Metsera Announces Positive Phase 1 Data of First-in-Class Once-Monthly Amylin Candidate MET-233i

Rhea-AI Summary

Metsera (NASDAQ: MTSR) announced positive Phase 1 trial results for MET-233i, their first-in-class ultra-long acting amylin analog. The drug demonstrated impressive efficacy with up to 8.4% mean placebo-subtracted weight loss at Day 36 and a 19-day half-life supporting monthly dosing. The trial involved 80 participants with overweight/obesity, testing doses from 0.15mg to 2.4mg. Key findings include dose-linear pharmacokinetics, sustained weight loss effects, and favorable tolerability with no safety signals. The drug shows potential for combination with Metsera's GLP-1 receptor agonist MET-097i, positioning it as a possible first monthly multi-NuSH combination therapy. Based on these results, Metsera is advancing both monotherapy and combination trials, with additional data expected in late 2025 or early 2026.

Positive

• Strong efficacy with 8.4% mean placebo-subtracted weight loss at Day 36
• 19-day half-life enables convenient once-monthly dosing potential
• Favorable safety profile with no severe or serious adverse events
• Starting doses (0.15mg and 0.3mg) showed placebo-like tolerability
• Potential for first-in-category monthly combination therapy with GLP-1 agonist MET-097i
• Individual weight loss responses as high as 10.2%

Negative

• Gastrointestinal adverse events reported in multiple ascending dose portion
• Three-fold accumulation of exposure over five weeks
• Limited trial duration and participant size (80 participants)
• Longer-term safety and efficacy data still pending

Insights

Pharmaceutical Clinical Trials Expert

Metsera's MET-233i shows remarkable 8.4% weight loss with monthly dosing potential, positioning it as a possible best-in-class amylin analog.

The Phase 1 results for Metsera's amylin analog MET-233i represent a significant clinical achievement. The reported 8.4% mean placebo-subtracted weight loss at Day 36 is remarkably high for a Phase 1 trial, especially for a non-GLP-1 mechanism. This efficacy level approaches what we typically see with established GLP-1 therapies over longer treatment periods.

The 19-day half-life is particularly noteworthy as it enables monthly dosing - a major competitive advantage in the metabolic disease space where most competitors require weekly administration. This pharmacokinetic profile significantly outperforms other amylin analogs in development and positions MET-233i as potentially best-in-class.

The tolerability profile is equally impressive. The trial showed gastrointestinal adverse events were only mild and primarily confined to the first week of dosing, suggesting rapid tolerance development despite drug accumulation. This is critical for patient adherence, especially considering that the anticipated starting doses (0.15mg and 0.3mg) showed placebo-comparable tolerability.

Most compelling is the combinability potential with their GLP-1 receptor agonist (MET-097i). The matched exposure profiles of these agents could enable the first once-monthly multi-mechanism therapy for metabolic disease. This approach aligns with emerging clinical evidence suggesting superior outcomes when targeting multiple metabolic pathways simultaneously.

The absence of serious adverse events and the dose-dependent weight loss (up to 10.2% in some individuals) further strengthen MET-233i's clinical profile. The extended durability of weight loss - maintained more than four weeks after single dosing - validates both the compound's half-life and its potential real-world efficacy.

Biotech Investment Analyst

Metsera's positive Phase 1 data positions them competitively in the lucrative obesity market with potential first-to-market monthly combination therapy.

This data represents a meaningful de-risking event for Metsera's metabolic disease pipeline. The 8.4% weight loss achieved in just 36 days positions MET-233i competitively against established obesity treatments, while the 19-day half-life enables a crucial monthly dosing advantage in an increasingly crowded market.

The company's HALO™ platform technology is proving its value, now having generated multiple long-acting peptide candidates with promising clinical profiles. This validates their technological approach and suggests potential for additional pipeline candidates beyond metabolic disease.

Metsera's strategic focus on combinability is particularly astute. By engineering MET-233i to match the pharmacokinetic profile of their GLP-1 candidate (MET-097i), they're positioning for a potential first-in-category monthly multi-mechanism treatment. The obesity treatment landscape is evolving toward combination therapies that can deliver enhanced efficacy with manageable side effects.

The clinical development timeline appears accelerated, with multiple data readouts expected within the next 6-12 months. Key catalysts include:

• Extended monotherapy data with dose titration (late 2025)
• Co-administration results with GLP-1 (late 2025/early 2026)
• GIP agonist combination data (late 2025)

The clean safety profile in Phase 1 reduces clinical development risk, though larger trials will be needed to confirm. The Phase 1 population's mean BMI of 32 aligns with the target demographic for obesity treatments. The balanced gender representation also strengthens the data's applicability.

While competition in the obesity market is intensifying, Metsera's approach of developing convenient monthly dosing with a multi-mechanism strategy addresses key unmet needs in patient convenience and enhanced efficacy beyond single-target approaches.

