CABA-201 data package and experience from prior autoimmune cell therapy INDs informed Phase 1/2 clinical trial design, including the initial dose to be evaluated and the patient dosing intervals –

-- Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases, today announced that the Company’s 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). The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 for the treatment of systemic lupus erythematosus (SLE) in patients with active lupus nephritis (LN) or active SLE without renal involvement.

“We believe the clearance of this IND application within 6 months of licensing the binder for CABA-201 is an important milestone for patients with autoimmune disease. The efficient clinical trial design was informed by the data package we submitted, including clinical safety data with the CABA-201 binder, our experience from prior autoimmune cell therapy IND applications and our exclusive translational research partnership with the senior author of the Nature Medicine paper, which demonstrated 5/5 durable remissions throughout the follow-up period up to 17 months in patients with refractory SLE,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. “The Phase 1/2 clinical trial will begin in patients with either active LN or SLE without renal involvement. Based on its similarity to the product used in the Nature Medicine paper, we believe CABA-201 has the potential to provide deep and durable responses for patients with SLE and possibly other autoimmune diseases where B cells play a role to initiate or sustain disease pathology. By achieving a timely IND clearance, we believe we are well positioned to generate 3-month clinical data on efficacy endpoints and tolerability for patients dosed with CABA-201 by the first half of 2024.”

SLE is a chronic, potentially severe, autoimmune disease, most commonly impacting young women between the ages of 15 and 40 with higher frequency and more severity in people of color, where the immune system attacks healthy tissue throughout the body. 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. It affects an estimated 160,000-320,000 patients in the U.S. in total. LN is the most common end-organ manifestation of SLE, 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.

CABA-201 is designed to be given as a one-time infusion, with the potential to transiently, but fully, eliminate B cells, thus enabling an “immune system reset” and durable remission in patients with SLE. The Phase 1/2 clinical trial is an open-label dose evaluation study designed to evaluate CABA-201 in SLE subjects with active LN or active SLE without renal involvement. Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to CABA-201 infusion. This represents the first trial that employs Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy.