Development of TP for the Induction and Maintenance of Remission in Ulcerative Colitis Patients

ABSTRACT Thetis plans to investigate TP an innovative and potential first in class therapeutic agent as an oral therapy for the induction and maintenance of remission of intestinal inflammation symptoms in ulcerative colitis UC patients While the precise etiology of UC is unknown it is thought to result from an inappropriate inflammatory response to commensal gut bacteria in genetically susceptible individuals Current treatment regimens for treatment of UC can be excessively broad in scope inducing a pan suppression of host immunity and a predisposition to infection and malignancy and not uniformly effective or durable as evidenced by the high percentage of complications of the disease Novel oral agents that are safe and effective for the induction and maintenance of UC remission would represent a major improvement in treatment options TP is a unique derivative of Resolvin E RvE a metabolite of the omega fatty acid eicosapentaenoic acid EPA RvE is part of the resolvin family of specialized proresolving mediators SPMs a group of enzymatically hydroxylated metabolites derived from EPA SPMs including RvE are particularly important for maintaining immunological homeostasis in the gastrointestinal GI tract which is constantly exposed to bacterial antigens and other inflammatory stimuli By delivering RvE to the intestinal mucosa TP has prospects to promote the resolution of inflammation accelerate intestinal tissue repair and minimize exposure to potentially harmful inflammation without sacrificing host protective functions of the innate immune system RvE has been shown in several well designed studies to be effective in treating UC in animal models Through innovative medicinal chemistry Thetis has developed proprietary technology to convert bioactive lipids into solid stable small molecule active pharmaceutical ingredients APIs Using this technology Thetis chemically transforms RvE into TP an innovative NME with pharmaceutical and IP credentials that represents a novel approach to immunoresolution based therapeutics for UC TP offers several key advantages including rapid dissociation in aqueous solution to deliver RvE as the natural material that is an endogenous mediator regulating inflammatory processes an anticipated favorable safety profile with prospects for minimal off target effects and favorable physico chemical properties that make TP amenable to formulation as a tablet or capsule for oral administration Phase of this SBIR Fast Track will demonstrate the efficacy of oral TP for the treatment of UC Specific Aim and characterize the pharmacokinetics of oral TP Specific Aim Phase of this project will include initial characterization of TP safety and toleration Specific Aim synthesis and qualification of TP for use in GLP studies Specific Aim and conduct of full GLP toxicology and safety pharmacology studies Specific Aim On completion of this Fast track SBIR project Thetis will be in a position to complete CMC activities and subsequently prepare and submit an IND filing to initiate Phase I clinical studies NARRATIVE Ulcerative colitis UC is a growing global health problem affecting between and cases per people in the US alone and is a growing and significant unmet medical concern Oral agents that are safe and effective for the induction and maintenance of UC remission are in dire need as additional treatment options and to limit the use of drugs with potentially severe side effects Thetis plans to investigate TP an innovative and potential first in class therapeutic agent as an oral therapy for the induction and maintenance of remission of intestinal inflammation symptoms in UC patients