Kyverna Therapeutics, Inc. · NASDAQ:KYTX
Kyverna Therapeutics — Investor Day (June 2024)
31 slides from Kyverna Therapeutics's investor day presentation, Jun 14, 2024
Slide 1: Lupus Warrior: Anti-CD19 CAR T-Cell Therapy in Rheumatologic Autoimmune Diseases and Beyond
Lupus warrior Anti-CD19 CAR T-Cell Therapy in Rheumatologic Autoimmune Diseases and Beyond Welcome and Introductions Peter Maag, PhD Chief Executive Officer, Kyverna Therapeutics June 14, 2024 Exhibit 99.1
Slide 2: Agenda and Session Presenters
Time Session Title Presenter 8:15-8:20 Welcome and Introduction Peter Maag, PhD Kyverna Therapeutics 8:20-8:35 Long-Term Clinical Experience and Mechanistic Insights Gerhard Krönke, MD Charité – University Medicine Berlin 8:35-8:50 Experience in Advancing CAR T Trials in Rheumatologic Diseases Peter
Slide 3: Disclaimer and Forward-Looking Statements
Disclaimer and Forward-Looking Statements This presentation contains forward-looking statements that are based on management’s beliefs and assumptions and on information currently available to management of Kyverna Therapeutics, Inc. (“Kyverna”, “we”, “our,” or the “Company”). All statements other t
Slide 4: Kyverna's 6 Years of Dedication to Autoimmune Disease
Note: Timeline not to scale. CAR, chimeric antigen receptor; IND, investigational new drug. 1. Brudno JN, et al. Nat Med. 2020;26:270-280. 2. Mougiakakos D, et al. N Engl J Med. 2021;385:567-569. 3. Mackensen A, et al. Nat Med. 2022;28:2124-2132. Kyverna’s First IND Cleared Kyverna’s CD19 CAR T-cell
Slide 5: Is a Reset of the Immune System Possible?
Is a Reset of the Immune System Possible?
Slide 6: Cell Therapy Is Shifting the Paradigm in Autoimmune Diseases
Cell Therapy Is Shifting the Paradigm in Autoimmune Diseases VALUE TIME Small molecules Biologics / mAB Cell therapy / CAR T Methotrexate KYV-101 Mycophenolate Cyclophosphamide CAR, chimeric antigen receptor, mAB, monoclonal antibodies.
Slide 7: Early KYV-101 Data Demonstrate Promising Outcomes Across Multiple Indications
Early KYV-101 Data Demonstrate Promising Outcomes Across Multiple Indications Total of 50 Patients Treated With CAR in KYV-1011,2 Hematology Neurology Rheumatology CAR, chimeric antigen receptor. 1. Brudno JN, et al. Nat Med. 2020;26:270-280. 2. Internal data from KYSA-1, KYSA-3, and investigator-
Slide 8: Acknowledgments – Creating the Kyverna Village
Patients and Their Families for their courage and trust Care Givers and Collaborators for their partnership Kyverna Employees for their hard work and dedication Acknowledgments – Creating the Kyverna Village
Slide 9: KYV-101 Experience Across Multiple Diseases and Sites
KYV-101 Experience Across Multiple Diseases and Sites Anti-CD19 CAR T-Cell Therapy in Rheumatologic Autoimmune Diseases and Beyond James Chung, MD, PhD Chief Medical Officer, Kyverna Therapeutics June 14, 2024
Slide 10: Commitment to Generating Clinical Insights Along 3 Pillars
Commitment to Generating Clinical Insights Along 3 Pillars Strategy Patient-Centric “Named Patient Use” In patients with highly-refractory, serious autoimmune disease with limited or no treatment options Indications include MG, SSc, and rare autoimmune diseases such as SPS and autoimmune encephaliti
Slide 11: First-in-Class KYV-101, an Autologous, Fully Human, Anti-CD19 CAR T-Cell Therapy
CAR, chimeric antigen receptor; costim, costimulatory; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; NIH, National Institutes of Health; scFv, single-chain variable fragment; TM, transmembrane. 1. Brudno JN, et al. Nat Med. 2020;26:270-280. 2. Alaba
