A New Pro-Resolving Treatment Paradigm for Inflammatory Bowel Disease (IBD)
IBD is a group of disorders characterized by inflammation and ulceration of the small and large intestines. The two major types of IBD are Ulcerative Colitis, which occurs in the colon and rectum, and Crohn’s Disease, which affects tissue throughout the intestinal tract.
Thetis agents offer a fundamentally new approach to the treatment of IBD. Nearly all approved IBD therapeutics are anti-inflammatory and work by blocking key steps in the inflammatory cascade. In contrast, Thetis agents enhance inflammation resolution by actively promoting clearance of inflammatory cells and the return to an uninflamed state.
Unlike anti-inflammatory drugs, Thetis agents actively promote tissue repair and healing, and do not suppress normal immune responses. As a result of this novel, non-immunosuppressive mechanism of action, our expectation is that Thetis agents will not carry the risks of infection and malignancy that are associated with some anti-inflammatory agents.
Importantly, due to their complimentary mechanisms of action, Thetis agents may work together with anti-inflammatory drugs to improve efficacy and reduce patient safety risks.
TP-252 for treatment of Ulcerative Colitis
TP-252: A pre-clinical asset with clinical proof of concept
TP-252 is a novel derivative of eicosapentaenoic acid free fatty acid (EPA-FFA), which has been shown in an independent Phase 2 RCT to have efficacy in reducing relapse in ulcerative colitis patients. TP-252 is being developed as adjunct oral therapy to 5-ASAs for the maintenance of remission in ulcerative colitis patients with a history of mild to moderate disease prior to escalation to immuno-suppressors and biologics. Thetis expects to begin clinic studies in 2018.
TP-317 for treatment of IBD
TP-317 is a novel derivative of a Specialized Pro-Resolving Mediator (SPM) for treatment of IBD.
SPMs are a potent class of endogenous metabolites of Omega-3 and Omega-6 fatty acids that have been shown pre-clinically to control gastrointestinal inflammation and gut mucosal immune responses at very small doses. These data suggest multiple mechanisms of action including inhibition of pro-inflammatory signals, reduced penetration of bacteria into the intestinal wall, and promotion of tissue repair and healing.