LONDON--(BUSINESS WIRE)--Kineta, Inc., a biotechnology company focused on the development of immune modulating drugs for critical diseases, and researchers from the University of Groningen, Netherlands, announced new data from a study that showed dalazatide (formerly ShK-186) is effective in immunomodulating the cells causing inflammation and damage of small blood vessels in various organs in samples from patients with Granulomatosis with Polyangiitis (GPA). ANCA-associated vasculitis illnesses such as GPA are rare autoimmune diseases but can be severe, affect multiple organ systems and lead to kidney failure and lung hemorrhage. In the US, vasculitis diseases account for 300,000 hospitalizations each year and are associated with significant morbidity and mortality. The data were presented at the 17th International ANCA and Vasculitis Workshop in London by Kineta collaborators Lucas L. Lintermans and Dr. Wayel H. Abdulahad.
The collaboration between Kineta and the University of Groningen was based on earlier published research by Dr. Abdulahad showing that during flares of disease, GPA patients had elevated numbers of effector memory T cells in their urine. “A key question was whether these effector memory T cells expressed high levels of Kv1.3 and could be functionally blocked by dalazatide,” stated Dr. Ernesto J. Muñoz, Associate Director of Translational Immunology at Kineta.
In today’s study data, funded by the Dutch Arthritis Foundation, circulating mononuclear cells were isolated from the blood of GPA patients and from healthy volunteers. The cells were treated in culture with dalazatide which is a selective Kv1.3 channel blocker. Results showed that the T cells from GPA patients made higher levels of inflammatory cytokines upon in vitro stimulation, and these inflammatory cytokines were lowered in the presence of dalazatide. Cytokines are the “communicators” and activators in the body’s immune system.
“Treatment with dalazatide caused the patient T cells to reduce their production of inflammatory cytokines including IL-7A, IFN gamma and TNF alpha to the levels observed in the healthy volunteer’s cells. Importantly, the cells that showed this reduction were only the effector memory T cells while naïve and central memory T cells were not affected,” said Lintermans, the PhD candidate performing the studies. This suggests that dalazatide may suppress the cells causing vascular inflammation in GPA patients without impairing the ability of patients to fight infections.
“Validation of Kv1.3 as a target for ANCA* vasculitis lends a rationale for exploring the therapeutic scope of dalazatide in other autoimmune diseases that affect the kidney, including most notably, lupus nephritis,” concluded Dr. Abdulahad, principal investigator of the study.
Previous research has also shown that systemic administration of dalazatide is effective in preventing disease in models of psoriasis, multiple sclerosis, rheumatoid arthritis and autoimmune kidney diseases, among others. Dalazatide is also currently being tested in a proof of concept Phase 1B clinical trial in psoriasis patients. Data is expected in the second quarter of 2015.
Dalazatide (formerly ShK-186) has a novel mechanism of action (MOA). Preclinical data have shown that dalazatide is a selective and potent blocker of the voltage-gated Kv1.3 potassium channel, which is a key channel in the activation of effector-memory T cells. Effector memory T cells are implicated in the pathology of many autoimmune diseases. Dalazatide was the first Kv1.3 specific inhibitor advanced into human clinical trials. Dalazatide is also being studied as a potential therapy in other autoimmune diseases, including multiple sclerosis, lupus, type 1 diabetes, inflammatory bowel diseases and autoimmune eye diseases. The lupus, multiple sclerosis, and inflammatory bowel disease research is being conducted in conjunction with the Alliance for Children’s Therapeutics, a drug development and funding collaboration between Kineta and Seattle Children’s Research Institute. *(ANCA) anti-neutrophil cytoplasmic antibodies
Kineta, Inc. is a Seattle-based privately held biotechnology company specializing in clinical advancement of novel drug candidates derived from leading edge scientific research. Our world-class scientists are pioneers in developing life-changing classes of new drugs designed to be more effective and safer than current medicines. Kineta seeks to improve the lives of millions of people suffering from autoimmune and viral diseases and from severe pain. Our progressive business model focuses on targeting unmet medical needs and rapid achievement of important clinical milestones. For more information on Kineta, Inc. visit our website, www.Kinetabio.com
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