Metsera, Inc. has announced positive topline results from its Phase 1 clinical trial of MET-097, an ultra-long-acting injectable GLP-1 receptor agonist. The trial, involving 125 healthy, non-diabetic, overweight or obese adults, demonstrated significant and durable weight loss, supporting the potential for a once-monthly dosing regimen. The results position MET-097 as a promising candidate in the competitive landscape of obesity and metabolic disease treatments.
Phase 1 Trial Results
The randomized, placebo-controlled, double-blind Phase 1 trial evaluated the tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneous MET-097. Participants received single doses ranging from 0.16 mg to 1.6 mg, or weekly doses from 0.2 mg to 1.2 mg, administered five times without titration.
Key findings from the trial include:
- Pharmacokinetics: MET-097 exhibited dose-linear pharmacokinetics with a half-life of 380 hours, attributed to Metsera's HALO™ platform technology. This half-life is 2-3 times longer than currently available and investigational nutrient-stimulated hormone (NuSH) products.
- Safety and Tolerability: Gastrointestinal adverse events were dose-related, mostly mild, and transient, consistent with other NuSH compounds. No severe treatment-related adverse events or study drug discontinuations were observed.
- Efficacy: At a dose of 1.2 mg, participants experienced a 7.5% reduction in body weight from baseline at day 36, one week after the final dose. Cumulative weight loss at the 1.2mg dose was 8.1% at day 57, four weeks after the final dose, suggesting durable pharmacodynamic effect consistent with the observed 380 hour half-life.
HALO™ Technology
MET-097 incorporates Metsera’s HALO™ platform technology, a novel peptide lipidation platform designed to extend the half-life of peptide therapeutics. According to Brian Hubbard, Ph.D., chief scientific officer of Metsera, the Phase 1 data validates the science underlying Metsera's discovery strategy, demonstrating that the HALO™ technology platform confers ultra-long product half-life in humans.
Future Development
Based on these results, Metsera plans to initiate a Phase 2b trial of MET-097 in Q4 2024, with data anticipated in the first half of 2025. This trial will further evaluate the efficacy and safety of MET-097 in a larger patient population.
Steve Marso, M.D., chief medical officer of Metsera, stated that the company is encouraged by both the safety profile and initial efficacy of MET-097. He noted that the data suggest the possibility for no titration and once-monthly dosing, potentially offering a more convenient, scalable, and better-tolerated method of administering GLP-1 medicines.
