Kymera Therapeutics presents preclinical data fror KT-621

Kymera Therapeutics announced the presentation of additional preclinical data for KT-621, a potent, selective, oral heterobifunctional degrader of STAT6, at the American Thoracic Society Annual Meeting in San Diego, California. The featured data demonstrate activity of KT-621 comparable to a saturating dose of the IL-4Ralpha antibody, dupilumab, in an asthma efficacy model which demonstrated that KT-621 robustly inhibited all the tested cytokines, chemokines, and cell infiltrates involved in TH2 inflammation in asthma. The Company shared additional new histology data showing amelioration of lung remodeling after low, daily oral doses of KT-621 that was comparable to dupilumab. These data highlight the compelling profile of KT-621 as a potential oral treatment for asthma and other TH2 respiratory diseases. Kymera intends to initiate Phase 1 testing for KT-621 in the second half of 2024 and expects data from the Phase 1 trial to be reported in the first half of 2025. The company previously presented data showing its first-in-class oral STAT6 degrader, KT-621, was exquisitely selective for STAT6 over other STATs and fully blocked IL-4/IL-13 functions in key human TH2 cellular assays with picomolar potency that was superior to dupilumab. In addition, at low daily oral doses, preclinical studies with KT-621 demonstrated near full in vivo STAT6 degradation in disease-relevant tissues that was well-tolerated. New data shared at ATS show that in the intranasal house dust mite-induced asthma model in hIL4/hIL4RA humanized mice, orally administered KT-621 was well tolerated with daily dosing for 30 days and demonstrated excellent in vivo efficacy comparable to an IL-4Ralpha saturating dose of dupilumab included in the same study. KT-621 robustly blocked TH2 inflammation including B cell activation, eosinophil recruitment, serum IgE and HDM-specific IgG1 induction, and reduced disease severity in the lung in this mouse model. Overall, the preclinical data generated to date demonstrate the potential of KT-621 for the treatment of TH2 allergic diseases with best-in-pathway potential given its dupilumab-like activity profile and the convenience of an oral pill. KT-621 preclinical data was also presented at Digestive Disease Week in Washington, D.C. The data demonstrated reversal of IL-13 stimulatory effects on esophageal smooth muscle cells, an important cell type involved in the pathophysiology of eosinophilic esophagitis. The company plans to share additional preclinical data for KT-621 at upcoming medical meetings in 2024.