WTX-712

WTX-712 is a systemically delivered, conditionally activated Interleukin-21 (IL-21) INDUKINETM molecule developed by Werewolf Therapeutics for cancer immunotherapy. It is engineered to be peripherally inactive, releasing wild-type human IL-21 selectively within the tumor microenvironment (TME) via protease-sensitive linkers. This selective activation aims to minimize severe toxicities associated with recombinant IL-21 therapy while maximizing clinical benefit as monotherapy or in combination with checkpoint inhibitors for refractory and/or immunologically unresponsive tumors. Preclinical studies show that WTX-712 drives CD8+ T cell polyfunctionality, induces a favorable M1/M2 macrophage ratio, promotes immune cell interactions, and demonstrates robust antitumor activity in mouse models such as MC38. Enhanced efficacy is observed when combined with immune checkpoint inhibitors targeting PD-1/PD-L1 or CTLA-4 pathways.