Study of ISIS 703802 in Subjects With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

Inclusion Criteria:

- Plasma TG at Screening > 200 mg/dL and at qualification of ≥ 150 mg/dL

- Documented history of hepatic steatosis with baseline MRI indicating hepatic fat
fraction (HFF) ≥ 10%

- Diagnosis of Type 2 Diabetes Mellitus with Hemoglobin A1c ≥ 7 and ≤ 10% at Screening

- Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months
prior to Screening

- Body mass index between 27- 40 kg/m2, inclusive, at Screening

Exclusion Criteria:

- Type 1 diabetes mellitus

- Active chronic liver disease, alcoholic liver disease, Wilson's disease
hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic
hemochromatosis, known or suspected hepatocellular carcinoma, history of or planned
liver transplant for end-stage liver disease of any etiology

- Documented history of advanced liver fibrosis

- History of cirrhosis and/or hepatic decompensation including ascites, hepatic
encephalopathy, or variceal bleeding

- History of clinically significant acute cardiac event within 6 months before Screening

- History of heart failure with NYHA greater than Class II

- Use of Insulin or insulin analogs, GLP-1 agonists, and PPARᵞ agonists (pioglitazone or
rosiglitazone)

- Weight change > 5% within 3 months before Screening

- Conditions contraindicated for MRI procedures including any metal implant (e.g., heart
pacemaker, rods, screws, aneurysm clips)