POXEL SA announced positive top-line results for DESTINY-1 (Deuterium-stabilized R-pioglitazone [PXL065] Efficacy and Safety Trial In NASH), the dose-ranging Phase 2 trial of PXL065 for the treatment of NASH. PXL065 is a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone which has reduced PPAR? activity but retains non-genomic thiazolidinedione (TZD) actions.

Summary of Phase 2 NASH (DESTINY-1) PXL065 Study Results: DESTINY-1 is a Phase 2, 36-week, randomized, dose-ranging, double-blind, placebo-controlled, parallel group study designed to assess the efficacy and safety of PXL065 in patients with noncirrhotic biopsy-proven NASH across multiple clinical sites in the US. The primary endpoint of the study measured the relative change in the percentage of liver fat content based on magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). The study also assessed the effects of PXL065 on liver histology and other metabolic and non-metabolic biomarkers.

Histology results are expected in September. Top-line results available at present include:

117 subjects were randomized to one of 4 daily (QD) treatment arms (7.5 mg, 15 mg, 22.5 mg, placebo).

The primary efficacy endpoint was achieved: a statistically significant (p=0.024 to p=0.008) mean relative decrease vs. placebo of 21% to 25% in liver fat content from baseline to 36 weeks was observed at all PXL065 doses. 40% of patients who received PXL065 at the 22.5 mg dose achieved a >30% relative reduction in liver fat content.

Non-invasive biomarker results to-date included: dose-dependent decreases in fibrogenesis markers Pro-C3 (significant vs. placebo at the 22.5 mg dose; p=0.02) and enhanced liver fibrosis (ELF) index. Trends in least-square mean ALT decreases up to 18.4 IU/L vs. baseline were observed. However, this parameter did not reach statistical significance. Further data analysis is ongoing.

There was no dose dependent increase in body weight: a minimal least-square mean increase of 0.68 kg was observed at the top dose of 22.5 mg vs. placebo. The incidence of edema did not show an observed treatment or dose relation when compared to placebo. With respect to other safety measures, PXL065 was observed to be generally safe and well tolerated; the number of patients presenting with treatment-emergent serious adverse events (TESAEs) were similar among all groups including placebo without dose effect.

As predicted, pharmacokinetic measurements showed dose-proportional drug levels with the desired degree of higher exposure to the pioglitazone R-stereoisomer and reduced exposure to the (PPARg active) S-stereoisomer. Additional data from histology results are expected in September. The full Phase 2 results will be submitted for presentation at an upcoming scientific meeting.