Thetis Pharmaceuticals LLC — Department of Health and Human Services SBIR Phase I: NIAID

Description

ABSTRACTThetis plans to investigate TPan innovative and potential first in class therapeutic agentas a therapy for the treatment of eosinophilic esophagitisEoEa chronicatopic disease characterized by eosinophilic inflammation and tissue remodeling of the esophagusAlthough the pathogenesis of EoE is not completely understoodrecent evidence suggests that it results from an inappropriate immune response to food allergens in genetically predisposed individualsThe defining histopathological feature of EoE is a dense eosinophilic infiltrate within the esophageal epitheliumIf left untreatedEoE results in esophageal fibrosis and dysfunction that can significantly reduce patient quality of lifeWhile currently available therapies can effectively treat symptomsthey are associated with potentially serious side effectssuch as infectionadrenal insufficiency and malnutritionwhich can be particularly problematic for pediatric patientsThusEoE represents a significant unmet medical need for which new treatment strategies are neededTo address this unmet needThetis is developing TPa unique derivative of Resolvin ERvERvEis part of a family known as specialized proresolving mediatorsSPMsa group of enzymatically hydroxylated metabolites derived from eicosapentaenoic acidSPMsincluding RvEare particularly important for maintaining immunological homeostasis in the gastrointestinalGItractwhich is constantly exposed to allergens and other inflammatory stimuliDelivering RvEto the esophagus has the potential to promote the resolution of inflammationaccelerate intestinal tissue repair and minimize exposure to harmful inflammation without sacrificing host protective functions of the innate immune systemRvEs inflammation resolving properties have been validated in animal models of many inflammatory diseaseincluding several models with pathophysiological features similar to human EoEThese studies have revealed that RvEpromotes the resolution of inflammation by acting on many of the same pathways implicated in EoE pathogenesisWhen administered prophylacticallyRvEhas been shown to potently inhibit the induction of allergic inflammationin part by limiting the recruitment and activation of eosinophilsImportantlyThetis has recently completed a series of preclinical studies demonstrating the ability of TPto counter regulate pathologic processes implicated in EoEincluding eosinophil infiltration of the mucosa and inflammation associated fibrosisUsing its proprietary technology platformThetis has chemically transformed RvEinto TPa novel salt of RvEthat overcomes some of the key barriers that have inhibited the development of an RvEbased agentThis SBIR Phaseprogramconducted in collaboration with leading EoE expert DrGlenn FurutaUniversity of ColoradoDenverwill demonstrate the efficacy of TPin an animal model of EoEOn completion of this projectThetis will have demonstrated proof of concept for TPin EoE and will be in a position to initiate key IND enabling studies through a Phaseprogram NARRATIVE Eosinophilic esophagitisEoEis a growing global health problem affecting betweenandcases perpeople in the US aloneand treatment are associated with significant side effectsEoE patients are in dire need of safe and effective treatment optionsThetis plans to investigate TPan innovative and potential first in class therapeutic agentas a therapy for the treatment of EoE