ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2696

Biomarker Data From an Open-Label, Phase 1/2 Study for YTB323 (Rapcabtagene Autoleucel, a Rapidly Manufactured CD19 CAR-T Therapy) Suggest Reset of the B Cell Compartment in Severe Refractory SLE

Eric Morand1, Josefina Cortés-Hernández2, Zahir AMOURA3, Julia Weinmann-Menke4, Britta Maurer5, Edouard Forcade6, Stephanie Finzel7, Jose Alvaro-Gracia8, Marc Scherlinger9, Alberta Hoi10, Yannick Muller11, Rangi Kandane-Rathnayake12, Ozana Fischer13, Beata Kovacs13, Frédérique Chaperon13, David Pearson13, Adrienne Lefeber14, Chih-Yung Sean Lee14, Jianping Yuan14, Vassilis Bitsikas13, Aditya Mahadevan Iyer15, Theodoulos Rodosthenous16, Melissa Fernandes13, Thomas Calzascia13, Richard Siegel13, Peter Gergely13 and Tamas Shisha13, 1Centre for Inflammatory Diseases, Monash University and Monash Health, Melbourne, Victoria, Australia, 2Hospital Universitari Vall d’Hebron-Universitat Autónoma de Barcelona, Barcelona, Spain, 3APHP, Paris, France, 4Department of Nephrology and Rheumatology and Center of Immunotherapy, Medical Center of the Johannes Gutenberg University, Mainz, Germany, 5Department of Rheumatology & Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, 6CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University and Service d'Hématologie Clinique et Thérapie Cellulaire, CHU Bordeaux, F-33000, Bordeaux, France, 7Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 8Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Department of Rheumatology, Hospital General Universitario Gregorio Marañón and Faculty of Medicine, Complutense University of Madrid, Madrid, Spain, 9Department of Rheumatology, Hopitaux Universitaires de Strasbourg, Centre National de Référence RESO, Strasbourg, France, 10Centre for Inflammatory Diseases, Monash University and Department of Rheumatology, Monash Health, Clayton, Victoria, Australia, 11Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, 12Center for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia, 13Novartis Biomedical Research, Basel, Switzerland, 14Novartis Biomedical Research, Cambridge, MA, 15Novartis Biomedical Research, Hyderabad, India, 16Novartis Pharmaceuticals UK Ltd, London, United Kingdom

Meeting: ACR Convergence 2025

Keywords:

Session Information

Date: Wednesday, October 29, 2025

Title: Abstracts: Systemic Lupus Erythematosus – Treatment II (2693–2698)

Session Type: Abstract Session

Session Time: 12:15PM-12:30PM

Background/Purpose: Current evidence suggests that B cell depletion through CD19-directed chimeric antigen receptor T cell (CAR-T) therapies may offer promise in improving outcomes in severe refractory systemic lupus erythematosus (srSLE).1 YTB323 (rapcabtagene autoleucel) is a rapidly manufactured, autologous CD19 CAR-T therapy that is also being investigated in hematological malignancies.2 Herein, we report interim biomarker data from a phase 1/2 open-label study investigating YTB323 in patients with srSLE.3

Methods: This ongoing open-label, single-arm, multicenter phase 1/2 study (NCT05798117) assesses the safety, efficacy and cellular kinetics of YTB323 in patients with srSLE (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] ≥8 with major organ involvement, having failed ≥2 standard immunosuppressive therapies and ≥1 biological agent).3 YTB323 treatment was administered as a single dose of 12.5 × 106 CAR-positive viable T cells, following lymphodepletion. Cellular kinetics, quantified by polymerase chain reaction and flow cytometry, and biomarkers, measured by transcriptome analysis, were assessed. Assessments of B cell counts and B cell subsets after recovery were monitored via flow cytometry.

Results: Data from all enrolled patients in the study (n=21) were analyzed. At baseline, mean (standard deviation [SD]) age was 36.6 years (10.6), and 90.5% of patients were female. The mean (SD) duration of follow-up was 11.2 months (4.5; Table 1). Cellular kinetics and pharmacodynamics data revealed peak expansion of CAR-T cells (median time to peak concentration [Tmax]) 2 weeks post-infusion and median time of clearance from peripheral blood of 2 months. YTB323 treatment induced a rapid, complete, and sustained depletion of CD19-positive B cells, with subsequent B cell recovery occurring at a median of 90 days post-infusion (Figure 1A). Analysis of B cell subsets at days 180 and 360 in patients with B cell recovery (n =15) showed that returning B cells had a predominantly naïve phenotype (CD27-IgD+), with a decrease in the proportion of other B cell subsets (Figure 1B). Expression of type I interferon (IFN) inducible genes was downregulated after YTB323 treatment (n =10; Figure 2).

Conclusion: Interim biomarker data from this phase 1/2 trial show complete CD19 B cell depletion and IFN pathway suppression, followed by repopulation with a naïve B cell phenotype. These findings support the concept of an immune “reset” of the B cell compartment via CD19 CAR-T therapy in srSLE.References1. 1. Müller F et al. N Eng J Med. 2024;390(8):687–700.< ! 2. Barba P et al. Blood. 2022;140(Suppl1):1056–9.< ! 3. ClinicalTrials.gov. NCT05798117. Accessed April 23, 2025. https://clinicaltrials.gov/study/NCT05798117

