Phase 1b Trial Begins Testing NKTR-358 in SLE Patients

The Phase 1b trial evaluating NKTR-358 — an investigational therapy that stimulates regulatory T-cell activation — in systemic lupus erythematosus (SLE) has begun dosing patients, Nektar Therapeutics announced.

Unlike immunosuppressive therapies that dampen the entire immune system, and are associated with potentially serious side effects, NKTR-358 was designed to restore the balance of the immune system, according to a press release from the company.

In particular, the medicine restores the ratio of regulatory T-cells (Tregs) to conventional T-cells, which is abnormal in most autoimmune disorders. Tregs are cells with immunosuppressive functions, keeping the immune system from going awry. But in autoimmune diseases, they usually are found in lower numbers and in a less active state.

That’s why Nektar developed NKTR-358, which targets the interleukin-2 receptor and selectively stimulates the growth and activation of Tregs, in an attempt to restore the body’s self-tolerance mechanisms.

The Phase 1b study will include about 50 SLE patients to determine if NKTR-358 is safe and reduces disease activity. Participants will receive multiple ascending doses of the medicine or a placebo.

Researchers also will study how NKTR-358 is metabolized in the body and how it affects the immune system. Additionally, they hope to determine the optimal dose for future trials.

In prior studies in mice and primates, Nektar already had seen that the therapy stimulated the growth and activation of Tregs, restoring the immune imbalance and halting inflammatory responses. Also, treatment of SLE mice for 12 weeks improved their kidney function, as seen by a decrease of protein levels in the urine.

“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,” Brian Kotzin, MD, said in the press release. Kotzine is senior vice president, Clinical Development and NKTR-358 Program Lead at Nektar.

“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,” he said.

NKTR-358 is being developed by Nektar in collaboration with Eli Lilly as a once or twice-monthly self-administered injection for patients with SLE and other autoimmune diseases.