FDA Clears Phase 1b/2 Trial of CAR T-Cell Therapy C-CAR168 for Refractory Progressive Multiple Sclerosis

The FDA has cleared AbelZeta Pharma’s investigational new drug (IND) application for a phase 1b/2 trial of C-CAR168, an autologous bispecific chimeric antigen receptor (CAR) T-cell therapy, in patients with progressive multiple sclerosis (MS) refractory to standard treatment.¹

“The FDA clearance of this Phase 1b/2 study represents another important step in realizing the potential of C-CAR168 across refractory chronic autoimmune diseases,” Tony (Bizuo) Liu, chairman and chief executive officer at AbelZeta, said in a statement.¹ “Progressive multiple sclerosis can cause significant and irreversible neurological disability, and there remains a considerable unmet medical need for therapies capable of addressing the underlying immune dysfunction driving disease progression.”

The multicenter study will evaluate C-CAR168 in patients with SPMS or primary progressive MS (PPMS) who have responded inadequately to standard therapies. Phase 1b is expected to enroll approximately 6 to 24 participants, with safety, tolerability, and selection of a recommended phase 2 dose as central objectives.

The phase 2 portion is planned to enroll approximately 95 patients in 2 independent cohorts. One cohort will include patients with active SPMS; the second will include patients with PPMS or nonactive SPMS with continued progression. The company reported that this portion will further assess clinical efficacy and safety.

Progressive MS encompasses PPMS, in which disability accumulates from disease onset, and SPMS, which follows an initial relapsing-remitting course.² As neurologic impairment progresses, patients may experience worsening mobility, weakness, fatigue, and cognitive dysfunction, with treatment options remaining limited, particularly in the absence of ongoing inflammatory activity.³

READ MORE: Polygenic Lymphocyte Score Predicts Lymphopenia Risk in Patients With MS Treated With Dimethyl Fumarate

C-CAR168 is designed to target CD20 and B-cell maturation antigen (BCMA). According to AbelZeta, simultaneously targeting these antigens is intended to deplete B cells and plasma cells implicated in autoimmune disease.¹ The approach differs from conventional repeated pharmacologic treatment because it uses patient-derived T cells engineered to recognize the target antigens.

The company previously reported early findings, presented as a late-breaking poster at the 2025 American College of Rheumatology (ACR) Convergence, held October 24-29, 2025, in Chicago, Illinois, from a first-in-human phase 1 program of patients with SPMS.¹ All told, findings showed that treatment with the investigational cell therapy showed promising efficacy, with improvements in gait and neurologic function as well as reductions in brain inflammation and lesion size.

“Based on updated preliminary efficacy data, including early and sustained Expanded Disability Status Scale (EDSS) reduction and functional improvement observed in two secondary progressive multiple sclerosis (SPMS) patients, one with active and the other with non-active disease, one of whom had over one year of follow-up, we remain cautiously optimistic that the deep immune-cell depletion and reset enabled by C-CAR168 can provide meaningful and durable benefit to these patients,” Liu said in a statement.¹

C-CAR168 is also being studied in systemic lupus erythematosus, lupus nephritis, and systemic sclerosis. AbelZeta reported that the FDA previously cleared a multicenter registrational phase 2 study in refractory systemic lupus erythematosus, including lupus nephritis, under regenerative medicine advanced therapy designation. The company also reported receipt of priority medicines designation from the European Medicines Agency for that program.

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REFERENCES
1. AbelZeta Pharma Inc. AbelZeta receives FDA IND clearance for phase 1b/2 clinical trial of C-CAR168 in progressive multiple sclerosis. Published September 12, 2026. https://www.prnewswire.com/news-releases/abelzeta-receives-fda-ind-clearance-for-phase-1b2-clinical-trial-of-c-car168-in-progressive-multiple-sclerosis-302877555.html
2. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278-286.
3. Rajabi M, et al. Primary progressive multiple sclerosis: new therapeutic approaches. Neuropsychopharmacol Rep. 2025;45(3):e70039.