Kymera Therapeutics has reported signfiicant early results for KT-621, the first oral STAT6 degrader to enter clinical trials, demonstrating biologic-like reductions in disease severity and type 2 (Th2) inflammation in individuals with moderate to severe atopic dermatitis (AD).

Data from the 22-participant phase 1b BroADen trial showed that once-daily KT-621 produced a 63% mean reduction in EASI scores at 4 weeks, rapid and meaningful itch improvement, and deep suppression of Th2 inflammatory biomarkers. The safety profile was favorable without treatment-related adverse events, according to a company statement.

If confirmed in larger controlled studies, KT-621 could represent a new class of oral therapies capable of replicating key pharmacodynamic signatures of IL-4/IL-13 biologics, potentially giving clinicians a more convenient systemic treatment option for AD and other Th2-tirggered diseases.

"The results were in line with, or in some cases numerically exceeded, published data for dupilumab at week 4 and we believe further reinforce Kymera’s pioneering expertise in developing transformative oral small molecules with the potential for the activity and safety of injectable biologics,” Nello Mainolfi, PhD, founder, president and CEO of Kymera Therapeutics, said in the statement.

A New Oral Strategy

STAT6 (signal transducer and activator of transcription 6) is the transcription factor that mediates signaling downstream of IL-4 and IL-13, the central drivers of Th2 inflammation and key therapeutic targets in AD, asthma, and related conditions.

Compared with blocking cytokines or their receptor, KT-621 uses targeted protein degradation to remove STAT6 itself from both blood and skin, theoretically shutting down all IL-4/IL-13-related signaling regardless of cytokine abundance. By acting at the transcription factor level, the drug has the potential to deliver the depth of pathway suppression usually associated with injectable biologics, but through a once-daily oral tablet. The phase 1b results provide the first clinical demonstration that STAT6 degradation is both feasible and clinically meaningful in AD.

The BroADen Phase 1b Trial

BroADen was an open-label, single-arm study enrolling 22 adults with moderate to severe AD. Participants received either 100 mg or 200 mg of KT-621 once daily for 28 days and were followed for another 14 days. Key objectives included assessing safety, evaluating the extent of STAT6 degradation in blood and skin, measuring changes in AD-relevant Th2 biomarkers, and documenting preliminary impacts on clinical endpoints.

Baseline disease severity was typical for a moderate–severe AD trial (mean Eczema Area and Severity Index [EASI] ~25). Nearly half of participants had comorbid asthma or allergic rhinitis, and about one-quarter had prior biologic exposure.

FINDINGS

KT-621 was well tolerated with:

• No serious adverse events
• No treatment-related adverse events
• No discontinuations
• No conjunctivitis, arthralgias, herpes infections, or lab/ECG abnormalities

For clinicians accustomed to the safety considerations of JAK inhibitors and IL-4R antagonists, this profile is particularly noteworthy.

“These results represent an innovative step forward in the treatment of atopic dermatitis,” Eric Simpson, MD, MCR, Frances J. Storrs Medical Dermatology Professor and Director of CLEAR Eczema Center, Oregon Health & Science University, said in the Kymera statement. “There remains a clear need for new oral therapies that can address the underlying biology of the disease while potentially offering patients greater convenience. KT-621’s novel mechanism and encouraging early data showing impact on clinical endpoints and biomarkers of Type 2 inflammation highlight the potential for this program to expand the options for people living with AD as well as other Type 2 allergic diseases.”

Phase 2b Trials Underway

Kymera has initiated the BROADEN2 phase 2b trial in moderate to severe AD, with data expected in mid-2027. A phase 2b asthma trial (BREADTH) is scheduled to begin in early 2026. Future parallel development is planned in multiple dermatologic, respiratory, and gastrointestinal Th2 diseases.