Slide 12: Patients Across Diverse Indications Treated With the KYV-101 CAR Construct
50 Patients Across Diverse Indications Treated With the KYV-101 CAR Construct Rheumatology Hematology Neurology 15 Autoimmune Indications: 6 in rheumatology and 9 in neurology KYV-101 CAR Experience Across Multiple Indications (N=50) AAV, ANCA-associated vasculitis; AE, autoimmune encephalitis; ASyS
Slide 13: KYV-101 CAR Safety and Efficacy Experience From Hematology
P ≤ 0.001 P ≤ 0.0001 1000 2000 Concentration of each protein in culture supernatant (pg ml-1) Concentration of each protein in culture supernatant (pg ml-1) Hu19-CD828Z (N=20 patients) FMC63-28Z (N=22 patients) P ≤ 0.0001 P ≤ 0.0001 P ≤ 0.01 P ≤ 0.01 P > 0.05 P ≤ 0.01 P ≤ 0.01 P > 0.05 KYV-101 CAR S
Slide 14: KYV-101 CAR-Related Safety Data Shows No CRS or ICANS Grade ≥3
KYV-101 CAR-Related Safety Data Shows No CRS or ICANS Grade ≥3 in First 30 Patients aReferences 3-6 are reported as neurological toxicities. bReported at 12% of 268 patients. cReported as 23% of 115 patients. dGrade 1 neurological AEs were not recorded in this trial. Three subjects had Grade 2 ICANS
Slide 15: KYV-101 Demonstrates Promising Outcomes Across Multiple Indications (N=30)
KYV-101 Effects in 30 Patients With Autoimmune Diseases Number of Patients Treated <90 days CAR T Expansiona B-Cell Depletion Autoantibody Reduction/Otherb KYV-101 Demonstrates Promising Outcomes Across Multiple Indications (N=30) aNo CAR T expansion defined as Cmax < 6 cells/μL and area under curve
Slide 16: Pharmacodynamic Activity and Return of B Cells
Note: Red triangles indicate median time to CAR T-cell peak expansion for all patients (left) and median time to CD19 B-cell reconstitution for patients whose B cells have returned (right). ABS, absolute; CAR, chimeric antigen receptor. 1. Internal data from KYSA-1, KYSA-3, and investigator-reported
Slide 17: Myasthenia Gravis Named Patient #1 – Lancet Neurology
Myasthenia Gravis Named Patient #1 – Lancet Neurology Within 60 Days of Infusion, Observed Improved Symptoms and Mobility IgG titer day CAR T-cells ▼ CAR T-cells ▼ 10 20 30 40 50 60 Mar-23 Jul-22 Nov-21 Mar-21 day QMG Score Walking distance(m) Arm holding time [sec] Observed dramatic reduction in AC
Slide 18: Denise – Year Anniversary
Denise – 1 Year Anniversary First KYV-101 autoimmune patient at 1 year Disease free No adverse events No background immunosuppressants or glucocorticoids B cells repopulated as of day 132 For detailed case description, see: Haghikia et al., Anti-CD19 CAR T Cells for Refractory Myasthenia Gravis, The
Slide 19: Our Pipeline of CAR T-Cell Therapies for Autoimmune Diseases
Our Pipeline of CAR T-Cell Therapies for Autoimmune Diseases Technology Candidates Target Indication Discovery / Validation Preclinical Clinical Phase 1 Clinical Phase 2 Clinical Phase 3 Partnership / Commercial Rights Key Milestone Achieved CAR T KYV-101 Rheumatology CD19 Lupus nephritis KYSA-1: IN
Slide 20: Demonstrating the Transformative Impact of KYV-101 on Lupus Nephritis Disease Control
Demonstrating the Transformative Impact of KYV-101 on Lupus Nephritis Disease Control Months Post Infusion KYV-101 infusion aPatient order based on time from CAR T infusion. bData Cutoff: May 24, 2024. Pred dose post-infusion listed as last reported dose after taper. 1. Internal data from KYSA-1, KY
Slide 21: Early Lupus Nephritis Patient Data: Pharmacokinetics and B-Cell Count
