Development of TP-317 for the Induction and Maintenance of Remission in Ulcerative Colitis Patients

ABSTRACTThetis plans to investigate TPan innovative and potential first in class therapeutic agentas an oral therapy for the induction and maintenance of remission of intestinal inflammation symptoms in ulcerative colitisUCpatientsWhile the precise etiology of UC is unknownit is thought to result from an inappropriate inflammatory response to commensal gut bacteria in genetically susceptible individualsCurrent treatment regimens for treatment of UC can beexcessively broad in scopeinducing a pan suppression of host immunity and a predisposition to infection and malignancyandnot uniformly effective or durableas evidenced by the high percentage of complications of the diseaseNovel oral agents that are safe and effective for the induction and maintenance of UC remission would represent a major improvement in treatment optionsTPis a unique derivative of Resolvin ERvEa metabolite of the omegafatty acideicosapentaenoic acidEPARvEis part of the resolvin family of specialized proresolving mediatorsSPMsa group of enzymatically hydroxylated metabolites derived from EPASPMsincluding RvEare particularly important for maintaining immunological homeostasis in the gastrointestinalGItractwhich is constantly exposed to bacterial antigens and other inflammatory stimuliBy delivering RvEto the intestinal mucosaTPhas prospects to promote the resolution of inflammationaccelerate intestinal tissue repair and minimize exposure to potentially harmful inflammation without sacrificing host protective functions of the innate immune systemRvEhas been shown in several well designed studies to be effective in treating UC in animal modelsThrough innovative medicinal chemistryThetis has developed proprietary technology to convert bioactive lipids into solidstablesmall molecule active pharmaceutical ingredientsAPIsUsing this technologyThetis chemically transforms RvEinto TPan innovative NME with pharmaceutical and IP credentials that represents a novel approach to immunoresolution based therapeutics for UCTPoffers several key advantages includingrapid dissociation in aqueous solution to deliver RvEas the natural material that is an endogenous mediator regulating inflammatory processesan anticipated favorable safety profile with prospects for minimal off target effectsandfavorable physico chemical properties that make TPamenable to formulation as a tablet or capsule for oral administrationPhaseof this SBIR Fast Track will demonstrate the efficacy of oral TPfor the treatment of UCSpecific Aimand characterize the pharmacokinetics of oral TPSpecific AimPhaseof this project will include initial characterization of TPsafety and tolerationSpecific Aimsynthesis and qualification of TPfor use in GLP studiesSpecific Aimand conduct of full GLP toxicology and safety pharmacology studiesSpecific AimOn completion of this Fast track SBIR projectThetis 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 colitisUCis a growing global health problem affecting betweenandcases perpeople in the US aloneand is a growing and significant unmet medical concernOral agents that are safe and effective for the induction and maintenance of UC remission are in dire need as additional treatment optionsand to limit the use of drugs with potentially severe side effectsThetis plans to investigate TPan innovative and potential first in class therapeutic agentas an oral therapy for the induction and maintenance of remission of intestinal inflammation symptoms in UC patients