KT-621 Achieves Deep STAT6 Degradation, Initial Respiratory, Skin Gains

KT-621, an investigational once-daily oral STAT6 degrader from Kymera Therapeutics, produced deep STAT6 suppression in blood and skin, up to a 63% reduction in Eczema Area and Severity Index (EASI) score, and improvements in asthma and allergic rhinitis symptom scores in patients with atopic dermatitis and comorbid type 2 respiratory disease, according to phase 1b data presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9.¹

STAT6 is the transcription factor responsible for IL-4/IL-13 signaling and is considered the central driver of type 2 inflammation, though it has historically been an undrugged target for oral therapy, according to the study investigators.¹ The phase 1b BroADen trial evaluated KT-621 in adults with moderate to severe AD, with an exploratory analysis examining patients with comorbid asthma or allergic rhinitis.¹

“[STAT6 is] probably the one thing I'm excited most about outside of [trispecifics] and [bispecifics],” Njira Lugogo, MD, MS, Associate Professor of Internal Medicine, Division of Pulmonary & Critical Care Medicine's Asthma Program Director at University of Michigan Health told HCPLive during the congress.

What was the BroADen trial’s design?

The open-label, multicenter, single-arm BroADen trial enrolled adults with moderate to severe atopic dermatitis, defined by an EASI score of 16 or higher and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or higher, into 1 of 2 cohorts: KT-621 100 mg once daily (n = 10) or 200 mg once daily (n = 12), each dosed for 28 days with a 14-day follow-up.¹ The primary endpoint was safety; secondary endpoints included STAT6 degradation and type 2 biomarkers in blood and skin, and exploratory endpoints included atopic dermatitis activity measures and, in patients with comorbid asthma or allergic rhinitis, respiratory and nasal symptom scores.¹

Baseline disease severity was balanced between cohorts, with 12 patients (54.5%) rated moderate and 10 (45.5%) rated severe by vIGA-AD, and an overall mean EASI score of 24.9 (SD, 8.3).¹ Comorbid asthma was present in 4 patients (18.2%), with a median baseline FeNO of 42.0 ppb and mean ACQ-5 of 2.50, while comorbid allergic rhinitis was present in 9 patients (40.9%), with mean baseline TNSS of 3.44 and RQLQ of 1.62.¹

How did KT-621 degrade STAT6?

Median STAT6 degradation of 98% in blood was maintained through day 29 in both dose cohorts, and median STAT6 degradation of 94% was observed in skin, with levels falling below the lower limit of quantification in multiple patients.¹ Mean EASI score fell by up to 63% by week 4 without an apparent plateau, and the magnitude of reduction was similar across the full range of baseline EASI scores.¹

Across the total study population, KT-621 produced median reductions at day 29 of 74% in thymus and activation-regulated chemokine (TARC/CCL17), 73% in eotaxin-3 (CCL26), 14% in IgE, and 33% in fractional exhaled nitric oxide (FeNO), reflecting broad suppression of type 2 inflammatory biomarkers alongside the clinical improvements.¹ TARC and eotaxin-3 are validated markers of type 2 inflammation and downstream chemokine activity in the IL-4/IL-13 pathway, while FeNO reflects IL-4/IL-13-driven airway epithelial nitric oxide synthase activity, according to the poster.¹

What were KT-621 respiratory and nasal outcomes?

In the subgroup with comorbid asthma, KT-621 achieved a 56% median FeNO reduction by day 29, exceeding the 31% reduction reported for dupilumab in asthma studies at week 4, along with a mean 1.2-point improvement in the Asthma Control Questionnaire (ACQ-5) and a 100% ACQ-5 responder rate.¹ In the subgroup with comorbid allergic rhinitis, mean improvements of 0.9 and 0.8 points were seen in Total Nasal Symptom Score (TNSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), respectively, with responder rates of 57% and 33%.¹

KT-621 was well tolerated at both doses, with no serious or severe adverse events (AEs), no dose-dependent pattern in treatment-emergent AEs, and no related AEs leading to discontinuation.¹ Kymera is advancing KT-621 in parallel phase 2b trials: BROADEN2 in AD has completed enrollment, with topline data expected by the end of 2026 and phase 3 trials planned to start by mid-2027, while BREADTH, a randomized, placebo-controlled, dose-ranging trial enrolling approximately 264 patients with moderate to severe eosinophilic asthma, is ongoing with topline data on its primary endpoint of change in forced expiratory volume in 1 second (FEV1) expected in late 2027.²

KT-621 is the first STAT6-directed drug to enter clinical evaluation, according to Kymera, and the company said it has the potential to address more than 140 million patients with type 2 inflammatory diseases, including atopic dermatitis, asthma, chronic obstructive pulmonary disease, eosinophilic esophagitis, chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria, prurigo nodularis, and bullous pemphigoid.² A companion poster on pruritus and sleep outcomes from BroADen will be presented separately at the European Academy of Dermatology & Venereology (EADV) Congress, running September 30 to October 3 in Vienna, Austria.²

References

1. Feldman MB, Gollob J, Dey J, Shi K, Agarwal S, Graham N, Mainolfi N. KT-621, an oral STAT6 degrader, in patients with moderate-to-severe atopic dermatitis and comorbid asthma or allergic rhinitis: safety and evidence of clinical activity across type 2 inflammatory diseases in a phase 1b trial. Poster PA5913. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Kymera Therapeutics, Inc. Kymera Therapeutics announces presentations on KT-621, a first-in-class, oral STAT6 degrader, at the European Respiratory Society and European Academy of Dermatology & Venereology congresses. Published September 1, 2026. Accessed September 6, 2026. https://www.globenewswire.com/news-release/2026/09/01/3353950/0/en/kymera-therapeutics-announces-presentations-on-kt-621-a-first-in-class-oral-stat6-degrader-at-the-european-respiratory-society-and-european-academy-of-dermatology-venereology-congr.html

3. HCPLive. STAT6, ITK inhibitors, IL-31, & IL-18 headline burgeoning pipeline in atopic dermatitis, with David Rosmarin, MD. Published June 19, 2026. Accessed September 6, 2026. https://www.hcplive.com/view/stat6-il-31-and-il-18-headline-burgeoning-pipeline-in-atopic-dermatitis-with-david-rosmarin-md