Werewolf Therapeutics, Inc. presented preclinical data on development candidates WTX-518 and WTX-712 in posters at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 5-10 in San Diego, California. WTX-518 exhibits remarkable tumor-selective activation, resistance to IL-18BP and robust immune activation, upcoming key hurdles in the use of this promising cytokine in cancer therapy. WTX-712 acts through a unique mechanism that robustly activates tumor-specific T lymphocytes with an expanded therapeutic window through its selective release of wild-type IL-21 in the TME.

These data collectively highlight the innovative strategies are pursuing to further expand the repertoire of unique immune stimulating cytokine mechanisms in the fight against cancer. Results highlighting WTX-518 findings are summarized in a poster titled, "Discovery of WTX-518, an IL-18 pro-drug that is conditionally activated within the tumor microenvironment and induces regressions in mouse tumor models". The WTX-712 data are summarized in a poster titled, ?WTX-712, a conditionally active IL-21 INDUKINE?

molecule, induces a strong anti-tumor phenotype through a differentiated mechanism? (Abstract #4078 [2]). Key takeaways reveal that: · WTX-712 demonstrates inducibility and antitumor activity with regressions in the MC38 mouse tumor model; IL-21 HLE (half-life extended) has superior anti-tumor efficacy compared to IL-2 HLE therapy in mouse tumor models that are highly resistant to anti-PD-1/PD-L1 treatment, in part due to the activation of type-I IFN pathways; and IL-21 HLE promotes sustained expansion and activation of tumor infiltrating CD8 T cells with increased polyfunctionality and induces expression of cytotoxic effector molecules (Granzyme A, Granzyme B, and perforin).