Cabaletta Bio, Inc., a U.S. clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted fast track designation to CABA-201.\n\n\n\nCabaletta Bio's CABA-201 is a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, designed to deplete CD19-positive B cells and improve disease activity in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN). \n\n\n\nCabaletta Bio has been cleared to initiate a phase 1/2 clinical trial of CABA-201 for the treatment of six SLE patients with active LN, and in a separate parallel cohort, six patients with active SLE without renal involvement, with an initial dose equivalent to the dose used in the September 2022 Nature Medicine publication of a 4-1BB containing CD19-CAR T construct evaluated in patients with SLE.\n\n\n\n“Despite advances over the last few decades, treatment options for SLE remain inadequate. There are currently no curative options available that achieve durable disease remission. Existing therapies typically result in general immunosuppression, require chronic administration, and are often administered in conjunction with steroids and other immunosuppressive medications to reduce disease burden, which can leave patients with continued disease activity, treatment-associated side effects, and impaired quality of life,” said David J. Chang, chief medical officer of Cabaletta Bio. \n\n\n\n“We believe the FDA’s decision to grant fast track designation for CABA-201 underscores the unmet need for a treatment that has the potential to provide deep and durable responses for people living with lupus and potentially other autoimmune diseases where B cells contribute to disease. We look forward to initiating the phase 1/2 trial for CABA-201 and further evaluating its therapeutic potential for patients in need.”\n\n\n\nCABA-201 is designed to be given as a one-time infusion, to evaluate its potential to transiently, but fully, eliminate B cells, enabling an “immune system reset” with durable remission in patients with SLE. The phase 1/2 clinical trial is an open-label study designed to evaluate CABA-201 in SLE subjects with active LN or active SLE without renal involvement. \n\n\n\nCABA-201 will be administered at a dose of 1.0 x 106 cells/kg, and the study will enroll 6 subjects in an active LN cohort and 6 subjects in an active SLE without renal involvement cohort, in parallel. Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to CABA-201 infusion. This represents the first trial assessing Cabaletta Bio’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy.\n\n\n\nAbout systemic lupus erythematosus\n\n\n\nSLE is a chronic, potentially severe, autoimmune disease in which the immune system attacks healthy tissue throughout the body, most commonly impacting young women between the ages of 15 and 40 with higher frequency and greater severity in people of color. 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. \n\n\n\nSLE affects an estimated 160,000-320,000 patients in the U.S, with LN as the most common end-organ manifestation, 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.