WTX-518, a conditionally activated IL-18 INDUKINETM molecule that resists suppression by IL-18BP, led to complete tumor regressions in preclinical models
WTX-712, a conditionally activated IL-21 INDUKINETM molecule has potent antitumor activity in preclinical models with a differentiated immune activation mechanism
“We are excited to share that both WTX-518 and WTX-712 demonstrate powerful immunotherapeutic effects in preclinical models,” said
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” (Abstract #4074). Key takeaways reveal that WTX-518:
- is inducible, and its in vitro activity is not impeded by IL-18BP;
- selectively delivers active binding protein resistant (BPR) IL-18 to the tumor microenvironment (TME); and
- promotes increased influx and activation of NK cells and polyfunctional CD8 T cells in the TME, and demonstrates complete tumor regression in the MC38 mouse tumor model.
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). 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).
Both posters can be viewed in person from
Werewolf plans to develop WTX-518 and WTX-712 as potential immunotherapies in refractory and/or immunologically unresponsive tumors.
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