In animal models, cells engraft and differentiate into hepatocyte-like cells expressing OTC enzyme. HHALPC improve bilirubin levels in Gunn rats. Hepastem was investigated in an open label, phase I/II safety study in patients with urea cycle

disorders (UCD) and Crigler-Najjar syndrome (CN) with preliminary efficacy secondary endpoints. Methods: Primary objective was safety at 6 months and secondary objectives, beside safety at 12 months, included efficacy at 6 and 12 months. Readouts included measure of de novo urea production in UCD patients based on 13C incorporation into urea up to 120 minutes after 1 dose of oral Na [1-13C] acetate (expressed as [13C] blood urea Area

Under the Curve or AUC-120), measures of blood ammonia and JQ1 glutamine in UCD patients, natural protein intake in UCD patients, blood total INCB018424 bilirubin in CN patients, as well as evaluation of quality of life (QoL) by PedsQL™ for both diseases. A dose equivalent to 0.4 to 6.1% of the liver mass was infused in the portal vein through a transhepatic catheter placed under radioguidance. Over 1 to 4 consecutive days, 1 cycle of cells was infused to 14 UCD patients (1.5m to 17yrs, 8 boys, 6 girls, ) and 6 CN patients (3.5yrs-9yrs, 2 boys, 4 girls). Results: Adverse events were more frequent during the infusion cycle and within 14 following days, e.g. abnormal lab values, non-specific symptoms, and transient metabolic decompensations. Two patients had a thrombotic event: one had a non-occlusive portal thrombus resolving after 1 month; one had a left portal vein thrombosis with stable liver function tests during 6 month follow-up. Rate of infection was within the expected incidence for the studied population. [13C] blood urea AUC-120, highly variable between patients at baseline, increased in all Methocarbamol but one patient

between baseline and six months (101 % increase (95%CI Lower Limit: 28%, Upper Limit 217%, p value: 0.004). Compared to 1 year pre-infusion available data, median ammonia post-infusion tended to decrease in <12yo UCD patients. Four patients increased slightly their natural protein tolerance. In CN patients median bilirubin values decreased in 3/6 CN (∼−40,−30 & −10%). Overall, QoL results remained stable. Conclusion: One cycle of hepastem (dose 0.4% to 6.1% of liver mass) is safe and preliminary data show functional metabolic changes in UCD and CN patients. Disclosures: Etienne M. Sokal – Board Membership: Promethera Biosciences; Management Position: Promethera Biosciences; Patent Held/Filed: Promethera Biosciences Patrick J.