HBM Holdings unveils strong pre-clinical results for AI-designed obesity antibody LET003

HBM Holdings Limited (HBM) on 18 May 2026 reported encouraging pre-clinical findings for LET003, its first artificial-intelligence–enabled monoclonal antibody targeting activin receptors ACVR2A/2B for obesity treatment.

Developed via the Hu-mAtrIx™ platform, LET003 displayed a markedly slower blood-clearance profile than multiple rival molecules in both human FcRn transgenic mice and cynomolgus monkeys following subcutaneous administration. Management highlighted the potential for longer dosing intervals or lower dosing levels relative to competing candidates.

Efficacy signals were strongest when LET003 was combined with the GLP-1 analogue semaglutide (30 nmol/kg). In wild-type obese mice, a once-weekly regimen of LET003 (20 mg/kg) plus semaglutide reduced fat mass by 76.0% versus vehicle and by 34.7% versus semaglutide monotherapy (both P<0.0001). While lean mass in the combination group dipped 6.5% against vehicle (P=0.0001), it rose 5.7% over semaglutide alone (P=0.0007).

In a high-fat diet model using human FcRn transgenic mice, the same combination cut the fat-to-body-weight ratio by 17.5% compared with vehicle and by 6.0% versus semaglutide monotherapy (P=0.0127). Concurrently, the lean mass-to-body-weight ratio advanced 15.2% over vehicle and 5.3% over semaglutide monotherapy (P=0.0194).

Head-to-head studies underscored LET003’s potency in enhancing lean mass. In normal-diet human FcRn mice, weekly 20 mg/kg dosing raised lean mass by 18.3% versus vehicle and by 13.5% over a comparator molecule (both P<0.0001). Overall body weight increased 11.1% and 9.3%, respectively, against the same benchmarks. A dose-ranging trial further showed that LET003 at 5 mg/kg achieved lean-mass gains on par with 15 mg/kg of bimagrumab, indicating a favorable dose-efficacy profile.

The company positions LET003 as a potential best-in-class adjunct to GLP-1 therapies, aiming to enhance fat loss while preserving—or boosting—lean mass. HBM cautioned that development and commercialisation are subject to clinical success and regulatory review, and the disclosed data are unaudited.

Investors are advised to exercise caution when dealing in HBM Holdings securities pending further updates on clinical progress.