Emricasan, an Oral Caspase Inhibitor, in Subjects With Non-Alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension

Inclusion Criteria:

- Male or female subjects 18 years or older, able to provide written informed consent
and able to understand and willing to comply with the requirements of the study.

- Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral
hepatitis, alcoholic liver disease, etc.)

- Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant
decompensating event

- Severe portal hypertension defined as HVPG ≥12 mmHg

- Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must
be on a stable dose for at least 3 months prior to Day 1

- Willingness to utilize effective contraception (for both males and females of
childbearing potential) from Screening to 4 weeks after the last dose of study drug

Exclusion Criteria:

- Evidence of severe decompensation

- Severe hepatic impairment defined as a Child-Pugh score ≥10

- ALT > 3 times upper limit of normal (ULN) or AST >5 times ULN during screening

- Estimated creatinine clearance <30 mL/min

- Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass
procedure

- Known portal vein thrombosis

- Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6
months, unless resolved following cholecystectomy

- Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3
transporters

- Alpha-fetoprotein >50 ng/mL

- History or presence of clinically concerning cardiac arrhythmias, or prolongation of
screening (pre-treatment) QTcF interval of >500 msec

- History of or active malignancies, other than those successfully treated with curative
intent and believed to be cured

- Prior liver transplant

- Change in diabetes medications or vitamin E within 3 months of screening

- Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening

- Significant systemic or major illness other than liver disease

- HIV infection

- Use of controlled substances (including inhaled or injected drugs) or non-prescribed
use of prescription drugs within 1 year of screening

- If female: planned or known pregnancy, positive urine or serum pregnancy test, or
lactating/breastfeeding

- Previous treatment with emricasan or active investigational medication (except
methacetin) in a clinical trial within 3 months prior to Day 1