Bristol Myers Squibb Presents Encouraging Data from Phase 1 Breakfree-1 Study of CD19 NEX-T™ CAR T Cell Therapy in Three Chronic Autoimmune Diseases at ACR Convergence 2025
Positive, early results from 71 patients treated across three disease cohorts – systemic sclerosis, systemic lupus erythematosus and idiopathic inflammatory myopathies – are being disclosed
Across all cohorts, results support potential for immune reset, with 94% of evaluable patients remaining off chronic immunosuppressive therapy at the time of analysis
Results demonstrate BMS' steady advancement toward its goal of bringing the science of cell therapy beyond blood cancer into autoimmune diseases
Bristol Myers Squibb (NYSE:BMY) today announced updated data and first disclosure of results in chronic, refractory autoimmune diseases from the Phase 1 Breakfree-1 study (NCT05869955) of its investigational, autologous CD19-targeted NEX-T™ CAR T cell therapy BMS-986353 (CC-97540). The data, evaluating a total of 71 treated patients across the systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and idiopathic inflammatory myopathies (IIM) cohorts, are being featured at the American College of Rheumatology (ACR) Convergence 2025, taking place from October 24-29 in Chicago, Illinois.
The preliminary Phase 1 safety and efficacy results presented are consistent with the potential for immune reset, as part of a treatment process that includes a one-time infusion of CD19 NEX-T, showing robust CAR T cell expansion, complete B cell depletion and re-emergence of a naive B cell phenotype across all three cohorts. At the time of analysis, 94% of evaluable patients remained off chronic immunosuppressive therapy.
All cohorts presented demonstrate an acceptable safety profile, with the majority of adverse events occurring shortly after infusion and resolving quickly with standard management protocols, as is expected with CAR T cell therapies.
"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. "While early, these data demonstrate our focus and steady advancement toward introducing the potential of treatment-free remission, which just a few years ago was not thought to be possible for patients with severe autoimmune disorders."
CD19 NEX-T pairs the CAR construct used in BMS' FDA-approved Breyanzi (lisocabtagene maraleucel; liso-cel), approved in certain hematologic malignancies, with the next-generation NEX-T platform which aims to optimize the manufacturing process. CD19 NEX-T is being investigated within a robust, multi-cohort clinical trial program, evaluating the potential for cell therapy to address the underlying cause of multiple severe/refractory autoimmune diseases by inducing immune reset.
Updated Results from Phase 1 Study of Breakfree-1 in SSc (Abstract #0843)
Updated Phase 1 results from the SSc cohort of Breakfree-1 demonstrate unprecedented improvement in pulmonary function in patients with SSc-interstitial lung disease (ILD) and clinically meaningful improvement in skin thickness.
The full SSc cohort included 26 treated patients, with 19 efficacy evaluable at the time of analysis. A median relative predicted forced vital capacity (pFVC) increase from baseline of 10% was seen at six months (n=6) in subjects with ILD at baseline. This increase is notable as improvement in pFVC has not been seen with any other therapeutic modalities.
The treated patients experienced a safety profile consistent with the expected safety profile of cell therapy. All cytokine release syndrome (CRS) events were low grade and resolved in a median of two days. Two grade three immune effector cell-associated neurotoxicity syndrome (ICANS) events were transient and resolved completely within five days. The majority of all related treatment-emergent adverse events (TEAEs) occurred shortly after infusion, were low grade and resolved quickly with standard management.
"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. "The potential for new treatment approaches to ‘reset' a patient's immune system, while early, is highly encouraging and provides hope for patients living with these chronic diseases."
Updated Results from Phase 1 Study of Breakfree-1 in SLE (Abstract #1529)
Updated results from the SLE cohort of Breakfree-1 show rapid improvement in disease activity sustained at the time of follow-up (up to 18 months), indicating potential for long-term treatment-free remission.
Thirty-two SLE patients with active, severe organ involvement and highly refractory to prior treatment (median 7 prior SLE-specific therapies; range 3-13) were treated across two dose levels (DL). Based on the cumulative safety, efficacy and pharmacokinetics and pharmacodynamics, DL1 was chosen as the Phase 2 recommended dose (RP2D). The disclosure focuses on 26 patients treated at DL1. All efficacy-evaluable patients except one had resolution of clinical symptoms, as shown by substantial reductions in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician's Global Assessment (PGA) scores by six months of follow-up. At the time of evaluation, 92% of patients remained off SLE-specific immuno-suppressive therapies (ISTs).
