STAT6 Degradation by KT-621 Correlates With Itch and Lesion Reduction in AD

Kymera Therapeutics recently presented expanded biomarker analyses from its phase 1b study of KT-621, a STAT6 degrader, at the 2026 Society for Investigative Dermatology Annual Meeting. In a recent interview, Jared Gollob, MD, chief medical officer, described findings linking deep STAT6 degradation in blood and skin to measurable reductions in type 2 inflammation and clinical endpoints in patients with atopic dermatitis (AD). The presentation built on previously reported efficacy and target-engagement data by drilling down on both systemic and tissue-level biomarker changes.^1,2

Blood Biomarkers and Clinical End Points

Reductions in skin lesion burden, as measured by the EASI score, were associated with substantial decreases in type 2 blood biomarkers. Gollob highlighted TARC and IL-31 as key markers, with IL-31 reductions linked specifically to improvements in itch. "Reductions in itch in these patients — with itch being a very important symptom in AD patients — were associated with reduction of another important blood biomarker very important in driving itch, which is interleukin 31," Gollob said. Connecting these systemic biomarker changes to clinical outcomes in skin lesion burden and itch was a central goal of the SID presentation.

Tissue-Level STAT6 Degradation

Immunohistochemistry data showed strong STAT6 reductions in both the epidermal and dermal compartments of skin lesions. Gollob noted the keratinocytes in the epidermis and the inflammatory cells in the dermis were both affected. "Being able to show exactly in which compartments in the skin we're lowering STAT6 — showing we're lowering it in both the epidermal and dermal compartment — was really important," Gollob said. Prior presentations had used mass spectrometry to quantify STAT6 degradation; the IHC data provided spatial localization of the effect.

Gene Expression Changes in Skin

Beyond protein-level changes, the team analyzed gene expression in skin lesions, focusing on genes driving type 2 inflammation and itch. Results showed substantial downregulation of these targets in treated lesions. "We were having a substantial impact on the expression of those genes in these skin lesions, which goes along with the finding we were lowering STAT6 in the skin as well," Gollob said. Taken together, the biomarker package connected KT-621's mechanism of action through STAT6 degradation to both tissue-level and clinical endpoints, providing a coherent picture of how the drug affects the signs and symptoms of atopic dermatitis.

References

1. Kymera Therapeutics announces presentations on KT-621, a first-in-class, oral STAT6 degrader, at the Society for Investigative Dermatology and American Thoracic Society Congresses. News release. Kymera Therapeutics. May 15, 2026. Accessed June 2, 2026. https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-announces-presentations-kt-621-first-class
2. Kymera Therapeutics presents KT-621 BroADen data in late-breaking research session at the American Academy of Dermatology (AAD) Annual Meeting. News release. Kymera Therapeutics. March 28, 2026. Accessed June 2, 2026. https://investors.kymeratx.com/news-releases/news-release-details/kymera-therapeutics-presents-kt-621-broaden-data-late-breaking