Metsera Announces Positive Topline Phase 2a Clinical Data for its Ultra-Long Acting GLP-1 Receptor Agonist, MET-097i

January 07, 2025 at 07:00 AM EST

Up to 11.3% mean placebo-adjusted weight loss at 12 weeks; no plateau observed

Attractive tolerability profile emerging

Demonstrated feasibility of switch from weekly to monthly dosing

Continued acceleration into late-stage clinical trials

Metsera, Inc., a clinical-stage biopharmaceutical company accelerating the next generation of medicines for obesity and metabolic diseases, today announced positive data from a 12-week Phase 2a clinical trial of MET-097i, its potential once-monthly, ultra-long acting, subcutaneously injectable, fully-biased, GLP-1 receptor agonist (RA).

The randomized, double blind, placebo-controlled, Phase 2a trial enrolled 120 participants with obesity and overweight who did not have Type 2 diabetes. MET-097i was tested in five cohorts of 24 participants (20 active drug, 4 placebo). In four of these cohorts, participants were given 0.6mg, 0.8mg, 1.0mg, or 1.2mg, weekly, without titration, for 12 weeks. Participants in the fifth cohort were also given weekly doses but this time with escalated doses of 0.4mg for 4 weeks, then 0.8mg for 4 weeks, then 1.2mg for 4 weeks. At week 13, all participants were given either a two- or four-fold step-up in dose, to assess the tolerability of switching to a pharmacologically matched, potential monthly dose.

Weight loss was dose-dependent, with substantial reductions in mean body weight of 11.3% (placebo-adjusted) and individual responses as high as ~20% in the 1.2mg dose cohort after 12 weekly doses. A weight loss plateau was not reached, suggesting additional weight loss potential with longer-term dosing. All cohorts achieved clinically meaningful and statistically significant weight loss after 12 weeks of dosing.

MET-097i was generally well tolerated in all dose groups regardless of schedule. Gastrointestinal adverse events (AEs) were all mild or moderate and short-lived. Compelling tolerability was observed in the fifth cohort given titrated doses. In this cohort of 20 participants, only one case of mild, transient nausea and two cases of mild, transient vomiting were observed. Mean body weight loss of 6.3% (placebo-adjusted) was observed in this dose-escalated cohort.

Pharmacological exposure accumulated approximately four-fold over the course of 12 weeks in the titration-free cohorts, driven by the 15-16 day half-life of MET-097i, reinforcing the potential for titration-free dosing. At week 13, step-up to a four-fold higher dose was well-tolerated in all cohorts, supporting the idea that monthly dosing is feasible with this unique, ultra-long acting, GLP-1RA. The company plans to launch an additional study to confirm this finding across multiple monthly doses in early 2025.

John Buse, M.D., Verne S. Caviness Distinguished Professor and Director of the UNC Diabetes Center at University of North Carolina School of Medicine, said, “Taken together, these data suggest that MET-097i has the potential to be a foundational therapy for people with obesity and overweight, by virtue of its effectiveness, compelling tolerability profile and flexible options for dosing, including titration-free weekly dosing and monthly dosing.”

“These data strengthen our view of MET-097i as the potential first ultra-long acting GLP-1RA,” added Steve Marso, M.D., Chief Medical Officer of Metsera. “The powerful reductions in weight affirm our earlier studies. We are also excited by the emerging tolerability and dosing profile of MET-097i, which may offer versatility and meaningful advantages for patients.”

In parallel, Metsera’s Phase 2b trial of MET-097i in people with obesity or overweight has been fully enrolled with 239 trial participants. The company anticipates topline data from this trial in mid-2025. Additional trials exploring MET-097i in people with obesity, overweight, and Type 2 diabetes, including participants given monthly dosing, are expected in 2025. If these trials are successful, Metsera plans to initiate Phase 3 trials shortly thereafter.

About MET-097i

MET-097i, Metsera’s most advanced product candidate, is a fully-biased, potential once-monthly, ultra-long acting, subcutaneously injectable GLP-1 receptor agonist. Positive 12-week results from a Phase 2a trial demonstrated substantial placebo-adjusted weight loss of up to 11.3% in the 1.2mg cohort at day 85 and was generally well tolerated across dose groups. MET-097i, incorporating Metsera’s HALO™ platform technology, demonstrated a preliminary half-life of 15-16 days, supporting the potential for once-monthly dosing and dosing regimens with or without titration. Future studies are planned to confirm its safety, tolerability, clinical efficacy and overall risk-benefit profile. MET-097i is currently in Phase 2b as a monotherapy, with additional plans to evaluate it in combination with Metsera’s ultra-long acting amylin analogue, MET-233i, and other ultra-long acting nutrient-stimulated hormone (NuSH) analog peptide injectables in future studies.

About Metsera’s HALO™ peptide lipidation platform

HALO™ is Metsera’s novel peptide lipidation platform technology that enables peptides to bind simultaneously to albumin and to a drug target, resulting in a half-life approaching that of albumin and exceeding that of other NuSH peptides by two-to-threefold. This ultra-long half-life enables four key advantages: titration-free dosing, monthly dosing, improved tolerability, and improved scalability.

About Metsera

Metsera is a clinical-stage biopharmaceutical company accelerating the next generation of medicines for obesity and metabolic diseases. Metsera is advancing a broad portfolio of oral and injectable incretin, non-incretin and combination therapies with potential best-in-class profiles to address multiple therapeutic targets and meet the future needs of a rapidly evolving weight loss treatment landscape. Founded in 2022 by Population Health Partners and ARCH Venture Partners, Metsera has raised over $500 million in financing from leading healthcare investors and is based in New York City.