KYV-101 / Kyverna - LARVOL DELTA

Effect of anti-CD19 CAR T cell therapy in the bone marrow of patients with systemic autoimmune diseases (EULAR 2025) - " Three patients with severe, treatment-resistant systemic autoimmune diseases (Table 1) received autologous anti-CD19 CAR T cell therapy following conditioning therapy with fludarabine and cyclophosphamide [3, 4]... Treatment with KYV-101 appeared to be safe (Table 1)... This study highlights that anti-CD19 CAR T cell therapy, combined with standard lymphodepleting regimens, promotes remission in patients with systemic autoimmune diseases by fully depleting B cells within primary lymphatic organs."

CAR T-Cell Therapy • Clinical • Immunology

Study of KYV-101 Anti-CD19 CAR T Therapy in Adult Dermatomyositis (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatomyositis • Immunology • Myositis

ANTI-CD19 CAR T-CELL THERAPY FOR HLA DESENSITIZATION IN A HIGHLY ALLOIMMUNIZED KIDNEY TRANSPLANT CANDIDATE (EHA 2025) - "We present a case involving a complement-dependent cytotoxicity (CDC) crossmatch-positive patient who achieved clinically meaningful HLA desensitization following a single dose of KYV-101, a fully human anti-CD19 CAR T-cell therapy... This case illustrates the potential of single-dose anti-CD19 CAR T-cell therapy in achieving meaningful HLA desensitization in highly sensitized kidney transplant candidate. The in-depth examination of HLA antibody, B cell, Plasma cell, and T cell responses following CD19 depletion challenges current paradigms regarding the optimal targets for disrupting anti-HLA immune memory. Long-term monitoring and evaluation of multiple patients within clinical trials are essential to determine the durability of this effect, evaluate the risk of antibody recurrence, and thoroughly establish the safety profile of this approach."

CAR T-Cell Therapy • Atypical Hemolytic Uremic Syndrome • Nephrology • Transplantation • CD19

Kyverna Therapeutics Provides Business Update and Reports First Quarter 2025 Financial Results (PRNewswire) - "Myasthenia Gravis (MG): Following a positive end-of-Phase 2 meeting with the FDA, Kyverna received written alignment confirming its plans to advance KYV-101 into a Phase 3 clinical trial. The Company plans to share details of the study design mid-year, including trial size and endpoints."

Clinical protocol • FDA event • Myasthenia Gravis

AAN 2025: CAR T-cell therapy for MS shows safety, efficacy in trials (Multiple Sclerosis News Today) - P1 | N=12 | NCT06138132 | "KYV-101 is being tested in an investigator-initiated open-label Phase 1 trial (NCT06138132) that’s taking place at the Stanford Multiple Sclerosis Center in California...Among these four participants, who ranged in age from 47 to 54, were three patients with SPMS and one with PPMS who failed to respond adequately to other treatments...The treatment was well tolerated, according to Dunn, with no reports of cytokine release syndrome, a potentially life-threatening side effect of CAR T-cell therapies marked by an excessive immune response. There were also no signs of severe brain toxicity in treated participants....Data showed that CAR T-cells were able to expand in the blood and spinal fluid, peaking between 10-21 days after KYV-101 infusion."

P1 data • Multiple Sclerosis

AAN 2025: CAR T-cell therapy for MS shows safety, efficacy in trials (Multiple Sclerosis News Today) - P1 | N=10 | NCT06451159 | "The second investigator-initiated Phase 1 trial (NCT06451159)...involves 10 participants with nonrelapsing SPMS or PPMS who are not responding adequately to other MS treatments...The two patients, ages 55 and 63, were both women with SPMS with a fairly high level of disability — according to Gupta, patients who have few treatment options and 'are at most need.'...The treatment also had a favorable safety profile in this trial, with no reported brain toxicity. However, the first patient experienced a prolonged and severe reduction in certain immune cells, which required supportive treatment, and the second had cytokine release syndrome manifesting as a mild fever that was easily managed with treatment...In addition to these two studies, Kyverna is also running a Phase 2 clinical trial called KYSA-7 (NCT06384976)....Top-line data is expected in 2027."

P1 data • P2 data • Multiple Sclerosis

An Investigator Initiated Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (S3.002). (PubMed, Neurology) - "Dr. Cree has received publishing royalties from a publication relating to health care."

