Kymera Therapeutics presents preclinical data for STAT6, TYK2 degrader programs

Kymera Therapeutics announced that its preclinical data demonstrating the therapeutic potential of its potent and selective heterobifunctional degraders of STAT6 and TYK2 are being presented in the poster session at the American Academy of Dermatology’s Annual Meeting in San Diego, California. Kymera’s oral STAT6 and TYK2 degraders have the potential to address multiple immune-mediated diseases and overcome the limitations of existing technologies and agents. Today’s poster presentations mark the first time that data from a STAT6 targeted agent and a TYK2 degrader have been shared at a major medical meeting. Based on the results generated to date, Kymera intends to initiate Phase 1 testing for KT-621 and KT-294 in the in the second half of 2024 and the first half of 2025, respectively. Data from both Phase 1 trials are expected to be reported in 2025. The findings presented today demonstrate that in preclinical studies, KT-621, Kymera’s first-in-class oral STAT6 degrader, 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. 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. In a MC903-induced atopic dermatitis mouse model, KT-621 demonstrated robust degradation of STAT6 in spleen and marked reduction of total serum IgE comparable to the activity of dupilumab. These data demonstrate the potential of KT-621 for the treatment of atopic dermatitis and other allergic diseases with best-in-pathway potential given its dupilumab-like activity profile and the convivence of an oral pill. Additionally, in preclinical studies, KT-294, Kymera’s first-in-class highly selective oral TYK2 degrader, demonstrated picomolar degradation potency and potent inhibition of the IL-23, IL-12 and Type I IFN pathways, showing its potential to recapitulate the biology of human TYK2 loss-of-function profile. KT-294, does not impact any of the other Janus kinase proteins and in doing so spares IL-10, unlike the TYK2 small molecule inhibitor, deucravacitinib, which is important in inflammatory bowel disease. In addition, TYK2 degradation leads to superior inhibition of the Type 1 IFN pathway compared to TAK-2791, which is relevant to the treatment of interferonopathies. The biological differentiation of the TYK2 degrader, KT-294, combined with the ability to provide deep and sustained TYK2 knockdown in vivo with low daily oral doses, has the potential to deliver a best-in-class TYK2 profile with broad activity across multiple IL-12/IL-23- and IFN-driven immune-inflammatory diseases potentially reaching pathway biologics activity. The company plans to share additional preclinical data for KT-621 and KT-294 at upcoming medical meetings in 2024.