12-month efficacy and safety data announced from the phase IIb trial of Descartes-08 in participants with generalized myasthenia gravis (MG).- Cartesian Therapeutics, Inc

Cartesian Therapeutics, Inc.  announced 12-month efficacy and safety data from the Phase IIb trial of Descartes-08 in participants with generalized myasthenia gravis (MG). Participants dosed with a single six-week course of treatment of Descartes-08 were observed to continue to experience a sustained benefit in symptoms of MG at the 12-month assessment. The data will be discussed by management at the 24th Annual Needham Virtual Healthcare Conference, April 8, 2025, and presented tomorrow, April 9, 2025, by Tuan Vu, M.D., Professor of Neurology at the University of South Florida Morsani College of Medicine, at the 2025 American Academy of Neurology Annual Meeting being held in San Diego.

Descartes-08, Cartesian’s lead cell therapy candidate, is an autologous engineered chimeric antigen receptor T-cell therapy (CAR-T) product candidate targeting B-cell maturation antigen (BCMA). Descartes-08 is designed to be administered without preconditioning chemotherapy in an outpatient setting and does not use integrating vectors.

12-Month Phase IIb Trial Results

In the Phase IIb double-blind, placebo-controlled, crossover trial, a total of 36 heavily pretreated, highly symptomatic participants with MG were randomized 1:1 to receive either Descartes-08 or placebo administered as six weekly outpatient infusions without preconditioning chemotherapy. As previously announced, the trial met its primary endpoint and demonstrated a safety profile supporting outpatient administration of Descartes-08. In December 2024, the Company reported updated efficacy and safety data from the trial in which deepening responses were observed over time and some participants were observed to have durable responses through to Month 12. The primary efficacy dataset for the follow-up portion of the trial 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 and completed at least one post-Month 3 MG Activities of Daily Living (MG-ADL) score follow-up assessment.

As of a March 31, 2025 cutoff date, 12 out of 15 participants who received Descartes-08 in the primary efficacy dataset completed their Month 12 follow-up assessments. Three participants, two of whom were MG Composite (MGC) responders at Month 3, were lost to follow-up after their Month 3 assessments.

12-Month Efficacy Results;

• Deep and sustained responses observed through Month 12 (n=12).
  • i. Participants treated with Descartes-08 were observed to have deep responses following initial treatment and sustained symptom improvement, with an average MG-ADL reduction of 5.5 (±1.1) at Month 4 and 4.8 (±1.4) at Month 12.
  • ii. Participants treated with Descartes-08 were observed to have an average Quantitative Myasthenia Gravis Score (QMG) reduction of 4.8 (±1.7) points at Month 4, which deepened through Month 12 (6.0±2.1).
  • iii. 3% (4/12) of participants achieved minimum symptom expression (MSE), defined as an MG-ADL score of 0 or 1, at Month 6, all of whom maintained MSE through Month 12.
  • iv. 83% (10/12) of evaluable participants maintained a clinically meaningful response through Month 12. Clinically meaningful response is defined as a reduction in MG-ADL score of at least 2 points.
• Deepest and most compelling sustained responses observed in participants without prior biologic therapies (n=7).
  • i. The subset of participants who did not have exposure to prior biologic therapies, including complement or neonatal fragment crystallizable receptor (FcRn) inhibitors, were observed to exhibit a deepening of responses throughout the year, with an average MG-ADL reduction of 6.6 (±1.5) at Month 4 and 7.1 (±1.9) at Month 12.
  • ii. The participants treated with Descartes-08 without exposure to prior biologic therapies were observed to have an average QMG reduction of 5.9 (±2.4) points at Month 4, which deepened through Month 12 (9.4±2.6).
  • iii. 57% (4/7) of these participants were observed to achieve MSE at Month 6 which was maintained through Month 12.
  • iv. 100% (7/7) of these participants were observed to maintain at least a clinically meaningful response through Month 12.

Safety;

• Well-tolerated safety profile supports outpatient administration without the need for lymphodepleting chemotherapy. Consistent with previously reported data, Descartes-08 was observed to be well-tolerated across the safety dataset through Month 12 (n=12), and adverse events were transient and mostly mild, with no new adverse events reported in the 12-month follow-up data. Notably, there were no cases of cytokine release syndrome (CRS), and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, treatment with Descartes-08 was not observed to lead to a decrease in vaccine titers for common viruses and was not associated with increased rates of infection or hypogammaglobulinemia.
  • There were no Descartes-08-related adverse events reported in Month 4 through Month 12 follow-up. As previously reported, common side effects through the Month 3 primary endpoint observed in participants who received any dose of Descartes-08 were infusion-related reactions manifesting as fever (60% of participants receiving Descartes-08), chills (60% of participants receiving Descartes-08), headache (55% of participants receiving Descartes-08) and nausea (45% of participants receiving Descartes-08), all of which typically resolved within 24 hours of infusion.
     

"This impressive data highlights the potential of Descartes-08 to serve as an important therapeutic option to deliver deep and sustained reductions in MG-ADL for patients with myasthenia gravis,” said Tuan Vu, M.D., Professor of Neurology at the University of South Florida Morsani College of Medicine, Division Director for Neuromuscular Medicine and EMG and investigator in the Phase 2b trial. “The data in participants who had not received prior biologic therapy is particularly striking as this population is most comparable to the patient populations in trials of standard-of-care biologics. Participants in this subgroup who were randomized to Descartes-08 were observed to experience a profound average 7.1-point reduction in MG-ADL and 57% these patients were observed to maintain MSE out to Month 12. I look forward to following the continued development of Descartes-08 in MG as it moves into the Phase 3 AURORA trial.”

“The remarkable results underscore the potential of utilizing our cell therapy to deliver deep and durable responses in MG patients one year after receiving a single course of therapy in a convenient outpatient setting with no preconditioning chemotherapy,” said Carsten Brunn, Ph.D., President and Chief Executive Officer of Cartesian. “The impressive strength and duration of response shown in the data reinforce our confidence in the potential of Descartes-08 to transform the current treatment landscape in MG, offering patients a safe, flexible, and durable treatment option. We look forward to dosing the first patient in our Phase 3 AURORA trial in the second quarter of this year.”

Descartes-08 was previously granted Regenerative Medicine Advanced Therapy (RMAT) Designation and Orphan Drug Designation by the FDA for the treatment of MG. Cartesian received written agreement from the FDA under the Special Protocol Assessment (SPA) process indicating the overall design of the planned Phase  III AURORA trial of Descartes-08 is acceptable to support a future Biologics License Application in MG, subject to the ultimate outcome of the trial. Cartesian remains on track to commence the Phase 3 AURORA trial of Descartes-08 in MG in the second quarter of 2025.