Genfit's Advanced Compound Status

GFT505:  A Pluripotent Multimodal Compound

GFT505 is a multimodal and pluripotent medication for treatment of atherogenic dyslipidemia for an overweight patient with or without diabetes.

GFT505 is the result of a rational design process to identify a new SPPARM (Selective PPAR Modulator) based on the compatibility analysis of the structural/activity relationships for the different sub-types of PPAR receptors. GFT505 was discovered using the technical platform developed by Genfit to optimize the safety/efficacy ratio of the PPAR agonists. GFT505 is an oral treatment that acts on the 3 sub-types of PPAR (PPARa, PPARg, PPARd) with a preferential action on PPARa.

GFT505 has completed Phase I with excellent results and has just entered Phase IIa. The promising results of the Phase I clinical trial revealed a highly satisfactory safety margin. In animal models, this drug candidate demonstrated significant positive effects on triglycerides, insulin resistance, HDL cholesterol, and the prevention and stabilization of the atherosclerotic plaque confirming the pluripotent nature of GFT505.

Genfit has simultaneously lunched 2 phase II clinical trials and results are expected in March and June 2008. These 2 phase II clinical trials are double-blinded, placebo-controlled and randomized. They aim to assess the safety and efficacy of once-a-day administration of a 30mg oral dose of GFT505 for 28 days. They are conducted in multiple clinical centers.

In the first study, the primary objectives are to evaluate the efficacy and the tolerability of GFT505 in patients with type IIb dyslipidemia. In the second study, the primary objectives are to evaluate the efficacy and the tolerability of GFT505 in pre-diabetic patients with atherogenic dyslipidemia and abdominal obesity.

GFT505 is the most advanced molecule of a new generation of drug candidates developed by Genfit which aims at the prevention of the global cardiometabolic risks. Stemming from the Selective Nuclear Receptor Modulator (SNuRM) platform developed by GENFIT, this new generation of drug candidates has a sophisticated mechanism of action. These compounds are able to differentially recruit cofactors to the nuclear receptor, which subsequently lead to differential regulation of genes and biological effect. Therefore, the ability to identify and profile the activity of SNuRMs is a powerful approach to select innovative drug candidates with improved efficacy and diminished side effects. These pluripotent and multimodal molecules have significant positive effects on obesity, insulin-resistance and diabetes, atherosclerosis, inflammation, and the lipid triad (increasing of HDL cholesterol, lowering of triglycerides and LDL cholesterol). These molecules also demonstrate neuro-protective effects in ischemia models and may therefore be used to prevent and treat neuro-degenerative diseases (such as Alzheimer and Parkinson diseases).