In the TGFTX1 program, Genfit has selected RORγt (RORgamma-t), a key Nuclear Receptor that directs IL-17 mediated immunity and represents an attractive and widely recognized target to treat inflammatory and auto-immune diseases.
The first TGFTX1 molecules developed by our chemists inhibit RORγt activity with good efficacy, and have already shown beneficial effects in functional assays that are highly relevant to the targeted pathologies.
We are currently exploring our proprietary RORγt inhibitors as innovative treatment approaches to diverse hepatic and intestinal inflammatory disorders.
Within the TGFTX1 program, we have also developed a comprehensive panel of tools and assays for the discovery of RORγt inhibitors as potential treatments for auto-immune diseases.
IL-17 as a key element
Overactive IL-17 mediated immune responses are clinically recognized as critical mediators in auto-immune diseases such as psoriasis or rheumatoid arthritis. IL-17 mediated immunity has also been shown to play a role in the development of other auto-immune and inflammatory diseases, such as Multiple Sclerosis, Systemic Lupus Erythematosus, obstructive respiratory diseases, Inflammatory Bowel Disease (IBD) and different forms of liver damage/fibrosis.
RORγt plays a key upstream role in the immune process as a lineage commitment factor for the production of Th17 lymphocytes that are instrumental for the induction of IL-17 and the ensuing immune responses.
Thus, the development of a drug candidate that inhibits RORγt represents a straightforward and efficient way to curb exacerbated IL-17-mediated immune responses, especially since such a drug could be an orally-administered small molecule.