Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect on Body Weight of RN3161 as Monotherapy and in Combination With Tirzepatide in Adults With Overweight and Obesity

Inclusion criteria

• BMI:

Obesity: BMI ≥ 30 kg/m² for participants with no Asian ancestry and ≥ 27.5 kg/m² for participants with Asian ancestry that has been stable (± 5%) for the previous 3 months (based on participant self-report or available medical records), with or without a weight-related comorbidity (excluding diabetes)

Overweight: BMI 27 to <30 kg/m² for participants with no Asian ancestry and 23.0 to <27.5 kg/m² for participants with Asian ancestry that has been stable (± 5%) for the previous 3 months (based on participant self-report or available medical records), with at least 1 weight-related comorbidity (excluding diabetes)

Weight-related comorbidities include a diagnosis of the following:

• Hypertension: seated BP ≤ 140/90 mm Hg; receiving ≤ 2 stable (≥ 4 weeks) agents limited to ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, or thiazide ≤ 25 mg, or untreated
• Dyslipidemia: stable use of lipid-lowering agents for dyslipidemia (LDL-C < 150 mg/dL, triglycerides < 300 mg/dL)
• Osteoarthritis

Exclusion criteria

• self-reported or documented weight gain or loss >5% within 3 months prior to screening
• use of GLP1R agonists within 6 months of screening
• intolerance to GLP-1 medications in the past
• use of non-GLP1R medications for weight loss within 3 months of screening
• HbA1c >6.5%
• diagnosis of significant liver disease
• history of malignancy or anaphylaxis
• use of any siRNA agent in the prior 12 months