Positive One-Year Results for Descartes-08 mRNA Cell Therapy in MG Patients

Cartesian Therapeutics, a clinical-stage biotechnology firm, has reported promising one-year follow-up results from its Phase 2a trial of Descartes-08, an mRNA cell therapy for patients with generalized myasthenia gravis (MG), a chronic autoimmune disorder characterized by muscle weakness and fatigue. The study, titled “Twelve-Month Follow-Up of Patients With Generalized Myasthenia Gravis Receiving BCMA-Directed mRNA Cell Therapy,” is currently under peer review and available on the medRxiv preprint server.

Descartes-08 is an innovative autologous anti-B-cell maturation antigen (BCMA) mRNA CAR-T therapy, which stands out from traditional DNA-based CAR T-cell treatments. It is designed to be administered without the need for preconditioning chemotherapy, offering predictable and controllable pharmacokinetics suitable for outpatient use. This approach also aims to mitigate the risks associated with genomic integration and cancer transformation.

Milos Miljkovic, M.D., Chief Medical Officer at Cartesian Therapeutics, highlighted the significance of the 12-month data, which corroborate earlier findings published in The Lancet Neurology. The data suggest that Descartes-08 can induce profound and enduring responses in MG patients. Notably, most participants maintained significant improvements across standard MG severity scores about 10 months post-final infusion. The sustained reduction in autoantibody levels aligns with clinical outcomes and the proposed mechanism of Descartes-08, indicating its potential for profound and lasting therapeutic effects.

In the Phase 1b/2a study, Descartes-08 was administered to 14 MG patients in an outpatient setting without lymphodepletion, demonstrating safety and tolerability, as well as inducing deep and durable responses.

The Phase 2a study reported long-term results for participants who received weekly infusions for six weeks. Descartes-08 was well-tolerated throughout the study, with no severe toxicities or adverse effects. At the nine-month follow-up, all participants showed substantial and enduring clinical improvements across four validated MG scoring systems. By the twelve-month mark, five out of seven maintained significant improvements. Two participants who lost clinical effect were eligible for retreatment, with one showing rapid clinical score improvement at the six-month follow-up.

All three participants with detectable anti-acetylcholine receptor (AChR) antibodies at baseline experienced significant reductions by the sixth month, which were further maintained at the twelve-month mark.

Cartesian Therapeutics is currently enrolling participants for a Phase 2b randomized, double-blind, placebo-controlled trial. The company has received Orphan Drug Designation from the U.S. Food and Drug Administration for MG treatment and has been granted Investigational New Drug (IND) allowance to initiate trials for lupus.

Descartes-08 represents a potential breakthrough in mRNA cell therapy for autoimmune diseases, with Cartesian Therapeutics leading the way in this innovative field. The company's clinical-stage pipeline also includes Descartes-15, another autologous anti-BCMA mRNA CAR-T candidate. Cartesian operates a cutting-edge cGMP manufacturing facility in Gaithersburg, Maryland, reinforcing its commitment to advancing mRNA cell therapies.