PHILADELPHIA, PA — Cabaletta Bio, Inc. (Nasdaq: CABA) announced that the Company’s second Investigational New Drug (IND) application for CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, has been cleared by the U.S. Food and Drug Administration (FDA) for a Phase 1/2 study in patients with active idiopathic inflammatory myopathy (IIM, or myositis). The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 for the treatment of six patients with dermatomyositis (DM), six patients with anti-synthetase syndrome (ASyS), and six patients with immune-mediated necrotizing myopathy (IMNM), all in separate parallel cohorts. The initial dose for the trial, 1 x 106 cells/kg, was informed by preclinical data evaluating the binder in CABA-201 and the binder used in the CD19-CAR T construct administered to a patient with myositis in the recent Lancet Rheumatology publication.
“The clearance of our second IND application for CABA-201 within two months of the first IND clearance in SLE allows us to initiate a clinical trial in patients with myositis and underscores the efficiency of our organization along with the value of our experience in the development of cellular therapies for patients with autoimmune diseases,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. “Similar to our Phase 1/2 trial design in SLE, this clinical trial will include patients with several different subtypes of myositis where B cells may be involved in disease pathology. With an experienced team well-versed in conducting autoimmune-focused cell therapy trials, and a product candidate specifically engineered for patients with autoimmune diseases, we look forward to evaluating the potential for CABA-201 to change the treatment paradigm for patients with autoimmune diseases.”
Myositis refers to a group of autoimmune diseases characterized by inflammation and muscle weakness. In some cases, myositis may also affect other organs and systems in the body, such as the lungs, heart, or skin. Myositis is classified into several subtypes based on the underlying immune mechanisms and clinical characteristics. Although the pathogenesis of myositis is not well understood, there are several subtypes thought to be driven by B cells, including dermatomyositis (DM), anti-synthetase syndrome (ASyS) and immune-mediated necrotizing myopathy (IMNM). These three subtypes impact approximately 66,000 patients in the US alone, and typically affect middle-aged individuals, particularly women. All three subtypes can lead to severe functional impairment and may be life-threatening. Current treatment typically involves medications to suppress the immune system and/or chronic intensive therapies such as intravenous immunoglobulin, or IVIg. Despite these therapies, a significant portion of myositis patients have disease that remains refractory to existing medications.
The Phase 1/2 clinical trial will be an open-label study of CABA-201 in subjects with active myositis, including the subtypes of DM, ASyS and IMNM. Subjects will receive a one-time infusion of CABA-201 at a dose of 1.0 x 106 cells/kg, preceded by a standard preconditioning regimen of fludarabine and cyclophosphamide. Key inclusion criteria include patients between ages 18 to 65 (inclusive), evidence of active disease and disease activity despite prior or current treatment with standard of care treatments. Key exclusion criteria include cancer-associated myositis, significant lung or cardiac impairment, treatment with a B cell depleting agent within approximately six months or treatment with a biologic agent within approximately three months. As the second trial within Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy, this study is intended to evaluate the potential ability of CABA-201 to transiently, but fully, eliminate B cells, enabling durable remissions via a “reset” of the immune system.
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