This is a randomized, blinded, placebo-controlled study of Efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (NASH), with a single arm open-label extension. It includes Parts A, B, C and D.

Inclusion Criteria (Part A and Part B):

• Participant is either male or female and 18 to 75 years of age inclusive, at the time of signing the informed consent
• Obese participants with body mass index (BMI) of ≥ 27 kg/m^2
• Hepatic fat fraction (HFF) measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) ≥8%
• Liver fibrosis assessment based on a vibration controlled transient elastography (VCTE) liver stiffness measurement (LSM) score of 7.0 to 9.9 kPa (Part A only) inclusive or 7.0 to 20.0 kPa (Part B only) inclusive and Liver injury assessment measured by aspartate aminotransferase (AST) >25U/L. A qualifying historical biopsy (confirmed eligibility based on the central pathology read) supersedes the LSM, controlled attenuation parameter (CAP) score criteria and AST criteria.
• Histopathologically confirmed F2 or F3 stage NASH on a diagnostic liver biopsy performed during Screening or within 6 months prior to the first day of dosing for historical biopsies (Part B only).
• History or presence of at least 2 of 4 components of metabolic syndrome: obesity/overweight, dyslipidemia (high triglycerides and/or low high density lipoprotein [HDL]), type 2 diabetes with elevated glycated hemoglobin (HbA1c), and hypertension.

Inclusion Criteria (Part C):

• Participant must have completed the Part B of the study.
• Participant willing to undergo liver biopsy at Week 56
• NASH F stage <F4 at 24 week assessment in Part B

Inclusion Criteria (Part D):

• BMI of ≥ 25 kg/m^2
• Liver fibrosis based on assessments taken during screening visit
• Participant should be willing and able to undergo liver biopsy during Screening (if a historical biopsy within 12 months prior to Screening is not available) and per protocol as judged by the Investigator.
• Other inclusion criteria may apply

Exclusion Criteria (Part A and Part B):

• Documented clinical, laboratory or radiologic evidence of cirrhosis (compensated or decompensated)
• Triglycerides ≥ 500 mg/dL
• Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months from Screening, whichever is smaller)
• History of type 1 diabetes, diabetic ketoacidosis, or positive glutamic acid decarboxylase (GAD) auto-antibodies (latent autoimmune diabetes in adults)
• Hemoglobin A1c > 9.5%
• Participants with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).

Exclusion Criteria (Part C):

• Participants that received their 24 week dose in Part B > 10 weeks prior to enrollment into Part C

Exclusion Criteria (Part D):

• Other causes of chronic liver disease
• Documented evidence or history of decompensated liver cirrhosis.
• History of type 1 diabetes or poorly controlled type 2 diabetes.
• History of malignancy.
• Use of other investigational drugs.
• Other exclusion criteria may apply

Part C - Open Label; Part D - Open Label