Oral STAT6 Degrader KT-621 Shows Early Promise in Atopic Dermatitis

Key Takeaways

• KT-621, an oral STAT6 degrader, demonstrated rapid and deep target engagement with robust biomarker suppression in a Phase 1b AD trial.
• Clinically meaningful improvements in EASI, itch, and patient-reported outcomes were observed within 4 weeks, without evidence of plateau.
• The therapy was well tolerated with no treatment-related adverse events, supporting further development.

A first-in-class oral STAT6 degrader, KT-621, demonstrated early clinical activity, robust biomarker suppression, and a favorable safety profile in adults with moderate-to-severe atopic dermatitis (AD), according to Phase 1b data presented by Mahta Mortezavi, MD, at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

KT-621 targets STAT6, a central transcription factor in IL-4 and IL-13 signaling, using targeted protein degradation.

“One copy of a degrader can potentially … take thousands of copies of that targeted protein to the proteasome,” Dr. Mortezavi said, describing a catalytic mechanism that enables “deep and continuous pathway blockade that’s similar to a biologic.” 

In the open-label study, 22 adults with moderate-to-severe AD (mean baseline EASI 24.9; 45.5% severe) received KT-621 100 mg or 200 mg once daily for 28 days. The agent achieved near-complete STAT6 degradation, with median reductions of approximately 97.5% in blood and 93.6% in lesional skin, with similar effects across doses.

This target engagement translated into suppression of type 2 inflammatory biomarkers, including TARC (−47.9% to −54.8%), eotaxin-3 (−62.0% to −72.9%), and IL-31 (−54.1% to −56.0%). Dr. Mortezavi highlighted the latter as notable: “This is the first known demonstration of IL-31 reduction in blood … in response to IL-4/13 pathway blockade.” 

Clinically, KT-621 produced a mean EASI reduction of 62.6% at 4 weeks, with 76.2% and 28.6% of patients achieving EASI-50 and EASI-75, respectively. Improvements were observed early and continued through the treatment period.

“The time course shows continuous improvement … without reaching an apparent plateau,” Dr. Mortezavi said. Reductions were also seen in body surface area (−49.0%), pruritus (−40.2%), and POEM scores, with 72.7% achieving clinically meaningful improvement.

KT-621 was well tolerated, with no treatment-related adverse events, serious adverse events, or clinically relevant laboratory or ECG changes reported.

“These data show… robust suppression of type 2 inflammation and improvements in clinical and patient-reported outcomes similar to pathway biologics,” Dr. Mortezavi said, noting that a Phase 2b trial is ongoing.