Pre-IND development of CBT-15 monoclonal antibody therapy against renal cell cancer

AbstractRenal cell cancerRCCis a devastating cancer with a very lowyear survival rate for patients who present with local or distant spreadRCC has stunning resistance to radiotherapy and chemotherapyrampant epithelial mesenchymal transitionEMTas well as a hypoxic microenvironmentall factors indicative of cancer stem cellsCSCsMany lines of treatment have been trialed against RCC with positive results for receptor tyrosine kinase inhibitorsmTOR inhibitorsand more recently anti PDtherapynivolumabHoweveralthough these drugs provide improvements in progression free survivalmost fail to improve overall survivalAn exception to this is nivolumabwhich targeted a new cell typeenhancing the immune system and leading to a paradigm shift in cancer treatmentCOARE Biotechnology s novel monoclonal antibody therapy CBTis targeted to a specific cell typeCSCsthat may result in a similar paradigm shiftDoublecortin like kinaseDCLKis a prominent stem cell marker in gastrointestinal cancers and that is emerging in othersOur preliminary data demonstrates that specific extracellular DCLKisoforms are overexpressed in RCC stem like cells and can be targeted to reverse drug resistanceEMTand oncogenic processesWith this knowledgewe developed an isoform specific monoclonal antibodyCBTto specifically target these CSCs in RCCIn vitro assays with this antibody demonstrate ADCC activity and in vivo studies using RCC xenografts demonstrate potent inhibition of tumorigenesisMoreoverwe have humanized CBTand engineered an ADCC enhanced version of the drug to increase potencyCBTACWe propose further development and safety studies for CBTto advance it to the market with the Fast Track SBIR studies proposed herePhase I AimEstablish optimal delivery of CBTand CBTAC DCLKtargeted mABs in immunocompetent Renca xenografts and standard human RCC cell line derived xenograftsAimEstablish CBTand CBTAC efficacy against tumorigenesis and metastasis in the clinically relevantorthotopic Renca model of RCC as a primary therapy and as an adjuvant to sunitinib or anti PDPhase II AimPerform IND enabling safety assessments for toxicitypharmacokineticsand tissue cross reactivity of hCBTCBTAC in murine and non human primate models in preparation for human clinical trialsDesired OutcomePhase I SBIR success will provide further proof of concept and be key to bringing investors on board to support clinical trials and commercializationPhase II SBIR success will provide the key results and data needed to pursue SBIR Phase IIB studies and engage the FDA for regulatory approval required to begin clinical trials in RCC patientsClinical trial success will lead to ultimate commercializationWhen CBTreaches the marketCOARE Holdings envisions a paradigm shift in RCC therapy and survival Project Narrative Renal cell cancerRCCis a deadly cancer that is notoriously resistant to therapies and highly prone to recurrence and metastasisBased on preliminary feasibility studies of a novel monoclonal antibodyCBTtargeting the DCLKtumor stem cell marker protein in RCCCOARE Holdings is proposing this Fast Track SBIR project to develop further proof of concept for CBTas a primary therapy and adjuvant therapy to currently approved targeted therapies in mouse models of RCC progressionPhase IMoreoverwe propose to accelerate progress by performing IND enabling studiesPhase IIto prepare for SBIR Phase IIBclinical trialsand ultimate commercialization of a next generation therapeutic that has the potential to positively impact health outcomes for RCC patients