This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2

Up to 50 sites in the following countries will take part in this study:

Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain,
Sweden, Turkey, United Kingdom, United States, and Saudi Arabia

Key Inclusion Criteria:

- A male or female patient with a clinical diagnosis of PFIC Type 1 or 2 and with a body
weight above 5 kg

- Patient must have clinical genetic confirmation of PFIC-1 or PFIC-2

- Patient must have elevated s-BA concentration

- Patient must have history of significant pruritus and a caregiver reported observed
scratching in the eDiary

- Patient and/or legal guardian must sign informed consent (and assent) as appropriate.

- Patients will be expected to have a consistent caregiver(s) for the duration of the
study

- Caregivers and age-appropriate patients (≥8 years of age) must be willing and able to
use an eDiary device as required by the study

Key Exclusion Criteria:

- Patient with pathologic variations of the ABCB11 gene that predict complete absence of
the BSEP protein

- Patient with past medical history or ongoing presence of other types of liver disease
including, but not limited to, the following:

1. Biliary atresia of any kind

2. Benign recurrent intrahepatic cholestasis, indicated by any history of normal s
BAs

3. Suspected or proven liver cancer or metastasis to the liver on imaging studies

4. Histopathology on liver biopsy that is suggestive of alternate non-PFIC related
etiology of cholestasis

- Patient with past medical history or ongoing chronic diarrhea

- Any patient with suspected or confirmed cancers except for basal cell carcinoma

- Patient with a past medical history of chronic kidney disease with an impaired renal
function and a glomerular filtration rate <70 mL/min/1.73 m^2

- Patient with surgical history of disruption of the enterohepatic circulation excluding
those who have undergone a successful reversal procedure that has permanently restored
flow of bile acids from the liver to the duodenum

- Patient has had a liver transplant or listed for liver transplant, excluding those who
have been listed for transplant for pruritus who have since been removed from the
transplant list

- Decompensated liver disease

- Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC

- Patient who has been previously treated with an IBAT inhibitor whose pruritus has not
responded to treatment