Kronos Bio's Breakthrough: A New Hope for Sjögren's Disease

Kronos Bio, Inc. (Nasdaq: KRON) has made a significant stride in the fight against autoimmune diseases with the nomination of KB-7898 as its first development candidate for Sjögren's disease. This orally available therapy targets the lysine acetyltransferase (KAT) domain of p300, a critical cofactor for immune responses across multiple cell types. The company plans to initiate Investigational New Drug (IND)-enabling studies of KB-7898 in the fourth quarter of 2024.

Sjögren's disease is a chronic autoimmune disorder characterized by the production of autoantibodies, chronic inflammation, and lymphocytic infiltration of the exocrine glands. It affects approximately two to four million people in the U.S., with women being significantly more impacted. The disease is associated with extensive dryness, profound fatigue, and chronic pain, as well as systemic effects on the lungs, kidneys, and nervous system. Currently, there are no approved treatments that target the underlying cause of Sjögren's disease.

Preclinical data presented by Kronos Bio supports the role of p300 KAT inhibition in inflammatory indications, including Sjögren's disease. Inhibition of p300 KAT activity resulted in selective downregulation of cytokines such as TNFα, IL-23, and IL-17A, as well as soluble IgG. Selective gene expression changes occurred at doses corresponding to partial inhibition of p300 KAT activity. Furthermore, p300 KAT inhibition led to significantly decreased inflammation in the rat CIA model and reduced IL-17 transcript and protein levels in Th17 cells. In vivo, it showed significant decreases in the secondary immune response (i.e., IgG production) in the KLH challenge model.

Kronos Bio's proprietary discovery engine has enabled the company to decode the multifaceted role of p300 across multiple cell types that drive inflammation. The development of KB-7898, a second p300 KAT inhibitor, could potentially treat autoimmune diseases, including Sjögren's disease. The company believes that KB-7898 has the potential to impact the etiology of Sjögren's disease by reducing antibody production in B cells and cytokine production in T cells.

The nomination of KB-7898 as a development candidate for Sjögren's disease has the potential to significantly impact the competitive landscape in the autoimmune disease treatment market. With no approved therapies targeting the underlying cause of Sjögren's disease, Kronos Bio's innovative approach offers hope for patients suffering from this debilitating condition.

The expected timelines and milestones for the IND-enabling studies and clinical trials of KB-7898 in Sjögren's disease are yet to be announced. However, Kronos Bio plans to present its preclinical data at the American College of Rheumatology's annual meeting, ACR Convergence 2024, on November 18, 2024, in Washington, DC. The data will be available under the Science & Pipeline section of the Kronos Bio website on November 14, 2024, and the abstract can be found on the American College of Rheumatology's website.

In conclusion, Kronos Bio's nomination of KB-7898 as a development candidate for Sjögren's disease represents a significant advancement in the fight against autoimmune diseases. The company's innovative approach, targeting the lysine acetyltransferase (KAT) domain of p300, offers hope for patients suffering from this chronic and debilitating condition. As the company continues to advance its pipeline, investors should keep a close eye on Kronos Bio's progress in the autoimmune disease treatment market.