KYV-101 was developed using the construct Kyverna licensed from the NIH in January 2022.
Kyverna Therapeutics has submitted its investigational new drug application (IND) for KYV-101, an autologous, fully human CD19+ chimeric antigen receptor (CAR) therapy for the potential treatment of lupus nephritis.1
"We are extremely proud to be leading a possible revolution in how we treat severe immune-related and inflammatory diseases. The filing of this IND for KYV-101 in lupus nephritis is an important milestone for Kyverna and we are excited by the prospect of KYV-101 opening a new era in the care of patients with LN. We strongly believe that KYV-101 may drastically change the course of this devastating disease," Peter Maag, PhD, chief executive officer,Kyverna Therapeutics, said in a statement.1 "We look forward to working with the FDA to initiate the KYV-101 clinical study."
KYV-101 is constructed using Kyverna’s therapeutic platform to imbue it with properties suited for B-cell driven autoimmune diseases like lupus nephritis and other such as systemic sclerosis and inflammatory myopathies. The platform uses synthetic biology technologies and T-cell engineering to eliminate autoreactive, autoinflammatory immune cells. The therapy has the potential to become a 1-time treatment for lupus nephritis, a serious complication of systemic lupus erythematosus (SLE). Around 40% of patients with SLE develop lupus nephritis and around 60% of these patients have disease refractory to standard of care. Current treatments include chronic corticosteroids and immunosuppressants and as a consequencemany patients with lupus nephritis develop kidney failure.
"Patients with lupus nephritis too often experience serious complications from the medications used to control the disease process or from the disease itself. We applaud the team at Kyverna for developing novel treatment approaches for these patients that today have very limited treatment options," Richard A. Furie, MD, The Marilyn and Barry Rubenstein Chair in Rheumatology, professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, chief of Division of Rheumatology, Northwell Health, and professor of medicine, Donald and Barbara Zucker School of Medicine at Hofstra University/Northwell Health, added to the statement.1
Kyverna obtained exclusive worldwide license to the CAR-T construct used in KYV-101, both for autologous and allogeneic therapies.2 The construct was developed in the laboratory of James N. Kochenderfer, MD, at the National Cancer Institute, part of the NIH, in which axicabtagene ciloleucel was also developed. The construct was designed to minimize cytokine release and improve clinical tolerability.
The construct previously showed efficacy in a 20-patient phase 1/2 study in patients with lymphomas.3 Investigators saw anti-lymphoma activity as well as a significant reduction of cytokine releases and immune effector cells-associated neurotoxicity syndrome. Reduced immunogenicity was also seen with the therapy which led to favorable cell persistence at 1 month.
"Targeting B cells has shown promise in treating many autoimmune diseases, but much room for improvement in efficacy remains," James Chung, MD, PhD, chief medical officer, said in an earlier statement.3 "We believe that a more complete depletion of circulating and tissue resident B cells expected with our CAR T therapy KYV-101 will translate to significantly greater efficacy.”