Placebo-subtracted mean weight loss up to 8.4% at Day 36

19-day observed half-life supports once-monthly dosing as monotherapy and potential first-in-category monthly GLP-1 + Amylin combination

Well-tolerated with no safety signals

Company to host conference call and webcast today at 8:00 A.M. ET

NEW YORK, June 09, 2025 (GLOBE NEWSWIRE) -- Metsera, Inc. (Nasdaq: MTSR), today announced positive topline data from the Phase 1 clinical trial of MET-233i, an ultra-long acting amylin analog engineered for class-leading durability, potency, and combinability with Metsera’s fully-biased monthly GLP-1 receptor agonist candidate, MET-097i. In the study, MET-233i demonstrated up to 8.4% mean placebo-subtracted weight loss at Day 36, a 19-day observed half-life supporting once-monthly dosing, and a favorable tolerability profile with no safety signals.

“We are excited by these impressive results from MET-233i, which demonstrate exceptional efficacy with no safety signals, and enable the potential first monthly multi-NuSH combination,” said Steve Marso, M.D., Chief Medical Officer of Metsera. “We observed five-week body weight loss comparable to that of leading GLP-1-based medicines, and we identified efficacious starting doses with placebo-like tolerability. These data position MET-233i as a potential best-in-class amylin and support a category-leading profile in combination with MET-097i.”

The randomized, placebo-controlled, double-blind Phase 1 trial was designed to evaluate the pharmacokinetics, efficacy, and safety of subcutaneous MET-233i in 80 participants with overweight or obesity without type 2 diabetes. MET-233i was evaluated at single doses from 0.15 mg to 2.4 mg, and multiple doses from 0.15 mg to 1.2 mg given once weekly over five weeks without titration. The trial population was broadly balanced in gender between MET-233i and placebo and had a mean baseline body mass index of approximately 32.

Topline results from the Phase 1 trial include:

• Dose-linear pharmacokinetics with an observed half-life of 19 days from dose to 50% of Cmax. This represents the most durable pharmacokinetic profile of any known amylin analog and supports the potential for once-monthly dosing with simplified titration. MET-233i’s exposure profile after multiple doses matched that of MET-097i, supporting combinability as a potential first-in-category once-monthly multi-NuSH combination. These data further substantiate HALO™, Metsera’s proprietary, novel peptide stabilization and lipidation platform technology.
  
  
• Body weight loss up to 8.4%. Body weight loss was dose-dependent, ranging up to a placebo-subtracted mean of 8.4% at Day 36 after five weekly doses of 1.2 mg, with individual responses as high as 10.2%. In the single ascending dose (SAD) portion of the trial, substantial weight loss was maintained more than four weeks after dosing, supported by the ultra-long pharmacokinetics observed for MET-233i.
  
  
• Favorable tolerability results. Gastrointestinal adverse events in the multiple ascending dose (MAD) portion of the trial were all mild, dose-dependent, and primarily confined to the first week of dosing, implying rapid onset of tolerance despite a three-fold accumulation of exposure over five weeks. Anticipated starting doses of 0.15 mg and 0.3 mg demonstrated tolerability results comparable to placebo in both the SAD and the MAD portions of the trial.
  
  
• No safety signals. There were no severe or serious adverse events observed in the SAD or MAD portion of the trial to date.

“Amylin agonism has emerged as a central therapeutic mechanism for metabolic diseases, but candidates in development have been limited to weekly dosing,” said Professor Carel le Roux, Director of the Metabolic Medicine Group and Chair in Experimental Pathology at University College Dublin. “The durability and efficacy of MET-233i in this trial, along with its combinability with Metsera’s GLP-1 RA, make it the potential first monthly multi-NuSH combination candidate for patients seeking greater levels of well-tolerated weight loss with a more convenient dosing schedule.”

Next Steps

Based on these positive topline data, Metsera is rapidly advancing MET-233i as a monotherapy and in combination with MET-097i:

• An ongoing monotherapy trial evaluates 12 weekly doses of MET-233i with dose titration, followed by an exposure-matched monthly dose at week 13. Topline data from this trial are expected in late 2025.
  
  
• Metsera has extended an ongoing co-administration trial of MET-233i and MET-097i to twelve weeks, with topline data expected by year-end 2025 or early 2026.
  

The Company also expects to report topline clinical data from its ultra-long acting GIP receptor agonist, MET-034i, in combination with MET-097i, in late 2025. We anticipate that MET-034i will be the third peptide engineered with Metsera’s HALO™ platform to enter clinical testing.

