AbelZeta Pharma has presented promising early clinical data from its Phase 1 first-in-human investigator-initiated trial of C-CAR168, a novel bispecific autologous CAR-T therapy targeting CD20 and B-cell maturation antigen (BCMA), for the treatment of autoimmune diseases. The results were shared at the 16th International Congress on Systemic Lupus Erythematosus (LUPUS 2025) in Toronto, Canada.
Early Clinical Results Show Promise in Refractory Autoimmune Diseases
The trial enrolled 10 patients with treatment-resistant autoimmune conditions, including seven with lupus nephritis (LN), one with Secondary Progressive Multiple Sclerosis (SPMS), one with Neuromyelitis Optica Spectrum Disorder (NMOSD), and one with Immune-Mediated Necrotizing Myopathy (IMNM).
Initial safety data indicate C-CAR168 was well-tolerated. Four LN patients and one SPMS patient experienced only low-grade (1-2) cytokine release syndrome (CRS), with median onset at 2 days post-treatment. Notably, no immune effector cell-associated neurotoxicity syndrome (ICANS) or severe infections were observed.
Professor Nan Shen from the Department of Rheumatology at Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, who serves as the study's Principal Investigator, presented the findings.
Mechanism of Action and Efficacy in Lupus Nephritis
The study demonstrated robust expansion of C-CAR168 cells following infusion, leading to rapid and complete depletion of B cells, CD20dim T cells, and plasma cells in peripheral blood. In one patient where bone marrow was examined, complete elimination of B cells and both CD19+ and CD19- long-lived plasma cells was observed.
Four LN patients reached the 6-month evaluation timepoint, with impressive results:
- All four achieved and maintained SRI(4) response
- Two patients achieved complete remission (CR)
- One patient achieved partial remission (PR) based on the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 LN Response Criteria
Importantly, all patients were able to discontinue immunosuppressive therapies and biologics after lymphodepletion, with most becoming steroid-free after C-CAR168 infusion. However, one LN patient experienced disease flare before the 6-month post-treatment mark.
Flow cytometry and RNA sequencing analysis of peripheral blood provided evidence of C-CAR168-induced immune reset in LN patients, suggesting a fundamental change in immune system function.
Promising Results in Multiple Sclerosis
Perhaps most intriguing was the response seen in a patient with Secondary Progressive Multiple Sclerosis (SPMS), a condition with limited effective treatment options. This patient showed very promising early efficacy signals, including:
- Improved gait and orbital movement
- Significant reduction in brain inflammation and lesion size
- Improvement in Expanded Disability Status Scale (EDSS)
- Better scores on functional tests including 9-Hole Peg Test (9-HPT) and Timed 25-Foot Walk (T25-FW)
- Improvement in biomarker levels
Study Design and Patient Population
The open-label, multicenter study (NCT06249438) is evaluating C-CAR168 in adult patients with autoimmune and neurological diseases resistant to standard therapy. As of February 28, 2025, seven patients with refractory LN had received C-CAR168 therapy, with four dosed at 0.75×10^6 cells/kg and three at 1.5×10^6 cells/kg.
The treated LN population had long-standing refractory disease, with median SLE duration of 9 years and LN duration of 5 years. These patients had previously been exposed to a median of 4 immunosuppressive or biologic agents without adequate response.
Future Development Plans
"The early clinical results for C-CAR168 mark a significant step forward in the treatment of patients suffering from LN and SPMS with severe manifestations and few effective treatment options," said Tony (Bizuo) Liu, AbelZeta's Chairman and CEO. "These findings support the extension of our bi-specific CAR-T platform, including anti CD20/19 bispecific CAR-T for NHL and now adding C-CAR168, anti-CD20/BCMA, for autoimmune diseases."
Liu added that success in treatment with C-CAR168 would enable patients to discontinue immunosuppressive therapy and substantially reduce disease activity. The company plans to work closely with the FDA and the scientific community to advance to Phase 1b and Phase 2 studies.
About C-CAR168 and AbelZeta
C-CAR168 is a novel autologous bi-specific CAR-T therapy targeting both CD20 and B-cell maturation antigens (BCMA). The FDA has granted clearance of the Investigational New Drug application, and preclinical data was previously presented at the American College of Rheumatology Convergence 2024.
AbelZeta Pharma is a global clinical-stage biopharmaceutical company with centers of excellence in Rockville, Maryland and Shanghai, China. The company focuses on developing innovative cell-based therapeutic products that harness the body's immune system to fight hematological malignancies, solid tumors, and inflammatory and immunological diseases. AbelZeta conducts research and development in its own GMP facilities for early-stage clinical studies, with a pipeline that includes CAR-T and tumor-infiltrating lymphocyte (TIL) therapies.
