Cabaletta Bio, Inc. (Nasdaq: CABA) has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, for the treatment of idiopathic inflammatory myopathies (IIM, or myositis). CABA-201 is being developed as a potential treatment for autoimmune diseases driven by B cells.
RESET-Myositis Trial
Cabaletta Bio is currently advancing four RESET™ (REstoring SElf-Tolerance) Phase 1/2 trials to evaluate CABA-201 across multiple autoimmune conditions, including the Phase 1/2 RESET-Myositis™ trial. The RESET-Myositis™ trial is an open-label study of CABA-201 in subjects with active idiopathic inflammatory myopathy (IIM, or myositis), including subtypes such as dermatomyositis (DM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathy (IMNM). Patients receive a one-time infusion of CABA-201 at a dose of 1 x 106 cells/kg, preceded by a preconditioning regimen of fludarabine and cyclophosphamide.
Key inclusion criteria include patients aged 18 to 65 with evidence of active disease despite prior or current standard of care treatments. Exclusion criteria involve cancer-associated myositis, significant lung or cardiac impairment, or recent treatment with B cell-depleting or biologic agents.
CABA-201: Mechanism and Potential
CABA-201 is designed to deeply and transiently deplete CD19-positive B cells following a single infusion, potentially enabling an "immune system reset" and durable remission off therapy in autoimmune diseases. Cabaletta has received FDA clearance for Investigational New Drug (IND) applications for CABA-201 in multiple autoimmune conditions, including systemic lupus erythematosus (SLE), myositis, systemic sclerosis (SSc), and generalized myasthenia gravis (gMG). The company is conducting four Phase 1/2 clinical trials with a total of nine cohorts, employing a parallel cohort design and a starting dose of 1 x 106 cells/kg without dose escalation.
Myositis: An Unmet Need
Myositis encompasses a group of autoimmune diseases characterized by inflammation and muscle weakness, potentially affecting other organs such as the lungs, heart, or skin. Subtypes like dermatomyositis (DM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathy (IMNM) are thought to be driven by B cells. These subtypes impact approximately 66,000 patients in the US, predominantly middle-aged women. These conditions can lead to severe functional impairment and may be life-threatening.
Current treatments typically involve immunosuppressants and intensive therapies like intravenous immunoglobulin (IVIg). However, a significant portion of myositis patients exhibit disease refractory to existing medications, underscoring the need for innovative therapeutic approaches.
"Myositis, believed to be driven by B cells, is a severe and potentially fatal autoimmune disease for which no curative therapy exists," said David J. Chang, M.D., Chief Medical Officer of Cabaletta. "Current treatment options provide modest efficacy, with a significant portion of diagnosed patients having an inadequate response to treatment, thus, there is a clear need for innovative medicines that can meaningfully change the treatment paradigm."
Orphan Drug Designation Benefits
The FDA grants Orphan Drug Designation to drugs or biologics intended to treat rare diseases or conditions affecting fewer than 200,000 individuals in the United States. This designation qualifies Cabaletta for incentives, including partial tax credits for clinical trial expenditures, waived user fees, and potential eligibility for seven years of marketing exclusivity.
