In what Guggenheim Partners called one of Metsera’s “critical program milestones” this year, its ultra-long-acting amylin injection MET-233i showed promising weight-loss after a little more than a month of treatment.
Metsera has once again jolted the weight loss space with Phase I results from an ultra-long-acting amylin injectable showing weight loss of 8.4% at 36 days. The biotech’s shares rose as much as 20% on Monday morning.
The results for the ultra-long-acting, early-stage amylin injection MET-233i had been hotly anticipated by analysts. In a Feb. 25 note to investors, analysts at Guggenheim Partners identified the early data for MET-233i as among Metsera’s most important “critical program milestones” this year, adding that the readout had the potential to “substantially de-risk the program.”
MET-233i, which Guggenheim noted is the only potential once-monthly amylin in clinical development, could also be combined with Metsera’s other pipeline assets that target GIP and glucagon, in turn opening up “pathways to differentiated products and market segmentation.”
Guggenheim estimated that the market for ultra-long-acting injectable incretin therapies could hit $19 billion by 2035.
Monday’s readout comes from a Phase I study that tested MET-233i as a monotherapy in 80 patients who were overweight or obese but who did not have type 2 diabetes. Results showed that at 36 days, patients treated with 1.2-mg of MET-233i saw an average weight reduction of 8.4% relative to placebo, with some individual responses reaching as high as 10.2%.
Pharmacokinetic analysis also pointed to a half-life of 19 days, which according to Metsera supports the once-monthly dosing regimen. Patients treated with MET-233i were also able to keep the weight off for more than four weeks, which is indicative of the amylin therapy’s ultra-long-acting profile, the biotech noted.
As for safety, MET-233i had a relatively clean profile, with no severe or serious toxicities to date. Gastrointestinal side effects—less common than with GLP-1s but still typical of the amylin drug class—were mild and limited to the first week of dosing, a pattern that Metsera claims is suggestive of the “rapid onset of tolerance.”
With Monday’s data, Metsera plans to continue its monotherapy study for MET-233i, for which topline findings are expected later this year. The biotech is also testing the amylin injection with its ultra-long-acting GLP-1 therapy MET-097i. Data from the combo trial could come as early as year-end 2025, or in early 2026, the company said. Guggenheim also noted that data from monthly dosing of MET-097i on its own is expected later this year or early next year, calling it a “key value-driving readout.”
Amylin Takes the Weight Loss Spotlight
Designed to be administered once a month via an injection under the skin, MET-233i is an analog of the amylin protein, a pancreatic hormone that works with insulin to slow the emptying of the stomach and lower glucose levels in the blood. Unlike the more entrenched GLP-1 drugs, amylin therapies could potentially offer several advantages, including better tolerability and lower loss of lean mass.
With this in mind, more and more biopharma players are studying amylin therapies for obesity. Leading the pack is weight loss frontrunner Novo Nordisk, which is developing CagriSema, a next-generation combination that uses its blockbuster GLP-1 drug semaglutide with the long-acting amylin analog cagrilintide.
Despite being the most mature amylin asset, CagriSema has struggled to meet the sky-high expectations of analysts and investors. In December 2024, weight-loss figures from the Phase III REDEFINE 1 study underwhelmed, with weight-loss reaching 22.7% at 68 weeks, versus a prior expectation of 25%. The blunder triggered a share selloff that wiped some $72 billion from Novo’s market cap.
In March, additional late-stage data likewise failed to make investors happy, resulting in a 7% dip in the pharma’s share price at the time.
In dissecting REDEFINE 1’s outcome, Guggenheim analysts in the February note flagged the study’s flexible dosing protocol, which they say resulted in only 56% of patients hitting the maximum dose of CagriSema. The analysts called this an “unforced error” that led to the underestimation of the full potential of CagiSema.
“However, in our view, [Novo] not only unequivocally validated the amylin mechanism in obesity, but their unforced error opened up a lane for other amylin competitors—particularly those that are differentiated like [Metsera’s] ultra-long acting MET-233i,” they wrote.
Other amylin players include Eli Lilly, which is expecting a Phase II readout for eloralintide in mid-2025, AbbVie, which bought into the space in March with a potential $2.2 billion deal with Denmark’s Gubra.
Correction (June 10): This story has been updated to state that MET-233i’s weight-loss effects were observed over 36 days, not 36 weeks. BioSpace regrets the error.
