therapeutic mission________________

crohn’s disease, CSF-1R and PRV-6527

Crohn’s disease is a chronic inflammatory bowel disease (IBD) characterized by inflammation of the gastrointestinal (GI) tract.  Myeloid cells, a species of antigen-presenting cells, are believed to play a central role in Crohn’s disease by presenting microbiome antigens to white blood cells in the gut. The Colony Stimulating Factor-1 Receptor (CSF-1R) drives myeloid cell differentiation in the bone marrow resulting in the maturation of inflammatory dendritic cells and macrophages, which then populate the gut and other tissues and trigger inflammatory processes. Human biomarker and animal model studies show that CSF-1R appears to be involved in the pathogenesis of Crohn’s Disease.

Based on this knowledge, we are developing PRV-6527, an inhibitor of CSF-1R in-licensed from Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), for the treatment of Crohn’s disease.  We anticipate that an inhibitor of CSF-1R will be able to “intercept” the differentiation of inflammatory dendritic cells, suppressing their migration to the intestinal mucosa (gut lining) in Crohn’s disease, resulting in clinical benefit.

To test this hypothesis, we are planning to initiate a Phase 2a proof-of-concept study of PRV-6527 in moderate to severe Crohn’s disease.  The clinical trial will be randomized, double-blind and placebo-controlled, with dosing for 12 weeks, and is expected to enroll approximately 80 patients who previously failed one biologic drug. The primary endpoint will be clinical effect at week 12, and secondary proof-of-mechanism endpoints will be assessed, including endoscopy and the presence of inflammatory myeloid cells in the gut.