.3% compared with semaglutide monotherapy.

In a separate study, LET003 at 5 mg/kg matched the lean mass benefits of 15 mg/kg bimagrumab. It also delivered an 18.3% increase in lean mass and an 11.1% rise in overall body weight compared with the control. The findings highlight LET003’s ability to enhance fat reduction while maintaining or increasing lean mass. Combined with semaglutide, it offers a promising approach for obesity treatment. The data support further development of the therapy.