Bristol Myers Squibb announced encouraging Phase 1 results from its Breakfree-1 study of CD19 NEX-T CAR-T cell therapy (BMS-986353) in severe autoimmune diseases at the American College of Rheumatology Convergence 2025. The data from 71 treated patients across three disease cohorts demonstrated the potential for immune reset, with 94% of evaluable patients remaining off chronic immunosuppressive therapy at the time of analysis.
The investigational therapy pairs the CAR construct used in BMS' FDA-approved Breyanzi with a next-generation NEX-T manufacturing platform designed to optimize the production process. Results showed robust CAR-T cell expansion, complete B cell depletion, and re-emergence of a naive B cell phenotype across all three cohorts, with an acceptable safety profile.
"Over the last decade, BMS has been a leader in revolutionizing the treatment of certain blood cancers with cell therapy. Now, we are building on this expertise to bring the modality into the new frontier of autoimmune diseases," said Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb.
Systemic Sclerosis Shows Unprecedented Lung Function Improvement
The systemic sclerosis (SSc) cohort included 26 treated patients, with 19 efficacy evaluable at analysis. Patients with SSc-interstitial lung disease demonstrated a median relative predicted forced vital capacity (pFVC) increase from baseline of 10% at six months. This improvement is notable as pFVC enhancement has not been observed with any other therapeutic modalities for this condition.
The cohort also showed clinically meaningful improvement in skin thickness alongside the pulmonary benefits. All cytokine release syndrome (CRS) events were low grade and resolved in a median of two days, while two grade three immune effector cell-associated neurotoxicity syndrome (ICANS) events were transient and resolved completely within five days.
"These updated results highlight the potential for patients with systemic sclerosis to achieve B cell depletion, with meaningful improvement in lung function and skin thickness, following a single infusion of CAR T cell therapy, even after discontinuing SSc-directed therapies prior to infusion," said Dr. Dinesh Khanna, Professor of Medicine and Director, University of Michigan Scleroderma Program.
Systemic Lupus Erythematosus Demonstrates Sustained Remission
The systemic lupus erythematosus (SLE) cohort treated 32 patients with active, severe organ involvement who were highly refractory to prior treatment, having received a median of 7 prior SLE-specific therapies. Results focused on 26 patients treated at the Phase 2 recommended dose showed rapid improvement in disease activity sustained up to 18 months of follow-up.
All efficacy-evaluable patients except one achieved resolution of clinical symptoms, demonstrated by substantial reductions in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician's Global Assessment (PGA) scores by six months. At evaluation, 92% of patients remained off SLE-specific immunosuppressive therapies.
Most CRS events were grade one or two (73.1% of patients at the recommended dose), with one patient experiencing a grade three event that resolved within one day. No high-grade ICANS was observed in the SLE cohort at the recommended dose.
Idiopathic Inflammatory Myopathies Achieves High Response Rates
The first disclosure of data from the idiopathic inflammatory myopathies (IIM) cohort showed 91% of efficacy-evaluable patients (n=11) achieved a moderate-major composite assessment of the total improvement score. Thirteen patients with severe muscle or skin involvement and highly-refractory disease (median 6 prior IIM-specific therapies) were treated.
Of the efficacy-evaluable patients, 64% achieved a major response and 27% achieved a moderate response based on Myositis Response Criteria-Total Improvement Score (MRC-TIS). All efficacy-evaluable patients experienced rapid and substantial improvement in muscle strength, with median increases in MMT-8 score of 17% at three months and 22% at six months.
All reported CRS was transient and low grade, with one patient experiencing grade three ICANS that resolved completely within three days of onset.
Manufacturing and Study Design
The Phase 1 Breakfree-1 study is an open-label, multicenter trial evaluating the tolerability, preliminary efficacy, and pharmacokinetics of BMS-986353 for severe, refractory autoimmune diseases. The therapy utilizes a five-day NEX-T manufacturing process following T cell collection via apheresis.
Patients undergo lymphodepletion before receiving a single infusion of CD19 NEX-T cell therapy. Primary outcomes assess safety measures for up to two years, while secondary outcomes include efficacy measures of disease remission, activity, and organ-specific parameters at 24 weeks.
Bristol Myers Squibb is currently the only company with two approved CAR-T cell therapies targeting distinct antigens, available in major markets worldwide. The company is advancing recruitment for the Phase 2 Breakfree-SLE study as part of its broader autoimmune disease program.
