A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients

Inclusion Criteria:

- Diagnosis of PBC as demonstrated by the presence of ≥ 2 of the following 3 diagnostic
criteria:

- History of Alkaline Phosphatase elevated above upper limit of normal for at least 6
months

- Positive anti-mitochondrial antibodies (AMA) titer or if AMA negative or in low titer
(<1:80) PBC specific antibodies (anti- GP210 and/or anti-SP100 and/or antibodies
against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex)

- Previous liver biopsy consistent with PBC

- At least 1 of the following markers of disease severity:

- ALP ≥ 1.67× upper limit of normal (ULN)

- Total bilirubin > ULN but < 1.5× ULN In addition, patients must meet the following
biochemical criteria at enrollment

- ALT or AST ≤ 5 × ULN

- Total bilirubin ≤ 1.5 × ULN

- INR ≤ ULN

- Subjects must weigh at least 40 kg to participate in the study, and must have a body
mass index (BMI) within the range of 18 - 40 kg/m^2. BMI = Body weight (kg) / [Height
(m)]^2.

- Able to communicate well with the investigator, to understand and comply with the
requirements of the study.

Exclusion Criteria:

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 30 days following end of treatment.

- History or presence of other concomitant liver diseases

- Cirrhosis with complications, including history or presence of:

- Variceal bleed

- Uncontrolled ascites

- Encephalopathy

- Spontaneous bacterial peritonitis

- Significant hepatic impairment as defined by Child-Pugh classification of B or C,
history of liver transplantation, current placement on a liver transplant list or
current Model for End Stage Liver Disease (MELD) score ≥15.

- History of conditions that may cause increases in ALP (e.g., Paget's disease).

- Use of other investigational drugs at the time of enrollment, or within 5 half-lives
of enrollment

- Elevated liver function tests at screening defined as follows:

- potential Hy's Law case (defined as ALT or AST > 3 × ULN and TBL > 2 × ULN
without notable increase in ALP to > 2 × ULN) or

- ALT or AST > 3 × ULN combined with INR > 1.5.

- Total bilirubin > ULN combined with albumin outside of the normal range.

- Currently taking obeticholic acid or have taken obeticholic acid within 30 days of
Randomization.