Oral STAT6 Degraders Fill Niche in Asthma Care, With Michael Wechsler, MD

Oral STAT6 degraders represent a mechanistically distinct addition to the asthma pipeline, working further downstream than the epithelial alarmin-targeted therapies now in use, according to Michael E. Wechsler, MD, MMSc, professor of medicine and director of the Cohen Family Asthma Institute at National Jewish Health. Speaking with HCPLive at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9, about new data on KT-621, Kymera Therapeutics' investigational STAT6 degrader, Wechsler said the drug class acts on signaling mediated by Janus kinases and STAT6, and to some extent STAT5, in contrast to therapies like those targeting thymic stromal lymphopoietin (TSLP) or interleukin-33 (IL-33), which act further upstream at the epithelial level.

Wechsler pointed to preliminary data showing KT-621 effective in atopic dermatitis as the basis for optimism that a similar effect could translate to asthma; in the phase 1b BroADen trial, the subgroup of patients with comorbid asthma had a median 56% reduction in fractional exhaled nitric oxide and a 100% Asthma Control Questionnaire-5 responder rate by day 29.¹ Kymera's phase 2b BREADTH trial is now testing KT-621 specifically in moderate to severe eosinophilic asthma, with topline lung function data expected in late 2027.² Wechsler said an oral option carries practical appeal on its own, since some patients simply prefer pills to injectable biologics, independent of any efficacy advantage.

On where the drug might fit, Wechsler said he could envision STAT6 inhibition slotting into the Global Initiative for Asthma treatment algorithm at more than one point: as an add-on to inhaled corticosteroids and long-acting beta-agonists before a patient escalates to a biologic, or as an added option for patients who remain poorly controlled despite biologic therapy, given its distinct mechanism. He was careful to note the distance still ahead.

“Of course, there's a long way to go from being a concept in atopic dermatitis to moving past phase 3 and into the FDA and getting approval,” he said, though he added that both the mechanistic rationale and the preliminary atopic dermatitis data support pursuing it.

Wechsler framed the broader need in terms of remission: even with current biologics, he said only about 25% to 40% of patients with asthma achieve remission, underscoring that matching the right drug to the right patient at the right time still requires more tools, not fewer. “It's good to have oral options, it's good to have biologic options, and it's good to have options for our patients who continue to have significant unmet needs,” he said.

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.