Experimental Sjögren’s therapy shows potential in early lab studies
KB-7898 reported to lower immune activity in animal and cell models
KB-7898, Kronos Bio’s investigational therapy for Sjögren’s disease, was shown to lower antibody production and the release of inflammatory molecules in lab studies involving cell and animal models of autoimmune conditions, the company announced.
Kronos is planning further preclinical studies to assess KB-7898’s safety and pharmacological properties later this year. These studies may support a request to bring KB-7898 into a clinical trial in people.
“Sjögren’s disease symptomatology can significantly impact quality of life and even be life threatening, and patients do not currently have access to an approved therapy that addresses the underlying disease mechanism,” Nobert Bischofberger, PhD, Kronos’ president and CEO, said in a company press release.
“KB-7898 has been shown preclinically to reduce antibody production in B cells and cytokine production in T cells, and we believe could impact the etiology [underlying cause] of Sjögren’s disease,” Bischofberger added.
KB-7898 is designed to block factors that underlie antibody production
An autoimmune disease, Sjögren’s is caused by self-reactive antibodies produced by the immune system that launch an inflammatory attack against the glands responsible for tears and saliva, leading to hallmark disease symptoms of dry eyes and mouth. Other organs, including the lungs, kidneys, and the nervous system, also can be affected.
These symptoms can significantly impact patients’ quality of life and lead to life-threatening complications. No approved treatments exist that work to target its underlying cause.
KB-7898 is being developed as an orally available therapy for Sjögren’s and possibly other autoimmune diseases. It works by inhibiting the lysine acetyltransferase (KAT) domain of p300, an activator of proinflammatory transcription factors that underlie antibody production by immune B-cells, and the release of molecules that regulate the activity of other immune cells, called cytokines, by another type of immune cell called T-cells.
A transcription factor is a molecule that regulates gene transcription — the process by which the information contained in a gene’s DNA sequence is transformed into messenger RNA, a molecule that’s used as a template for protein production.
KB-7898 was identified through the company’s proprietary screening platform, which enables the detection of proteins that can bind to transcription factors and modulate their activity.
“Our proprietary discovery engine has enabled us to decode the multifaceted role of p300 across multiple cell types that drive inflammation and to create our second p300 KAT inhibitor — one that may treat autoimmune diseases,” Bischofberger said.
In the preclinical studies, p300 inhibition was shown to reduce the production of inflammatory molecules, including tumor necrosis factor-alpha, interleukin (IL)-23, IL-17A, as well as the production of antibodies.
Blocking p300 also was shown to lessen inflammation in a rat model of rheumatoid arthritis, another autoimmune disease, and to decrease antibody production in another model of induced immunity.
Detailed preclinical data will be presented on Nov. 18 at the American College of Rheumatology’s annual meeting, now running through Nov. 19 in Washington, D.C.
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