All inflammatory adverse events (AEs) were transient and fully reversible. Most CRS events were grade one or two (73.1% of patients at RP2D), 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 RP2D.
First Disclosure of Preliminary Results from Phase 1 Breakfree-1 Study in IIM (Abstract #LB14)
A late-breaking abstract at ACR, the first disclosure of data from the Breakfree-1 IIM cohort shows 91% of efficacy-evaluable patients (n=11) achieved a moderate-major composite assessment of the total improvement score.
Thirteen patients with IIM, characterized by severe muscle or skin involvement and highly-refractory disease (median 6 prior IIM-specific therapies; range 3-9), were treated at DL1. Promising initial results showed that of the efficacy-evaluable patients, 64% of patients 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 a rapid and substantial improvement in muscle strength; median increase in MMT-8 score change from baseline was 17% at three months (n=6) and 22% at six months (n=3).
Most TEAEs occurred within 90 days; the highest proportion of patients experiencing TEAEs occurred within the first 29 days following infusion. All reported CRS was transient and low grade. One patient experienced grade three ICANS that resolved completely within three days of onset.
Updated Data from Broader Immunology Portfolio
BMS is also presenting findings at ACR that support its immunology portfolio, including pivotal Phase 3 POETYK PsA-1 trial of Sotyktu (deucravacitinib) in adults with active psoriatic arthritis (abstract #LB20), as well as new findings from the Phase 2 PAISLEY-SLE and PAISLEY long-term extension (LTE) studies for moderate-to-severe SLE (abstract #LB10).
ACTioN at ACR
In addition to advancing research, BMS is continuing to champion interdisciplinary collaboration to progress the promise of cell therapy across the spectrum of autoimmune diseases. At ACR Convergence 2025, BMS is convening a forum of ACTioN (Autoimmunity Cell Therapy Network), a group of leading academics and physicians across rheumatology, hematology, neurology and immunology – working to advance cell therapy in autoimmune diseases. This event brings together different experts of the Network, with the goals of gathering insights and discussing strategies for investment into research that can accelerate the development of treatments for patients. Learn more about ACTioN here.
About the CD19 NEX-T™ Breakfree-1 Study
The Phase 1 Breakfree-1 study is an open-label, multicenter study to evaluate the tolerability, preliminary efficacy and pharmacokinetics of BMS-986353 (CC-97540), a CD19-directed CAR T cell therapy, for severe, refractory autoimmune diseases (systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies and rheumatoid arthritis). CD19 NEX-T is an investigational CD19-targeted CAR T cell therapy that expresses the CD19 CAR used in Breyanzi (lisocabtagene maraleucel; liso-cel), FDA-approved in certain hematologic malignancies, and is manufactured using a next-generation process (NEX-T) that aims to optimize manufacturing processes to help CAR T cells recognize and fight specific pathogenic cells.
Trial patients across cohorts follow a similar process: apheresis to collect T cells, after which the cells are manufactured into CD19 CAR T cells at a specialized facility utilizing the optimized, five-day NEX-T manufacturing process. After undergoing lymphodepletion, patients receive a single infusion of CD19 NEX-T cell therapy.
Primary outcomes are safety measures assessed for up to two years, and secondary outcomes include efficacy measures of disease remission, activity, and organ-specific parameters at 24 weeks, as well as pharmacokinetic outcomes. This study will also determine the recommended Phase 2 dose based on the dose-limiting toxicities observed in the dose-escalation phase to optimize the benefit-risk of this therapy in patients. As we continue to progress Breakfree-1, recruitment for the Phase 2 Breakfree-SLE study is currently ongoing.
Bristol Myers Squibb: Unlocking the Full Potential of Cell Therapy
A pioneer in harnessing the immune system to fight cancer and an established leader in cell therapy, Bristol Myers Squibb is uniquely positioned to explore the potential of this technology across blood cancers and into new frontiers, including autoimmune disease.
Bristol Myers Squibb is currently the only company with two approved CAR T cell therapies with two distinct targets, available in major markets around the world. Our bold vision for the future is one in which hundreds of thousands of appropriate patients can be treated with cell therapy's transformational potential.
The building blocks to realize this ambition—a promising and differentiated pipeline, extensive translational and clinical data sets, a deep bench of talent, and robust manufacturing capabilities—are in our cells. We are laser-focused on advancing the field of cell therapy toward a true revolution for patients. Learn more about the science behind cell therapy and ongoing progress at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, X, YouTube, Facebook and Instagram.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that BMS-986353 may not achieve its primary study endpoints or receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether BMS-986353 for such indications will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2024, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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