Week-2 biomarker changes tracked with Week-16 EASI improvement in patients with moderate-to-severe atopic dermatitis treated with rezpegaldesleukin, according to a biomarker sub-study of the Phase 2b REZOLVE-AD trial presented September 30 at the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna.

Nektar Therapeutics, headquartered in San Francisco, analyzed blood and skin samples from 100 patients: 59 who received rezpegaldesleukin at 24 µg/kg every two weeks and 41 who received placebo. The sub-study sat within the global Phase 2b REZOLVE-AD study, which enrolled 393 patients with moderate-to-severe atopic dermatitis who had not previously been treated with a JAK inhibitor or biologic.

The molecular data point to a rapid pharmacodynamic effect. At week 2, treated patients showed up-regulation of FOXP3 and IL2RA compared with baseline — two markers tied to regulatory T cell activation, consistent with the drug's mechanism. Rezpegaldesleukin is an investigational agent designed to stimulate regulatory T cells, a mechanistic approach distinct from current biologic classes in atopic dermatitis.

The analysis also documented normalization across four immune signaling pathways at week 2: Th1, Th2, Th17, and JAK-STAT. That breadth matters clinically. Atopic dermatitis has long been characterized as a Th2-dominant disease, but the Week-2 data suggest rezpegaldesleukin acted on a wider inflammatory network rather than a single axis.

Early serum changes carried predictive weight. Increases in IL-10 and TGFΒ1 expression, together with a reduction in CCL17/TARC expression at week 2, associated with Eczema Area and Severity Index (EASI) improvement at week 16 in rezpegaldesleukin-treated patients. The same associations did not appear in the placebo arm. TARC, a keratinocyte-derived chemokine and established AD disease-activity marker, fell early in responders — a pattern clinicians could eventually use to flag likely responders before meaningful clinical change is visible.

Clinical outcomes in the molecular cohort matched the parent trial. Patients in the biomarker sub-study achieved a mean EASI reduction from baseline of 64% at week 16, consistent with the 61% reduction observed in the overall 24 µg/kg cohort of REZOLVE-AD. That concordance indicates the 100-patient sub-study population was representative of the broader trial cohort, strengthening the biomarker-to-outcome linkage.

The regulatory pathway for rezpegaldesleukin is already advancing. The FDA granted Fast Track designation for the drug in February 2025 for moderate-to-severe atopic dermatitis and in July 2025 for severe alopecia areata — a second dermatologic indication that reflects the same Treg-based mechanism.

For dermatologists, the data raise a practical question: if week-2 serum markers such as TARC, IL-10, and TGFΒ1 reliably predict week-16 EASI response, early biomarker monitoring could eventually complement — or replace — the current wait-and-see approach after initiating therapy. The sub-study was not designed to validate a clinical decision tool, and the findings require confirmation in larger datasets.

The REZOLVE-AD population also deserves attention. By excluding patients with prior JAK inhibitor or biologic exposure, the trial tests rezpegaldesleukin in a bio-naïve cohort — a population where a Treg-stimulating mechanism could offer an alternative to IL-4Rα, IL-13, and JAK-targeted agents as first-line systemic options.

Nektar disclosed the results in a press release issued from San Francisco and Vienna; full congress presentation data have not yet been published in a peer-reviewed journal. Whether the week-2 biomarker signature holds as a response predictor — and whether rezpegaldesleukin advances through Phase 3 — will shape its place in an increasingly crowded systemic atopic dermatitis pipeline.