KT-621 is an investigational first-in-class once daily, oral STAT6 degrader with dupilumab-like activity in preclinical models and the potential to address multiple allergic and atopic diseases including atopic dermatitis, asthma, and chronic obstructive pulmonary disease, among others.
The Company expects to initiate dosing in a Phase 1 clinical trial in healthy volunteers in October 2024 and to report data from the Phase 1 study in the first half of 2025. The Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of KT-621 compared to placebo.
“FDA clearance of the KT-621 IND is a significant milestone for Kymera, patients, and the whole industry, allowing Kymera to be the first company to advance a STAT6 targeted medicine into clinical evaluation,” says Nello Mainolfi, PhD, Founder, President and CEO, Kymera Therapeutics, in a news release. “Unlike traditional oral small molecule inhibitors, we believe that our oral STAT6 degrader, KT-621, has the potential to combine the complete pathway blockade of upstream biologics with the convenience of oral administration and in doing so has the opportunity to transform the current treatment paradigm for atopic and allergic diseases. We are excited to advance KT-621 into Phase 1 clinical testing and look forward to sharing updates on this program in the near future.”
About STAT6 Degrader
STAT6 is a historically undrugged essential transcription factor in the interleukin (IL)-4/IL-13 signaling pathways and the central driver of T helper type 2 (TH2) inflammation in allergic diseases. Multiple gain of function mutations of STAT6 were identified to cause severe allergic diseases in humans. Dupilumab, an injectable monoclonal antibody that blocks IL-4/IL-13 signaling, is an approved therapy for multiple allergic and atopic diseases. STAT6 targeting is therefore supported by both human genetics and clinical pathway validation. STAT6 functions through protein-protein and protein-DNA interactions, and it has been challenging to selectively and potently inhibit STAT6 with small molecule inhibitors. However, the Company believes it is well suited for a targeted protein degradation approach, where a binding event is sufficient to drive degradation.
