Kymera Therapeutics and Atopic Dermatitis: Results from the BroADen Phase 1b Trial

KT-621 showed clinically meaningful activity in the BroADen Phase 1b trial, demonstrating a first-in-class oral STAT6 degrader with rapid improvements in disease severity for patients with moderate–to–severe atopic dermatitis. An oral degrader with systemic activity could expand non‑injectable options for patients requiring systemic therapy and may shift the treatment landscape toward pathway-directed, oral agents.

KT-621 produced deep target engagement via STAT6 degradation, with median reductions of 98% in blood and 94% in skin at Day 29 across the 100 mg and 200 mg dose groups. The molecule’s oral mechanism directly depletes STAT6, the transcription factor central to IL‑4/IL‑13 signaling, and pharmacodynamic effects translated from healthy volunteers to patients, supporting potent on‑target activity in lesional skin and circulation.

Clinical efficacy included rapid, measurable improvements in core endpoints. Mean EASI fell by roughly 63% and mean peak pruritus declined by about 40% by day 29, with onset of effect evident by day 8.

Biomarker analyses paralleled the clinical signal. The report noted a 74% median TARC reduction in a subgroup with higher baseline levels and broader reductions across other Type 2 markers—changes comparable in scale to established Type 2–targeting therapies and likely underpinning the observed clinical responses.

Safety in this 28‑day phase 1b cohort was reassuring. KT‑621 was generally well tolerated, with no serious adverse events or treatment‑related discontinuations reported. There were no cases of conjunctivitis and no clinically relevant changes in vital signs, laboratory parameters, or ECGs in the study summary—supporting continued dose escalation and enrollment in larger efficacy trials.

Taken together, deep STAT6 engagement, robust biomarker reductions, early clinical activity, and a clean short‑term safety signal position KT‑621 as a credible oral systemic option for moderate-to-severe atopic dermatitis. Next steps are randomized phase 2/3 trials with longer follow‑up to define comparative efficacy, durability of response, and optimal dosing.

Key Takeaways:

• KT‑621 achieved marked STAT6 depletion in blood (median 98%) and skin (median 94%), demonstrating strong on‑target pharmacology.
• Biomarker suppression included a 74% median TARC reduction in a high‑baseline subgroup, concurrent with rapid clinical improvements (mean ~63% EASI reduction by Day 29).
• Short‑term safety in Phase 1b was favorable with no serious adverse events reported, supporting further development.