Study of INT-747 as Monotherapy in Patients With PBC

Inclusion Criteria:

- Male or female age 18 to 70 years.

- Female patients must be postmenopausal, surgically sterile, or prepared to use 2
methods of contraception with all sexual partners during the study and for 14 days
after the end of dosing.

- Male patients must be prepared to use 2 methods of contraception with all sexual
partners during the study and for 14 days after the end of the dosing.

- Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the
following 3 diagnostic factors:

- History of increased AP levels for at least 6 months prior to Day 0

- Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or
PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)

- Liver biopsy consistent with PBC

- Screening AP value between 1.5 and 10 × ULN

Exclusion Criteria:

- Administration of the following drugs at any time during the 3 months prior to
screening for the study: ursodeoxycholic acid (UDCA, URSO®), colchicine, methotrexate,
azathioprine, or systemic corticosteroids.

- Screening conjugated (direct) bilirubin >2 × ULN.

- Screening ALT or AST >5 × ULN.

- Screening serum creatinine >133 μmol/L (1.5 mg/dL). History or presence of hepatic
decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).

- History or presence of other concomitant liver diseases including hepatitis due to
hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC),
alcoholic liver disease, definite autoimmune liver disease or biopsy proven
nonalcoholic steatohepatitis (NASH).

- Pregnancy.