Our Pipeline & Expanded Access

Cell Therapy: A Potentially Curative Approach to Autoimmunity

Kyverna is on the forefront of developing advanced cellular therapies designed to be selective, potent, and durable with sustained therapeutic effect. Our therapeutic platform leverages T cell engineering to target the underpinnings of autoimmunity, including chimeric antigen receptor T (CAR T) cells.

Creating “smarter” CAR T cells

Leveraging advances in CAR T engineering and insights from the use of conventional CAR T cell therapies for cancer, Kyverna is building a robust collection of cell therapy assets and tools to address multiple targets implicated in the pathogenesis of autoimmune diseases.

Targeted cellular therapies that address the complexities of the immune system and its various disease mechanisms

Using our T cell engineering platform, we are programming immune cells with instructions to eliminate pathogenic cells in the diseased tissues in which they are exerting their deleterious effects. Our product candidates leverage our deep understanding of the pathogenesis of autoimmune diseases to select the appropriate technology for each disease.

CAR T cells with the potential for therapeutic breakthrough in B-cell driven autoimmune diseases.

Kyverna is the exclusive world-wide licensee of a next-generation CAR T construct targeting CD19 for use in autologous (KYV-101) and allogeneic (KYV-201) cell therapies for B-cell driven autoimmune diseases. Designed with favorable characteristics for use in autoimmunity, KYV-101 and KYV-201 combine a fully human anti-CD19 CAR with costimulatory domains designed to minimize cytokine release, maximize B-cell depletion, and improve clinical tolerability.

In a 20-patient Phase 1/2 study in oncology, expected anti-lymphoma activity was associated with a significant reduction of cytokines released. Of note, in patients who received the new construct, a ten-fold reduction in the rate of severe neurological toxicity was observed compared to patients who received T cells transduced with an earlier generation, murine-based construct. The fully human anti-CD19 CAR also translated into reduced immunogenicity that favorably impacted cell persistence at one month.1

Preclinically, CD19-targeted CAR T-cell therapies have been shown to induce deep and complete B cell depletion in both the circulation and tissues resulting in striking efficacy in disease models supporting the promise of a transformative impact for the approach in patients with B-cell driven autoimmune diseases.2 B cells are important for disease pathogenesis, and tissue-based B cells are resistant to depletion by existing agents. Overall, existing approaches to address B-cell driven autoimmune diseases are often limited by either modest effects, leading to resistant and uncontrolled disease, or significant treatment-related morbidity and mortality.

Prior generations of anti-CD19 CAR T cells rely on mouse-derived CD19 binding domains and are associated with high levels of cytokine production. Importantly, high cytokine production has been shown to translate to cytokine release syndrome.3 In contrast, KYV-101 and KYV-201 use a fully human anti-CD19 CAR and costimulatory domains designed to minimize cytokine production. These two combined attributes are of particular importance for use in autoimmune disease patients because (i) autoimmune disease patients are known to mount immune reactions against foreign mouse proteins and (ii) the cytokines released in high amounts by traditional CAR T cells are the same cytokines that can drive autoimmune diseases. The impact our anti-CD19 CAR has had on reducing clinically relevant immunogenicity and on minimizing the production of disease-driving cytokines has been extensively characterized.1

Expanded access policy

Kyverna Therapeutics is committed to developing a safe and effective autologous anti-CD19 CAR-T cell therapy for the treatment of lupus nephritis. Participation in clinical trials is the best way to access our investigational product.

Expanded access is the use of an investigational product outside of a clinical trial for the treatment of a serious or life-threatening condition. When participating in a clinical study is not possible, Kyverna may consider requests for expanded access in rare circumstances when an individual has no other comparable or satisfactory alternative therapy options available or is not eligible to participate in a current Kyverna clinical trial.

Patients are encouraged to speak to their doctors about whether a clinical trial is right for them. Treating physicians can find more information on our ongoing clinical trials by visiting clinicaltrials.gov or request information about our clinical trials or expanded access for a Kyverna therapy by contacting Kyverna at clinicaltrials@kyvernatx.com. Kyverna will acknowledge inquiries as soon as possible, usually within 5 business days of receipt.

Pursuant to the 21st Century Cures Act, Kyverna may revise this policy at any time and this policy shall not serve as a guarantee of access to any specific investigational therapy by any individual.

 

References

  1. Brudno J et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nature Medicine 2020;26:270-280.
  2. Kansal R et al. Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Science Translational Medicine 2019; 11(482):eaav1648.
  3. Frigault et. al. State of the art in CAR T cell therapy for CD19+ B cell malignancies. JCI 2020; 130(4):1586-1594.

 

Haghikia A, et al. Anti-CD19 CAR T cells for refractory myasthenia gravis. Lancet Neurology 2023;22:P1104-1105

Park S. et al. KYV-101, a Fully Human Anti-CD19 CAR T Cell Therapy, Demonstrates CAR-Mediated and CD19-Dependent Activity Against Autologous B Cells from Patients with Autoimmune Disease. ACR Convergence 2023, Abstract #0904

Schett, G., et al. CAR T-cell therapy in autoimmune diseases. Lancet, 2023 Nov 25;402(10416):2034-2044.

Mackensen A, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022, 28:2124-2132

Mougiakakos D, et al. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med 2021;385:567-569

Müller F, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. Lancet 2023;401(10379):815-818

Bergmann C, et al. Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann Rheum Dis 2023; 82(8):1117-1120

Pecher AC, et al. CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome. JAMA 2023;329(24):2154-2162

Alabanza L, et al. Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains. Mol Ther 2017 Nov 1;25(11):2452-2465

Harrison S, et al. CAR+ T-Cell Lymphoma Post Ciltacabtagene Autoleucel Therapy for Relapsed Refractory Multiple Myeloma. Blood (2023) 142 (Supplement 1): 6939