Cabaletta Bio's novel CAR-T cell therapy, resecabtagene autoleucel (rese-cel), is demonstrating increasingly positive results across multiple autoimmune conditions, offering new hope for patients with treatment-resistant diseases.
The latest clinical data, presented at the 2025 American Association for the Advancement of Science meeting in Boston, reveals compelling efficacy across systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, and systemic sclerosis patients.
Breakthrough Results Across Multiple Indications
In a significant development for lupus treatment, three out of four non-renal SLE patients achieved DORIS remission, while the first lupus nephritis patient reached complete renal response. Notably, all patients successfully discontinued immunosuppressants and steroids during follow-up.
The first dermatomyositis patient maintained a major total improvement score (TIS) at three months post-infusion without requiring additional medications. Meanwhile, immune-mediated necrotizing myopathy patients showed gradual improvement, suggesting varying response patterns among myositis subtypes.
Robust Safety Profile
The safety data from the first 10 treated patients continues to support a favorable risk-benefit ratio. Nine out of ten patients experienced either no cytokine release syndrome (CRS) or only Grade 1 CRS manifesting as fever. Similarly, 90% of patients showed no signs of immune effector cell-associated neurotoxicity syndrome (ICANS).
Mechanism of Action and B Cell Dynamics
Dr. David J. Chang, Chief Medical Officer of Cabaletta, explained the treatment's mechanism: "Rese-cel demonstrates consistent deep B cell depletion within the first month of infusion, with B cell repopulation typically beginning around two months post-treatment, showing a transitional naïve phenotype."
A landmark lymph node biopsy in a systemic sclerosis patient confirmed the elimination of tissue-resident B cells, validating the therapy's systemic effectiveness.
Expanding Clinical Program
The RESET clinical development program has gained significant momentum, with 50 active clinical sites across the United States and Europe. As of February 13, 2025, 26 patients have been enrolled across various trials, with enrollment averaging one patient per week since November.
"These results underscore rese-cel's potential to provide compelling clinical responses without the need for ongoing immunosuppression," noted Dr. Chang. "We believe this therapy could transform the lives of patients with autoimmune diseases."
Trial Design and Future Plans
The RESET program encompasses six Phase 1/2 clinical trials across rheumatology, neurology, and dermatology. Most cohorts receive a weight-based single infusion of rese-cel following fludarabine and cyclophosphamide preconditioning, except for the RESET-PV trial, which evaluates rese-cel without preconditioning.
Cabaletta Bio plans to meet with the FDA in the first half of 2025 to discuss registrational trial designs, incorporating these promising results into their regulatory strategy.