1. Internal data from KYSA-1, KYSA-3, and investigator-reported named patient experience. ABS, absolute; CAR, chimeric antigen receptor. Early Lupus Nephritis Patient Data: Pharmacokinetics and B-Cell Count Days Post-Infusion Pharmacodynamic Activity and Return of B Cells Urine Protein Creatinine Ra
Slide 22: Improvement in Biomarkers and Overall Disease Activity
Improvement at 3 Months in Biomarkers and Overall Disease Activity Rapid decrease in anti-dsDNA antibodies in all subjects Normalization of complement components (C3/C4) Overall improvement in clinical disease activity Reduction in Autoantibodies (RIA) Days Post-Infusion Baseline Month 3 Complement
Slide 23: Proteinuria Clinical Trial Experience and Case Reports
Wang et al.2 (iCell) Proteinuria Clinical Trial Experience and Case Reports High variability observed in the short term Months Post-Infusion Protein:Creatinine Ratio Urinary Protein Excretion Müller et al.1 (Erlangen) Days Post-Infusion Urine Protein Creatinine Ratio z Urine Protein Creatinine Ratio
Slide 24: Short-Term Disease Control in One Patient With Lupus Nephritis
Short-Term Disease Control in One Patient With Lupus Nephritis Promising safety profile Initial disease response Disease recurrence after 5 months Patient with high BMI and treated with 50M cells Low CAR exposure associated with initial response but disease recurrence Low CAR expansion at 50M cells
Slide 25: Safety: CAR T Cell-Related Safety Events Are Readily Manageable
Safety: CAR T Cell-Related Safety Events, If Encountered, Are Readily Manageable No ≥ Grade 3 CRS or ICANS Observed aAdverse events report pending. Note: Time from infusion as of May 29, 2024 (days). Internal data from KYSA-1, KYSA-3, and investigator-reported named patient experience. AAV, ANCA-ass
Slide 26: Published Case Reports – Neuron: KYV-101 in Myasthenia Gravis
Published Case Reports – Neuron KYV-101 in Myasthenia Gravis AChR, acetylcholine receptor; CAR, chimeric antigen receptor; LEMS, Lambert-Eaton myasthenic syndrome; MG, myasthenia gravis; MG-ADL, MG activities of daily living scale. 1. Motte J, et al. Neuron 2024;112:1–7. Impact on Autoantibodies and
Slide 27: Published Case Reports – MED: KYV-101 in Multiple Sclerosis
CAR, chimeric antigen receptor; CSF, cerebrospinal fluid; ICANS, immune effector cell-associated neurotoxicity syndrome; MS, multiple sclerosis; OCB, oligoclonal band. 1. Fischbach F, et al. Med. 2024;22:S2666-6340(24)00114-4. Published Case Reports – MED KYV-101 in Multiple Sclerosis Evidence of Bi
Slide 28: CAR T-Cell Therapy May Allow Complete Disease Control in a Treatment-Free Setting
CAR T-Cell Therapy May Allow Complete Disease Control in a Treatment-Free Setting (Immune Reset) Moderate/Limited Chronic administration. (e.g. cycle Q24 weeks) Yes Concurrent Immunomodulation (e.g. MTX, GC) Improved in treatment-refractory patients Two cycles, on background MTX Continuous immunomod
Slide 29: Conceptual Considerations for Various B-Cell Targeting Approaches Favor CAR T
Monoclonal antibodies Bispecific antibody case reports TREATMENT-FREE Anti-CD19 CAR T case reports HOSPITALIZATION HOSPITALIZATION WEEKS 1 4 8 12 16 20 24 28 32 36 42 LD Conceptual Considerations for Various B-Cell Targeting Approaches Favor CAR T-Cell Therapy (Immune Reset) Dosing Short- term risk
Slide 30: Conclusions
Over 50 patients have received the KYV-101 CAR construct The 30-patient experience in autoimmune diseases shows a promising safety profile, expected CAR T-cell expansion, and effective B-cell depletion There is reduction in autoantibodies and overall improvement of disease activity in the setting of
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