Kineta, Inc, a biotechnology company focused on the development of immune modulating drugs for critical diseases, announced safety and clinical results from its proof-of-concept phase 1b clinical trial of dalazatide in patients with active plaque psoriasis.

Dalazatide, formerly ShK-186, is a potent inhibitor of the Kv1.3 potassium channel, and a first-in-class drug candidate that has the potential to selectively target autoimmune disease-causing cells while leaving the patient’s protective immune response unaffected.

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 specific Kv1.3 inhibitor advanced into human clinical trials.

Dalazatide has shown promise in nonclinical studies involving a number of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, psoriasis, psoriatic arthritis, type 1 diabetes mellitus, atopic dermatitis, asthma, ANCA vasculitis and autoimmune uveitis. Kineta was the first company to bring a Kv1.3 inhibitor into human clinical trials and has conducted two previous safety and tolerability studies of dalazatide in healthy volunteers. The current trial (186-03) was designed to further assess the safety, tolerability and broader pharmacodynamic opportunity for Kv1.3 blockade in a prototypical T-cell mediated autoimmune disease.

“With this trial, Kineta has shown that dalazatide is well positioned for phase 2 clinical development to explore efficacy in a number of prominent autoimmune diseases with significant unmet medical needs including lupus and multiple sclerosis, as well as for rarer diseases like vasculitis.”

A total of 24 patients with active plaque psoriasis and 3 per cent or more body surface area involvement were enrolled. Patients were required to have an adequate number of moderate-severity plaques to permit the longitudinal assessment of disease activity and biomarkers from serially collected skin biopsies. Patients were randomised to receive placebo, 30 mcg or 60 mcg doses of dalazatide twice weekly by subcutaneous injection for four weeks, followed by four weeks of follow-up. The treatment was well-tolerated with all subjects completing their scheduled doses. Biomarker analysis of blood and skin biopsies is ongoing. Kineta expects the biomarker results to be available later in the second quarter.

While the study was not powered to assess clinical efficacy, several relevant clinical disease endpoints were evaluated. At the end-of-treatment evaluation (day 32), one of ten and five of ten patients in the 30 mcg and 60 mcg groups, respectively, showed improvements in their target lesion score relative to baseline.

None of the placebo patients showed a similar improvement. Furthermore, patients experienced improvements as early as day 15 that were sustained throughout the follow-up period (four weeks following the last dose). Investigator and patient global assessments of psoriasis also improved, consistent with improvements in the target lesion score. Notably, nine of ten patients in the 60 mcg group showed an improvement in their psoriasis area and severity index (PASI) at the end-of-treatment evaluation. The mean improvement in PASI score in this group reached statistical significance.

Dalazatide potently inhibits the Kv1.3 potassium channel, a new and potentially important pharmaceutical target due to its expression on effector memory T-cells. Effector memory T-cells are a subset of the T-cell family that cause inflammation and tissue damage in a range of autoimmune diseases.

“The results of this trial indicate a potentially important advance in developing the next generation of treatments for autoimmune disease that specifically regulate the immune response without broad immune suppression,” said Kineta’s chief scientific officer, Shawn Iadonato. “Our hope is that future studies will confirm that other T-cells required for infection control and cancer surveillance do not depend on Kv1.3 and therefore are not blocked by dalazatide.”

“Kineta’s clinical development programme for dalazatide is intended to demonstrate the importance of selective Kv1.3 blockade in autoimmune disease,” Kineta’s CEO Charles Magness said. “With this trial, Kineta has shown that dalazatide is well positioned for phase 2 clinical development to explore efficacy in a number of prominent autoimmune diseases with significant unmet medical needs including lupus and multiple sclerosis, as well as for rarer diseases like vasculitis.”

“I am very excited to see the results of this study. Having taken care of patients with multiple sclerosis for over 25 years, dalazatide may offer a targeted treatment approach, unlike any we have seen before,” said Dr. Sylvia Lucas, M.D., Ph.D., clinical professor of Neurology & Neurological Surgery and adjunct clinical professor of Rehabilitation Medicine at the University of Washington Medical Center.

Alice Gottlieb M.D., Ph.D, dermatologist-in-chief, Tufts Medical Centre said “These clinical results in psoriasis are encouraging, not only as a validation of a potential role for dalazatide in these patients, but also as an indicator of a broader role for dalazatide in other autoimmune diseases where Kv1.3 is implicated. Additionally, as demonstrated in this trial, the potential for a durable response following treatment is also very intriguing.”

“This is the first potential demonstration of clinical activity for a Kv1.3 inhibitor. This mechanism could provide an important new approach to treating lupus where there currently are limited options available,” said Joan T. Merrill, M.D., head, Clinical Pharmacology Research Programme, Oklahoma Medical Research Foundation and Medical Director, Lupus Foundation of America.