Development of Antagonists to ROR-gamma

Orphagen has pioneered the discovery of selective small molecule inhibitors of the orphan nuclear receptor RORγ. RORγ controls the activity of a new class of T helper cells, known as Th-17 cells. Animal studies show that RORγ antagonists could be effective treatments for many forms of autoimmune disease including psoriasis, juvenile arthritis, Crohn’s disease, multiple sclerosis (MS), and rheumatoid arthritis.

In April 2008, building on growing interest in this area, Orphagen signed an industry partnership with with the Pharmaceutical Division of Japan Tobacco for further development of RORγ antagonists which it had discovered during 2003-2007. The partnership was the first of seven publicly-announced preclinical-stage partnerships for RORγ antagonists that have swept the pharmaceutical industry, involving giants such as Merck, Pfizer, Amgen, J&J, Sanofi-Aventis and AstraZeneca.

The Pharmaceutical Division of Japan Tobacco recently announced the initiation of clinical trials for JTE-451, an RORγ antagonist. The RORγ program has demonstrated Orphagen’s capability to successfully initiate first-in-class discovery.