Cartesian Therapeutics’ Myasthenia Gravis mRNA CAR-T Descartes-08 Garners FDA RMAT Designation

Cartesian Therapeutics’ Descartes-08, an investigational autologous mRNA-engineered chimeric antigen receptor T-cell therapy (CAR-T) therapy intended for the treatment of autoimmune diseases including myasthenia gravis (MG), has received regenerative medicine advanced therapy (RMAT) designation from the FDA for MG.¹

Descartes-08 is comprised of patients’ own T-cells that have been modified ex-vivo with RNA to target B-Cell Maturation Antigen (BCMA).² The use of RNA engineering is intended to avoid risks of genomic integration associated with DNA-based CAR-T therapies and to allow for control of pharmacokinetics.

The CAR-T product is currently being evaluated in the phase 2b portion of a clinical trial (NCT04146051) for MG. The first patient in this portion was dosed in January 2023.

“Receipt of RMAT designation underscores our belief that Descartes-08, our potential first-in-class mRNA CAR-T cell therapy, could serve as a meaningful addition to the MG treatment landscape,” Carsten Brunn, PhD, the president and chief executive officer of Cartesian Therapeutics, said in a statement.¹ “We look forward to working closely with the FDA to efficiently advance the development of Descartes-08 for this underserved population. Looking ahead, we remain on track to report topline data from our ongoing phase 2b study in patients with MG in the middle of this year.”

Cartesian reported long-term follow-up results from the earlier 2a portion of the aforementioned trial in January 2024.³ Among 7 patients in the phase 2a portion of the study who were treated with a single infusion of Descartes-08 each week for 6 weeks, all 7 continued to show marked and long-lasting clinical improvements across the MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised instruments at 9 months after beginning treatment. The 7 patients underwent assessment on the 4 aforementioned instruments again at 12 months of follow-up and 5 maintained clinically meaningful improvement. The company noted that the 2 patients who did not maintain clinical improvement were eligible for retreatment, and 1 of these 2 patients chose to undergo retreatment. This patient later showed minimal symptom expression and an ongoing improvement in clinical scores at 6 months after starting retreatment.

“The 12-month data build on the positive data reported earlier this year in The Lancet Neurology, underscoring the potential of Descartes-08 to drive deep and durable responses in patients with MG,” Milos Miljkovic, MD, the chief medical officer of Cartesian Therapeutics, said in a January 2024 statement.³ “Notably, most patients maintained robust, clinically meaningful improvements across all 4 standard MG severity scores approximately 10 months after the last infusion. In addition, the lasting reductions in autoantibody titers are consistent with the observed clinical responses and the proposed mechanism of action for Descartes-08, supporting the deep and long-lasting effects observed in the study. As the first clinical trial using mRNA CAR-T to treat autoimmunity, the study also highlights the potential of our approach to expand the capabilities of cell therapy to address a variety of autoimmune diseases.”

In addition to MG, Cartesian Therapeutics is also developing Descartes-08 for the treatment of systemic lupus erythematosus (SLE).^1,4 The company is planning to carry out a phase 2 clinical trial in SLE under an allowed investigational new drug application, with dosing of the first patient expected to take place within the second quarter of this year. Descartes-08 will be administered in the trial in an outpatient setting without the use of a chemotherapy regimen for preconditioning. In addition to Descartes-08, Cartesian is also developing Descartes-15, a next-generation autologous BCMA-directed mRNA CAR-T therapy intended to treat multiple myeloma. The company notes that Descartes-15 may eventually be evaluated for use in autoimmune diseases as well.

REFERENCES
1. Cartesian Therapeutics receives FDA regenerative medicine advanced therapy (RMAT) designation for Descartes-08 for the treatment of myasthenia gravis. News release. Cartesian Therapeutics, Inc. May 22, 2024. Accessed May 24, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-receives-fda-regenerative-medicine
2. Cartesian Therapeutics announces dosing of first participant in a phase 2b randomized clinical trial for generalized myasthenia gravis. News release. Cartesian Therapeutics. January 31, 2023. Accessed May 24, 2024. https://www.cartesiantherapeutics.com/2023/01/31/cartesian-therapeutics-announces-dosing-of-first-participant-in-a-phase-2b-randomized-clinical-trial/
3. Cartesian Therapeutics announces positive long-term follow-up data from phase 2a study of lead mRNA cell therapy candidate Descartes-08 in patients with myasthenia gravis. News release. Cartesian Therapeutics, Inc. January 8, 2024. Accessed May 24, 2024. https://www.cartesiantherapeutics.com/2024/01/08/cartesian-therapeutics-announces-positive-long-term-follow-up-data-from-phase-2a-study-of-lead-mrna-cell-therapy-candidate-descartes-08-in-patients-with-myasthenia-gravis/
4. Cartesian Therapeutics reports first quarter 2024 financial results and provides business update. News release. Cartesian Therapeutics, Inc. May 22, 2024. Accessed May 24, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-reports-first-quarter-2024-financial