Lupus Nephritis CAR-T Therapy Cleared for Phase 1/2 Clinical Trial


KYV-101 is an autologous version of a CD19-directed fully human CAR-T construct.

Kyverna Therapeutics’ KYV-101, an investigational chimeric antigen receptor (CAR) T-cell therapy intended to treat lupus nephritis, has received clearance of its investigational new drug (IND) application, which was submitted to the FDA in October of this year.1,2

“We are pleased with the FDA’s clearance of our IND application for our lead candidate KY-101 in lupus nephritis,” Peter Maag, PhD, chief executive officer, Kyverna Therapeutics, said in a statement regarding the news.1 “This is a huge achievement for Kyverna and a significant moment in the field of cell therapies targeting autoimmune disease. We look forward to working with investigators to initiate our phase 1 clinical trial in early 2023 and to continue our commitment to bringing novel treatment options to this vulnerable patient population living with this devastating disease.”

KYV-101 is an autologous version of a CD19-directed fully human CAR-T construct.1,2 The construct also has potential applications for autologous and allogeneic treatments for systemic sclerosis and inflammatory myopathies. The construct has previously been evaluated in a phase 1 clinical trial for patients with B-cell lymphomas and patients with chronic lymphocytic leukemia (NCT02659943).The trial, sponsored by the National Cancer Institute, was open to patients aged 18 to 73 years and ultimately included 20 patients. The study demonstrated anti-lymphoma activity which was associated with a reduction in cytokine-driven adverse events, including immune effector cells-associated neurotoxicity syndrome (ICANS). The cell product also showed reduced immunogenicity which had a beneficial effect on cell persistence at 1 month.

Based on these results, Kyverna Therapeutics decided to obtain exclusive worldwide rights to the construct from the National Institutes of Health for the use in autologous and allogeneic CAR-T therapies. The company believes the construct has potential for the treatment of patients with autoimmune diseases, including lupus nephritis. Notably, Kyverna’s fully human construct may be better tolerated by patients with autoimmune disorders, as traditional anti-CD19 CAR-T cells have relied on mouse-derived CD19 which can cause significant immune reactions against the foreign mouse proteins and generate significant cytokine release–the same cytokines behind many autoimmune diseases. It is now working with clinical trial sites in both the United States and Europe to initiate a phase 1/2 trial to evaluate KYV-101 for this indication.

“There is a clear need for additional therapies for lupus nephritis, as current interventions are limited in their rates of response,” Peter A. Merkel, MD, MPH, chief of rheumatology and professor of medicine and epidemiology, University of Pennsylvania, added to the statement.1 “Given recent publications showing the potential of cell-based therapy for patients with lupus nephritis, it is exciting to see that a clinical trial is commencing in this indication. This work also holds promise for other B-cell-driven autoimmune diseases.”

CGTLive previously spoke with Kyverna’s chief technology officer, Karen Walker, about the company’s SmarTcell genetic engineering platform being used to develop candidates, including CAR-T and synthetic regulatory T-cells. Watch now.

1. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat lupus nephritis. News release. Kyverna Therapeutics. November 11, 2022. 
2. Kyverna Therapeutics submits IND for novel CAR T-cell therapy to treat lupus nephritis. News release. Kyverna Therapeutics. October 18, 2022. 
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