NKTR-358 is designed to treat autoimmune and inflammatory conditions by correcting the immune system imbalance that results from increased levels of inflammatory T cells and reduced numbers and impaired function of immune regulating Treg cells.

Nektar Therapeutics and its partner Eli Lilly & Company’s NKTR-358 (LY3471851), a novel T regulatory (Treg) cell stimulator, demonstrated proof of concept in a Phase 1b study of patients with moderate-to-severe atopic dermatitis.

The findings were presented at Eli Lilly & Company’s Investment Community Meeting.

NKTR-358 is designed to treat autoimmune and inflammatory conditions by correcting the immune system imbalance that results from increased levels of inflammatory T cells and reduced numbers and impaired function of immune regulating Treg cells.  NKTR-358 targets the interleukin-2 receptor complex to selectively stimulate the proliferation and overall abundance of Tregs and increase their suppressive functional activity.

The proof-of-concept data show that NKTR-358 (Q2W for 12-week treatment duration) resulted in a dose-dependent reduction in Eczema Area and Severity Index (EASI) scores in patients with moderate-to-severe atopic dermatitis.  Treatment with NKTR-358 at the 24 ug/kg dose resulted in a 70% maximum reduction in EASI scores at week 12, and treatment with NKTR-358 over a 12-week period at the 24 ug/kg Q2W dose resulted in sustained disease control for at least 6 months after last dose demonstrating the potential for NKTR-358 to differentiate from standard of care, the study found.

"This is a truly remarkable result which demonstrates the potential for NKTR-358 to differentiate from current standard of care for patients with atopic dermatitis and supports Lilly's planned Phase 2 study in this indication," says Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar Therapeutics, in a news release. "These proof-of-concept data presented today show that, in patients with moderate to severe atopic dermatitis, NKTR-358 given every two weeks over a 12-week period resulted in a dose-dependent reduction in EASI scores. Importantly, at the highest dose tested, the majority of patients maintained this disease reduction for at least 6 months after the last dose of NKTR-358."

"NKTR-358 has demonstrated that it can drive expansion of Tregs, which we believe could help to regulate and control pathogenic T cells, to potentially modify disease through restoration of normal self-tolerance mechanisms," continues Zalevsky. "We are especially excited because we have now demonstrated the potential benefit of NKTR-358 in two different dermal disease settings. NKTR-358 produced a reduction in CLASI scores in lupus patients in our Phase 1b study, and here showed a reduction in EASI in Lilly's study in atopic dermatitis."  

NKTR-358 exhibited a similar tolerability profile in the Phase 1b study in atopic dermatitis as shown in prior studies conducted in patients with mild-to-moderate SLE and healthy volunteers.