Syneos Health (Beijing) Inc.Ltd.

Primary Objective: To demonstrate the sustained effect of odevixibat on native liver survival in children with biliary atresia (BA) who have completed Study A4250-011 (BOLD)

Part A1: The primary objective is to determine the safety, tolerability and DLT of oral administration of KIN-2787 in the treatment of subjects with BRAF mutation-positive advanced or metastatic solid tumors or subjects with NRAS mutation melanoma; and to determine the MTD and/or appropriate dose for further clinical studies in the dose expansion part (Part B). Secondary objectives include characterizing the PK properties of KIN-2787 and the effect of food on the PK of KIN-2787. Exploratory objectives include additional KIN-2787 PK characterization, evaluation of the effect of KIN-2787 on survival and other time-to-event endpoints, estimation of the PD effect of KIN-2787 using blood samples and tumor biopsy samples, genotype assessment, and evaluation of the effect of genotype changes during treatment on outcomes. Part B: The primary objective is to evaluate preliminary evidence of antitumor activity of KIN-2787 in subjects with advanced or metastatic solid tumors with Class II or Class III BRAF genomic alterations. The secondary objective is to further evaluate the safety, tolerability and PK characteristics of KIN-2787 at the RP2D dose level. Exploratory objectives include additional KIN-2787 PK characterization, evaluation of the effect of KIN-2787 on survival and other time-to-event endpoints, estimation of the PD effect of KIN-2787 using blood samples and tumor biopsy samples, genotype assessment, and the impact of genotype changes during treatment on outcomes and on patient-reported outcome (PRO) measures.

The primary objective was to evaluate the effectiveness of maralixibat for biliary drainage after hepatoportoenterostomy (HPE) in patients with biliary atresia (BA). Secondary objectives were to evaluate changes in sBA (serum bile acid) levels after maralixibat treatment, to evaluate the rate of bilirubin normalization after maralixibat treatment, to evaluate transplant-free survival after maralixibat treatment, to evaluate biochemical markers of cholestasis and liver disease after maralixibat treatment, and to evaluate the safety, tolerability, and pharmacokinetics of maralixibat.