Descartes-08

P1, N=32, Terminated, Cartesian Therapeutics | Phase classification: P2 --> P1 | Completed --> Terminated; Phase 1 enrollment completed. Further clinical development terminated

P2, N=13, Terminated, Cartesian Therapeutics | N=30 --> 13 | Recruiting --> Terminated; Sponsor decision

P2, N=30, Recruiting, Cartesian Therapeutics | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Cartesian Therapeutics | Initiation date: Nov 2023 --> Feb 2024

P2, N=30, Recruiting, Cartesian Therapeutics | Trial completion date: Dec 2023 --> Mar 2026 | Trial primary completion date: Dec 2023 --> Mar 2025

In this first study of an rCAR-T therapy in individuals with an autoimmune disease, Descartes-08 appeared to be safe and was well tolerated. Descartes-08 infusions were followed by clinically meaningful decreases on myasthenia gravis severity scales at up to 9 months of follow-up. rCAR-T therapy warrants further investigation as a potential new treatment approach for individuals with myasthenia gravis and other autoimmune diseases.

In the mouse model of aggressive disseminated human myeloma, Descartes-08 induces BCMA CAR-specific myeloma growth inhibition and significantly prolongs host survival (p < 0.0001). These preclinical data, coupled with an ongoing clinical trial of Descartes-08 in relapsed/refractory myeloma (NCT03448978) showing preliminary durable responses and a favorable therapeutic index, have provided the framework for a recently initiated trial of an optimized/humanized version of Descartes-08 (i.e., Descartes-11) in newly diagnosed myeloma patients with residual disease after induction therapy.

Furthermore, Descartes-08 kills MM lines that are both resistant and sensitive to lenalidomide and pomalidomide, and/or MM cells that are grown in the presence of bone marrow stromal cells that clinically support MM survival. In a mouse model of disseminated human MM, Descartes-08 shows CAR-specific suppression of myeloma that is maintained throughout the duration of treatment. Taken together, these results illustrate features of RNA-generated anti-BCMA CAR T cells that promise key clinical advantages, thereby supporting ongoing clinical development of Descartes-08 for treatment of MM (NCT03448978).