Cartesian Therapeutics, Inc. announced positive topline results from its Phase 2b trial of Descartes-08 in patients with generalized myasthenia gravis (MG). Descartes-08, Cartesian?s lead product candidate, is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) directed against the B cell maturation antigen (BCMA). It is designed to be administered as an outpatient treatment without the need for lymphodepleting chemotherapy required to achieve activity with conventional CAR-T cell therapies.

Descartes-08 was previously granted Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of MG. Trial Overview and Topline Results: In the Phase 2b double-blind, placebo-controlled, crossover trial, a total of 36 heavily pre-treated, highly symptomatic patients with MG were randomized 1:1 to receive either Descartes-08 or placebo administered as six weekly outpatient infusions without preconditioning chemotherapy. At the conclusion of the trial?s Month 3 blinded follow-up assessment, patients receiving placebo were eligible to cross over to Descartes-08 treatment.

The primary efficacy endpoint assessed the proportion of patients with a reduction of five points or more in the MG Composite (MGC) score, a 10-item, 60-point weighted instrument composed of selected components of other validated scales to measure MG severity and impact. Whereas a reduction of three points or more is generally regarded as clinically meaningful, the more stringent endpoint of five points was selected based on clinical responses observed in an earlier study with Descartes-08 in MG. Secondary endpoints assessed safety and tolerability and other validated MG severity scales, including Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and MG Quality of Life Revised Scale (MG-QoL-15R).

The pre-specified primary efficacy dataset (n=26) consisted of a modified intent-to-treat (mITT) population of all subjects enrolled at academic medical centers who received at least one dose of Descartes-08 (n=14) or placebo (n=12) and completed at least one post-baseline MGC score follow-up assessment. The safety dataset comprised all subjects who received at least one dose of Descartes-08 (n=19) or placebo (n=17). Primary Endpoint The trial achieved its primary endpoint with statistical significance in the pre-specified mITT efficacy population, with 71% (10/14) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 25% (3/12) of patients treated with placebo (p=0.018).

In addition, the trial also achieved its primary endpoint with statistical significance in the per-protocol population, with 69% (11/16) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 33% (5/15) of patients treated with placebo (p=0.048). Secondary Endpoints Consistent with previously reported results from the Phase 2a open-label portion of the trial, Descartes-08 responders experienced deep improvements across the MG severity scales at Month 3 (average MG-ADL = -5.6; MGC= -8.3; QMG = -5.0; QoL-15r = -7.9). The improvements seen at Month 3 persisted or further improved in patients evaluated at their Month 4 (n=5) and Month 6 (n=3) follow-up visits, as of the June 19, 2024 data cutoff date.

Safety Results Descartes-08 continues to demonstrate a favorable safety profile supporting outpatient administration without the need for lymphodepleting chemotherapy. Consistent with findings from the Phase 2a open-label portion of the trial, Descartes-08 was observed to be well tolerated, and adverse events were transient and mostly mild. Notably, there were no cases of cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome.

Updated Phase 2a Open-Label Trial Results: Cartesian also announced positive updated results from two patients enrolled in the Phase 2a open-label portion of the trial. Both retreated patients experienced rapid improvement in clinical scores and maintained minimal symptom expression for up to one year after receiving a second treatment cycle. The time course and magnitude of treatment response upon retreatment were similar to those seen when the patients were first treated.

Four of the seven patients from the Phase 2a portion of the trial maintained clinically meaningful responses for at least one year following initial dosing. The Company previously announced positive long-term follow up data from the Phase 2a trial in which Descartes-08 was administered in an outpatient setting without preconditioning chemotherapy. Durable depletion of autoantibodies and clinically meaningful improvements in MG severity scores were observed at the one-year follow-up period.

The data were subsequently featured during an oral session at the American Society of Gene and Cell Therapy 27th Annual Meeting in May 2024.