Cabaletta Bio (CABA) Status Update summary

Clinical Program Overview and Expansion

• The RESET program evaluates CABA-201, a fully human CD19 CAR T therapy, in myositis, SLE, systemic sclerosis, myasthenia gravis, and pemphigus vulgaris across five Phase 1/2 trials, with 40 US sites open, 16 patients enrolled, and 10 dosed as of November 12, 2024.

• European expansion is underway, with EMA CTA authorization for RESET SLE and a new head of international appointed; European trials are anticipated in 2025.

• The program uses consistent trial designs with autologous CAR T, preconditioning (except RESET-PV), and weight-based dosing, with a 15-year follow-up period.

• FDA Fast Track Designation has been granted for multiple indications, and additional data will be presented at ACR 2024, with initial MG data expected in 1H25.

• Cash runway extends into the first half of 2026, supporting ongoing and planned studies.

Patient Population and Unmet Needs

• Patients enrolled had active, refractory autoimmune disease, most having failed prior B cell-targeting therapies.

• Autoimmune conditions targeted include myositis, SLE, and systemic sclerosis, all associated with high morbidity, mortality, and reduced quality of life.

• Key inclusion criteria required evidence of active disease despite standard treatments; exclusion criteria focused on prior B cell depletion, CAR T therapy, or significant organ impairment.

Safety and Efficacy Findings

• CABA-201 showed a favorable safety profile: most patients had no CRS, ICANS, or serious infections; low-grade CRS occurred in three patients, all resolved with standard care, and one Grade 4 ICANS event was linked to a possible occult infection.

• No new ICANS events were observed since August 2024; protocol refinements now include delaying infusion for recent fever/infection and recommending antiseizure prophylaxis.

• All patients discontinued immunosuppressants post-infusion and remained off them during follow-up; SLE patients completed or continued steroid tapering.

• Consistent and complete B cell depletion was observed by day 22 in all patients, with repopulation of naive B cells starting as early as eight weeks in some.

• Compelling early clinical responses were observed in myositis, lupus, and systemic sclerosis, with improvements in muscle strength, disease activity, and laboratory markers; some patients achieved drug-free remission.