W161 - Immune Reset in B Cell Mediated Autoimmune Diseases Using BCMA-CD19 Compound CAR (cCAR) in an Open Label Phase I Clinical Trial

Yong Yuan – Department of Translational Medicine – Zhongshan People's Hospital; Shanzhi He – Department of Rheumatoid Immunology – Zhongshan People's Hospital; Wenli Zhang – Department of Hematology – Peking University Shenzhen Hospital; Hongyu Zhang – Department of Hematology – Peking University Shenzhen Hospital; Vincent DeStefano – Research & Development Division – iCell Gene Therapeutics Inc.; Masayuki Wada – Research & Development Division – iCell Gene Therapeutics Inc.; Kevin Pinz – Research & Development Division – iCell Gene Therapeutics Inc.; Greg Deener – Research & Development Division – iCell Gene Therapeutics Inc.; Yu Ma – Research & Development Division – iCAR Bio Therapeutics Ltd.; Min Wang – Department of Rheumatoid Immunology – Zhongshan People's Hospital; Fugui Li – Department of Translational Medicine – Zhongshan People's Hospital; Ming Hong – Department of Translational Medicine – Zhongshan People's Hospital; Lan Ting – Department of Translational Medicine – Zhongshan People's Hospital; Chanjuan Zou – Department of Rheumatoid Immunology – Zhongshan People's Hospital; Mingxia Wang – Department of Rheumatoid Immunology – Zhongshan People's Hospital; Ling Ding – Department of Rheumatoid Immunology – Zhongshan People's Hospital; Yingwen Liang – Department of Translational Medicine – Zhongshan People's Hospital; Yupo Ma – Research & Development Division – iCell Gene Therapeutics Inc.; Weijia Wang – Department of Translational Medicine – Zhongshan People's Hospital

Abstract Text: Seventeen patients (Lupus-12, NMOSD-1, transplant DSA-4) dosed 7 Sept 2019 to 19 Dec 2022. Cessation of immunosuppressing medications prior to cCAR. Monthly IgG until B cells recovered. Pre/Post cCAR percent total B lymphocytes, BCR sequence measured in subset. Age range: 20-58, 15 females/2 males. Lupus (12 patients): mean baseline SLEDAI-2K=10.1, mean 4 elevated autoantibodies, 8/12 low C3.

Results: cCAR well tolerated, no SAEs or cCAR related infection, no CRES, no CRS >Grade 1, mild fever only ( < 40OC) resolved in a week. B cells depleted in 3-14 days. IgA, IgM undetectable at ~1 month. Autoantibodies negative 1-4 months (most undetectable 2 months). An immune reset confirmed via flow cytometry revealed predominantly naïve and non-class switched B cells Post-cCAR, as compared to Pre-cCAR (memory and class switched B cells). BCR deep sequencing (patients 3-4), showing IgG and IgA clonotypes are absent and non-class-switched BCR repertoires >95% IgM heavy chain.
All patients treated >6 months in remission (SLEDAI-2K = 0, autoantibodies negative, normal complement including C3, no medications). Lupus symptoms improve quickly, 2.7 mean 1 month. Transient increase in cytokines Post cCAR returning at or below baseline in 3-6 months (no immunosuppression). All B cells recovered in 2-6 months with no relapses (7 of 1st 9 lupus pts SLEDAI-2K=0 by 3 months, no relapses). 1st patient at 38 months: no symptoms, no autoantibodies, no medication.

Conclusion: Well tolerated immune reset achievable & homeostasis maintained without need for continuous treatment. Monitoring patients to ensure reconstituted their immunocompetent B cells & maintain long-term remission.