Cabaletta Bio (CABA) Reports Preclinical Data Supporting PLA2R-CAART as a Potential Precision Therapy for Antigen-Specific B Cell Depletion in PLA2R Membranous Nephropathy

Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for patients with B cell-mediated autoimmune diseases, today announced that data from in vitro studies supporting the early preclinical validation of PLA2R-Chimeric AutoAntibody Receptor T (CAART) cell candidates will be presented at ASN Kidney Week 2021. The data will be presented as an oral abstract by Aimee Payne, M.D., Ph.D., Professor of Dermatology at the University of Pennsylvania’s Perelman School of Medicine and co-chair of the Scientific Advisory Board and co-founder at Cabaletta Bio at the American Society of Nephrology (ASN) Kidney Week 2021 being held virtually from November 4-7, 2021.

“Current therapeutic strategies for PLA2R membranous nephropathy patients include generalized immune suppression, including B cell depletion with rituximab, which often requires repeat treatments and may cause serious infections in certain patients. Building on the platform for CAART product candidates that are more advanced in development, including DSG3-CAART and MuSK-CAART, we aim to develop a highly specific therapy that provides safety, efficacy, and durability for patients suffering from this autoimmune disease,” said Dr. Payne “This initial preclinical data is promising, as it demonstrates the in vitro function of PLA2R-CAART cells against autoantibody-binding epitopes relevant to pathogenic B cells from patients with primary membranous nephropathy, with no evidence of off-target interactions.”

For this study, the Payne Laboratory generated multiple CAARs comprised of the PLA2R epitopes targeted by autoantibodies in PLA2R membranous nephropathy patients, as an extracellular decoy on the surface of T cells. These CAARs were observed to direct specific cytolysis of B cells expressing each of the anti-PLA2R autoantibodies tested. The data suggest that PLA2R-CAAR T cell therapy has the potential to target pathogenic B cells expressing autoantibodies against PLA2R while sparing healthy B cells, which could provide a novel precision therapeutic approach for patients with PLA2R membranous nephropathy. Membrane proteome arrays screened against leading PLA2R CAAR candidates did not identify any off-target interactions.

“These discovery and early preclinical studies conducted by our co-founder Dr. Aimee Payne and colleagues at the University of Pennsylvania are a meaningful step for Cabaletta Bio, as they further support the breadth of the CABA™ platform for patients with B cell-mediated autoimmune diseases and high unmet clinical need,” said Gwendolyn Binder, Ph.D., EVP Science and Technology at Cabaletta Bio. “These data provide the scientific rationale to commit our lead PLA2R-CAART candidate to preclinical development for patients with PLA2R membranous nephropathy.”

PLA2R-CAART is one of seven CAAR T programs that have emerged from the Cabaletta Approach to selective B cell Ablation (CABA™) platform. Cabaletta’s lead product candidate, DSG3-CAART, is currently being evaluated in the DesCAARTes™ Phase 1 clinical trial as a potential treatment for patients with mucosal pemphigus vulgaris (mPV). The lead preclinical product candidate, MuSK-CAART, is designed as a potential treatment for patients with MuSK-associated myasthenia gravis, with an IND submission planned by the end of 2021. Cabaletta has four additional discovery programs derived from the CABA™ platform.

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