Cartesian Therapeutics, Inc. announced positive twelve-month follow-up data from its Phase 2a trial of Descartes-08 in patients with generalized myasthenia gravis (MG), a chronic autoimmune disorder that causes disabling muscle weakness and fatigue. The manuscript titled, ?Twelve-Month Follow-Up of Patients With Generalized Myasthenia Gravis Receiving BCMA-Directed mRNA Cell Therapy,? has been submitted for peer-review and can be accessed on the online preprint server, medRxiv.

Descartes-08, Cartesian?s lead mRNA cell therapy candidate and a potential first-in-class mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T), is an autologous anti-B-cell maturation antigen (BCMA) mRNA CAR-T. In contrast to conventional DNA-based CAR T-cell therapies, mRNA CAR-T administration is designed to not require preconditioning chemotherapy and has been observed to have predictable and controllable pharmacokinetics that allow outpatient administration and is designed to avoid the risk of genomic integration and cancer transformation. The Company previously announced positive data from a Phase 1b/2a study of 14 patients with MG who received Descartes-08 in the outpatient setting and without lymphodepletion. In that dataset, Descartes-08 was observed to be safe and well-tolerated and was observed to induce deep and durable responses.

Data reported are headlined by long-term results from all participants who received a once-weekly infusion for six weeks (N=7) during the Phase 2a portion of the study: Descartes-08 was infused in an outpatient setting without lymphodepleting chemotherapy. Throughout the study and long-term follow-up interval, Descartes-08 was well-tolerated, with no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity. At Month 9 follow-up, all participants continued to experience marked and long-lasting clinical improvements across four validated MG disease scoring systems: MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised.

These assessments occurred approximately 7 months after the last Descartes-08 infusion, and no participants received new or increased MG-directed drugs during the study period. At Month 12, five of the seven participants maintained clinically meaningful improvement in the same four scoring systems. These assessments occurred approximately 10 months after the final Descartes-08 infusion. Two participants experienced loss of clinical effect at Month 12 and were eligible for retreatment.

One participant was retreated, and experienced rapid improvement in clinical scores, which was ongoing at Month 6 of follow-up with minimal symptom expression. All three participants with detectable anti-acetylcholine receptor (AChR) antibody levels at baseline experienced marked anti-AChR antibody reductions by Month 6, which deepened further by Month 9, and were maintained at Month 12. Enrollment is ongoing in a Phase 2b randomized, double-blind, placebo-controlled trial (NCT04146051) in patients with MG.

Topline results are expected in mid-2024. Descartes-08 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of MG, and Investigational New Drug (IND) allowance to begin trials in patients with an additional autoimmune disease, lupus.