Study to Explore the Efficacy and Safety of BIO89-100 (Pegozafermin) in Participants With Severe Hypertriglyceridemia

Inclusion Criteria: 1. Male or female age ≥21 to ≤75 years. 2. Screening fasting triglyceride ≥500 milligrams (mg)/deciliters (dL) and ≤2000 mg/dL. 3. Willing to maintain current eating and exercise habits from time of signing the informed consent and for the duration of the study. 4. Participants could be taking statins and/or prescription fish oil as background therapy or not be taking any background therapy. 5. Magnetic resonance imaging - whole liver proton density fat fraction (MRI-PDFF) of ≥6% for participants screened for the Fibrate Expansion cohort. Exclusion Criteria: 1. Uncontrolled or newly diagnosed hypertension. 2. Body mass index \>45 kilograms (kg)/meters squared (m\^2). 3. Receiving niacin, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, or supplements that could lower lipid levels. 4. Type 1 diabetes mellitus. 5. Diagnosis of Type 2 diabetes mellitus \<6 months prior to screening. 6. History of malignancy within 5 years prior to screening. 7. Participants with known lipoprotein lipase impairment or deficiency (Fredrickson Type 1), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type 3). 8. Clinically or otherwise documented cardiovascular or cerebrovascular disease. 9. Weight change ≥5% in 3 months prior to first screening visit or weight change ≥5% during screening or planning to try to lose weight during conduct of study.