Cabaletta's CAR-T Therapy Shows Promise in Autoimmune Diseases, Paving Way for Registrational Trials

Cabaletta Bio's CD19-CAR T cell therapy, resecabtagene autoleucel (rese-cel), has demonstrated significant benefits for patients with lupus and dermatomyositis, according to updated phase 1/2 data presented at the American Association for the Advancement of Science annual meeting in Boston. The therapy, previously known as CABA-201, has shown robust efficacy without the need for steroids or immunosuppressants, potentially offering a new treatment paradigm for these challenging autoimmune conditions.

Promising Results Across Multiple Indications

The RESET program, which encompasses six trials across various autoimmune indications, has now dosed 10 patients with at least one month of follow-up. In systemic lupus erythematosus (SLE), three out of four patients in the non-renal cohort achieved remission, while the first patient with lupus nephritis (LN) achieved a complete renal response. Notably, all six SLE and LN patients were able to discontinue immunosuppressants and steroids.

In dermatomyositis (DM), the first patient treated maintained a major total improvement score three months post-infusion and is currently undergoing steroid tapering while remaining immunosuppressant-free. The therapy also showed encouraging results in systemic sclerosis (SSc), with the first patient demonstrating clinically meaningful skin improvements and enhanced lung function after discontinuing all disease-specific therapies.

Safety Profile and Expansion of Clinical Program

Rese-cel has exhibited a favorable safety profile, with 90% of patients experiencing either no cytokine release syndrome (CRS) or only grade 1 CRS. Only one patient reported immune effector cell-associated neurotoxicity syndrome. These safety data, combined with the efficacy results, have bolstered confidence in the therapy's potential.

As of February 13, 2025, Cabaletta has enrolled a total of 26 patients across the RESET program, which includes trials in immune-mediated necrotizing myopathy (IMNM), generalized myasthenia gravis, multiple sclerosis, and pemphigus vulgaris (PV). The company plans to share initial data from the PV trial later this year.

Regulatory Pathway and Future Outlook

The promising results in SLE/LN and DM have positioned Cabaletta to engage in discussions with the FDA regarding registrational trial designs. Both indications have already received fast-track designation from the agency, potentially accelerating the development timeline.

Dr. David J. Chang, Cabaletta's Chief Medical Officer, stated, "We plan to meet with the FDA to align on registrational trial designs in the first half of 2025." This strategic move could expedite the therapy's path to market, with William Blair analysts suggesting that rese-cel "could rapidly advance through clinical development for multiple indications and potentially be first-in-class."

As the pharmaceutical industry closely watches the development of this innovative CAR-T therapy for autoimmune diseases, Cabaletta Bio continues to expand its clinical program and gather long-term data on the durability of treatment responses. The coming months will be crucial in determining the full potential of rese-cel and its impact on the treatment landscape for autoimmune disorders.