- mWTX-330 is designed as a systemically delivered, conditionally activated IL-12 therapy and is a member of a novel class of INDUKINE™ therapeutics -
- Preclinical data supports the development of WTX-330, Werewolf’s product candidate, for the potential treatment of selected advanced or metastatic solid tumors or lymphoma -
Details will be presented in a poster titled, “mWTX-330, an IL-12 INDUKINE™ Molecule, Selectively Activates Tumor Infiltrating Lymphocytes and Reprograms the Tumor Microenvironment in Murine Syngeneic Tumor Models” (Abstract #1096) on
Study data demonstrate that systemic administration of mWTX-330, a mouse surrogate INDUKINE molecule, generates potent anti-tumor activity in a cleavage-dependent manner and protective memory against re-challenge in multiple murine syngeneic tumor models. Additionally, the data showed substantial infiltration and robust IL-12 signaling in intratumoral CD8+ T cells.
“These promising preclinical data add to a growing body of evidence demonstrating the potential of WTX-330 to drive targeted anti-tumor immune responses selectively in the tumor microenvironment (TME),” said
INDUKINE molecules are intended to remain inactive in peripheral tissue yet activate selectively in the TME through a unique combination of molecular components, including: (1) a fully potent wild-type cytokine; (2) a high affinity blockade element that allows for systemic circulation among non-tumor tissues in a “prodrug” state; (3) half-life extension for maximal tumor exposure; and (4) proprietary tumor-selective proteases for selective activation in the TME.
Systemic therapy with proinflammatory interleukin-12 (“IL-12”) immune modulators is a validated approach for the treatment of cancer, as the cytokine is a potent inducer of innate and adaptive anti-tumor immunity, but potentially severe toxicities associated with systemic administration of IL-12 has prevented IL-12 treatment strategies from successful clinical application.
WTX-330 is a systemically delivered, conditionally activated IL-12 INDUKINE molecule designed to minimize toxicities and maximize clinical benefit that have been observed with recombinant IL-12 therapy, which Werewolf is developing as a potential first-in-class treatment for selected advanced or metastatic solid tumors or lymphoma resistant to checkpoint inhibitors or for which checkpoint inhibitors are not approved.
Data from the SITC poster presentation demonstrate that mWTX-330:
- generates robust anti-tumor immunity following activation in the tumor microenvironment;
- activates multiple immune cell populations, including CD8+ T cells, CD4+ T cells, and NK cells;
- protects against later rechallenge with the same tumor cell line in mice that rejected primary tumors;
- selectively activates various tumor infiltrating effector cells, with little evidence of immune cell activation in the peripheral blood or secondary lymphoid tissues;
- is better tolerated than chimeric IL-12, significantly expanding the therapeutic window of this cytokine due to the INDUKINE molecule design;
- increases the frequency of polyfunctional CD8+ T cells, skewed CD4+ non-Tregs towards a TH1 phenotype, and drives robust NK cell production of effector cytokines within the tumor; and
- metabolically reinvigorates effector cells in the tumor microenvironment, significantly increasing mitochondrial respiration by tumor infiltrating CD8+ T cells as well as NK cells.
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