Kymera Therapeutics Unveils Preclinical Data for KT-621, an Oral STAT6 Degrader, at EADV Congress

On September 25, 2024, Kymera Therapeutics, Inc., a clinical-stage biopharmaceutical company, announced new preclinical data for KT-621 at the European Academy of Dermatology and Venereology (EADV) Congress in Amsterdam. KT-621 is a potent, selective oral degrader of STAT6, a transcription factor central to TH2 inflammation. This data showcases KT-621's potential as a once-daily oral treatment for TH2-driven allergic and atopic diseases. The company has completed studies enabling Investigational New Drug (IND) application and plans to begin Phase 1 clinical trials in the latter half of 2024, with results expected in the first half of 2025.

Nello Mainolfi, PhD, Founder, President, and CEO of Kymera Therapeutics, emphasized the significance of STAT6 degradation, likening its potential to that of dupilumab but with the convenience of an oral medication. Mainolfi highlighted the opportunity to expand patient access to treatments for diseases currently dominated by injectable agents, such as atopic dermatitis, asthma, and COPD. He expressed confidence that Kymera could provide innovative therapeutic solutions to millions of patients worldwide suffering from these chronic conditions.

In preclinical trials, KT-621 demonstrated high selectivity for STAT6 over other STAT proteins and effectively blocked the function of IL-4/IL-13 cytokines, which are essential in allergic and atopic inflammation. With picomolar potency, KT-621's performance was comparable or superior to dupilumab. Low daily oral doses of KT-621 resulted in near-complete degradation of STAT6 in relevant tissues and were well-tolerated. In a mouse model of atopic dermatitis induced by MC903, KT-621 showed significant STAT6 degradation in vivo and reduced total serum IgE levels similarly to the IL-4RA saturating dose of dupilumab. Additionally, in an asthma model induced by house dust mites, KT-621 exhibited robust STAT6 degradation and reduced cytokine levels, cell infiltration, and disease severity indicators in the lung and bronchoalveolar lavage fluid, performing comparably or better than dupilumab.

New findings presented at the EADV Congress underscore the potential role of the STAT6 signaling pathway in causing itch and pain in atopic dermatitis. KT-621 showed strong degradation of STAT6 in human iPSC-derived sensory neurons, inhibiting IL-13-induced itch- and pain-related gene transcripts. This ability to block the IL-4/IL-13 pathways in sensory neurons suggests that KT-621 could alleviate these symptoms in atopic dermatitis patients by targeting and modulating the STAT6 pathway.

STAT6 is a critical transcription factor in the IL-4/IL-13 signaling pathways and drives TH2 inflammation in allergic diseases. Historical challenges in inhibiting STAT6 with small molecules have made it a suitable target for a protein degradation approach. KT-621, a once-daily oral STAT6 degrader, exhibits dupilumab-like activity and holds promise for treating multiple allergic and atopic diseases, including atopic dermatitis, asthma, and chronic obstructive pulmonary disorder.

Kymera Therapeutics is a biotechnology company focused on targeted protein degradation (TPD) to develop new medicines. By advancing TPD, Kymera aims to address disease targets and pathways that traditional therapeutics cannot reach, offering a new generation of effective therapies for immunological diseases and cancer. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces and is committed to improving patients’ lives through innovative science and treatments.