Nektar Therapeutics has commenced dosing patients with systemic lupus erythematosus (SLE) in a Phase 1b clinical study evaluating NKTR-358, a first-in-class regulatory T cell stimulator. NKTR-358 selectively stimulates the proliferation and activation of regulatory T cells (Tregs) in the body in order to restore the body's self-tolerance mechanisms. Unlike immunosuppressant medicines that treat the symptoms of autoimmune disease by inhibiting the entire immune system which can cause unwanted side effects, NKTR-358 is designed to correct the underlying immune system dysfunction found in patients with immune disorders such as SLE.
"NKTR-358 has the potential to address the immune system imbalance that underlies autoimmune diseases such as lupus by driving the expansion and functional activity of Tregs to restore immune homeostasis in the body," said Brian Kotzin, M.D., Senior Vice President, Clinical Development and NKTR-358 Program Lead at Nektar Therapeutics. "We are excited about the start of the clinical study and the potential of NKTR-358 to provide a positive benefit for patients with SLE."
The Phase 1b study is a double-blind, randomized, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics and immunological effects of multiple ascending doses of NKTR-358 in approximately 50 patients with systemic lupus erythematosus (SLE). The study will also evaluate the effects of NKTR-358 on disease activity in SLE patients.
A progressive imbalance of regulatory T cells relative to conventional T cells is shared by many autoimmune diseases, including SLE. During disease flares, the number of circulating Tregs decreases in SLE patients and their immune suppressive function is impaired contributing to a loss of self-tolerance, the production of autoantibodies, and development of disease manifestations.
In July 2017, Nektar entered into a strategic collaboration with Eli Lilly and Company to develop and commercialize NKTR-358 in multiple autoimmune conditions.
Autoimmune diseases cause the immune system to mistakenly attack healthy cells in a person's body. 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 Tregs. By increasing the number of Tregs, the pathogenic auto-reactive T cells can be controlled and the proper balance of effector and Treg cells can be achieved to restore the body's self-tolerance mechanisms.
In preclinical studies, NKTR-358 has demonstrated that it could suppress antigen-driven inflammation in a model of cutaneous hypersensitivity.4 NKTR-358 has also shown that it reduces markers of progression in a mouse model of SLE.
NKTR-358 is being developed as a once or twice-monthly self-administered injection for a number of auto-immune diseases.