Nektar Therapeutics (NKTR) Study update summary

Study design and objectives

• REZPEG (rezpegaldesleukin) is a first-in-class IL-2 pathway agonist designed to expand regulatory T cells and address immune dysregulation in autoimmune diseases, including alopecia areata and atopic dermatitis.

• Phase IIb REZOLVE-AA and REZOLVE-AD trials evaluated efficacy, safety, and molecular effects in severe alopecia areata and moderate-to-severe atopic dermatitis, with patients randomized to different dosing regimens.

• The REZOLVE-AA trial enrolled 92 adults with severe alopecia areata, while the REZOLVE-AD trial screened 581 patients, with 393 entering induction and 100 in the molecular cohort.

• Primary endpoints included mean percent change in EASI for AD and SALT ≤20 response for AA, with exploratory biomarker analyses.

• Maintenance and off-treatment periods assessed durability and deepening of response, and phase III studies are planned or underway in both indications.

Key efficacy and durability findings

• REZPEG showed consistent separation from placebo, with rising response curves and no plateau through week 52 in AA; 29% (18 mcg) and 31% (24 mcg) achieved SALT ≤20 at week 52.

• In AA, 75% maintained SALT ≤20 at 4 months off treatment, and 63% at 6 months; 19% achieved SALT ≤10 at 6 months, up from 7% at week 52.

• Efficacy in AA was similar regardless of episode duration, and nearly half maintained or improved hair regrowth six months after stopping REZPEG.

• In AD, REZPEG produced rapid and significant EASI improvement as early as week 2, with 42% achieving EASI-75 and 75% EASI-50 at week 16; monthly and quarterly dosing maintained high EASI-75 and EASI-90 at week 52.

• EASI-100 responses increased 2- to 5-fold during maintenance, with some patients achieving complete skin clearance.

Safety and tolerability

• REZPEG demonstrated a favorable and consistent safety profile through 52 weeks in both AA and AD, with no increased risk or new safety signals and low discontinuation rates.

• No routine lab monitoring was required, and the safety profile differentiates REZPEG from oral JAK inhibitors.