ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0471

An Open-label, Randomized, Controlled Phase 1/2 Study to Assess the Safety and Efficacy of KYV-101 Anti-CD19 CAR-T Cell Therapy in Active and Difficult-to-treat ACPA positive Rheumatoid Arthritis: Preliminary Results of the COMPARE Trial

Fredrik Albach1, Ioanna Minopoulou1, Artur Wilhelm2, Robert Biesen1, Arnd Kleyer1, Norman Drzeniek3, Edgar Wiebe4, Anja Fleischmann3, Dominic Borie5, Vincent Casteleyn3, Tobias Alexander3, Christian Furth6, Jan Zernicke3, Burkhard Muche7, Sandra Hermann4, Pfeil Alexander8, Veronika Scholz3, Elpida Phithak3, Olaf Penack9, Kamran Movassaghi9, Eva Vanessa Schrezenmeier10, Udo Schneider3, Antonia Busse11, Georg Schett12, Ulrich Keller11, Lars Bullinger9, Gerhard Krönke13, Marie Luise Hütter-Krönke14 and David Simon15, 1Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, Berlin, Germany, 2Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, Berlin, 3Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, Berlin, 4Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, Berlin, Berlin, Germany, 5Kyverna Therapeutics, Emeryville, CA, 6Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany, Berlin, 7Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany, 8Department of Internal Medicine III, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, 9Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany, Berlin, 10Department of Nephrology, Charité - Universitätsmedizin Berlin, Berlin, Germany, Berlin, 11Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Campus Steglitz, Berlin, Germany; Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; German Cancer Consortium (DKTK) partner site Charité Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany, Berlin, 12Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany, Erlangen, Germany, 13Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, Berlin, Berlin, Germany, 14Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Campus Steglitz, Berlin, Germany, Berlin, 15Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany, Berlin, Germany

Meeting: ACR Convergence 2025

Keywords: , , , ,

Session Information

Date: Sunday, October 26, 2025

Title: (0470–0505) Rheumatoid Arthritis – Treatment Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by autoreactive B cells that produce anti-citrullinated protein antibodies (ACPA), contributing to sustained synovial inflammation and joint destruction. Recent clinical reports indicate that anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows promise in inducing drug-free clinical remission in difficult-to-treat RA (D2T-RA, Lidar 2025; Li 2025). The COMPARE (COMparison of B-cell dePletion by rituximAb and anti-CD 19 CAR-T therapy in Patients with rhEumatoid arthritis) trial was designed to (i) evaluate the safety and efficacy of the anti-CD19 CAR-T cell therapy KYV-101 in ACPA-positive patients with active, treatment refractory D2T-RA and (ii) to compare the impact of KYV-101 on disease activity to the standard-of-care anti-CD20 monoclonal antibody rituximab (RTX). KYV-101 is a fully human, autologous anti-CD19 CAR T-cell therapy with CD28 costimulation, which is under investigation in B-cell driven autoimmune disease. With a single administration, KYV-101 has potential to achieve durable drug-free and disease-free remission via deep B-cell depletion and immune reset. Preliminary data suggest its potential for durable effects across rheumatic (Albach 2025, Minopoulou 2025, Haase 2025) and neuroimmune indications (Haghikia 2023; Faissner 2024).

Methods: COMPARE, an open-label, randomized, controlled Phase 1/2 trial (EU CT:2024-514955-13-00) is currently enrolling the safety run-in of the trial (Phase 1; n=6) during which all participants receive 1×108 CAR T cells after lymphodepletion. The primary endpoint in Phase 1 is safety (Cytokine Release Syndrome (CRS), Immune Cell Associated Neurotoxicity Syndrome (ICANS), adverse events). Additional endpoints include pharmacokinetics of KYV-101, B-cell and autoantibody levels, and disease activity scores.

Results: At the time of submission, Phase 1 is fully recruited with 6 participants apheresed; two participants have received KYV-101 by 12 May 2025, with follow-ups up to 28 and 56 days. Participants had active disease for a mean of 10.8 (±6.9) years duration and 5.8 (±1.7) prior therapies (Table 1). Both treated participants experienced expected transient cytopenias due to lymphodepletion and CRS (grade I and II), which promptly resolved following tocilizumab and dexamethasone administration. No ICANS, serious adverse events or deaths occurred. CAR T-cells expanded rapidly, reaching peaks of 479 and 122 cells/mL at days 21 and 10 after KYV-101 infusion. Both patients exhibited complete peripheral B-cell depletion and a decline in ACPA values to 19% and 5% of screening values at the latest follow-up.

