We are developing our lead product candidate, lanifibranor, for the treatment of patients with non-alcoholic steatohepatitis, or NASH, for which there are currently no approved therapy.
Lanifibranor is an orally-available small molecule that acts to induce anti-fibrotic, anti-inflammatory and beneficial metabolic changes in the body by activating each of the three PPAR isoforms, known as PPARα, PPARδ and PPAR𝛄.
PPARs are ligand-activated transcription factors belonging to the nuclear hormone receptor family that regulate the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development and tumorigenesis.
Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPAR𝛿 , and a partial activation of PPAR𝛄. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development. For an extensive discussion on the benefit of PPAR agonism in NASH please visit the panNASH Initiative website.
in Non-Alcoholic Steatohepatitis (NASH)
PPAR activation has been established to play a role in regulating each of the four components of NASH:
- Metabolism: Activation of PPARα and PPARδ has been demonstrated to reduce triglyceride levels and increase HDL cholesterol levels, while activation of PPAR𝞬 has been demonstrated to increase insulin sensitization, all of which are key metabolic markers in patients with NASH.
- Steatosis: Activation of PPARα and PPAR𝞬 addresses key elements of steatosis by enhancing fatty acid metabolism and ultimately decreasing lipogenesis.
- Inflammation and ballooning: Activation of PPARα, PPARδ and PPAR𝞬 has been associated with statistically significant reductions in inflammation and ballooning.
- Fibrosis: Activation of PPAR𝞬 is associated with anti-fibrotic effects across the process of fibrosis, from the production of stellate cells to the production of fibrotic proteins such as collagen and fibronectin.
In addition lanifibranor has shown clear beneficial effects in a pre-clinical model of decompensated cirrhosis, which lead to a marked improvement in fibrosis and portal hypertension. Based on the established role that PPAR activation plays in regulating metabolic processes, including steatosis, as well as in inflammatory and fibrotic processes, we are developing lanifibranor for the treatment of NASH.
Lanifibranor is the only product candidate in clinical development targeting all three PPAR isoforms. We believe that this pan-PPAR approach provides for a combination of anti-fibrotic, anti-inflammatory and beneficial metabolic effects that cannot be obtained with single and dual PPAR agonists.