11 minute read
Nov. 28, 2023

KT-474 Brings IRAK4 Back: The First Clinically Active Bifunctional Degrader Outside Oncology


oral IRAK4 degrader Ph. II in AD and HS via optimization of ligands for CRBN and IRAK4, and linker Nature Medicine, Nov. 2023 Kymera Therapeutics, Watertown, MA

Drug Hunter Team

Kymera's KT-474 is the first oral degrader to demonstrate activity in clinical trials outside cancer. Sanofi recently started a Ph. II trial with the molecule in AD, restoring life to IRAK4 as an immunology target.

This article highlights several reasons why Kymera’s KT-474 program is scientifically notable, including but not limited to differentiation from small molecules, potential competitiveness with biologics, the first reported Cryo-EM ternary complex of a heterobifunctional degrader, and more. The molecule will likely be considered a modern “classic in drug discovery” for some time.



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