To determine the effect of Pegozafermin on fasting serum triglyceride levels in subjects with Severe Hypertriglyceridemia (TG ≥500 to ≤2000 mg/dL) after 26 weeks of treatment.

Inclusion Criteria:

• Age ≥22 years
• Willing to enter a medication/lifestyle stabilization period during the screening period, which means maintaining those stable medication, eating, and exercise habits for the duration of the study
• Subjects should be on stable background Lipid Modifying Therapy (LMT) to manage ASCVD for a minimum of 4 weeks prior to first qualifying TG

Exclusion Criteria:

• Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
• Uncontrolled or newly diagnosed (≤3 months since diagnosis) Type 2 diabetes mellitus as determined by the Principal Investigator. Subjects must have HbA1c level ≤9.5% at Screening. Medications for glucose management must be stable for at least 4 weeks prior to Screening
• Type 1 diabetes mellitus
• A history of symptomatic gallstone disease, gallstone pancreatitis (unless treated with cholecystectomy), or any other ongoing symptomatic biliary disease
• Acute pancreatitis within 6 months prior to Screening
• Subjects with chronic pancreatitis
• Known or suspected familial chylomicronemia syndrome (FCS) (Type 1 hyperlipoproteinemia)

Other inclusion and exclusion criteria may apply.