PPARγ is a nuclear receptor that plays an important role in regulating inflammation, fibrosis and immunity. Alterations in this ligand-activated transcription factor are associated with metabolic disorders, in particular with type II diabetes, as well as with cancer.
Full agonists of PPARγ have been shown to reduce inflammatory cytokines in Crohn’s Disease patients and to induce clinical benefit. PPARγ agonists also inhibitor TGFβ, a master regulator of fibrosis signalling , their safety profile limits their long-term use.
MBF-118 is a small molecule designed as a partial agonist of PPARγ, which covalently binds to the target and has high off-target selectivity. MBF-118 has an excellent safety profile. It is non-toxic in pre-clinical toxicity assays, well-tolerated and shows no genotoxic potential. The compound is GI-enriched in humans, with limited systemic exposure, and therefore ideally positioned for Crohn’s Disease.
It has demonstrated high efficacy in pre-clinical animal models of inflammation and fibrosis. We believe this fact gives MBF-118 a unique profile as an anti-inflammatory and antifibrotic molecule, with great potential for the treatment of Crohn’s Disease.
MBF-118 has successfully completed Phase I evaluation in healthy volunteers and a phase IIa proof-of-concept trial in Crohn’s patients is now recruiting.
The patent protecting MBF-118 has been granted in the US and EU and is, wholly owned by Medibiofarma.