Werewolf Therapeutics Presents Preclinical Data on mWTX-330, a Surrogate IL-12 INDUKINE™ Molecule, at the Society for Immunotherapy of Cancer Annual Meeting

- 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 -

WATERTOWN, Mass., Nov. 10, 2022 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer, today announced that it will present preclinical data on mWTX-330, a mouse surrogate of its interleukin-12 (“IL-12”) INDUKINE^TM product candidate, WTX-330, at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (“SITC”) being held November 8-12, 2022, in Boston, and virtually.

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 Friday, November 11, 11:55 am - 1:25 pm, in Hall C. The full abstract is available on the website.

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 Cynthia Seidel-Dugan, Ph.D., Chief Scientific Officer of Werewolf Therapeutics. “This morning, in our Third Quarter 2022 release, we announced that the FDA has granted clearance of the investigational new drug (IND) application for WTX-330. We are excited to advance WTX-330 into the clinic and to continue developing a pipeline of novel proinflammatory cytokine therapies that have the potential to change the lives of cancer patients.”

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.
  
  

About Werewolf Therapeutics

Werewolf Therapeutics, Inc., is an innovative biopharmaceutical company pioneering the development of therapeutics engineered to stimulate the body’s immune system for the treatment of cancer. We are leveraging our proprietary PREDATOR™ platform to design conditionally activated molecules that stimulate both adaptive and innate immunity with the goal of addressing the limitations of conventional proinflammatory immune therapies. Our INDUKINE™ molecules are intended to remain inactive in peripheral tissue yet activate selectively in the tumor microenvironment. Our most advanced product candidates, WTX-124 and WTX-330, are systemically delivered, conditionally activated Interleukin-2 (IL-2), and Interleukin-12 (IL-12) INDUKINE molecules, respectively, for the treatment of solid tumors. To learn more visit .

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