Early Data Shows CAR T Cell Therapy May Lead to Autoimmune Disease Remission

David J. Chang, MD

Credit: LinkedIn

Early clinical data shows CAR T Cell Therapy may be able to “reset” the body’s immune system, putting patients with an autoimmune disease in remission.¹

Cabaletta designed CABA-201, the CAR T Cell therapy that can deplete CD19-positive B cells after a one-time infusion. As of May 28, 2024, the cut-off date, the success of CABA-201 has come from 2 patients in the trials RESET-Myositits (participants aged 18 – 75 years with active idiopathic inflammatory myopathy (IIM or myositis)) and RESET-systematic lupus erythematosus (SLE) (participants aged 18 – 65 years with SLE and lupus nephritis). Cabaletta Bio presented the initial research on Friday, June 14, 2024, at the 2024 European Congress of Rheumatology (EULAR) in Vienna, Austria.

“We are encouraged by the initial safety, clinical, and translational data from the RESET-Myositis and RESET-SLE trials, which we believe provide important early validation regarding the potential of the selected clinical dose of CABA-201 to enable an immune system reset for patients with autoimmune diseases,” said David J. Chang, MD, chief medical officer at Cabaletta, in a statement.

Before CABA-201, bispecific and antibody-based B cell targeting therapies rarely led to drug-free remission in autoimmune disease.² The hope with the new therapy is to have a “living drug” target resident autoimmune B cell clones, creating an immune tolerance so long-term drug therapy is not needed.1

The primary endpoints of RESET trials are safety and tolerability within 28 days of CABA-201 infusion, and the secondary endpoints include translational assessments and clinical outcomes.¹ In both trials, participants had to discontinue all chronic maintenance therapy or concomitant medications, aside from a planned prednisone taper for the SLE patient. After a preconditioning regimen of fludarabine and cyclophosphamide, participants were evaluated with the same single, weight-based dose of 1 x 106 cells/mg, administered during a 4-day hospital stay.

One patient from the RESET-Myositis trial who had available data at the cut-off date was a 33-year-old male with a 2-year history of immune-mediated necrotizing myopathy, was positive for anti-SRP antibody, and had previous disease-specific therapy such as IVIg, rituximab, methotrexate, and glucocorticoids. He completed 3 months of follow-up.

The other patient with available data came from the RESET-SLE trial. He was a 26-year-old male with a 6-year history of systemic lupus erythematosus, was positive for anti-dsDNA antibody, and had previous disease-specific therapy of cyclophosphamide, voclosporin, belimumab, tacrolimus, mycophenolate mofetil, hydroxychloroquine, and glucocorticoids. He completed 1 month of follow-up.

The team observed complete B cell depletion within 15 days post-infusion with CABA-201 in both patients. Both patients had early, transient leukopenia.

The IMNM patient had week 12 of follow-up had a decline in creatinine kinase from 617 at infusion to 308. They had a clinically meaningful total improvement score of 30. A B cell repopulation was observed in this patient at week 8 with immature, naïve B cell phenotypes. This suggests CABA-201 may potentially reset the immune system.

Furthermore, the SLE patient had an improved systematic lupus erythematosus disease activity index score from 26 at baseline to 10 at week 4 of follow-up.

Neither of those 2 patients experienced serious adverse events throughout the follow-up period. Investigators observed no sign of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and no infections. No participant needed tocilizumab to be administered.

Along with the SLE and myositis trials, investigators have recently opened enrollment for the RESET-SSc and RESET-MG trials. They also plan on adding a cohort evaluating patients with juvenile myositis in the RESET-Myositis trial. Cabaletta also plans on having 4 phase ½ RESET trials assessing CABA-201 within 10 cohorts containing 6 patients in each.

“By demonstrating a potentially well-tolerated safety profile along with initial clinical and translational data consistent with the academic experience of a similar 4-1BB CD19-CAR T construct, we believe CABA-201 may be uniquely positioned to fulfill unmet patient needs across a broad range of autoimmune diseases,” Chang said.

References

1. ^{Cabaletta Bio Reports Positive Initial Clinical Data from Phase 1/2 RESET-Myositis™ and RESET-SLE™ Trials of CABA-201. GlobeNewswire. June 14, 2024. https://www.globenewswire.com/news-release/2024/06/14/2898772/0/en/Cabaletta-Bio-Reports-Positive-Initial-Clinical-Data-from-Phase-1-2-RESET-Myositis-and-RESET-SLE-Trials-of-CABA-201.html. Accessed June 20, 2024.}
2. ^{June, C, Schett, G, Chang, D. Immune Reset: The Potential of Cart T Cell Therapy to Transform the Treatment of Patients with Autoimmune Disease. Session presented on June 14 at EULAR 2024 in Vienna, Austria.}