Belgium: • Amendment I: Protocol version 2.1 dated 13-Feb-2012, o The total l amount of cells that could be infused at once was defined. A second HepaStem bag could be infused directly after the first bag for the children who were to receive a high total cell count requiring several cell bags. o Description of the anticoagulation treatment after last infusion/completion of the cycle: once the last infusion was finished, anticoagulation was to be given at a lower concentration for 30 min and stopped. The removal of the catheter was recommended 30 min after bivalirudin stop because the half-life of bivalirudin is +/- 15 min. o Addition of the long term safety FU study (SAF001) upon request of the MHRA during the CTA evaluation. In accordance with ATMP guidance regular collection and review of safety data were to be proposed to the patient and will continue for 5 years after the infusion of HepaStem. o Addition of of oxygen saturation measurement prior to, during and after each infusion. o The guideline on liver biopsy harvest and sample preparation were annexed to the study protocol to reduce the potential risk inherent to liver biopsies, reducing the number of liver biopsies and the requested amount of tissue per biopsy. o 13C-sodium acetate route of administration was changed from IV to oral. o The guideline for the PBMC sub-study was also annexed.

Belgium: • Amendment II: Two additional sites were added: o UZ Gent, PI Ruth de Bruyne, Pediatry o UZ Leuven, PI Luc Régal, Pediatry

Belgium: • Amendment III: Additional study documents: o Patient notebook: CN diary_version 1.0_120621 o Patient notebook: UCD diary_ version 1.0_120621 o Patient study card version 1.0_120621

Belgium: • Amendment IV: Protocol version 3.0 dated 01-Aug-2012, o The minimum flow rate of infusion was decreased in order to allow more flexibility in applying the optimal flow rate for cell infusion especially in small children, o The dose escalation process was clarified, o A random allocation dose from the third patient onwards was described for CN patients, o Appropriate target and way to reach the recommended level were clarified for the immunosuppressive treatment. o ACT values which should be observed at each infusion stage to ensure appropriate anticoagulation at the time of cell infusion were specified in order to increase safety, o The anticoagulation protocol was clarified, o Protocol for D-dimer measurements was clarified, o Use of a patient diary to collect diet/phototherapy, medication and any other relevant events occurring at the patient’s home, o Description of some investigational events (tacrolimus blood levels, urine tests, D-dimer, ammonia blood level and general laboratory tests) to be reported as AEs were added, o The fasting requirements for the 13C test were modified to avoid prolonged fasting in patients with a metabolic disorder, o The aim of the PBMC sub-study was clarified and its study design updated.

UK: • Amendment I: Protocol version 3.0 dated 01-Aug-2012 + change of PI o Protocol amendment: see amendment IV from Belgium. o Change of PI: - Former PI: Dr. Anhil Dhawan – King’s College Hospital – London - New PI: Dr. Patrick McKiernan – Birmingham Children’s Hospital – Birmingham.

France: • Amendment II: One additional site o CHU Toulouse, PI Pierre Broué, Pediatric hepatology, gastroenterology, and nutrition unit.

France: • Amendment I: Protocol version 3.0 dated 01-Aug-2012 + two additional sites o Protocol amendment: see amendment IV from Belgium. o Two additional sites: - CHRU Tours, PI François Labarthe, Pediatric Medecine - CHU Paris-Robert Debré, PI Hélène Ogier, Pediatric neurology and metabolic diseases.

Israel: • Amendment I: HEP001-IL Protocol version 1.0 dated 20-Mar-2013 o Israel-specific procedures were highlighted to emphasize the responsibility of each physician, and to clearly explain who is responsible for which specific study procedure. o The timeline set for Europe (recruitment ended March 2013) was prolonged for an additional 3 months specifically for Israel due to prolonged study set-up. This was to provide sufficient time to enroll 5 patients. o It was highlighted that the monitoring of the data collected from the Israeli subjects was to be performed by an Israeli CRO, Clinipace Worldwide, representing Promethera Biosciences (PB). o Informed consent procedure was clarified.

