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

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 60 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
• Have Pre T2D or T2D

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 7 half-lives (whichever is longer) before the first dose of study drug, except for allowed antihypertensive medications and statins.
• Taking \>2 antihypertensive medications, or antihypertensive medication dose was changed in the 60 days prior to Screening.
• Taking \>1 cholesterol-lowering medication, or cholesterol-lowering medication dose was changed in the 60 days prior to Screening.
• Cohorts 1 and 2 (preT2D) only: use of any GLP-1 receptor agonists or dual incretin agonists within the 4 months prior to Screening.
• Cohorts 4 and 5 (T2D) only: use of insulin or any medication that directly stimulates pancreatic insulin within the 60 days prior to Screening, including sulfonylureas, meglitinides, GLP-1 receptor agonists, dual incretin agonists, and DPP-4 inhibitors.
• 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.