Reata Pharmaceuticals, Inc, of Dallas, Texas, has been granted exclusive worldwide rights to a novel class of anti-inflammatory compounds, tricyclic-bis-enones (TBEs), developed by Michael Sporn, the Oscar M. Cohn '34 Professor of Pharmacology and Medicine at Dartmouth Medical School, in collaboration with Gordon Gribble, Dartmouth Professor of Chemistry, Dartmouth College, and Tadashi Honda, Dartmouth Professor of Chemistry and Research Assistant Professor of Chemistry at the University of Texas MD Anderson Cancer Center.

TBEs are potent activators of the basic leucine zipper transcription factor, NF-E2-related factor-2 (Nrf2). The major functional categories of Nrf2-dependent genes are 1) detoxification; 2) phase 2 antioxidant response/reducing potential; 3) growth; and 4) defense/immune/inflammation. TBEs have shown potent anti-inflammatory activity in early preclinical studies. Among TBEs initially synthesized, one derivative shows high inhibitory activity (IC50 = 1 nM level) against production of nitric oxide (NO) induced by interferon-gamma in mouse macrophages, and is orally active at 15 mg/kg (single administration) in a preliminary in vivo study using mouse peritoneal inflammation induced by thioglycollate and interferon-gamma. TBEs have been shown to increase the expression levels of major cytoprotective and antioxidant proteins, including inducible heme oxygenase (HO-1). Activation of Nrf2 and induction of HO-1 are therapeutic strategies for treating a variety of inflammation-related medical conditions including autoimmune diseases (eg, rheumatoid arthritis, Crohn's disease, and multiple sclerosis), cardiovascular disease, asthma, chronic obstructive pulmonary disease, Alzheimer's disease, and Parkinson's disease.

Although not specifically mentioned in the company's announcement, it is likely that the license rights are based on US Patent Application 20030232786, filed December 18, 2003, with listed inventors T. Honda, F. Favaloro, G. Gribble, M. Sporn, and N. Suh, and entitled "Tricyclic-bis-enone derivatives and methods of use thereof." The patent application claims novel TBE derivatives as well as the process for the preparation of such TBEs. Also provided are methods for the prevention and/or treatment of cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotropic lateral sclerosis, rheumatoid arthritis, inflammatory bowel disease, and all other diseases whose pathogenesis is believed to involve excessive production of either NO or prostaglandins or the overexpression of iNOS or COX-2 genes or gene products. The application claims priority to provisional US Patent Application Serial No. 60/348,594 filed January 15, 2002; provisional US Patent Application Serial No. 60/376,040, filed April 26, 2002; and provisional US Patent Application Serial No. 60/402,966, filed August 13, 2002.

— A. Techman