A Phase 1/2a Study of WVE-007 in Adults Living With Overweight or Obesity

The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending doses of WVE-007 when administered subcutaneously (SC) . Part A is a single ascending dose study in adults living with overweight and obesity. The Part B of the study is a repeat dose administration in adult with obesity, with or without Type 2 Diabetes (T2D and non-T2D, respectively). In addition, Part B includes two dose groups that will receive WVE-007 and tirzepatide in adults living with obesity and T2D.

Inclusion Criteria: Part A * Male and female participants aged 18 to 60 years * BMI 28 to 35 kg/m2 which has been stable (±5%) for the previous 3 to 6 months (based on participant self-report or medical records). For participants considered for enrollment in a cohort expansion, BMI 28 to 40 kg/ m2 will be allowed. * Healthy, in the opinion of the Investigator, as determined by prestudy medical history, physical examination, and clinical laboratory assessments Inclusion Criteria : Part B * Male and female participants aged 18 to 75 years * BMI 35 to 50 kg/m2 (inclusive) * Thyroid stimulating hormone is within normal range at Screening. May be on supplemental thyroid hormone as managed by their prescribing physician and stable within the last 60 days * Participants with or without Type 2 Diabetes (T2D and non-T2D, respectively) Exclusion Criteria: Part A * History or presence of CV disease, including heart failure (New York Heart Association \[NYHA\] Class III or IV), myocardial infarction, angina, or clinically significant abnormal laboratory assessments * History or presence of thyroid disorders * Medical history or diagnosis of causes of liver disease * Use of any siRNA agent in the prior 12 months * Received an investigational agent within 90 days or 5 half-lives, whichever is longer, before the first dose of study drug or are in follow-up of another clinical study Exclusion Criteria: Part B * History of significant CV disease in the opinion of the Investigator. * Use of prescription medications (ie, anti-obesity or psychiatric medications) within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug, except for allowed antihypertensive medications and lipid lowering medications. * Taking \>3 antihypertensive medications, or antihypertensive medication dose was changed in the 60 days prior to Screening. * Taking \>2 cholesterol-lowering medication, or cholesterol-lowering medication dose was changed in the 60 days prior to Screening. * Cohorts 1 and 2 only: use of any GLP-1 receptor agonists or dual incretin agonists within the 4 months prior to Screening. * Cohorts 4 to 7 only: use of sulfonylurea and meglitinides within 60 days prior to Screening and insulin, GLP-1 receptor agonist, and dual incretin agonist within 90 days prior to Screening * Cohorts 6 and 7 only: Known serious hypersensitivity to tirzepatide or any excipients * Diagnosis of Type 1 diabetes mellitus, or dependence on daily or ongoing use of insulin or insulin analogs for glycemic control. * Use of any siRNA agent in the prior 12 months. * Received an investigational agent within 90 days or 5 half-lives, whichever is longer, before the first dose of study drug or are in follow-up of another clinical study.