CABA-201 is a 4-1BB-containing fully human CD19-CAR T cell investigational therapy.

The U.S. Food and Drug Administration (FDA) is allowing Cabaletta Bio, Inc.’s third Investigational New Drug (IND) application for CABA-201 to proceed. for a Phase 1/2 study in patients with systemic sclerosis (SSc). 

CABA-201 is a 4-1BB-containing fully human CD19-CAR T cell investigational therapy.

The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 across two parallel SSc cohorts – one cohort of six patients with severe skin manifestations and a separate cohort of six patients with severe organ involvement associated with systemic sclerosis. 

Consistent with the previously announced CABA-201 IND clearances for lupus and myositis, the starting dose for the trial, 1 x 106 cells/kg, was informed by the high degree of similarity between CABA-201 and the CD19-CAR T construct administered to a patient with severe, diffuse SSc in the recent Annals of Rheumatic Diseases publication.

“As we remain on track to deliver three-month clinical data from the initial patients treated with CABA-201 by the first half of 2024, the clearance of our third IND application for CABA-201 within the past 6 months demonstrates our relentless focus on developing CABA-201 for a broad portfolio of potential indications in patients with autoimmune diseases,” says Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta, in a news release. “Based on published, third-party academic clinical data and a recently released abstract by the same academic group at the upcoming American College of Rheumatology Convergence 2023 meeting reporting administration of CD19-CAR T cells to treat additional patients with systemic sclerosis, we believe CABA-201 has the potential to slow or halt the progression of this autoimmune disease, thereby providing an important treatment option for these patients who currently have very few available treatments.”

Check out our exclusive interview with Dr. Nichtberger. 

More on the Phase 1/2 Clinical Trial of CABA-201 in SSc
 

The Phase 1/2 clinical trial will be an open-label study of CABA-201 in subjects with SSc across two parallel cohorts. The severe skin cohort will include six patients with severe skin involvement, and the organ cohort will include six patients who meet the pulmonary, cardiac, or renal involvement criteria regardless of skin involvement. Subjects will receive a one-time infusion of CABA-201, using the same dose being used in the lupus and myositis clinical trials of CABA-201, 1 x 106 cells/kg, preceded by a standard preconditioning regimen of fludarabine and cyclophosphamide. Key inclusion criteria include patients between ages 18 and 70 (inclusive), evidence of significant skin, pulmonary, renal, or cardiac involvement, and significant organ involvement despite use of immunosuppressants. Key exclusion criteria include a primary diagnosis of another rheumatic autoimmune disease, treatment with a B cell depleting agent within six months or treatment with a biologic agent within three months. As the third 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 completely, eliminate B cells throughout the body, potentially enabling an immune system reset associated with a slowing or halting of active inflammatory disease progression in patients with SSc.