Therapy Areas: Inflammatory Diseases
Poxel Presents Data for PXL770 and PXL065 for the Treatment of NASH at the American Association for the Study of Liver Diseases Meeting
15 November 2018 - - French biopharmaceutical company Poxel SA (Euronext: POXEL - FR0012432516) made presentations for PXL770 and PXL065 (formerly DRX-065; acquired from DeuteRx LLC) showing promising data for the treatment of NASH last week at the American Association for the Study of Liver Diseases (AASLD) meeting in San Francisco, California, the company said.

In the first poster presentation, PXL770 was shown to have a beneficial effect on the two key pathways involved in non-alcoholic fatty liver disease (NAFLD), the lipolysis in the adipose tissue and de novo lipogenesis in the liver, through direct activation of adenosine monophosphate-activated protein kinase in a diet-induced obesity non-alcoholic steatohepatitis (DIO-NASH) model.

NAFLD is characterized by hepatic lipid accumulation resulting primarily from AT lipolysis, and de novo lipogenesis, highlighting the key role of AT in the development of NAFLD.

In the second poster presentation, PXL065 Phase 1 results demonstrated that PXL065 was shown to be safe and well-tolerated with no adverse events.

Based on the pharmacokinetic results, modeling predicts that a 15 mg dose of PXL065, a deuterium-stabilized R-stereoisomer of pioglitazone, is expected to yield similar efficacy as 45 mg of the parent drug, pioglitazone (Actos) with an improved side effect profile, including reduced weight gain and fluid retention.

In the poster presentation, PXL770 was shown to have a beneficial effect on the liver and AT metabolism in a DIO-NASH mouse model. After 41 weeks, only DIO-NASH mice with biopsy-confirmed steatosis (score ≥2) and fibrosis (stage ≥1) were included and received orally vehicle (control) or PXL770 35 or 75 mg/kg twice-daily for eight weeks.

The DIO-NASH mouse model showed that DIO-NASH mice compared to normal chow diet mice exhibited characteristics of NASH, including steatohepatitis (NAFLD Activity Score, NAS=7), liver fibrosis (score=2), elevated liver triglycerides (TG, x26) as well as inflammation.

In this model, PXL770 at both doses, increased AMPK activity in the liver (P-AMPK/AMPK, +128%; p
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