Inclusion Criteria:

- Fasting triglycerides (TG) ≥ 880mg/dL that is not sufficiently controlled on
standard lipid-lowering therapy

- Established diagnosis of FCS based on documented history of fasting TG levels in
excess of 1000 mg/dL on repeated testing (for at least 3 prior occasions), and at
least one of the following: a supportive genetic test, documented history of
recurrent episodes of acute pancreatitis not caused by alcohol or cholelithiasis,
documented history of recurrent hospitalizations for severe abdominal pain without
other explainable cause, documented history of childhood pancreatitis, family
history of hypertriglyceridemia-induced pancreatitis

- Willing to follow dietary counseling based on local standard of care, consistent
with an intake of ≤ 20 g of fat per day

- If on medications for management of type 2 diabetes the dosing regimen must be
stable.

- Participants of childbearing potential must agree to use a highly effective form of
contraception in addition to a male condom during the program and for at least 90
days after the last dose of plozasiran

Exclusion Criteria:

- Diabetes mellitus with any of the following at Day 1: newly diagnosed within the
past 24 weeks, HbA1c ≥9.0% within the past 4 weeks, meaningful medical events
relating to poor glycemic control, changes in basal insulin regimen of more than =/-
10 units within 12 weeks if insulin-dependent

- History of acute coronary syndrome events

- New York Heart Association Class III or IV heart failure or last known ejection
fraction of <30%

- Clinical evidence of primary hypothyroidism, primary subclinical hypothyroidism, or
secondary hypothyroidism

- History of stroke, transient ischemic attack, or peripheral artery disease within 24
weeks of first dose

- History of bleeding diathesis or coagulopathy

- Current diagnosis of nephrotic syndrome

- Eligible to receive any commercially available FDA-approved therapeutic for
treatment of FCS unless proven to be ineffective or judged inappropriate by the
treating physician

Note: Additional inclusion/exclusion criteria may apply per protocol