Metsera Inc.

06/09/2025 | Press release | Distributed by Public on 06/09/2025 05:04

Material Event (Form 8-K)

Item 8.01.

Other Events.

On June 9, 2025, Metsera, Inc. (the "Company") announced topline results from its Phase 1 clinical trial of MET-233i. MET-233iis a subcutaneously injectable ultra-long acting amylin analog that the Company is developing for the treatment of obesity and overweight. The Phase 1 clinical trial is a randomized, placebo-controlled, double-blind clinical trial with a single ascending dose ("SAD") portion and a five-week multiple ascending dose ("MAD") portion.

The primary endpoint was the safety and tolerability of MET-233ibased on laboratory findings, vital signs, 12-leadelectrocardiogram measurements, physical examinations, injection site reactions, and occurrence, severity and relatedness of treatment-emergent adverse events ("TEAEs"), as compared to placebo. The key secondary endpoints were related to the pharmacokinetic ("PK") profile and the effects of MET-233ion body weight in participants receiving SAD and MAD of MET-233i.

SAD

A total of 40 participants were enrolled in five SAD cohorts. Participants received a single dose of placebo or of 0.15 mg, 0.30 mg, 0.60 mg, 1.2 mg or 2.4 mg MET-233i.Ten participants received a placebo dose. The Company observed dose-dependent weight loss across all cohorts, with a mean placebo-subtracted weight loss of 5.3% at day 8 for the 2.4 mg dose, with the other doses reflected in the table below. Placebo change from baseline body weight was 0.9% at day 8.

MET-233iwas found to be generally well-tolerated. The most frequent TEAEs were gastrointestinal-related and dose-dependent, most of which were mild. As summarized in the table below, of the gastrointestinal-related TEAEs, nausea and vomiting were the most common:

GASTROINTESTINAL ADVERSE EVENTS BY TYPE AND SEVERITY IN SAD

Pooled Placebo

MET-233i

0.15 mg

0.30 mg

0.60 mg

1.2 mg

2.4 mg

         N

10 6 6 6 6 6

At Least One GI AE

0 0 1 (16.7%) 2 (33.3%) 5 (83.3%) 6 (100.0%)

Nausea

0 0 1 (16.7%) 2 (33.3%) 5 (83.3%) 6 (100.0%)

Mild

0 0 1 (16.7%) 2 (33.3%) 3 (50.0%) 6 (100.0%)

Moderate

0 0 0 0 2 (33.3%) 0

Severe

0 0 0 0 0 0

Vomiting

0 0 0 1 (16.7%) 4 (66.7%) 5 (83.3%)

Mild

0 0 0 1 (16.7%) 3 (50.0%) 5 (83.3%)

Moderate

0 0 0 0 1 (16.7%) 0

Severe

0 0 0 0 0 0

Diarrhea

0 0 0 0 1 (16.7%) 0

N represents the number of treated participants.

Number of unique participants for each Preferred Term (PT) and severity is presented.

PK analysis following a single dose of MET-233ishowed dose-proportional pharmacokinetics with an observed half-life (time from administration to 50% maximum observed concentration ("Cmax")) of approximately 19 days. The figure below shows the MET-233iPK profile from the SAD portion of the trial.

MAD

A total of 40 participants were enrolled in four MAD cohorts. Participants received five weekly doses of placebo or 0.15 mg, 0.30 mg, 0.60 mg or 1.2 mg MET-233i.Eight participants received a placebo dose. The Company observed dose-dependent weight loss across most cohorts, with a mean placebo-subtracted weight loss of 8.4% at day 36 for the 1.2 mg dose, with the other doses reflected in the table below. Placebo change from baseline body weight was 0.6% at day 36.

In each cohort, MET-233iwas found to be generally well-tolerated. The most frequent TEAEs were gastrointestinal-related and dose-dependent, all of which were mild. Gastrointestinal-related TEAEs were mostly confined to the first week, while exposure to MET-233iincreased over the course of the clinical trial. Out of the 40 participants, 3 (7.5%) discontinued and none were attributed to the TEAEs. As summarized in the table below, of the gastrointestinal-related TEAEs, nausea and vomiting were the most common:

GASTROINTESTINAL ADVERSE EVENTS BY TYPE AND SEVERITY IN MAD

Pooled Placebo

MET-233i

0.15 mg

0.30 mg

0.60 mg

1.2 mg

        N

8 8 8 8 8

At Least One GI AE

2 (25%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%)

Nausea

1 (12.5%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%)

Mild

1 (12.5%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%)

Moderate

0 0 0 0 0

Severe

0 0 0 0 0

Vomiting

0 1 (12.5%) 0 3 (37.5%) 3 (37.5%)

Mild

0 1 (12.5%) 0 3 (37.5%) 3 (37.5%)

Moderate

0 0 0 0 0

Severe

0 0 0 0 0

Diarrhea

1 (12.5%) 0 0 1 (12.5%) 0

N represents the number of treated participants.

Number of unique participants for each PT and severity is presented.

PK analysis of multiple-doses of MET-233iwas consistent with that of MET-097i,which the Company believes supports the potential for MET-233iand MET-097ias a monthly multi-nutrient stimulated hormone combination.

Upcoming Milestones

Based on these positive data, the Company is advancing MET-233ias a potential monotherapy and in combination with MET-097i:

An ongoing monotherapy trial evaluates 12 weekly doses of MET-233iwith dose titration, followed by an exposure-matched monthly dose at week 13. Topline data from this trial are expected in late 2025.

The Company has extended an ongoing co-administrationtrial of MET-233iand MET-097ito twelve weeks, with topline data expected by year-end2025 or early 2026.

The Company also expects to report topline clinical data from its ultra-long acting glucose-dependent insulinotropic polypeptide receptor agonist, MET-034i,in combination with MET-097i,in late 2025.

Metsera Inc. published this content on June 09, 2025, and is solely responsible for the information contained herein. Distributed via SEC EDGAR on June 09, 2025 at 11:05 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at support@pubt.io