Study of Plozasiran in Adults With Severe Hypertriglyceridemia

Inclusion Criteria:

1. Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/L)
2. Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
3. Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
4. Screening HbA1C ≤8.5%
5. Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Exclusion Criteria:

1. Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks
2. Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer (except inclisiran, which is permitted)
3. Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1- causing genes
4. Body mass index >45kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol