Pilot Study of FFP104 Dose Escalation in PBC Subjects

Inclusion Criteria:

• Male or female Age between 18 and 75 years of age inclusive at the time of signing theinformed consent

• Established diagnosis of PBC according to the EASL criteria (European Association forthe Study of the Liver 2009): A diagnosis of PBC can be made with confidence in adultpatients with otherwise unexplained elevation of ALP and presence ofanti-mitochondrial antibody (AMA≥1:40), and/or AMA type M2. A liver biopsy is notessential for the diagnosis of PBC in these patients, but allows activity and stage ofthe disease to be assessed.

• Having a screening ALP serum level between 1.67 and 5x ULN inclusive.

• Be on a stable dose of ursodeoxycholic acid (UDCA) 12-20 mg/kg/day for at least 3months prior to Screening or intolerant of UDCA in the opinion of the investigator (noUDCA for at least 8 weeks prior to Screening).

• Are not pregnant or breast feeding and do not plan to become pregnant or father achild during the study. Female subjects (of childbearing potential) must be willing touse two medically accepted forms of contraception throughout the study and must bewilling to submit to pregnancy test(s). Male subjects must agree to use medicallyaccepted contraception methods with their partners throughout the study as describedabove, unless they have had a prior vasectomy.

• Has the ability to communicate adequately with the study staff and to comply with therequirements of the entire study, with the help of a caregiver, if applicable.

Exclusion Criteria:

• Laboratory screening results

• alanine transaminase (ALT) >5x ULN

• aspartate transaminase (AST) >5x ULN

• Total bilirubin >2x ULN. Isolated bilirubin >2x ULN is acceptable if bilirubin isfractionated and direct bilirubin <35%

• Total white blood cells (WBC) <3000 cells/mm3

• Absolute neutrophil count (ANC) <1500 cells/mm3

• Platelet count <100,000/mm3

• Prothrombin time (international normalized ratio (INR)> 1.2

• Body mass index (BMI) ≥35 or suspected to have relevant nonalcoholic fatty liverdisease (NAFLD) as based on the judgment of the Investigator at screening

• Subject has a history of, or current viral hepatitis B or C (including hepatitis Bsurface antigen [HBsAg], hepatitis B core antibody and hepatitis C virus (HCV)antibody [anti-HCV] positivity), or a positive HIV antibody screen at time ofscreening

• Recipients of liver or other organ transplantation or anticipated need for orthotropicorgan transplantation in one year as determined by the Mayo Risk Score

• Co-existing liver or biliary diseases, such as primary sclerosing cholangitis,choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liverdisease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system orgall bladder, history of gastrointestinal bleeding (secondary to portal hypertension),cholangiocarcinoma diagnosed or suspected liver cancers

• Recurrent variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class B/C,Esophageal Varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)

• Have a family history (more than one first degree relative) of multiple thromboticevents or a personal history of any venous or arterial thrombotic event including deepvein thrombosis, stroke, myocardial infarction, pulmonary embolus, or peripheralarterial thromboembolic events

• Prohibited medications 6 months prior to Screening: azathioprine, colchicine,cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline; fenofibrate orother fibrates; budesonide and other systemic corticosteroids; potentially hepatotoxicdrugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin)

• Prohibited medications 12 months prior to Screening: antibodies or immunotherapydirected against interleukins or other cytokines or chemokines

• Subjects with recurrent bacterial infections (as judged by the Investigator) within 6months prior to first dose of FFP104, active bacterial, fungal or mycobacterialinfections observed during screening, or any recent episode of infection requiringhospitalizations or treatment with antibiotics (within the 3 months prior to firstdose)

• History of malignancy, with the exception of resected basal cell carcinoma, squamouscell carcinoma of the skin, or resected cervical atypia or carcinoma in situ

• Immunization with a live vaccine within 4 weeks of Screening with the exception ofinfluenza vaccine and no planned immunisations within the period of the study

• Known clinically significant cardiac disease (e.g., myocardial infarction or stroke,unstable angina, claudication, etc.), or evidence of a clinically significantelectrocardiogram (ECG) abnormality within the previous 12 months prior to Screening

• Subjects with evidence of other serious, significant, acute or chronic medical orpsychiatric illness that, in the judgment of the Investigator, could compromisesubject safety, limit the subject's ability to complete the study, and/or compromisethe objectives of the study

• History of recent (within 12 months of study) alcohol or drug abuse

• Use of other immunosuppressive medications 4 weeks prior to Screening

• Active tuberculosis (TB) in the past or currently suspected TB which is presentlyreceiving treatment or prophylactic therapy, has a positive TB test (as defined bylocal biological requirements), or any significant abnormality on chest X-ray within 3months prior to Screening

• Subjects who have planned surgery during the study period or have undergone majorsurgery within the 3 months prior to Screening

• Known clinically significant allergy or known hypersensitivity to drugs that, in theopinion of the Investigator, may affect the patient's safety

• Known sensitivity to any component of the study drug or previous sensitivity reactionor other clinically significant reaction to intravenous medications or biologictherapy

• Participated to another clinical trial within the past 30 days prior to Screening, oris still within a washout period of a previous clinical trial or has previouslyreceived FFP104 (PG102) or ch5D12 in this or any study