Update on the Phase Two Portion of KYSA-6, an Open-label, Single-arm, Multicenter Study of KYV-101, a Fully Human CD19 Chimeric Antigen Receptor (CAR) T-cell Therapy in Generalized Myasthenia Gravis (gMG)
Srikanth Muppidi1, Michael C Hunter2, Sarah Hoffmann3, Tobias Hegelmaier4, Jeremias Motte5, Ralf Gold5, Charlotte Schubert6, Bradley D Hunter7, Everett Meyer1, Marie Luise Hütter-Krönke3, Christian Schultze-Florey4, Roland Schroers5, Francis Ayuk6, Justin Chou8, Baodong Xing8, Naji Gehchan8, Aiden Haghikia4
1Stanford University, 2Intermountain Medical Center, 3Charité-Universitätsmedizin Berlin, 4Hannover Medical School, 5Ruhr University Bochum, 6University Medical Center Hamburg-Eppendorf, 7Intermountain Health, 8Kyverna Therapeutics Inc.
Objective:
Evaluate clinical outcomes with KYV-101 in patients with gMG.
Background:
MG is a B-cell and antibody-mediated neuromuscular autoimmune disease that can result in substantial disability. Novel therapies that provide greater absolute reduction in MG Activities of Daily Living (MG-ADL) to minimize or eliminate disease symptoms are needed. KYV-101 is a fully human, autologous CD19 CAR T-cell therapy with CD28 costimulation, designed for potency and tolerability. With a single dose, KYV-101 has potential to achieve deep B-cell depletion and immune reset to deliver durable, drug-free, disease-free remission. This is an update of KYSA-6 (NCT06193889) a phase 2, open-label, single-arm, multicenter study of KYV-101 in gMG.
Design/Methods:
Adults (18-75y) with gMG (MGFA class IIb-IV), history of AChR or MuSK autoantibodies, MG-ADL score ≥6, and ≥2 immunosuppressant/immunomodulator failures, received lymphodepletion and a single infusion of 1×108 CAR T cells.
Results:
As of October 3, 2025, 6 patients were dosed (mean [range]: age 45.5y [21-62]; MG-ADL 11.2 [7-16]; quantitative MG [QMG] 17.3 [9-28]). Follow-up ranged from 28 days to 9 months; 3 had ≥24-weeks follow-up. Robust CAR T-cell expansion and B-cell depletion occurred in all patients. With a single dose, 100% of patients had ≥3-point improvement in MG-ADL from baseline with 50% achieving minimal symptom expression (MG-ADL ≤1) at last follow-up. At 24-weeks, KYV-101 treatment resulted in 8.0-point (range, 7-9) and 7.7-point (range, 5-11) mean reductions from baseline in MG-ADL and QMG scores, respectively. Of the 6 patients, 5 became nonsteroidal immunosuppressant therapy-free. No ICANS and no high-grade CRS events occurred.
Conclusions:
These findings support the potential of KYV-101 to deliver durable, drug-free, disease-free remission in patients with moderate to severe MG. KYV-101 treatment resulted in robust and sustained improvements in disease severity with an acceptable safety profile, while eliminating background immunosuppressants in the majority of patients. Phase 3 is ongoing; updated phase 2 follow-up will be presented.
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