FDA Approves CABA-201 IND Application: Cabaletta Bio Advances CAR-T Therapy for Autoimmune Myositis

Cabaletta Bio has reached a significant milestone with the U.S. Food and Drug Administration’s clearance of an Investigational New Drug (IND) application for CABA-201, marking the company’s expansion into treating inflammatory myopathy conditions. The green light came just two months after the company’s initial IND clearance for the same therapeutic candidate in systemic lupus erythematosus (SLE), demonstrating accelerated clinical development momentum.

The CABA-201 Therapeutic Approach

CABA-201 represents an engineered cellular therapy utilizing a 4-1BB-containing fully human CD19-CAR T cell construct designed to target B cells implicated in autoimmune disease pathology. The therapeutic strategy operates on a novel principle: transiently eliminating B cells to enable what the company describes as an “immune system reset,” potentially facilitating durable disease remission through controlled immune reconstitution.

The approach builds on established clinical observations. The initial dosing regimen of 1 x 10^6 cells/kg—selected for the upcoming Phase 1/2 trial—derives from preclinical evaluation and real-world clinical data published in Lancet Rheumatology, where a similarly constructed CD19-CAR T therapy demonstrated clinical activity in a myositis patient.

Clinical Trial Design and Patient Population

The Phase 1/2 study will evaluate CABA-201’s safety and efficacy across three distinct myositis subtypes in an open-label design. The trial structure encompasses separate parallel cohorts: six patients with dermatomyositis (DM), six patients with anti-synthetase syndrome (ASyS), and six patients with immune-mediated necrotizing myopathy (IMNM). These subtypes collectively represent the B cell-driven forms of idiopathic inflammatory myopathy.

All enrolled subjects will receive a single CABA-201 infusion preceded by a standard lymphodepleting preconditioning regimen of fludarabine and cyclophosphamide. Enrollment will target patients aged 18 to 65 with documented active disease resistant to standard-of-care treatments, excluding those with cancer-associated myositis, significant cardiopulmonary compromise, or recent exposure to B cell-depleting or biologic agents.

Myositis: Clinical Burden and Unmet Need

Myositis comprises a spectrum of autoimmune inflammatory muscle disorders with potentially severe systemic manifestations affecting the lungs, heart, and skin. Approximately 66,000 patients in the United States develop these B cell-mediated subtypes, predominantly affecting middle-aged individuals with a female predominance.

Current therapeutic management relies on immunosuppressive medications and intensive interventions such as intravenous immunoglobulin (IVIg). Despite these options, a substantial proportion of patients develop treatment-refractory disease, creating a significant clinical void that cellular immunotherapy may address.

Strategic Expansion Within Cabaletta’s Platform

This myositis program represents the second major application within Cabaletta Bio’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) clinical development strategy. The dual-indication approach—simultaneously advancing CABA-201 in SLE and myositis—leverages the company’s specialized expertise in autoimmune-targeted cell therapy development and demonstrates the versatility of the platform technology across multiple B cell-driven autoimmune conditions.

Beyond CABA-201, Cabaletta Bio’s pipeline includes the CAART (Chimeric Autoantibody Receptor T cells) strategy, encompassing clinical-stage candidates DSG3-CAART for mucosal pemphigus vulgaris and MuSK-CAART for MuSK myasthenia gravis, collectively positioning the company to address a broad spectrum of autoimmune pathologies through engineered cellular therapeutics.