COARE BIOTECHNOLOGY, INC. — Department of Health and Human Services SBIR Phase II: NCI

Description

Abstract Pancreatic ductal adenocarcinoma PDAC is a devastating cancer with an extremely low year survival rate even for those who are diagnosed early Novel research suggests that this may be the result of metastatic dissemination preceding or concurrent to the development of the primary tumor Epithelial mesenchymal transition EMT is one of the key pathways in pancreatic cancer invasion and metastasis and is linked to a tumor stem cell phenotype The COARE Biotechnology Randamp D team believes that targeting this process will ultimately allow us to significantly increase patient survival COAREandapos s primary expertise is in targeting cancer through the doublecortin like kinase DCLK tumor stem cell marker During COAREandapos s Phase I SBIR study of a mouse monoclonal antibody mAb raised against DCLK CBT that showed promising results in vitro and in vivo COARE Biotechnology engineered a newer generation of mAb designed to take advantage of DCLK andapos s cell surface antigen expressed on pancreatic cancer tumors circulating tumor cells and metastases which led to a powerful anti tumorigenic effect in PDAC tumor xenografts For this Phase II project we propose to further develop this mAb termed raphtumomab in preparation for commercialization and human clinical trials We will pursue this objective with the following three specific aims Aim COARE in collaboration with Panorama Research Institute will humanize raphtumomab to create raphtuzumab and will confirm retained binding affinity for DCLK by BIAcore and other techniques Aim COARE in collaboration with the University of Oklahoma Health Sciences Center will assess raphtuzumab to determine its pharmacokinetic dynamic PK PD properties mechanism of action MOA and its continued preclinical efficacy in patient derived orthotopic models of PDAC Aim COARE in collaboration with WIL Research will perform IND enabling toxicity and immunogenicity studies of raphtuzumab in Sprague Dawley rats SDR and non human primates NHPs Milestones Raphtuzumab will demonstrate retained DCLK affinity nM a DCLK MOA andgt reduction in EMT and DCLK expression continued preclinical efficacy including a andgt fold reduction in patient derived orthotopic model tumorigenesis suitable PK PD toxicity and immunogenicity in SDR and NHPs Desired Outcome Phase II SBIR success provide the key results and data needed to engage private sector investors partners in carrying out the next steps toward the regulatory approval required to begin clinical trials in PDAC patients Success with the clinical trials will lead to ultimate commercialization When raphtuzumab reaches the market COARE Biotechnology envisions that it will be the first treatment for PDAC that can significantly increase patient overall survival Project Narrative Pancreatic ductal adenocarcinoma PDAC is one of the deadliest cancers with dismal survival even in patients with early stage disease Based on successful Phase I SBIR feasibility studies of a novel monoclonal antibody CBT targeting the DCLK tumor stem cell marker protein in PDAC COARE Biotechnology has developed a next generation therapeutic monoclonal antibody raphtumomab with the potential to improve PDAC patient outcomes by decreasing the tumor stem cell supported epithelial mesenchymal transition process that fuels metastasis For the follow on Phase II SBIR study proposed here COARE will team with several expert collaborators to humanize this promising antibody drug and will perform IND enabling studies to prepare for clinical trials and ultimate commercialization of a next generation therapeutic that has the potential to greatly impact positive human health outcomes for PDAC patients