Rezpegaldesleukin Shifts Atopic Dermatitis Biomarkers: Emma Guttman-Yassky, MD

Rezpegaldesleukin, an investigational interleukin-2 (IL-2) receptor agonist designed to selectively expand regulatory T cells (Tregs), upregulated Treg markers and suppressed multiple inflammatory axes in atopic dermatitis skin as early as week 2 in a biomarker substudy of the phase 2b REZOLVE-AD trial.¹ Emma Guttman-Yassky, MD, PhD, Waldman Professor of Dermatology and Immunology, health system chair of the Kimberly and Eric J. Waldman Department of Dermatology, and director of the Laboratory for Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, discussed the findings with HCPLive.

The data were presented as a late-breaking oral presentation at the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna, Austria. The substudy analyzed 59 patients receiving rezpegaldesleukin 24 µg/kg every 2 weeks and 41 receiving placebo from REZOLVE-AD (NCT06136741), with lesional tape strips and blood collected at baseline, week 2, and week 4.¹ The parent trial met its primary and secondary endpoints after the 16-week induction phase.²

"Typically, when you look at the skin, it tells you things earlier than the clinical results, and we saw things much, much earlier. In fact, even week 2 we saw meaningful data, and based on week 2 biomarkers, we could even predict week 16 responses," Guttman-Yassky said.

Current type 2-targeted biologics miss a portion of patients because of disease heterogeneity, and many patients and dermatologists avoid JAK inhibitors because of boxed warnings, Guttman-Yassky said. She described Treg-directed therapy as acting on multiple pathways with potential for disease modification, though it may be slower to take effect.

RNA sequencing of tape strips showed significant upregulation of Treg and T-cell activation markers, including FOXP3, CTLA4, ICOS, and IL2RA, versus baseline and placebo at week 2, alongside reductions in Th1, Th2, Th17, and Th22 markers and fibrosis-associated genes such as POSTN and COL1A1.¹ Gene set variation analysis showed reduced Th17 (P < .01) and JAK-STAT signaling (P < .05) by week 4. Guttman-Yassky said the fibrosis findings may support other indications and noted pathways relevant to alopecia areata were also modulated.

Serum IL-10, CD274, and TNFRSF9 rose from week 2, and week 2 levels of IL-10 (R = −0.621), CCL17 (R = 0.524), and TGF-β1 (R = −0.573) correlated with week 16 Eczema Area and Severity Index (EASI) scores in the rezpegaldesleukin arm only (all P < .0001).¹ Mean EASI fell 64.3% by week 16 among substudy patients receiving rezpegaldesleukin, and 42.4% reached EASI-75. These congress data have not been peer reviewed.

Relevant disclosures include Nektar Therapeutics.

References

1. Manson M, Manzo Margiotta F, Del Duca E, et al. Multi-omic profiling identifies early molecular responses to rezpegaldesleukin, a novel regulatory T cell-inducing therapy, in atopic dermatitis. Abstract LB-219. Presented at: EADV Congress 2026; September 30–October 3, 2026; Vienna, Austria.

2. Nektar announces publication in The Lancet of positive phase 2b REZOLVE-AD 16-week induction results of rezpegaldesleukin in moderate-to-severe atopic dermatitis. News release. Nektar Therapeutics. August 25, 2026. Accessed October 29, 2026.