COARE HOLDINGS INC — Department of Health and Human Services SBIR Phase I: NCI

Description

AbstractPancreatic ductal adenocarcinomaPDACis one of the most devastating human cancersIt is the fourth leading cause of cancer related deaths in the U Sannuallywith a andltyear survival rateDespite FDA approved therapeutic regimens and marked improvements in medical and surgical careno significant impact on PDAC patient survival has been achievedInsomeAmericans are expected to be diagnosedandare expected to die from PDACThere is increasing evidence that most solid tumors such as PDAC have a subpopulation of tumor initiating cells termed tumor stem cellsTSCsthat are involved in cancer invasion metastasis through a process called epithelial mesenchymal transitionEMTAdditionallystudies have demonstrated that DCLKmarks TSCs in the Apcminmouse model of intestinal neoplasiaCOARE has shown that the TSC marker DCLKis upregulated in PDAC and is a central regulator of key oncogenicpluripotency pathways and EMTAlsothe Dclkrole in PDAC initiation is demonstrated by lineage tracing and TSC initiating mouse modelsCOAREandapos s pre clinical data shows that targeting of cells that overexpress DCLKarrests xenograft tumor growthDCLKsignaling inhibition using DCLKspecific siRNAs delivered via PLGA nanoparticlesNPstriggers induction and activation of several critical endogenous tumorsuppressor pathwayswhich in turn regulate oncogenic pathways and EMT related transcription factorsCOAREin collaboration with Bioneer Inchas developed CBTEDCLKsiRNAs encapsulated into SAMiRNATM conjugated with EGFR antibodieswhich has several advantages over PLGA NPs including enhanced efficacyreduce off target toxicityincrease siRNA half lifeand minimal cytokine or interferon induction in human PBMCsThe potential outcome of this Fast Track SBIR project is improved inhibition of PDAC and preparation for human clinical trials and commercializationWe will pursue four Phase I II AimsFast Track Phase IAimFormulate and standardize CBTEAimDemonstrate effectiveness of CBTE against PDAC in vitro and in vivoFast Track Phase IIAimObtain optimum pharmacokineticPKand pharmacodynamicPDpropertiesand continued preclinical efficacy of CBTE in patient derived tumor xenograft models of PDACAimPerform IND enabling toxicity and immunogenicity studies for CBTE in Sprague Dawley ratsSDRand non human primatesNHPsMilestonesCBTE will show andgtinhibition of DCLKactivitynMa DCLKMOAandgtreduction in EMT factorsoncogenesNOTCHMYCVEGFand COXand DCLKexpressioncontinued preclinical efficacy incla andgtfold reduction in patient derived model tumorigenesissuitable PK PDand andltmeasureable toxicity in SDR and NHPsDesired OutcomePhase I II SBIR success will provide the results and data needed to engage private sector investors partners in funding the regulatory approval needed for clinical trials in PDAC patientsSuccess will lead to marketing CBTE as the first PDAC treatment for significantly increasing patient survival Project Narrative Pancreatic ductal adenocarcinomaPDACis one of the deadliest cancerswith dismal survival even in patients with early stage diseaseCOARE Holdings has developed a next generation therapeutic siRNA targeting DCLKa tumor stem cell markerwith the potential to improve PDAC patient outcomes by decreasing the tumor stem cell supported epithelial mesenchymal transition process that fuels metastasisIn this Fast Track SBIR projectCOARE will team with several expert collaborators to formulate and standardize DCLKsiRNAs in SAMiRNATM nanoparticles conjugated with anti EGFR antibodiestermed as CBTEand to perform preclinical and IND enabling studies to prepare for the clinical trials that will lead to ultimate commercialization of a next generation therapeutic that has the potential to greatly impact positive human health outcomes for PDAC patients