6 August 2019 - - Study will assess full PK profile and PD effect on target pathways and metabolic parameters in parallel with
France-based biopharmaceutical company Poxel SA (Euronext: POXEL - FR0012432516) has initiated a PK/PD study, which is part of the Phase 2a clinical programme for PXL770, a first-in-class direct adenosine monophosphate-activated protein kinase activator, for the treatment of NASH, the company said.

The four-week PK/PD study of PXL770 is expected to enroll approximately 16 patients per dose, with the primary objective to assess the full PK profile of PXL770 in nonalcoholic fatty liver disease (NAFLD) patients, who likely have NASH, as well as evaluate the safety and tolerability.

The study will also evaluate the effect of PXL770 on its two main targeted metabolic pathways, which include hepatic de novo lipogenesis and lipolysis.

It will also assess several other glycemic and lipidic metabolic parameters as well as non-metabolic biomarkers.

Data results from the PK/PD study are expected during the fourth quarter of 2019.

Concurrently, PXL770 is being evaluated in an ongoing efficacy and safety Phase 2a twelve-week, multicenter, randomised, double-blind, placebo-controlled, parallel group study.

This study is expected to enroll approximately 100 NAFLD patients in the US who likely have NASH and will investigate three doses of PXL770 versus placebo.

The primary endpoint of the study will measure the change in liver fat mass based on magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), an imaging-based biomarker that allows fat mapping of the entire liver.

The study will also assess the effects of PXL770 on other metabolic and non-metabolic biomarkers as well as safety and tolerability.

Non-alcoholic steatohepatitis is a metabolic disease with no clear disease origin that is quickly becoming a worldwide epidemic.

It is characterised by the accumulation of fat in the liver causing inflammation and fibrosis.

The disease can be silent for a long period of time, but once it accelerates, severe damage and liver cirrhosis can occur, which can significantly impact liver function or can even result in liver failure or liver cancer.

Typical risk factors for NASH include obesity, elevated levels of blood lipids (such as cholesterol and triglycerides) and diabetes. Currently no curative or specific therapies are available.

PXL770 is a first-in-class direct adenosine monophosphate-activated protein kinase activator. AMPK is a central regulator of multiple metabolic pathways leading to the control of lipid metabolism, glucose homeostasis and inflammation.

Based on its central metabolic role, targeting AMPK offers the opportunity to pursue a wide range of indications to treat chronic metabolic diseases, including diseases that affect the liver, such as non-alcoholic steatohepatitis.

Poxel uses its development expertise in metabolism to advance a pipeline of drug candidates focused on the treatment of metabolic disorders, including type 2 diabetes and non-alcoholic steatohepatitis.

The company has completed the Phase 2 clinical programme for its first-in-class lead product, Imeglimin, which targets mitochondrial dysfunction, in the US, Europe and Japan.

Together, with partner Sumitomo Dainippon Pharma, Poxel is conducting the Phase 3 Trials of IMeglimin for Efficacy and Safety (TIMES) programme for the treatment of type 2 diabetes in Japan.

Its partner Roivant Sciences is responsible for Imeglimin's development and commercialisation in countries outside of Poxel's partnership with Sumitomo Dainippon Pharma, including the US and Europe.

PXL770, a first in class direct adenosine monophosphate-activated protein kinase activator, is in a Phase 2a proof-of-concept programme for the treatment of NASH. PXL770 could also have the potential to treat additional metabolic diseases.

PXL065 (deuterium-stabilised R-pioglitazone), a mitochondrial pyruvate carrier inhibitor, is in Phase 1 and being developed for the treatment of NASH. Poxel also has additional earlier-stage programmes, including deuterated drug candidates for metabolic, specialty and rare diseases.