Clinical protocol • Journal • CNS Disorders • Inflammation • Multiple Sclerosis • Oncology • Solid Tumor

INDUCTION OF B CELL DEPLETION IN THE BONE MARROW THROUGH ANTI-CD19 CAR T CELL THERAPY IN PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES (EBMT 2025) - " Three patients with severe, treatment-refractory SARDs (Table 1) underwent autologous anti-CD19 CAR T cell therapy using KYV-101 (Kyverna Therapeutics, Emeryville, CA, USA) following lymphodepletion with fludarabine and cyclophosphamide. This study supports the notion that anti-CD19 CAR T cell therapy, in conjunction with standard lymphodepleting therapy, induces remission in patients with SARDs by achieving complete depletion of autoreactive B cells within primary lymphatic organs. References: 1 Müller F et al. N Engl J Med 20242 Tur C et al."

CAR T-Cell Therapy • Clinical • ANCA Vasculitis • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis • CD27

A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell ( CAR-T) Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Stanford University | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Kyverna Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Kyverna is currently advancing two Phase 1/2 trials in LN, KYSA-1 and KYSA-3. Kyverna has completed the dose-escalation cohort of KYSA-1 and is now treating patients at the target dose and expects to report Phase 1 data from both of these trials in the second half of 2025....Kyverna expects to file an investigational new drug application for KYV-102 in the second half of 2025."

IND • P1 data • Trial status • Lupus Nephritis

Kyverna Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Kyverna has aligned with the FDA on a registrational Phase 2 design for its ongoing KYSA-8 trial in SPS, which has enrolled 70% of study participants. Completion of enrollment is expected in mid-2025. The Company expects to report topline data from this study in the first half of 2026 and anticipates submitting its first BLA in 2026....Kyverna's Phase 2 trial in MG, KYSA-6, has completed patient enrollment in an initial 6-patient cohort and the Company plans to report interim data from this cohort in the second half of 2025. The Company continues to engage in positive dialogue with the FDA and plans to provide an update on the registrational path for KYV-101 in the first half of this year."

FDA event • FDA filing • P2 data • Trial status • Immunology • Myasthenia Gravis

Design of KYSA-6, a Phase 2, Open-label, Multicenter Study of KYV-101, a Novel Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Refractory Generalized Myasthenia Gravis (AAN 2025) - P2 | "After lymphodepletion (fludarabine 30 mg/m2/day, cyclophosphamide 300 mg/m2/day; 3 days), patients will receive a single infusion of KYV-101 at the target dose of 1×108 CAR T cells. KYV-101 is a novel therapy with the potential to change the treatment paradigm through deep B-cell depletion and immune reset with a single infusion in patients with B-cell driven autoimmune diseases like MG. KYV-101 is also under investigation in additional neurologic and rheumatologic diseases."

CAR T-Cell Therapy • Clinical • P2 data • CNS Disorders • Hematological Disorders • Immunology • Myasthenia Gravis • Rheumatology

Design of KYSA-8, A Phase 2, Open-Label, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Treatment-Refractory Stiff-Person Syndrome (AAN 2025) - P2 | "Design/Twenty-five patients 18-75 years old, with active seropositive SPS and inadequate response to at least 1 immunomodulatory therapy (IVIG, rituximab, or plasmapheresis), and stiffness index ≥2, are eligible...Following lymphodepletion (fludarabine 30 mg/m2/day, cyclophosphamide 300 mg/m2/day; 3 days), patients will receive a single infusion of KYV-101 at the target dose of 1×108 CAR T cells...KYSA-8 is the first phase 2 study of anti-CD19 CAR T-cell therapy in refractory SPS. KYV-101 may potentially change the immunotherapy paradigm through deep B-cell depletion and immune reset in autoimmune diseases like SPS."

Clinical • IO biomarker • P2 data • Bone Marrow Transplantation • CNS Disorders • Immunology • Inflammation

An Investigator Initiated Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (AAN 2025) - "The present trial will provide preliminary data which we expect will support the use of CD19 CAR T-cell therapy for this disease. All available data will be presented at the time of the conference."

CAR T-Cell Therapy • CNS Disorders • Inflammation • Multiple Sclerosis

A Phase 1, Open-label, Single Center Study of KYV-101, an Autologous Fully-human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis (AAN 2025) - "We report initial results of a Phase 1 open-label trial of CAR-T/CD-19 immunotherapy in progressive Multiple Sclerosis. Subjects enrolled to date have shown excellent tolerance without CRS, ICANS or greater than Grade 1 adverse events according to the CTCAE Version 5 rating scale. CAR-T/CD-19 IV infusion generated robust in vivo CAR-T cell proliferation, robust CNS penetration, and evidence of peak immunomodulation at Day 14 post-infusion."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis

An Investigator Initiated Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (ACTRIMS Forum 2025) - "She was noted to have grade 3 transaminitis and a cutaneous erythematous response on day 38 requiring oral prednisone suspicious for late CAR expansion. Improving treatments for patients with progressive MS is a major unmet need. The present trial will provide preliminary data which we expect will support the use of CD19 CAR T-cell therapy for this disease. As of Oct 2024, one patient has been treated."

