Kronos Bio nominates development candidate for Sjogren’s Disease

Kronos Bio announced the nomination of a development candidate, KB-7898, a p300 lysine acetyltransferase inhibitor for the potential treatment of Sjogren’s disease, a chronic autoimmune disease that is characterized by the production of autoantibodies, chronic inflammation and lymphocytic infiltration of the exocrine glands that lead to uncomfortable dryness symptoms, known as sicca. Systemic effects are common and impact the lungs, kidneys and nervous system in addition to extensive dryness, profound fatigue and chronic pain. There are no approved treatments that target the underlying cause of Sjogren’s disease. Kronos Bio plans to initiate Investigational New Drug-enabling studies of KB-7898 in the fourth quarter of 2024. KB-7898 is being developed as an orally available therapy for people with Sjogren’s disease. p300 is an important cofactor for interferon regulatory factor 4 to enact immune responses across multiple cell types, including those that produce antibodies and cytokines. Given this, Kronos Bio also intends to explore the utility of KB-7898 in other autoimmune diseases in the future. The Company’s preclinical data that support the role of p300 in inflammatory indications, including Sjogren’s disease, will be presented at the American College of Rheumatology’s annual meeting, ACR Convergence 2024, on November 18, 2024, in Washington, DC. The data are summarized as follows: Inhibition of the KAT activity of p300, a critical cofactor of proinflammatory transcription factors, resulted in selective downregulation of cytokines such as TNFalpha, IL-23, IL-17A as well as soluble IgG Selective gene expression changes occurred at doses corresponding to partial inhibition of p300 KAT activity p300 KAT inhibition also led to significantly decreased inflammation in the rat CIA model, as measured by joint swelling, clinical score and histopathology In addition, p300 KAT inhibition in vitro showed a reduction in IL-17 transcript and protein levels in Th17 cells and, in vivo, showed significant decreases in the secondary immune response in the KLH challenge model.