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Disclosures: E. Morand: AbbVie, 2, 5, Amgen, 5, AstraZeneca, 1, 2, 5, 6, Biogen, 1, 2, 5, 6, Bristol Meyers Squibb, 1, 2, 5, 6, Dragonfly, 1, 2, 6, Eli Lilly, 1, 2, 5, 6, EMD Serono, 1, 2, 5, 6, Genentech, 5, GSK, 1, 2, 5, 6, Johnson & Johnson, 5, Novartis, 2, 5, 6, Quell, 1, 2, 6, Remegen, 1, 2, 6, Takeda, 5, UCB, 1, 2, 5, Zenas, 1, 2, 6; J. Cortés-Hernández: AstraZeneca, 6, Bristol-Myers Squibb (BMS), 1, GlaxoSmithKline (GSK), 6, Novartis, 1, 5, 6; Z. AMOURA: AstraZeneca, 6, Bristol-Myers Squibb(BMS), 6, GlaxoSmithKlein(GSK), 6, Merck/MSD, 6, Novartis, 6, Roche, 6; J. Weinmann-Menke: AstraZeneca, 2, 6, Boehringer-Ingelheim, 2, 6, Diamed, 5, GlaxoSmithKlein(GSK), 2, 6, Miltenyi, 5, Novartis, 2, 6, Otsuka, 2, 6, Takeda, 6, Toray, 5, Vifor, 6; B. Maurer: AbbVie/Abbott, 5, Actelion, 12, Congress support, Boehringer-Ingelheim, 1, 5, 6, GlaxoSmithKlein(GSK), 2, Janssen, 2, Medtalk, 12, Congress support, Mepha, 12, Congress support, Merck/MSD, 12, Congress support, Novartis, 2, 5, 6, Otsuka, 6, Pfizer, 12, Congress support, Protogen, 5, Roche, 12, Congress support, UCB, 12, Congress support; E. Forcade: Alexion, 6, Astellas, 6, Gilead, 6, GlaxoSmithKlein(GSK), 6, Jazz, 6, Merck/MSD, 6, Novartis, 6, Sobi, 6; S. Finzel: AbbVie/Abbott, 6, Alfasigma/Galapagos, 6, 12, meeting or travel grant, AstraZeneca, 2, Biotest, 6, 12, meeting or travel grant, Celltrion, 6, Chugai, 6, Eli Lilly, 12, meeting or travel grant, GlaxoSmithKlein(GSK), 2, 6, Johnson&Johnson, 2, 6, 12, meeting or travel grant, Novartis, 2, 6, 12, meeting or travel grant, NovoNordisk, 2, Sobi, 12, meeting or travel grant, UCB, 2, 6, 12, meeting or travel grant; J. Alvaro-Gracia: AbbVie/Abbott, 2, 6, AstraZeneca, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, Galapagos, 2, 6, GlaxoSmithKlein(GSK), 2, 6, Novartis, 2, 6, Pfizer, 2, 6, UCB, 2, 6; M. Scherlinger: AbbVie/Abbott, 6, Amgen, 6, AstraZeneca, 6, Biogen, 6, Bristol-Myers Squibb(BMS), 6, Fresenius, 6, Galapagos, 6, GlaxoSmithKlein(GSK), 6, Innate Pharma, 6, Nordic Pharma, 6, Novartis, 6, Roche, 6, Sandoz, 6; A. Hoi: AstraZeneca, 1, 5, 12, contract research, Bristol-Myers Squibb(BMS), 5, Eli Lilly, 5, GlaxoSmithKline (GSK), 1, Johnson & Johnson, 1, Merck/MSD, 12, contract research, UCB, 5; Y. Muller: AstraZeneca, 1, 5, 6, Blueprint Medicines, 1, 5, 6, GlaxoSmithKlein(GSK), 1, 5, 6, Sanofi, 1, 5, 6, Takeda, 1, 5, 6, Thermofisher, 1, 5, 6, US 2023/0340068 A1, 12, an inventor of a CAR-T licence, Viatris, 1, 5, 6; R. Kandane-Rathnayake: Bristol-Myers Squibb(BMS), 5, GlaxoSmithKline (GSK), 5, Novartis, 5; O. Fischer: Novartis, 3, 11; B. Kovacs: Novartis, 3, 11; F. Chaperon: Novartis, 3, 11; D. Pearson: Novartis, 3, 11; A. Lefeber: Novartis, 3, 11; C. Sean Lee: Novartis, 3, 11; J. Yuan: Novartis, 3, 11; V. Bitsikas: Novartis, 3, 11; A. Iyer: Novartis, 3, 11; T. Rodosthenous: Novartis, 3, 11; M. Fernandes: Novartis, 3, 11; T. Calzascia: Novartis, 3, 11; R. Siegel: Novartis, 3, 11; P. Gergely: Novartis, 3, 11; T. Shisha: Novartis, 3, 11.

To cite this abstract in AMA style:

Morand E, Cortés-Hernández J, AMOURA Z, Weinmann-Menke J, Maurer B, Forcade E, Finzel S, Alvaro-Gracia J, Scherlinger M, Hoi A, Muller Y, Kandane-Rathnayake R, Fischer O, Kovacs B, Chaperon F, Pearson D, Lefeber A, Sean Lee C, Yuan J, Bitsikas V, Iyer A, Rodosthenous T, Fernandes M, Calzascia T, Siegel R, Gergely P, Shisha T. Biomarker Data From an Open-Label, Phase 1/2 Study for YTB323 (Rapcabtagene Autoleucel, a Rapidly Manufactured CD19 CAR-T Therapy) Suggest Reset of the B Cell Compartment in Severe Refractory SLE [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/biomarker-data-from-an-open-label-phase-1-2-study-for-ytb323-rapcabtagene-autoleucel-a-rapidly-manufactured-cd19-car-t-therapy-suggest-reset-of-the-b-cell-compartment-in-severe-refractory-sle/. Accessed .

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