March Biosciences Inc

Dual-targeting Allogeneic Car T-cells for Universal Therapy of T-cell Malignancies - Abstract Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia (t-all) and T-cell Lymphoma (TCL) Are Aggressive Hematologic Malignancies With Limited Therapeutic Options and 3-YEAR Survival Rates Below 20 Percent. While the Development of Chimeric Antigen Receptor (car)-t Cell Therapies Have Shown Promise in B-cell Cancers, Targeting T-cell Malignancies Has Been Hindered by the Shared Antigen Space Between Healthy and Malignant Cells Leading to Car T Cell Self-targeting and a Heightened Risk of T- Cell Aplasia. CD5 and CD7 Are Key Surface Markers for T-all/tcl, With About 90% of T-cell Malignancies Expressing One or Both Markers. the Autologous CD5.CAR-T and CD7.CAR-T Cell Therapies Developed at Baylor College of Medicine and Licensed to March Biosciences Show Safety, Feasibility, and Signs of Durable Efficacy in Phase 1 Clinical Trials for T-cell Malignancies. However, These Trials Have Faced Manufacturing Challenges in Many Patients and Benefits to Others Have Been Abrogated by Antigenically Heterogenous Tumors. to Overcome These Limitations and Enhance Anti-tumor Activity Against T-cell Cancers, March Biosciences Proposes to Develop Partially- Matched Donor-derived, Dual-specific Car-t Cells (CD5/CD7.CAR-T Cells). These CD5/CD7.CAR-T Cells Are Uniquely Engineered for Fratricide Resistance and Are Produced From Haploidentical, CD45RA-DEPLETED Donor T- Cells (rad-t) to Minimize the Risk of Graft Versus Host Disease Using a Rapid Current Good Manufacturing Practice (CGMP) Compliant Process. Safety and Controllability Will Be Further Augmented by Integrating a Drug-inducible Caspase 9 (IC9) System Allowing Precise in Vivo Control of Car-t Cells Post-infusion. This Project Aims to Develop CD5/CD7.CAR.RAD-T Cells for Highest Activity Against Malignant T-cells With Varying Antigen Expression in Both in Vitro and in Vivo Models, and to Demonstrate Controlled Car-t Cell Elimination by Activating the Caspase 9- Induced Apoptosis. to Streamline Car-t Cell Production and Reduce Costs for Optimal Scalability, March Biosciences Is Optimizing CGMP Process to Accelerate the Manufacturing of CD5/CD7.CAR.RAD-T Cells. by Transitioning to a Rapid, Closed-circuit System, March Biosciences Seeks to Consolidate T-cell Stimulation, Transduction, and Expansion Into a Single Vessel Over 4 Days. the Target Total Production Timeline Is 9 Days Inclusive of Final Release Testing Thus Ensuring a Potent and Rapidly Available Product for Patients With Aggressive Disease. Upon Completion of This Project, March Biosciences Will Have Selected a Lead Candidate and Finalized a Cgmp-ready Process for Manufacturing Dual-targeting Car-ts Enabling Subsequent Clinical Testing in Phase 1/2 Trials in Patients With Refractory and Relapsed T-cell Malignancies.