Cabaletta Bio (CABA) Study Update summary

Study Design and Objectives

• RESET-Myositis and RESET-SLE Phase 1/2 trials evaluate a single dose of CABA-201 in autoimmune diseases, using preconditioning regimens identical to academic studies.

• Trials include multiple cohorts for disease subtypes, with primary endpoints focused on safety and secondary endpoints on clinical and translational markers.

• Pediatric cohorts and additional indications (systemic sclerosis, myasthenia gravis, pemphigus vulgaris) are included, with 18 clinical sites open and plans for further expansion.

• Enrollment is ramping up, with five patients enrolled as of June 12, 2024, and accelerated recruitment expected in the second half of 2024.

• The program aims to generate rigorous, homogeneous data to support potential registrational trials and regulatory discussions.

Initial Clinical Data and Safety Profile

• First two patients (one myositis, one lupus) received CABA-201 at 1 × 10^6 cells/kg after standard preconditioning, with no serious adverse events, CRS, ICANS, or infections observed through the follow-up period.

• Both patients discontinued all chronic therapies prior to infusion, except for a prednisone taper in the lupus patient.

• Safety profile is consistent with academic experience, supporting continued use of the selected dose.

• Tocilizumab was not required for either patient.

• Early, transient leukopenia was observed in both patients, as expected with preconditioning.

Pharmacodynamics and Translational Findings

• CAR T-cell expansion peaked at day 15 post-infusion, with complete B-cell depletion observed at the same time.

• B-cell depletion was sustained through the first month, with repopulation characterized by naïve transitional B cells, indicating potential immune reset.

• Serologic and clinical markers in the myositis patient improved, with CK levels nearing normal and autoantibodies declining.

• Early lupus patient data showed SLEDAI-2K improvement from 26 to 10 at week 4, with resolution of vasculitis, arthritis, and hematuria.

• Vaccine and infection antibody titers were preserved post-infusion.