CAR T-Cell Therapy • IO biomarker • CNS Disorders • Inflammation • Multiple Sclerosis

A Phase 1 Open-Label, Single Center Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Progressive Forms of Multiple Sclerosis (ACTRIMS Forum 2025) - "12 subjects aged 18-65 years in open label undergo apheresis, lymphodepletion with bendamustine 90 mg/m2 IV on days 5 and 4 prior to infusion of autologously derived lentivirus engineered CAR-T/CD-19 cells at an initial dose of 33 million cells IV with inpatient observation over 8 days, upscaling to a single 100M dose according to tolerance in the 3 x 3 study design. CAR-T immunotherapy in progressive MS patients enrolling in this Phase 1 prospective open label trial has been well tolerated to date. No treated subjects have experienced CRS, ICANS, seizures, or adverse events greater than Grade 1 in CTCAE v.5 assessment. Infused CAR-T cells have shown robust expansion in vivo, and have been shown by CAR-FACS analysis of cerebrospinal fluid to access the central nervous system in high numbers."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • CNS Disorders • Epilepsy • Inflammation • Multiple Sclerosis

CARTIMMUNE: Study of Patients with Autoimmune Diseases Receiving KYV-101 (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: David Porter | Recruiting ➔ Active, not recruiting

Enrollment closed • ANCA Vasculitis • Immunology • Inflammatory Arthritis • Myositis • Nephrology • Scleroderma • Systemic Sclerosis • Vasculitis

Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients. (PubMed, Int J Mol Sci) - "Notably, autoimmune-patient-derived CAR T-cells produced lower levels of inflammatory cytokines than healthy-donor-derived CAR T-cells in response to CD19+ B-cell targets. These data support the potential of Hu19-CD828Z and its therapeutic cell product KYV-101 as a therapeutic strategy to achieve deep B-cell depletion in SLE, IIM, and SSc patients, and highlights its promise for broader application in B-cell-driven autoimmune disorders."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Bruce Cree | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Kyverna Therapeutics to Highlight Near-Term Strategic Priorities and Key Milestones at the 43rd Annual J.P. Morgan Healthcare Conference (PRNewswire) - "Stiff Person Syndrome: Complete pivotal Phase 2 enrollment mid-2025; Report topline pivotal Phase 2 data 1H 2026; BLA filing in 2026; Myasthenia Gravis: Confirm registrational path with regulators 1H 2025; Report interim Phase 2 data 2H 2025; Lupus Nephritis: Report Phase 1 data 2H 2025..."

Enrollment status • FDA filing • P1 data • P2 data • Regulatory • Immunology • Lupus Nephritis • Myasthenia Gravis

Successful Generation of Anti-CD19 CAR T-Cells (KYV-101) for Clinical Use in Patients with Clinically Diverse Autoimmune Disorders (TCT-ASTCT-CIBMTR 2025) - "KYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results demonstrate the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types, supporting ongoing clinical trials in lupus nephritis (KYSA-1, KYSA-3), systemic sclerosis (KYSA-5), myasthenia gravis (KYSA-6), multiple sclerosis (KYSA-7), and stiff person syndrome (KYSA-8)."

CAR T-Cell Therapy • Clinical • CNS Disorders • Glomerulonephritis • Hematological Disorders • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Multiple Sclerosis • Myasthenia Gravis • Nephrology • Rheumatology • Scleroderma • Systemic Sclerosis • CD4 • CD8 • IFNG

KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Kyverna Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

A Study of Kyv-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis (ASH 2024) - P1 | "Currently approved treatments include siponimod, an S1P receptor modulator, and ocrelizumab, an anti-CD20 monoclonal antibody...After apheresis and CAR T-cell production, participants will receive standard lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single infusion of KYV-101 at one of two dose levels...The study is expected to complete in 2026. MRS and SG contributed equally to the work"

CAR T-Cell Therapy • CNS Disorders • Hematological Disorders • Multiple Sclerosis

CD19-Directed CAR T Cell Therapy in 4 Patients with Refractory Multiple Sclerosis (ASH 2024) - "A single dose of 1 x 108 second-generation anti-CD19-directed CAR T cells (KYV-101, Kyverna Therapeutics) was administered following lymphodepletion with fludarabine (30 mg/m2 on day -5, -4, -3) and cyclophosphamide (300 mg/m2 on day -5, -4, -3)...After CAR T infusion 3 of the 4 patients experienced reoccurring CRS grade 1 requiring treatment with tocilizumab, dexamethasone or anakinra...Short term follow-up indicates temporary target effects with at the same time signs of new inflammation in MRI imaging as well as clinical progression in one patient although long term data is needed. Further data will be presented."

CAR T-Cell Therapy • Clinical • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Multiple Sclerosis • Neutropenia • Pain