NKTR-358 is designed to correct the underlying immune system dysfunction shared by several autoimmune diseases. The drug candidate selectively stimulates the growth and activation of regulatory T-cells to restore the body’s self-tolerance mechanisms.
Having an autoimmune disease means that our immune system mistakenly attacks healthy cells. A failure of the body’s self-tolerance mechanisms (meaning the recognition of the body’s own molecules) enables the formation of harmful T-cells, which conduct these attacks.
NKTR-358 targets the interleukin-2 (IL-2) receptor complex to stimulate the proliferation and activation of regulatory T-cells, which can control auto-reactive T-cells, thereby balancing the body’s self-tolerance mechanisms.
The Phase 1 trial will evaluate the pharmacokinetics (how the drug behaves in the body) and safety of NKTR-358 in single-ascending doses of the drug in approximately 50 healthy volunteers.
Researchers will assess changes and functional activity of regulatory T-cells, aiming to establish a range of dose levels that could be used in future trial studies.
In preclinical studies, NKTR-358 has been shown to effectively suppress inflammation in a model of cutaneous hypersensitivity. The investigational drug was also shown to reduce markers of disease progression in a mouse model of lupus.
“NKTR-358 has the potential to be a first-in-class key resolution therapeutic in immunology,” Jonathan Zalevsky, PhD, vice president of biology at Nektar Therapeutics, said in a press release.
“Data from non-human primate studies show that NKTR-358 drives proliferation and increased functional activity of regulatory T-cells (Tregs),” Zalevsky said. “Suboptimal Treg numbers and their lack of activity underlie many autoimmune diseases, including lupus, Crohn’s disease, psoriasis, rheumatoid arthritis and multiple sclerosis.”
“As the first potential medicine to restore appropriate Treg levels and function, NKTR-358 could address a critical unmet need for patients with serious and debilitating immune disorders,” he added.
In the U.S., 23.5 million Americans are estimated to live with an autoimmune disease – accounting for nearly 8 percent of the total U.S. population. There are over 80 known types of autoimmune diseases, including lupus, Crohn’s disease, psoriasis, and rheumatoid arthritis.
A multiple-ascending dose trial is planned to evaluate NKTR-358 in patients with lupus in the second half of 2017.