Kineta, Inc., a biotechnology company focused on the development of immune modulating drugs for critical diseases, today presented encouraging pre-clinical animal results using ShK-186 in a novel ocular formulation as a topical therapy for autoimmune eye disease. The results presented at the 7th Ocular Diseases Drug Discovery Conference showed topical administration of ShK-186 reduced disease severity and the infiltration of damaging inflammatory cells in an animal model of anterior uveitis. Previous research has also shown that systemic administration of Kineta’s ShK-186 is effective in preventing and treating disease in models of psoriasis, multiple sclerosis, rheumatoid arthritis and autoimmune kidney diseases, among others.
“Initial work with ShK-186 demonstrated that topical administration of the drug to the surface of the eye is well-tolerated and results in significant accumulation in the anterior chamber, inside the eye,” said Ernesto J. Muñoz, Associate Director Translational Immunology and Preclinical Development at Kineta in a talk at the meeting. “Our work using a model of anterior uveitis, an autoimmune eye disease, shows that ShK-186 is able to prevent disease and inflammatory cell infiltration including T cells expressing the Kv1.3 channel. Blocking effector memory T cells via targeting of Kv1.3 is a novel strategy to treat ocular autoimmune diseases including chronic anterior uveitis, Sjogren’s syndrome and dry-eye disease.”
In these diseases, it was already suspected that inflammation was driven by pathogenic T cells. However, it was not known whether these cells were dependent on Kv1.3 for function.
“In this work, we show that the T cells infiltrating the anterior chamber of the eye express Kv1.3 and are sensitive to treatment with ShK-186. The next step is to validate Kv1.3 as a target in uveitis and dry eye in human patients. This is being done through translational research collaboration with Drs. Cintia De Paiva and Stephen Pflugfelder from the Ocular Surface Center-Baylor College of Medicine,” Dr. Muñoz concluded.
Link to poster: ShK-186 Poster
Kv 1.3 MOA webcast On April 2, 10 a.m. pacific, Kineta will host an online introduction and discussion of the Kv1.3 channel as a novel, high potential drug target for autoimmune diseases. Speakers will include Dr. Christine Beeton of Baylor College of Medicine and Dr. Anne Stevens of Seattle Children’s Hospital. Reporters are invited to contact email@example.com for link to registration.
Shk-186 has a novel mechanism of action (MOA). Preclinical data have shown that ShK-186 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. ShK-186 was the first Kv1.3 specific inhibitor advanced into human clinical trials and Kineta is nearing completion of a Phase 1b clinical trial studying ShK-186 in psoriasis patients. ShK-186 is also being studied as a potential therapy in other autoimmune diseases, including multiple sclerosis, lupus, type 1 diabetes and inflammatory bowel disease.
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Image Credit: Kineta