In the TGFTX4 program, we have identified a novel class of compounds with strong anti-fibrotic properties in cell-based assays and in vivo models.
We have identified a proprietary series of compounds that inhibit both the proliferation and the pro-fibrotic activation of primary human Hepatic Stellate Cells (HSCs) with high efficacy. The anti-fibrotic properties of this compound series were also confirmed in vivo, in well established liver fibrosis models.
In parallel, we have identified a group of molecular targets, including Receptor Tyrosine Kinases (RTKs), that explain the anti-fibrotic properties of the TGFTX4 series. We are currently working on a hit to lead optimization program to design high quality drug candidates for development in fibrotic liver diseases.
Effects on fibrosis
Since fibrosis is a complex and highly adaptive process that depends on a cross-talk between many signaling pathways, at Genfit we have used in this program a disease-relevant functional assay as opposed to a classical target-centered approach, in order to enhance the probability of successful clinical translation.
Pathologic activation of HSCs, which release excessive amounts of extracellular matrix components, is a recognized hallmark of the fibrotic process. It is expected that interference with common pro-fibrotic actions will result in a therapeutic benefit in chronic liver diseases of various origins and etiologies.