Conclusion: Preliminary data from the COMPARE trial suggest that KYV-101 has a favorable safety profile and leads to robust CAR T-cell expansion and complete peripheral B-cell depletion in seropositive, active, treatment refractory D2T-RA. With apheresis completed and planned KYV-101 infusion for all Phase 1 patients by July 2025 completion of safety run-in is anticipated shortly, followed by the randomized portion of the trial. Updated data summarizing Phase 1 experience with estimated follow-up post-infusion of 4 months will be presented.

Supporting image 1

Disclosures: F. Albach: Kyverna Therapeutics, 12, Financial/Material Study Support; I. Minopoulou: AbbVie/Abbott, 6, Kyverna Therapeutics, 12, Financial/Material Study Support, Novartis, 6; A. Wilhelm: None; R. Biesen: None; A. Kleyer: AbbVie/Abbott, 1, 6, Alfasigma, 6, Bristol-Myers Squibb(BMS), 1, 6, Eli Lilly, 1, 6, Gilead, 1, Janssen, 1, 6, Novartis, 1, 6, UCB, 1, 6; N. Drzeniek: None; E. Wiebe: Sobi, 6; A. Fleischmann: None; D. Borie: Kyverna Therapeutics, 3, 8; V. Casteleyn: None; T. Alexander: None; C. Furth: None; J. Zernicke: None; B. Muche: AbbVie/Abbott, 6, Amgen, 6, Celltrion, 6, Theramex, 6, UCB, 6; S. Hermann: None; P. Alexander: None; V. Scholz: None; E. Phithak: None; O. Penack: Alexion, 1, 6, Apogepha, 1, Equillium Bio, 1, Gilead, 1, 6, Incyte, 5, Jazz, 1, 6, Merck/MSD, 1, 6, Neovii, 6, Novartis, 1, 6, Omeros, 1, Orca Bio, 1, Pfizer, 6, Priothera, 1, 5, Sanofi, 1, Shionogi, 1, SOBI, 1, Therakos, 6; K. Movassaghi: None; E. Schrezenmeier: None; U. Schneider: None; A. Busse: None; G. Schett: Cabaletta, 6, Eli Lilly, 6, Janssen, 6, Kyverna, 6, Novartis, 6, UCB, 6; U. Keller: None; L. Bullinger: None; G. Krönke: None; M. Hütter-Krönke: None; D. Simon: AbbVie, 2, 6, Bristol Myers Squibb, 2, 6, Gilead, 2, Janssen-Cilag, 2, 6, Kyverna Therapeutics, 12, Financial/Material Study Support, Lilly, 2, 6, Medac, 2, 6, Novartis, 2, 6, UCB, 2, 6.

To cite this abstract in AMA style:

Albach F, Minopoulou I, Wilhelm A, Biesen R, Kleyer A, Drzeniek N, Wiebe E, Fleischmann A, Borie D, Casteleyn V, Alexander T, Furth C, Zernicke J, Muche B, Hermann S, Alexander P, Scholz V, Phithak E, Penack O, Movassaghi K, Schrezenmeier E, Schneider U, Busse A, Schett G, Keller U, Bullinger L, Krönke G, Hütter-Krönke M, Simon D. An Open-label, Randomized, Controlled Phase 1/2 Study to Assess the Safety and Efficacy of KYV-101 Anti-CD19 CAR-T Cell Therapy in Active and Difficult-to-treat ACPA positive Rheumatoid Arthritis: Preliminary Results of the COMPARE Trial [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/an-open-label-randomized-controlled-phase-1-2-study-to-assess-the-safety-and-efficacy-of-kyv-101-anti-cd19-car-t-cell-therapy-in-active-and-difficult-to-treat-acpa-positive-rheumatoid-arthritis-pre/. Accessed .

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