Cartesian Therapeutics Reports Positive Phase 2b Results for Descartes-08 in Myasthenia Gravis and Previews Phase 3 Trial Design

Cartesian Therapeutics, Inc., a clinical-stage biotechnology firm specializing in mRNA cell therapy for autoimmune diseases, recently shared new efficacy and safety data from its Phase 2b trial of Descartes-08, aimed at treating generalized myasthenia gravis (MG). Additionally, the company outlined plans for its upcoming Phase 3 AURORA trial. These revelations were made at the 2nd Annual Cell Therapy for Autoimmune Disease Summit in Philadelphia.

Descartes-08 is Cartesian's foremost mRNA cell therapy candidate. It's an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) product that targets B-cell maturation antigen (BCMA). The treatment is notable for not requiring preconditioning chemotherapy and avoiding integrating vectors. The U.S. Food and Drug Administration (FDA) has previously granted Descartes-08 both Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation for MG treatment.

Dr. James F. Howard Jr., Professor of Neurology at the University of North Carolina School of Medicine and an investigator in the Phase 2b trial, emphasized the need for new treatment options for MG, a rare and incurable autoimmune disorder. He highlighted that current treatments often involve broad immunosuppression with limited efficacy. The updated trial results suggested sustained, significant responses lasting months after treatment, even in heavily pre-treated participants and those without prior exposure to biologic drugs.

Carsten Brunn, President and CEO of Cartesian, pointed out that the new data corroborate the potential of Descartes-08 for providing substantial and lasting improvements in MG patients without the need for preconditioning chemotherapy. This supports the design of the Phase 3 trial, which is set to begin in the first half of 2025.

The Phase 3 AURORA trial will be a randomized, double-blind, placebo-controlled study. It will compare Descartes-08 with a placebo in about 100 participants with acetylcholine receptor autoantibody-positive MG. The primary endpoint will be the proportion of Descartes-08-treated participants showing an improvement of at least three points in the MG Activities of Daily Living (MG-ADL) score at Month 4 compared to the placebo group. Additional endpoints will evaluate safety, tolerability, and improvements in other MG severity scales.

In the Phase 2b trial, 36 participants were randomized to receive either Descartes-08 or a placebo in six weekly outpatient infusions. The trial met its primary endpoint and showed a safety profile that supports outpatient administration. The primary efficacy dataset included participants who completed follow-up assessments after receiving at least one dose of Descartes-08. On average, these participants experienced a 5.5-point reduction in MG-ADL at Month 4, with deeper responses in those without prior biologic therapy exposure. By Month 6, 33% of all participants and 57% of participants without prior biologic therapy had minimal symptom expression. The effects were durable through Month 12 for most participants.

Descartes-08 was well-tolerated throughout the trial, with adverse events being mostly mild and transient. Importantly, there were no cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). There was also no observed decrease in vaccine titers for common viruses, nor an increase in infection rates or hypogammaglobulinemia.

The company also reported positive results from the Phase 2a open-label trial, where participants who were retreated showed rapid improvement and sustained minimal symptom expression up to a year after a second treatment cycle.

In conclusion, the updated data from the Phase 2b trial of Descartes-08 for MG are promising, showing significant and durable responses without preconditioning chemotherapy. Cartesian Therapeutics is preparing for the Phase 3 AURORA trial to further confirm these findings and potentially provide a new, effective treatment option for MG patients.