Orphagen Pharmaceuticals Receives NIH Funding Award to Advance a Novel Drug for Inflammatory Bowel Disease
Summary
"Well use this funding from the NIDDK to further evaluate the properties of our lead compound, OR-812, a potent and selective RAR antagonist with promising preclinical efficacy, safety, and pharmacokinetics for the treatment of IBD. However, despite development of novel therapies including monoclonal antibodies to TNF and IL-12/IL-23, and inhibitors of T cell gut homing such as vedolizumab and ozanimod, less than half of patients experience a sustained therapeutic benefit.The research leading to this award grows out of investigations at Orphagen into unexplored members of the nuclear receptor family, which has been the source of major drugs in cancer, metabolic disease, and inflammation. In vivo pharmacological studies at Orphagen have shown that RAR antagonists will, with very high potency, block the induction of the gut homing integrin 47, the target for vedolizumab, a major inflammatory bowel disease drug. Induction of a second important gut homing receptor, CCR9, is also blocked by OR-812 during T cell activation.Potential for efficacy in this drug class was supported by studies carried out in the laboratory of Professor Casey Weaver, the Leonard H. Robinson Endowed Chair in Pathology at the University of Alabama, Birmingham, a noted pioneer in mucosal immunology. His group showed that an RAR antagonist will inhibit 47 expression and cause a significant reduction in accumulation of inflammatory T cells in the lamina propria of the colon of Citrobacter rodentium-infected mice, a model of gut mucosal inflammation resembling IBD.