The purpose of this study is to evaluate the safety and efficacy of solbinsiran in lowering triglycerides and other lipid measures compared to placebo in participants with severe hypertriglyceridemia. Participants will receive two subcutaneous injections.

Inclusion Criteria:

• History of fasting triglyceride levels of ≥500 milligrams per deciliter (mg/dL), based on medical history
• Fasting triglyceride level ≥500 mg/dL at two separate visits during screening (at least 7 days apart)
• Have a body mass index (BMI) within the range of 18.5 to 45.0 kilograms per square meter (kg/m2) (inclusive)

Exclusion Criteria:

• Have had a major atherosclerotic cardiovascular event within the past 3 months prior to screening
• Have a known genetically confirmed diagnosis of Familial Chylomicronemia Syndrome
• Have a history of or planned treatment involving any gene editing or gene therapy modalities, including but not limited to CRISPR-based, viral vector-mediated, or other genetic modification techniques
• Have a history of chronic alcohol abuse within 3 years prior to screening

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.