Targeting Irritable Bowel Syndrome (IBS) with astressins

Abstract Sentia seeks to bring to fruitionyearsof NIDDK fundedPDKPIsWValeCRivierJSpiess and JRivieracademic research to achieve translational drug candidacy by blocking both corticotropin releasing factorCRFreceptors CRFwith potent astressin peptide antagonistsPresent assets of Sentia include world widepatent protectedandquot first in classandquotpeptide drug candidates and intellectual property that targetsamong othersthe regulation of the stress response systemScientific evidence documents that potentially dozens of current human ailments can benefit from the use of stress neutralizing compounds to achieve temporal or permanent homeostasisIn particularirritable bowel syndromeIBSis well established to be a stress sensitive condition with visceral pain being the hallmarkAlleviating visceral pain in IBS patients is still an unmet need and the market for managing and or curing the symptoms is conservatively estimated to be in the $B rangeAstressin therapeutics would represent a andquot first in classandquotopportunity to safely and effectively treat IBS patients with injectable peptide analogs that could represent a paradigm shift in therapeutic intervention away from conventional short acting oral small molecules providing patients a different option for long acting reliefThereforethe objective of the Phase I application is to obtain relevant quantities of astressin CRFantagonistscompoundsmanufactured following the Fmoc strategythat is likely the approach to be taken commercially by CROsand provide preclinical evidence of their safetyefficacy and long lasting effects to reduce stress related visceral hyperalgesiaIn aima potential clinical candidate for development will be selected from the acetate salts of compoundsi eastressin CC MeValastressin C and hexanoyl astressin Doriginally synthesized and tested using the Boc strategyTheir MW is arounddaltonswell within the desirable range for chemical total synthesisbiological characterization and fibrils formation for long duration of actionIt is expected that the acetate salts of these analogs will share the favorable physiochemical properties of the corresponding tri fluoro acetateSubstantiallythere are no obvious properties that would disqualify a selected candidateIn Aimthese CRF receptor antagonists will be tested preclinically for their ability to modulate visceral hypersensitivity in an experimental stress related model of IBS developed by the subcontracted academic institutionthe UCLA Center for Digestive Diseases ResearchIf validatedresults from these preclinical experiments will allow Sentia to select a first candidate and back up compound sNarrative Sentia Medical SciencesIncof La JollaCAJRivierFounderis a biotech company that designs and develops peptide antagonists targeting G protein coupled receptors with a focus on the corticotropin releasing factorCRFpathways involved in the stress responseSentia now seeks to translateyearsof NIDDK fundedPDKPIsWValeCRivierJSpiess and JRivieracademic research on CRF signaling to advance novelfirst in classinjectable peptide CRFantagonists thatif approvedwould represent a paradigm shift for IBS patients who are currently treated with short acting oral small molecules that have limited efficacysignificant side effects and do not address visceral painIn this regardthe proposal seeks to provide preclinical evidence that novelpotentlong actingsafe and patented CRFantagonists can provide benefit in IBSa well established stress sensitive conditionby alleviating visceral pain which is a major unmet need for patients