The goal of this clinical trial is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous injections of MET233 in otherwise healthy adults with overweight or obesity.

This study will be conducted in four parts:

• Part A will evaluate single ascending doses of MET233 or placebo.
• Part B will evaluate multiple ascending doses, with participants receiving five once-weekly doses of MET233 or placebo.
• Part C will evaluate once-weekly dosing of MET233 or placebo for 12 weeks, followed by a single higher, potential monthly dose.
• Part D will evaluate a longer dosing schedule, in which participants will receive twelve once-weekly doses, followed by three monthly doses of MET233 or placebo. Participants in this part will be followed for 14 weeks after the final dose.

This is a randomized, placebo-controlled, double-blind study designed to investigate the safety, tolerability, PK and pharmacodynamic (PD) of single and multiple ascending subcutaneous (SC) doses of MET233 in otherwise healthy adult participants with obesity or overweight (body mass index [BMI] 27.0 kg/m2 to 38.0 kg/m2, inclusive for Parts A-C and BMI in Part D 30- 45.0 kg/m2 (inclusive).

• In Part A, participants will receive a single dose of MET233 at up to five dose levels.
• In Part B, participants will receive five weekly doses of MET233 at up to four dose levels.
• In Part C, participants will receive 12 weekly doses of MET233. These doses may include titration. For all cohorts in Part C, a 13th dose administered on Day 85 may be a monthly-equivalent dose to evaluate the potential for switching to a monthly dosing regimen.
• In Part D, participants will receive 12 once-weekly doses, followed by three monthly doses of MET233 or placebo.

Inclusion Criteria:

• Adult (≥18 to ≤70 years) male and female participants with obesity or overweight (BMI 27.0 kg/m2 to 38.0 kg/m2, inclusive) but otherwise healthy.

Exclusion Criteria:

• Female who is lactating or who is pregnant according to the pregnancy test at the Screening visit or prior to the first study drug administration
• Seated blood pressure higher than 160/95 mmHg at the Screening visit
• Elevated resting pulse greater than 100 beats per minute at Screening visit
• Presence of clinically significant ECG abnormalities
• Diagnosis of diabetes (type 1 or type 2)
• Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration
• Obesity induced by endocrinologic disorders (e.g., Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome).

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.