We are developing our lead product candidate, lanifibranor, for the treatment of patients with systemic sclerosis, or SSc, and non-alcoholic steatohepatitis, or NASH, both diseases for which there are currently no approved therapies.
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.
in Systemic Sclerosis (SSc)
Based on the established role that the activation of PPAR isoforms plays in the fibrotic and inflammatory processes, we are developing lanifibranor for the treatment of SSc.
Because lanifibranor acts on all PPAR isoforms, we believe that lanifibranor has the potential to positively affect all phases of SSc pathogenesis. Furthermore, in pre-clinical studies, we observed that the administration of lanifibranor positively impacted several biomarkers of fibrosis from SSc patients.
We also observed that lanifibranor was associated with consistent anti-fibrotic effects across several organs that are relevant to the SSc pathology. Based on these pre-clinical studies, we believe that lanifibranor has the potential to address all of the key clinical manifestations of the disease, including in the skin, heart, lung and kidneys.
We are currently conducting the FASST Phase IIb clinical trial of lanifibranor for the treatment of patients with dcSSc. We plan to report data in the first quarter of 2019 and, if positive, we plan to initiate Phase III clinical development. Lanifibranor has received orphan drug designation from the FDA and the EMA for the treatment of SSc.
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.
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.