Poxel SA announced that an oral presentation, including data for PXL065, the deuterium-stabilized R-stereoisomer of pioglitazone, was made at the 2019 NASH-TAG Conference. The presentation titled “PXL065, Pioglitazone (pio), and Thiazolidinediones (TZDs): Unravelling Pio’s superior efficacy for NASH and role of stereoisomers” was given on January 5, 2019 in Park City, Utah. The presentation highlighted key aspects related to the pharmacokinetic (PK) and pharmacodynamic (PD) role of stereoisomers within the class of compounds known as TZDs and the potential relevance for the treatment of NASH. Representative TZDs included rosiglitazone, pioglitazone and lobeglitazone, all of which are a mixture of interconverting R- and S- stereoisomers that have exhibited varying levels of efficacy for NASH in animal and/or human studies. Key findings presented included: a comparison of the striking species-dependent stereoselectivity of the PK for pioglitazone with other TZDs, a comparison of unexpected differences in peroxisome proliferator-activated receptor gamma (PPAR?) activity with the eight stereoisomers that make up pioglitazone and its two active metabolites and 3) stabilization of pioglitazone’s stereoisomers with deuterium to characterize and identify R-pioglitazone as the preferred stereoisomer for the treatment of NASH. Data presented demonstrated that each stereoisomer of pioglitazone and its active metabolites exhibits different PPAR? activity. The presentation also included data showing that PXL065 is a mitochondrial pyruvate carrier (MPC) inhibitor without PPAR? activity in a cofactor recruitment assay. In mouse models, PXL065 demonstrated the hepatic benefits observed with pioglitazone in NASH patients. In preclinical models, PXL065 exhibited little or no weight gain or fluid retention, side effects mainly associated with the PPAR? active, S-pioglitazone. About the PXL065 Results: PPAR? activity and MPC inhibition were measured in vitro. Single and multi-dose PK studies were conducted in mouse, rat and dog. Weight gain and edema were evaluated in C57BL/6J mice and NASH efficacy was assessed in diet-induced mouse models. Safety, tolerability and PK of 22.5 mg PXL065 were compared to 45 mg Actos® in a single-dose Phase 1a study. In man, PK results and modelling predict that 15 mg of PXL065 has the potential to provide efficacy for NASH similar to 45 mg Actos® with little or no weight gain or fluid retention. As part of the Phase 1 program, additional single doses are currently being studied and will be followed by a multiple ascending dose trial.