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Nektar Presents New Preclinical Data for NKTR-358, a First-in-Class Regulatory T Cell Stimulator, at 13th World Congress of Inflammation in London

"These studies show that NKTR-358 increases the suppressive capacity and prolongs activation and proliferation of regulatory T cells with limited effects on conventional T cells in order to address the imbalance found in many autoimmune diseases," said Jonathan Zalevsky, PhD, Senior Vice President, Biology and Preclinical Development at Nektar Therapeutics. "NKTR-358 also demonstrated suppression of antigen-driven inflammation in multiple preclinical models including systemic lupus erythematosus. We are very excited about NKTR-358's potential as a resolution therapy in autoimmune disease."

More than 23 million Americans have an autoimmune disease - nearly eight percent of the U.S. population - and the prevalence is continuing to rise.i,ii There are more than 80 known types of autoimmune diseases, including lupus, Crohn's disease, psoriasis and rheumatoid arthritis.iii

Autoimmune diseases cause the immune system to mistakenly attack healthy cells in a person's body.iv A failure of the body's self-tolerance mechanisms enables the formation of the pathogenic auto-reactive T lymphocytes that conduct this attack. NKTR-358 works by optimally targeting the interleukin-2 (IL-2) receptor complex in order to stimulate proliferation and activation of regulatory T cells. By increasing the number of regulatory T cells, the pathogenic auto-reactive T cells can be controlled and the proper balance of effector and regulatory T cells can be achieved to restore the body's self-tolerance mechanisms.

In preclinical studies, NKTR-358 demonstrates attenuated and optimized affinity for human IL-2 receptors to promote biological activity favoring activation of regulatory T cells over conventional T cells. This preferential activity combined with prolonged exposure in vivo led to significant Treg mobilization in blood and spleen following a single subcutaneous administration in rodents. Increases in regulatory T cells were sustained for 7 to 10 days, and were concomitant with increases in cytometric markers of activation and increased suppressive capacity.

In non-human primates, a single administration of NKTR-358 led to increases in Treg mobilization and activity sustained for over 14 days, a response greatly superior in magnitude, duration and specificity compared to an equivalent total dose of rhIL-2 administered daily for five days. In a mouse model of cutaneous hypersensitivity, NKTR-358 administration significantly suppressed antigen-induced inflammatory responses, an effect which was antigen-specific and associated with establishment of Treg memory. Similar results were achieved in analogous model using...


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