Potential treatment for patients with severe autoimmune diseases

Expanding Our Impact in Autoimmune Disease

Our newly designed product candidate, CABA-201, is a fully human CD19 chimeric antigen receptor (CAR) containing a 4-1BB co-stimulatory domain. As part of our Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) approach within our CABA™ platform, CABA-201 represents an opportunity to potentially address a broad range of autoimmune diseases.

CABA-201 pipeline

1Being evaluated in a single clinical trial for CABA-201.

Potential of CD19-CAR T Cell Therapy

Academic clinical data1 published in Nature Medicine in September 2022 demonstrate that a CD19-CAR T cell therapy with a 4-1BB co-stimulatory domain following lymphodepletion with fludarabine and cyclophosphamide induced a clinical remission in five out of five patients with severe, refractory SLE, with up to 17 months of follow up. The safety data demonstrated low risk of cytokine release syndrome (CRS), with grade 1 CRS observed in 3 out of 5 patients, and no observation of neurotoxicity (immune effector cell-associated neurotoxicity syndrome, or ICANS), of any grade. New B cells repopulated within 2-5 months of CAR T infusion in all patients, with no evidence of recurrence of disease or autoantibodies following repopulation. A similar efficacy and safety profile was observed in a case report of a patient with anti-synthetase syndrome, a subtype of myositis, as published The Lancet in February 20232.

Our licensed fully human CD19 binder has been clinically evaluated in a dual-CD19xCD22 CAR T under development for B cell leukemia and lymphoma in an investigator-initiated trial in China, where it has shown promising tolerability in ~20 patients. Developed through screening of 100 billion antibody fragments, our CD19 binder was identified and evaluated using FMC63 – the CD19 binder employed in the Nature Medicine and The Lancet studies1,2 – as a benchmark. Compared to FMC63, our binder exhibits comparable biologic activity, with lower levels of cytokine secretion, which may decrease risk of cytokine release syndrome.3 Given its similarity to the CD19-CAR T construct employed in the trial conducted by Professor Georg Schett and his colleagues, including incorporation of a 4-1BB co-stimulatory domain, CABA-201 may have the potential to transform the treatment of autoimmune diseases.

1 Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
2 Müller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023).
3 Dai, Zhenyu, et al. "Development and functional characterization of novel fully human anti‐CD19 chimeric antigen receptors for T‐cell therapy." Journal of Cellular Physiology 236.8 (2021): 5832-5847.

About Systemic Lupus Erythematosus

SLE is a chronic, potentially severe, autoimmune disease, most commonly impacting young women between the ages of 15 and 40 with higher frequency and more severity in people of color, where the immune system attacks healthy tissue throughout the body. It is characterized by abnormal B cell function and autoantibody production resulting in a range of clinical manifestations including end organ damage and an increased risk of death. It affects an estimated 160,000-320,000 patients in the U.S. in total. LN is the most common end-organ manifestation of SLE, affecting approximately 40% of SLE patients. Among these patients, the risk of end-stage renal disease is approximately 17% and the risk of death is approximately 12%, each within 10 years of diagnosis.

CABA-201 is designed to be given as a one-time infusion, with the potential to transiently, but fully, eliminate B cells, thus enabling an “immune system reset” and durable remission in patients with SLE. The Phase 1/2 clinical trial is an open-label dose evaluation study designed to evaluate CABA-201 in SLE subjects with active LN or active SLE without renal involvement. Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to CABA-201 infusion. This represents the first trial that employs Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy.

CABA-201 Development

IND Clearance

Following clearance of the IND, we are preparing to launch the study and to evaluate CABA-201 in patients with SLE. We are also advancing CABA-201 in other autoimmune diseases with high unmet need. Initial clinical data for CABA-201 is anticipated in the first half of 2024.