Cabaletta Bio’s CAR-T CABA-201 Shows Safety for First Patients Dosed in Myositis and Lupus Trials


The data comes from the phase 1/2 RESET-Myositis clinical trial (NCT06154252) and the phase 1/2 RESET-SLE clinical trial (NCT06121297).

Cabaletta Bio’s CABA-201, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy intended to treat various indications, has demonstrated safety in initial data from the first patients dosed in separate clinical trials for active idiopathic inflammatory myopathy (IIM), also referred to as myositis, and systemic lupus erythematosus (SLE) and lupus nephritis (LN).1

The data comes from the phase 1/2 RESET-Myositis clinical trial (NCT06154252) and the phase 1/2 RESET-SLE clinical trial (NCT06121297). The first patients dosed in each trial have completed their 28-day dose-limiting toxicity observation window after receiving the CAR-T, with neither patient showing evidence of any grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

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). Cabaletta Bio expects to report initial clinical data from these 2 trials in the second half of this year.

Cabaletta also announced that it will be incorporating use of CABA-201 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 (PV). CABA-201 will be assessed as a monotherapy for PV in this substudy.

“With no CRS or ICANS of any grade observed in either of the first patients from the RESET-Myositis and RESET-SLE trials, we look forward to presenting initial translational and clinical data from both patients during a satellite symposium at the EULAR 2024 Congress on June 14th,” Steven Nichtberger, MD, the chief executive officer and cofounder of Cabaletta, said in a statement.1 “In addition to implementing our development path for CABA-201, we have made substantial progress on 2 innovations designed to optimize the patient and physician experience. First, we are evaluating CABA-201 without preconditioning through the incorporation of the RESET-PV substudy within the ongoing DesCAARTes trial in patients with PV, expanding CABA-201 development into dermatology. Second, we demonstrated the potential to eliminate the need for apheresis by using a blood draw to obtain the starting material for the CABA-201 manufacturing process as presented at the ASGCT meeting. We are evaluating the opportunity to incorporate an apheresis-free process into our ongoing CABA-201 clinical program. By executing on our CABA-201 development strategy and integrating these types of innovations, we believe that we are well positioned to deliver on the full potential of the targeted cell therapies that we are developing to provide durable, drug-free remissions for patients with a broad range of autoimmune diseases.”

Long-term, 2-year data from a case series involving 15 total patients treated with single infusion of CD19 CAR T-cells recently published in the New England Journal of Medicine suggest that CAR-T is a feasible, safe, and efficacious approach to treating autoimmune diseases like SLE and IIM.2,3 Led by a group of investigators based in Germany headed by Georg Schett, MD, the vice president of research and a professor of internal medicine at Friedrich-Alexander University Erlangen-Nürnberg, the series included 8 patients with severe SLE, 3 patients with IIM, and 4 patients with SSc.

“Despite differences in disease entities and previous treatments, the dynamics of CAR T-cell expansion and of B-cell ablation were highly consistent among patients. CD19 CAR T-cell therapy was effective independent of previous B-cell targeting by monoclonal antibodies,” Schett and colleagues wrote, adding that because of the lack of approved monoclonal antibodies targeting B cells for these 3 autoimmune diseases, they did not require participating patients to have prior exposure to these therapies.2 “It is notable that all the patients could successfully stop their immunosuppressive medication without having relapses or worsening of their disease,” they noted.

1. Cabaletta Bio reports first quarter 2024 financial results and provides business update. News release. Cabaletta Bio, Inc. May 15, 2024. Accessed May 24, 2024.
2. Fabian M, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up. N Engl J Med. 2024;390(8):687-700. doi:10.1056/NEJMoa2308917
3. Isaacs JD. CAR T Cells — A New Horizon for Autoimmunity? N Engl J Med. 2024;390(8):758-759. doi:10.1056/NEJMe240020
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