Conference Call and Webcast Information
Metsera will host a conference call and webcast today, June 9, 2025, at 8:00 A.M. Eastern Time to discuss the Phase 1 clinical trial of MET-233i. A live webcast of the call and a replay will be available on the Events page in the Investors & News section of the Metsera website at investors.metsera.com. To access the call by phone, participants should visit this link to receive dial-in details: https://register-conf.media-server.com/register/BI658482ecfbdb4146996744dd3d86c481.

About MET-233i
MET-233i is an ultra-long acting, subcutaneously injectable monthly amylin analog engineered for class-leading durability, potency, and combinability in solution with Metsera’s fully-biased, ultra-long acting GLP-1 RA candidate MET-097i, with matched solubility parameters and observed half-lives. MET-233i is being explored in clinical studies as a monotherapy and in combination with MET-097i. Metsera is developing the combination of MET-233i and MET-097i via the FDA biologic pathway with the intent to pursue the combination’s regulatory approval in the United States under a BLA.

About Metsera’s HALO™ peptide stabilization and lipidation platform
HALO™ is Metsera’s novel peptide stabilization and lipidation platform technology that enables peptides to bind simultaneously to albumin and to a drug target, designed to facilitate a half-life approaching that of albumin and exceeding that of other NuSH peptides. This ultra-long half-life may enable monthly dosing, improved tolerability, and improved scalability.

About Metsera, Inc.
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. Metsera was founded in 2022 and is based in New York City. For more information, please visit us at www.metsera.com and follow us on LinkedIn and X.

Metsera may use its website as a distribution channel of material information about the Company. Financial and other important information regarding the Company is routinely posted on and accessible through the Investors & News section of its website at investors.metsera.com. In addition, you may sign up to automatically receive email alerts and other information about the Company by using the “Email Alerts” option on the Investors & Media page and submitting your email address.

Forward Looking Statements
This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this press release other than statements of historical fact should be considered forward-looking statements, including, without limitation, statements related to the timelines, design and results of the Company’s clinical trials and data releases; the Company’s product candidate pipeline and milestone events; potential benefits of treatment with the Company’s product candidates; and anticipated market opportunity and strategy. When used herein, words including “anticipate,” “believe,” “can,” “continue,” “could,” “designed,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. All forward-looking statements are based upon the Company’s current expectations and various assumptions. The Company believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. The Company may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, our limited operating history; our ability to generate revenue or become profitable; failure to obtain additional capital when needed on acceptable terms or at all; raising additional capital may cause dilution to our stockholders or require us to relinquish rights to our technologies or product candidates; our dependence on the success of our product candidates; risks associated with preclinical and clinical development; difficulties or delays in the commencement or completion, or the termination or suspension, of clinical trials; our ability to timely enroll patients in our clinical trials; if our current or future product candidates are associated with side effects, adverse events or other properties or safety risks; risks associated with the regulatory approval processes of the FDA and comparable foreign authorities; risks associated with conducting clinical trials and preclinical studies outside of the United States; our reliance on third parties to conduct clinical trials and preclinical studies; our reliance on third parties for the manufacture and shipping of our product candidates; risks associated with our license and collaboration agreements and future strategic alliances; significant competition in our industry; product candidates for which we intend to seek approval as biologic products may face competition sooner than anticipated; our success is dependent on our ability to attract and retain highly qualified management and other clinical and scientific personal; if we or our licensors are unable to obtain, maintain, defend and enforce patent or other intellectual property protection for our current or future product candidates or technology; risks associated with our common stock and the other important factors discussed under the caption “Risk Factors” in its filings with the Securities and Exchange Commission, including in its Annual Report on Form 10-K for the year ended December 31, 2024 and its Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which are accessible on the SEC’s website at www.sec.gov and the Investors section of the Company’s website at investors.metsera.com. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause the Company’s views to change. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release.

Contact:
Jono Emmett
Metsera
media@metsera.com

FAQ

What were the key results from Metsera's (MTSR) Phase 1 trial of MET-233i?

The trial showed up to 8.4% mean placebo-subtracted weight loss at Day 36, a 19-day half-life supporting monthly dosing, and favorable tolerability with no safety signals.

How many participants were in Metsera's MET-233i Phase 1 trial?

The Phase 1 trial included 80 participants with overweight or obesity without type 2 diabetes, with a mean baseline BMI of approximately 32.

What dosing ranges were tested in Metsera's MET-233i trial?

Single doses from 0.15 mg to 2.4 mg were tested, and multiple doses from 0.15 mg to 1.2 mg were given once weekly over five weeks without titration.

When will Metsera (MTSR) report additional clinical data for MET-233i?

Topline data from the monotherapy trial is expected in late 2025, while combination trial data with MET-097i is expected by year-end 2025 or early 2026.

What makes Metsera's MET-233i unique in the amylin analog space?

MET-233i has the most durable pharmacokinetic profile of any known amylin analog, with a 19-day half-life enabling potential monthly dosing, compared to weekly dosing for other candidates.