Metsera Reports Promising Results from Trial of Monthly Injectable GLP-1 Agonist MET-097

Metsera, Inc., a clinical-stage biopharmaceutical company focused on advancing new medicines for obesity and metabolic diseases, has announced promising topline results from their Phase 1 clinical trial of MET-097. This trial centers on MET-097, an ultra long-acting injectable GLP-1 receptor agonist. The results indicate significant and sustainable weight loss, suggesting the potential for a once-monthly dosing regimen.

Steve Marso, M.D., Metsera’s chief medical officer, expressed enthusiasm for the outcomes, highlighting MET-097’s potential as a potent and well-tolerated GLP-1 drug candidate. He emphasized the drug’s promising safety profile and efficacy, noting that the weight loss achieved by MET-097 may equal or surpass that of existing GLP-1 drugs and those currently under investigation. The possibility of no titration and once-monthly dosing could lead to a more convenient and scalable delivery method for GLP-1 medications.

The Phase 1 trial was a randomized, placebo-controlled, double-blind study designed to assess the tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneous MET-097. The trial involved 125 healthy, non-diabetic, overweight, or obese adults. Participants received single doses ranging from 0.16 mg to 1.6 mg and weekly doses from 0.2 mg to 1.2 mg, administered five times without titration.

Key findings from the Phase 1 trial are as follows:
- The pharmacokinetics of MET-097 showed dose-linearity with a half-life of 380 hours, consistent across subjects. This is attributed to HALO™, Metsera’s proprietary peptide lipidation technology, resulting in a 2-3 fold longer half-life compared to other nutrient-stimulated hormone (NuSH) products.
- Gastrointestinal adverse events were generally mild, dose-related, and transient, aligning with those observed in marketed and clinical-stage NuSH compounds. No severe treatment-related adverse events or study drug discontinuations were reported.
- Body weight reduction from baseline was dose-dependent, with a 7.5% decrease at day 36 for the 1.2 mg dose, comparable to or exceeding those seen with current GLP-1 / GIP compounds.
- At day 57, four weeks post-final dose, a cumulative weight loss of 8.1% was observed at the 1.2 mg dose, indicating a durable pharmacodynamic effect consistent with the 380-hour half-life.

Brian Hubbard, Ph.D., Metsera’s chief scientific officer, highlighted that the Phase 1 data validate their HALO™ technology platform, demonstrating an ultra-long half-life in humans. He is optimistic that these findings will enable the production of NuSH analogs with significantly extended half-lives, on par with antibody-conjugated NuSH analogs.

Looking ahead, Metsera plans to commence a Phase 2b trial for MET-097 in Q4 2024, with data expected in the first half of 2025.

Metsera is driving innovation in the treatment of obesity and metabolic disorders through a broad portfolio of oral and injectable therapies. Founded in 2022 by Population Health Partners and ARCH Venture Partners, the company has secured $322 million in financing and is headquartered in New York City.