Cabaletta Bio’s CAR-T CABA-201 Shows Initial Signs of Efficacy in Myositis and Lupus Trials


The data, from the first patients dosed in each trial, also continues to show safety.

Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat various indications, has shown initial signs of efficacy and safety in data from the first patient dosed in the phase 1/2 RESET-Myositis clinical trial (NCT06154252) for active idiopathic inflammatory myopathy (IIM), also referred to as myositis, and the first patient dosed in the the phase 1/2 RESET-SLE clinical trial (NCT06121297) for systemic lupus erythematosus (SLE) and lupus nephritis (LN).1 The data were presented at the European Alliance of Associations for Rheumatology (EULAR) European Congress of Rheumatology 2024 Industry Symposia, held from June 12 to 15 in Vienna, Austria.2

Cabaletta noted that the patient with IIM, who was treated in the immune-mediated necrotizing myopathy (IMNM) cohort in RESET-Myositis, had 3 months of follow-up and the patient with SLE, who was treated in RESET-SLE's nonrenal cohort, had 1 month of follow-up, as of the May 28, 2024, data cutoff for both patients.1 For both patients, within 15 days of treatment B-cell depletion had been observed, and on the 15th day posttreatment CAR T-cell expansion showed its peak magnitude in both patients.

In the patient with IMNM, creatine kinase levels were reduced to 308 at 12 weeks posttreatment, down from 617 at the time of CAR-T administration, constituting a total improvement score of 30. Furthermore, a successful immune system reset was suggested by flow cytometry conducted after B-cell repopulation in this patient, which had occurred at week 8, that showed B-cells with immature and naïve phenotypes. The patient with SLE notably achieved a score of 10 on the systemic lupus erythematosus disease activity index at 4 weeks posttreatment, an improvement from the score of 26 observed at baseline.

In terms of safety, Cabaletta characterized CABA-201 as “generally well-tolerated" in these 2 patients and stated that no serious adverse events had occurred. Furthermore, there no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or infections of any grade reported in the 2 patients. The company noted that early, transient leukopenia was observed in both patients, but that this was an expected outcome of the preconditioning regimen received prior to CABA-201. Overall, the positive safety data continues the promising trend reported in an earlier update from these 2 patients in May 2024.3

“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,” David J. Chang, MD, the chief medical officer of Cabaletta, said in a statement.1 “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.”

The patient with SLE discontinued concomitant disease-specific therapies MMF and HCQ before receiving CABA-201, and is currently on an ongoing 8-week prednisone taper from 10mg daily.2 The patient with IMNM discontinued methotrexate (MTX) before receiving CABA-201 and prednisone on the third day after receiving the CAR-T.

At baseline the patient with IMNM was a 33-year-old man whose disease has lasted about 2 years, with manifestations including muscle weakness and dysphagia.2 His prior disease-specific therapies included MTX, glucocorticoids, intravenous immune globulin, and rituximab. Meanwhile, the patient with SLE was a 26-year-old man whose disease has lasted about 6 years with manifestations including vasculitis, arthritis, alopecia, hematuria, proteinuria (isolated class V LN), and low complement. His prior disease-specific therapies included glucocorticoids, mycophenolate mofetil, hydroxychloroquine, cyclophosphamide, voclosporin, belimumab, and tacrolimus.

In addition to the aforementioned trials, CABA-201 has also received clearance from the FDA for a phase 1/2 clinical trial (RESET-MG; NCT06359041) in generalized myasthenia gravis and phase 1/2 clinical trial (RESET-SSc; NCT06328777) in systemic sclerosis (SSc).3 In May 2024, Cabaletta also announced that it will be incorporating use of CABA-201 as a monotherapy into a substudy (RESET-PV, NCT04422912) within its phase 1 DesCAARTes clinical trial for DSG3-CAART, an autologous Desmoglein 3 chimeric autoantibody receptor T-cell (CAART) therapy being evaluated for pemphigus vulgaris.

“With the RESET-SSc™ and RESET-MG™ trials recently opening for enrollment, an additional cohort evaluating patients with juvenile myositis incorporated into the RESET-Myositis trial, and the momentum provided by the promising early clinical data, we are looking forward to accelerating clinical trial enrollment in the RESET clinical program,” Chang continued.1 “We continue to expect to report initial clinical data from the phase 1/2 RESET-SSc and RESET-MG trials as well as additional data from the RESET-Myositis and RESET-SLE trials in the second half of this year.”

1. Cabaletta Bio reports positive initial clinical data from phase 1/2 RESET-Myositis™ and RESET-SLE™ trials of CABA-201. News release. Cabaletta Bio, Inc. June 14, 2024. Accessed June 20, 2024.
2. June CH, Schett G, Chang DJ. Immune reset: the potential of CAR T cell therapy to transform the treatment of patients with autoimmune disease. Presented at: EULAR European Congress of Rheumatology 2024 Industry Symposia, held from June 12 to 15 in Vienna, Austria.
3. Cabaletta Bio reports first quarter 2024 financial results and provides business update. News release. Cabaletta Bio, Inc. May 15, 2024. Accessed May 24, 2024.
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