KT-621, an investigational oral STAT6 degrader, nearly eliminated STAT6 protein in blood and lesional skin and reduced disease severity by a mean of 62.6% after 4 weeks in adults with moderate to severe atopic dermatitis. The phase 1b results were presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, Nevada.¹ No treatment-related adverse events were reported.
Signal transducer and activator of transcription 6 (STAT6) sits downstream of both interleukin (IL)-4 and IL-13, the cytokines targeted by current injectable biologics for atopic dermatitis. KT-621, developed by Kymera Therapeutics, is a first-in-class, once-daily small molecule designed to degrade STAT6 rather than inhibit it.¹
The poster was presented by Jared Gollob, MD, of Kymera Therapeutics. His co-authors included investigators from Red River Research Partners, Clinical Science Institute, and Cahaba Dermatology & Skin Health Center.¹
How Was KT-621 Studied in Atopic Dermatitis?
The single-arm, open-label phase 1b trial enrolled adults with a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or higher and an Eczema Area and Severity Index (EASI) score of at least 16.¹ Participants received KT-621 100 mg (n = 10) or 200 mg (n = 12) once daily for 28 days, followed by 14 days of follow-up.
The 22 treated patients had a mean baseline EASI score of 24.9, and 45.5% had severe disease (vIGA-AD of 4).¹ End points at week 4 included STAT6 degradation in blood and skin, Type 2 inflammatory biomarkers, clinical activity and safety.
How Deeply Did KT-621 Degrade STAT6?
Both doses produced comparable degradation, with median STAT6 reductions of 97.5% in blood and 93.6% in lesional skin.¹ Across doses, median reductions in blood biomarkers were 47.9% to 54.8% for thymus and activation-regulated chemokine (TARC), 62.0% to 72.9% for eotaxin-3 and 54.1% to 56.0% for IL-31. Immunoglobulin E declined more modestly, by 5.3% to 14.2%.
What Clinical Activity Did KT-621 Show at 4 Weeks?
Across doses, mean EASI improved by 62.6%; 76.2% of patients reached EASI-50, and 28.6% reached EASI-75.¹ vIGA-AD 0/1 was achieved by 19.0%, and mean affected body surface area fell by 49.0%.
Patient-reported outcomes moved in the same direction. Mean Peak Pruritus Numerical Rating Scale scores improved by 40.2%, and 72.7% of patients had a clinically meaningful improvement of at least 4 points on the Patient-Oriented Eczema Measure.¹
KT-621 was shown to be well tolerated, with investigators finding no serious or severe adverse events (AEs) and no clinically relevant changes in laboratory values or electrocardiograms.¹ With no placebo arm, a 4-week treatment window, and 22 patients, the open-label study wasn’t designed to establish efficacy.
What Comes Next for KT-621?
Kymera has completed enrollment in BROADEN2 (NCT07217015), its phase 2b trial of KT-621 in those with moderate to severe atopic dermatitis, nearly 6 months ahead of its original timeline.² In a release, the company noted its move of topline results up to the end of 2026. They plan to start phase 3 trials in atopic dermatitis by mid-2027, pending regulatory discussions.²
Editor's Note: This summary has been edited for grammar and clarity using artificial intelligence tools.
References
Gollob J, Blankinship M, Yamauchi P, et al. Clinical activity and safety of KT-621, an oral STAT6 degrader, in moderate-to-severe atopic dermatitis: phase 1b trial results. Presented at: 2026 Fall Clinical Dermatology Conference; Las Vegas, NV. Dermatol Online J. doi:10.25251/zqpe4k95
