Kymera Therapeutics Unveils Preclinical Data for Oral STAT6 Degrader KT-621 at ATS Meeting

Kymera Therapeutics, Inc., a clinical-stage biopharmaceutical company, recently unveiled new preclinical data for its drug KT-621. This data was presented at the American Thoracic Society (ATS) Annual Meeting in San Diego, California, where KT-621 demonstrated activity comparable to or better than dupilumab in an asthma efficacy model. The results showed that KT-621 robustly inhibited a range of cytokines, chemokines, and cell infiltrates involved in TH2 inflammation, which is central to asthma. Additional histology data revealed that low, daily oral doses of KT-621 could ameliorate lung remodeling, an effect comparable to that of dupilumab. These findings underscore the potential of KT-621 as an oral treatment for asthma and other TH2-mediated respiratory diseases.

Kymera plans to commence Phase 1 testing for KT-621 in the latter half of 2024, with initial data expected in the first half of 2025. Nello Mainolfi, PhD, the company's Founder, President, and CEO, emphasized the importance of KT-621, stating that the drug has the potential to address multiple TH2 immune-mediated diseases and overcome the limitations of existing therapies, including biologics and traditional small molecule inhibitors. Mainolfi suggested that KT-621 could provide the convenience of a once-daily oral medication while delivering dupilumab-like efficacy, thereby transforming current treatment paradigms and expanding patient reach.

Previously, Kymera presented data indicating that KT-621, an oral STAT6 degrader, is highly selective for STAT6 over other STATs. The drug fully blocked IL-4/IL-13 functions in critical human TH2 cellular assays with superior potency to dupilumab. In preclinical studies, KT-621 demonstrated near-complete STAT6 degradation in disease-relevant tissues at low daily doses and was well-tolerated. At the ATS meeting, new data showed that orally administered KT-621 was well-tolerated over 30 days in an intranasal house dust mite-induced asthma model in humanized mice. KT-621 effectively blocked TH2 inflammation, including B cell activation, eosinophil recruitment, and serum IgE induction, reducing lung disease severity in the mouse model. These preclinical results highlight KT-621's potential as a best-in-pathway treatment for TH2 allergic diseases, offering the dual benefits of dupilumab-like activity and oral administration.

In addition to the ATS presentation, KT-621 preclinical data was showcased at Digestive Disease Week in Washington, D.C. This data demonstrated the drug's ability to reverse IL-13’s stimulatory effects on esophageal smooth muscle cells, which are crucial in eosinophilic esophagitis. Kymera plans to present more preclinical data for KT-621 at upcoming medical meetings in 2024.

STAT6, a vital transcription factor in the IL-4/IL-13 signaling pathways, is a central driver of TH2 inflammation in allergic diseases. Multiple gain-of-function mutations in STAT6 have been linked to severe allergic conditions in humans. Dupilumab, an injectable monoclonal antibody, is an approved therapy for various allergic diseases by blocking IL-4/IL-13 signaling. Targeting STAT6 is supported by human genetics and clinical validation of the pathway. STAT6 functions via protein-protein and protein-DNA interactions, making it challenging to inhibit selectively and potently with small molecule inhibitors. However, it is well-suited for targeted protein degradation, where a binding event leads to degradation. KT-621, an oral STAT6 degrader, shows promise for treating multiple diseases, including atopic dermatitis, asthma, and chronic obstructive pulmonary disorder.

Kymera Therapeutics, founded in 2016, focuses on developing medicines through targeted protein degradation to address critical health issues. The company aims to provide a new generation of therapies that are both convenient and highly effective, thus improving patient outcomes significantly. Kymera has been recognized as one of Boston's top workplaces for several years.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!