Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia

Inclusion Criteria:

• Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, whoare ≥18 years of age at screening

• Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documentedevidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/L)

• Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate andconsecutive visits at least 7 days apart and no more than 17 days apart during thescreening period

• Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) atscreening

• Screening HbA1C ≤9.0%

• Willing to follow diet counseling and maintain a stable low-fat diet

• Must be on standard of care lipid and TG lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including aninability to safely administer or re-administer a specific drug because of fear,preference, genetic, clinical, or metabolic considerations, or due to a previousadverse reaction associated with, attributed to, or caused by specific drug)

Exclusion Criteria:

• Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) thattargets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran,which is permitted). Administration of investigational drug and inclisiran must beseparated by at least 4 weeks

• Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide moleculewithin 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer

• Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1Hyperlipoproteinemia) by documentation of confirmed homozygote or doubleheterozygote for loss-of-function mutations in type 1-causing genes

• Acute pancreatitis within 4 weeks prior to screening

• Body mass index >45kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol