Oral STAT6 Degrader KT-621 Shows Biologic-Comparable Activity in Atopic Dermatitis

"Having a drug, an oral drug that could do something similar to dupilumab, has been sort of a holy grail, if you will, in the atopic dermatitis field,” said Jared Gollob, MD, in a recent interview.

Gollob, chief medical officer at Kymera Therapeutics, described how KT-621, the company's oral STAT6 degrader, achieved effects on itch and skin lesion burden comparable to dupilumab (Dupixent; Sanofi and Regeneron) in the phase 1b BroADen study (NCT06945458) of atopic dermatitis (AD). Results of the phase 1b study were presented at the recent 2026 Society for Investigative Dermatology Annual Meeting. KT-621 drug targets STAT6, an intracellular transcription factor required for IL-4 and IL-13 signaling, and is designed to fill a long-standing gap in the field: an oral agent capable of fully blocking those pathways.^1,2

In a previous interview, Gollob described findings linking deep STAT6 degradation in blood and skin to measurable reductions in type 2 inflammation and clinical end points.

The Case for Oral STAT6 Degradation

Dupilumab, a monoclonal antibody targeting IL-4 receptor alpha, has been among the most significant advances in AD treatment over the past decade, according to Gollob. Its central limitation is its injectable delivery. "[Dupilumab] has been very effective because it's able to fully block both of these pathways, IL-4 and IL-13, which are driving the signs and symptoms of the disease. However, this is an injection, and injections are not easy for either adults or children," Gollob said. KT-621 degrades STAT6 within the cell rather than blocking the extracellular receptor, allowing once-daily oral dosing to achieve the same downstream pathway suppression.

Phase 1b Efficacy and Cross-Study Comparison

The phase 1b study treated patients with KT-621 once daily for 4 weeks, a shorter duration than the 16-week timelines used in larger pivotal trials. Despite the abbreviated course, the drug produced reductions in inflammatory biomarkers, itch, and skin lesion burden. "For our drug to show a similar effect to dupilumab in this 4-week period—understanding this is a cross-study comparison—what it seems to be showing is targeting STAT6 in this unique way with an oral drug can potentially give activity comparable to the injectable dupilumab," Gollob said. He emphasized no head-to-head comparison with dupilumab was conducted, and results are being compared against published dupilumab data.

IL-31 Reduction as a Biomarker Signal

A notable finding from the study was a mean 54% reduction in blood IL-31 levels after 4 weeks of treatment. IL-31 is a pruritogenic cytokine produced downstream of IL-4 and IL-13 receptor activation, and its suppression tracked closely with clinical itch reduction in the study population. "This is the first known demonstration of IL-31 reduction by a drug targeting the IL-4 and IL-13 pathway in atopic dermatitis," Gollob said. He noted published data showing IL-31 changes with dupilumab have not previously been available, making the KT-621 finding a novel biomarker connection between pathway inhibition and symptom relief.

The IL-31 data provided a mechanistic link between STAT6 degradation, downstream cytokine suppression, and patient-reported itch, a connection Gollob described as validating both the drug's mechanism and its clinical signal in this early-phase study.

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