Data reinforce the potential for immune reset with zolacabtagene autoleucel to address an underlying cause of multiple sclerosis

Company Website: https://www.bms.com
PRINCETON, N.J. -- (Business Wire)

Bristol Myers Squibb (NYSE: BMY) today announced disclosure of interim safety and efficacy results from the multiple sclerosis (MS) cohorts of the Phase 1, single-arm, dose-escalation Breakfree-2 study evaluating zolacabtagene autoleucel (zola-cel; BMS-986353), an investigational, autologous CD19-directed CAR T cell therapy, in patients with highly active relapsing MS (haRMS) and progressive forms of MS (PMS). The data are being presented today in an oral presentation (Abstract #1615) at MSToronto 2026, the 10^th Joint ACTRIMS-ECTRIMS Meeting taking place in Toronto, Canada.

The study included 66 patients (30 patients with haRMS and 36 patients with PMS) with ongoing disease activity or worsening disability despite treatment. Patients had a median of two prior disease-modifying therapies (DMTs) (range: 1-8 haRMS; 1-6 PMS). The primary endpoint of the study was safety, with efficacy as the secondary endpoint. The data presented show a safety profile consistent with previously reported zola-cel Phase 1 clinical trial data and early, promising efficacy across both haRMS and PMS with all patients treated at dose level 2 (DL2) (60/60) remaining off DMTs.

In the Breakfree-2 study, the majority of adverse events were brief and reversible, generally consistent with previously reported zola-cel Phase 1 clinical trial data.

• Overall, 42.4% of patients (28/66) had cytokine release syndrome (CRS) events. Majority were Grade 1 (36.4%), with some Grade 2 (6.1%) and all resolved in a median of two days.
• 7.6% of patients (5/66) had immune effector cell-associated neurotoxicity syndrome (ICANS), most of which were Grade 1/2, which resolved in a median of two days.
• One Grade 4 ICANS event occurred in a patient with PMS and was managed with corticosteroids and anakinra and resolved within four days.

After the data cutoff, one patient with haRMS experienced a fatal event of septic pneumonia. Following zola-cel infusion, the patient experienced late onset, non-ICANS motor symptoms that were not resolved by treatment with intermittent corticosteroids and intravenous immunoglobulin (IVIG). Although the patient’s CAR T cell expansion was consistent with that observed across the study, high-dose cyclophosphamide was administered and the patient developed septic pneumonia and died the following day, 44 days after infusion. No additional Grade 5 events have been reported across all zola-cel programs in autoimmune diseases, which include 190 patients treated in Phase 1 studies.

Secondary endpoints included measurements of efficacy, with zola-cel demonstrating potential for immune reset via complete B-cell depletion. At last follow up, all patients treated at DL2 (60/60) remained off DMTs, including nine patients with more than 12 months of follow-up.

Additional efficacy results from the study among evaluable patients (patients receiving DL2 with ≥ Week 26 follow-up; n=32) included:

• Six of seven haRMS patients evaluable for no evidence of disease activity (NEDA) met criteria at ≥ Week 26, with all patients achieving no relapse, disability progression or MRI activity.
• All eight haRMS patients evaluable for Expanded Disability Status Scale (EDSS) at ≥ Week 26 demonstrated stability or improvement (range: 3.0-5.5 haRMS; 4.0-6.0 PMS).
• Despite prior worsening at baseline, 22 of 24 (92%) PMS patients demonstrated stability or improvement in disability progression.
• All 24 PMS patients demonstrated no new MRI activity.

“People living with relapsing and progressive forms of multiple sclerosis need treatment options that address the underlying disease while helping control relapses and preserve function,” said Dr. Jeffrey A. Cohen, Professor of Neurology and Staff Physician, Mellen Center, Cleveland Clinic. “These data suggest that CD19-directed CAR T cell therapy may offer a new approach to treating multiple sclerosis. While more research is needed, the potential to control relapses, stabilize disability and reduce reliance on disease-modifying medications is encouraging.”

“BMS is at the forefront of cell therapy science, pioneering a new era by exploring the potential for immune reset in patients living with autoimmune diseases,” said Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb. “The Breakfree-2 data demonstrate clinical potential for zola-cel in multiple sclerosis, showcasing the opportunity for treatment-free remission in patients who have depended on chronic therapies for years. We are advancing zola-cel with the goal to redefine autoimmune care with a single, transformative treatment.”

Bristol Myers Squibb extends its gratitude to the patients, families and investigators involved in the Breakfree-2 clinical trial.

About the Breakfree-2 Study

Breakfree-2 (NCT06220201) is a Phase 1, multicenter, single-arm, dose-escalation study evaluating the safety and efficacy of zolacabtagene autoleucel (zola-cel; BMS-986353), in patients with autoimmune neurological diseases: relapsing forms of multiple sclerosis, progressive forms of multiple sclerosis or refractory myasthenia gravis. Zola-cel is an investigational CD19-directed CAR T cell therapy that expresses the CD19 CAR and is manufactured using a next-generation process (NEX-T™). This platform uses an intentional five-day manufacturing process optimized so the CAR T cells reach a stable vector integration and early-differentiated phenotype prior to infusion.

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 specialized facilities utilizing the NEX-T manufacturing process. After undergoing lymphodepletion, patients receive a single infusion of zola-cel.

The primary endpoint is safety. Key secondary endpoints include number of patients meeting no evidence of disease activity criteria, number of patients with confirmed disability progression confirmed per EDSS, as well as pharmacokinetic outcomes.

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 unlock the full potential of this technology across blood cancers and within 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 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: Transforming Patients’ Lives Through Science

At Bristol Myers Squibb, our mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. We are pursuing bold science to define what’s possible for the future of medicine and the patients we serve. For more information, 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 zola-cel may not receive regulatory approval for the indication 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 zola-cel for the indication described in this release 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, 2025, 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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