The primary objective of the study is to evaluate the safety and tolerability of REGN4461 in healthy participants. The secondary objectives of the study are to:

• Characterize the Pharmacokinetic (PK) profile of single and repeated doses of REGN4461 and evaluate the effects of baseline covariates on PK profile
• Estimate the effects of repeated doses of REGN4461 on body weight over 12 weeks in overweight and obese participants
• Assess the effects of repeated doses of REGN4461 on ad lib energy intake in overweight and obese participants
• Evaluate the effects of single and repeated doses of REGN4461 on soluble forms of lipid-regulating proteins levels over time
• Assess the immunogenicity of single and repeated doses of REGN4461

This is a 2-part study of the safety, tolerability, PK and pharmacodynamic (PD) of single and repeated doses of REGN4461 in healthy participants. In Part A, healthy lean or overweight participants will be enrolled to evaluate the safety, tolerability, PK, and PD of single ascending intravenous (IV) and subcutaneous (SC) doses. Interim PK and safety information from Part A will be used to select the dose level, frequency, and mode of administration (IV or SC) for repeat dosing in Part B. In Part B, overweight/obese participants with body mass index (BMI) 25-40 kg/m2 will be enrolled to evaluate the safety, tolerability, PK, and PD of repeated doses of REGN4461 in 4 distinct cohorts defined by baseline leptin levels.

Key Inclusion Criteria

Part A:

• Males and females 18 to 50 years of age, inclusive
• Body mass index (BMI) from 18.5 to <30.0 kg/m^2
• Participant is judged by the investigator to be in good health and free from major comorbidities based on medical history, physical examination, laboratory safety tests performed at screening and/or prior to administration of initial dose of study drug

Part B:

• Males and females 18 to 65 years of age, inclusive
• Have a body mass index (BMI) from 25.0 to 40.0 kg/m^2
• Participant is judged by the investigator to be free from major comorbidities based upon medical history, physical examination, laboratory safety tests performed at screening and/or prior to administration of initial dose of study drug. Participants can have a history of mild hyperlipidemia and/or mild hypertension but should be on stable doses of lipid lowering or blood pressure lowering medicines for at least 2 months prior to screening

Key Exclusion Criteria

Part A:

• History of type 1 or 2 diabetes or prediabetes or with fasting blood glucose (FBG) at screening ≥ 100mg/dL or with HbA1c at screening of ≥ 5.7%.
• Fasting LDL-C ≥ 130mg/dL, TG ≥ 250 mg/dL

Part B:

• History of type 1 or 2 diabetes or with FBG at screening ≥ 126 mg/dL or with HbA1c at screening of ≥ 6.5%. A diagnosis of "pre-diabetes" is allowed.
• Fasting LDL-C ≥ 160 or TG ≥ 500 mg/dL

Key Exclusion Criteria (Parts A and B):

• Hospitalization (ie, >24 hours) for any reason within 60 days of the screening visit
• History of hypothalamic amenorrhea or lipodystrophy.
• Change in body weight of more than 5% over the past 3 months prior to screening.
• Previous history of bariatric procedures for obesity (eg, sleeve gastrectomy, gastric bypass, banding, etc).
• Procedures for weight reduction (eg, liposuction) or body contouring in the past 6 months.
• Treatment with medications for (over-the-counter [OTC] or prescribed) weight loss (eg, lorcaserin, phentermine/topiramate, naltrexone HCl/bupropion HCl, liraglutide) in the past 3 months.
• History of major psychiatric disorders, eating disorders (eg, bulimia, anorexia).
• Current cigarette smoker or former smoker (cigarettes or e-cigarettes) who stopped smoking within 3 months prior to screening.
• History of recreational drug (including marijuana) or alcohol abuse (>2 drinks per day) within a year prior to the screening visit.
• History of hepatitis B infection or a positive hepatitis B surface antigen (HbsAg+) at screening
• History of HIV infection or HIV seropositive at the screening visit.
• History of hepatitis C infection or positive hepatitis C antibody test result at screening.
• Pregnant or breastfeeding women.

Note: Other inclusion/ exclusion criteria apply