Belgium: • Amendment V: Protocol version 3.1 dated 25-Jul-2013. o The study was opened to centers outside Europe (Israel), o The number of participating patients was increased and the recruitment period was extended, o The location of formulation of the drug product was updated (IMP could be formulated in Promethera Biosciences or in a mobile unit/hospital laboratory with a fully closed formulation system based on SEPAX device), o The collection of a 5 mL blood sample to collect DNA was added to be used as control for the chimerism analysis and for HLA typing, o The laboratory tests were clarified, o The possibility to prolong hospitalization after the 24h following catheter removal was added, o The placement of the catheter was allowed in the left branch of the portal vein to increase feasibility, o The recommendation to perform hepatic US and Doppler one hour after catheter removal was added to increase safety for the patient, o Some corrections to units were made.

France: • Amendment III : Protocol version 3.1 dated 25-Jul-2013 o See amendment V from Belgium. Belgium: • Amendment V: Protocol version 3.1 dated 25-Jul-2013. o The study was opened to centers outside Europe (Israel), o The number of participating patients was increased and the recruitment period was extended, o The location of formulation of the drug product was updated (IMP could be formulated in Promethera Biosciences or in a mobile unit/hospital laboratory with a fully closed formulation system based on SEPAX device), o The collection of a 5 mL blood sample to collect DNA was added to be used as control for the chimerism analysis and for HLA typing, o The laboratory tests were clarified, o The possibility to prolong hospitalization after the 24h following catheter removal was added, o The placement of the catheter was allowed in the left branch of the portal vein to increase feasibility, o The recommendation to perform hepatic US and Doppler one hour after catheter removal was added to increase safety for the patient, o Some corrections to units were made.

UK: • Amendment IV: Protocol version 3.1 dated 25-Jul-2013. o same as amendment V from Belgium. Belgium: • Amendment V: Protocol version 3.1 dated 25-Jul-2013. o The study was opened to centers outside Europe (Israel), o The number of participating patients was increased and the recruitment period was extended, o The location of formulation of the drug product was updated (IMP could be formulated in Promethera Biosciences or in a mobile unit/hospital laboratory with a fully closed formulation system based on SEPAX device), o The collection of a 5 mL blood sample to collect DNA was added to be used as control for the chimerism analysis and for HLA typing, o The laboratory tests were clarified, o The possibility to prolong hospitalization after the 24h following catheter removal was added, o The placement of the catheter was allowed in the left branch of the portal vein to increase feasibility, o The recommendation to perform hepatic US and Doppler one hour after catheter removal was added to increase safety for the patient, o Some corrections to units were made.

UK: • Amendment II: Due to change of PI, the initial approach to surgically insert the catheter changed. BCH’s approach to insert the catheter percutaneously was then considered as a national approach. A national review by a Medical Physics expert and a Clinical Radiation Expert was required. PIS were updated accordingly.

Italy: • Amendment I: Protocol version 3.1 dated 25-Jul-2013 o See amendment V from Belgium. Belgium: • Amendment V: Protocol version 3.1 dated 25-Jul-2013. o The study was opened to centers outside Europe (Israel), o The number of participating patients was increased and the recruitment period was extended, o The location of formulation of the drug product was updated (IMP could be formulated in Promethera Biosciences or in a mobile unit/hospital laboratory with a fully closed formulation system based on SEPAX device), o The collection of a 5 mL blood sample to collect DNA was added to be used as control for the chimerism analysis and for HLA typing, o The laboratory tests were clarified, o The possibility to prolong hospitalization after the 24h following catheter removal was added, o The placement of the catheter was allowed in the left branch of the portal vein to increase feasibility, o The recommendation to perform hepatic US and Doppler one hour after catheter removal was added to increase safety for the patient, o Some corrections to units were made.