Kymera's STAT6 Degrader KT-621 Shows Impressive Clinical Performance in Atopic Dermatitis Phase 1b Trial

Kymera Therapeutics revealed compelling efficacy and safety data from its BroADen Phase 1b clinical trial evaluating KT-621, an investigational oral STAT6 protein degrader designed to treat Type 2 inflammatory diseases. The findings suggest that KT-621 may represent a meaningful advancement in oral therapies for atopic dermatitis and related conditions.

Deep STAT6 Suppression Demonstrated Across Patient Groups

The Phase 1b study enrolled 22 patients with moderate-to-severe atopic dermatitis across two dosing cohorts. Kymera Therapeutics observed profound suppression of STAT6 protein in both systemic circulation and affected skin tissue following four weeks of daily dosing. At the 200 mg dose level, blood-based STAT6 levels declined by a median of 98%, with skin tissue showing 94% reduction—demonstrating the drug’s ability to penetrate target tissues effectively. Even at the lower 100 mg dose, comparable degradation patterns emerged, suggesting a consistent pharmacodynamic response.

Notably, the degree of STAT6 suppression in atopic dermatitis patients mirrored what was achieved in prior healthy volunteer studies, indicating robust translation of the mechanism from early-stage development to the disease population.

Type 2 Inflammation Markers Show Substantial Reduction

The trial measured multiple circulating biomarkers associated with Type 2-driven inflammation. Patients showed median TARC (thymus and activation-regulated chemokine) reductions of 74% when baseline levels were comparable to those observed in published dupilumab studies—aligning with the established comparator drug’s performance at four weeks.

Additional biomarker reductions included:

• Eotaxin-3: median decline of 62-73%, numerically exceeding historical dupilumab data in asthma and chronic rhinosinusitis
• IL-31: median reduction of 54-56%, representing the first documented IL-31 suppression via IL-4/IL-13 pathway blockade in atopic dermatitis patients
• FeNO (fractional exhaled nitric oxide): 25-33% median reduction, also a first in the atopic dermatitis patient population

These findings suggest KT-621 engages the Type 2 immune axis systemically, with implications extending beyond dermatologic disease.

Clinical Endpoints Reflect Rapid Therapeutic Benefit

KT-621 demonstrated meaningful clinical improvements across objective and patient-reported measures. Mean EASI (Eczema Area and Severity Index) scores decreased by 63% across all treated patients, with measurable improvement apparent by day 8—notably early for onset of action. Approximately 76% of patients achieved at least 50% EASI improvement (EASI-50 response), while 29% achieved 75% improvement thresholds.

Peak pruritus (itch severity) showed a mean 40% reduction across the population, with similarly rapid onset. Quality-of-life measures including DLQI and POEM scores improved steadily throughout the four-week dosing period, reflecting both objective lesion improvement and subjective symptom relief. The SCORAD index declined by 48% overall, with sleeplessness scores improving by 76%.

Implications for Comorbid Type 2 Conditions

A subset of trial participants with concurrent asthma (n=4) exhibited a median FeNO reduction of 56% and achieved 100% responder rate on ACQ-5 asthma control assessment, suggesting systemic efficacy in Type 2 lung disease. Among patients with allergic rhinitis, meaningful improvements in nasal symptom scores and quality-of-life questionnaires were documented, further supporting the breadth of KT-621’s pharmacologic activity.

Safety Profile Supports Further Development

Kymera Therapeutics reported a favorable safety and tolerability profile consistent with earlier healthy volunteer studies. No serious adverse events, treatment-related severe events, or discontinuations due to safety concerns were documented. Notably absent were cases of conjunctivitis, herpes reactivation, or joint symptoms—adverse events associated with certain biologic Type 2 therapeutics. Vital signs, laboratory parameters, and electrocardiograms remained unremarkable across both dose levels.

Clinical Development Path Forward

The company’s BROADEN2 Phase 2b trial in moderate-to-severe atopic dermatitis is actively enrolling, with data anticipated by mid-2027. A separate BREADTH Phase 2b trial in asthma patients is planned to initiate in the first quarter of 2026. This parallel development approach is intended to accelerate dose optimization and inform registration strategies across multiple Type 2-driven indications, potentially including dermatologic, gastrointestinal, and respiratory diseases.

The mechanistic specificity of KT-621 as a STAT6-targeted degrader positions it within an emerging class of oral small molecule therapeutics designed to replicate the efficacy of injectable biologic drugs with potentially improved patient convenience and tolerability.