Cambium Oncology LLC

Development of a Novel Armored Car-t Immunotherapeutic for Pancreatic Cancer - Pancreatic Ductal Adenocarcinoma (PDAC) Represents a Major Challenge in Oncology, the Third Leading Cause of Cancer-related Death, and a 5-YEAR Survival Rate of Only 11%. the Dense, Immunosuppressive Tumor Microenvironment (TME) of Pdac Significantly Hinders the Efficacy of Current Therapeutic Strategies, Including the Innovative Car T Cell Therapies That Have Shown Promise in Hematologic Malignancies. a Significant Contributor to This Immunosuppression Is the Secretion of Vasoactive Intestinal Peptide (VIP) Within the Pdac Tme by Cancer Cells and Immune Cells That Limits the Efficacy of Adoptive T Cell Therapies. Addressing This Urgent Need, Cambium Oncology Proposes a Novel Approach to Enhance Car T Cell Therapy's Potency Against Pdac by Countering the Immunosuppressive Effects of Vip Prevalent in Pdac Tumors. Our Pioneering Strategy Involves Engineering Car T Cells That Target the Extracellular Domain of MUC16 (MUC16CD), a Marker Abundant in Pdac Tumors and Stroma, to Secrete an Optimized Form of the Vip Receptor (VIPR) Antagonist, ANT308FC. Preliminary Findings Indicate That Car T Cells Endowed With the Capability to Secrete Vipr Antagonists Demonstrate Enhanced Metabolic Flexibility, a Predominance of Memory T Cell Subsets, and Superior Anti-tumor Activity. This Project Is Structured to Validate the ANT308-FC Fusion as a Secreted Agent From Car T Cells to Disrupt the Vip-mediated Immunosuppression Within the Pdac Tme, Thereby Enhancing T Cell Functionality and Persistence, Remodeling the Pdac Tme, and Facilitating the Eradication of Pdac Cells. the Proposed “fast-track” Sbir Research and Develop Plan Is Divided Into Two Phases: Phase 1 Aims to Develop and Validate ANT308FC for Secretion by Car T Cells (aim 1) and to Identify the Form of Vipr Antagonism That Exhibits the Most Potent Anti-tumor Effects in Pdac Models (aim 2). a Go/no- Go Decision Based on the in Vivo Efficacy of ANT308 Variants Will Determine the Progression to Phase 2. Phase 2 Is Focused on Evaluating the Toxicity and Biodistribution (aim 3), and Mechanism of Action of the Selected Car/vipra T Cells (aim 4), Alongside Preparing for Ind Submission (aim 5). Our Aims Are Rooted in Solid Preliminary Data and Leverage a Clinically Validated Car Target (MUC16CD), Positioning This Work at the Forefront of Translational Research for Pdac. This Project Stands to Significantly Impact the Treatment Landscape for Pdac by Providing a Novel, Efficacious Therapy Option. the Successful Development and Clinical Translation of Car/vipra T Cells Could Not Only Revolutionize Pdac Treatment But Also Serve as a Platform Technology Applicable to a Broad Range of Cancers, Underscoring the Potential of Car T Cell Therapies in Solid Tumors. Impact: Cambium Oncology's Endeavor Into Commercialization of Car T Cells That Secrete a Vip Receptor Antagonist Is Aligned With the Company’s Core Competency in Developing Novel Immune-oncology Drugs and Addresses the Pressing Need for Innovative, Effective Treatments for Pdac. Results From the Proposed Sbir Can Dramatically Improve Patient Outcomes in This High-mortality Cancer.