Werewolf Therapeutics Publishes Preclinical Data on mWTX-330, an IL-12 INDUKINE™ Molecule, in Cancer Immunology Research

April 19, 2023

WATERTOWN, Mass., April 19, 2023 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics, announced the publication in Cancer Immunology Research Online First of preclinical data for mWTX-330, a systemically delivered Interleukin-12 (IL-12) INDUKINETM molecule. The article, entitled “mWTX-330, an IL-12 INDUKINE Molecule, Activates and Reshapes Tumor-infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity,” includes preclinical data that demonstrates that mWTX-330 delivers IL-12 selectively to the tumor microenvironment, where it stimulates a potent anti-tumor immune response [DOI: 10.1158/2326-6066.CIR-22-0705].

“IL-12 is a cytokine with broad stimulatory effects on various immune cell populations, having the ability to regulate antitumor immunity through numerous innate and adaptive immune pathways, but clinical administration has been limited due to serious toxicities when administered systemically,” said Cynthia Seidel-Dugan, Ph.D., Chief Scientific Officer of Werewolf and one of the article’s authors. “Our published preclinical data show that mWTX-330 generates potent anti-tumor immunity in mice by activating and restoring the metabolic health of tumor-infiltrating lymphocytes, with the potential to minimize the toxicity previously associated with systemic IL-12 administration.”

Other key findings and data outlined in the article include:

  • mWTX-330 treatment generates a robust, cleavage-dependent anti-tumor immune response in multiple syngeneic tumor models and is well tolerated.
  • mWTX-330 delivery expands the therapeutic window of the IL-12 cytokine.
  • mWTX-330 treatment activates various tumor-infiltrating lymphocyte populations in the MC38 mouse model and results in the transcriptional reprogramming of the tumor microenvironment and the subsequent activation of various tumor-infiltrating effector-cell populations.
  • mWTX-330 treatment expands unique T-cell receptor (TCR) clones and increases TCR clonality in the tumor microenvironment.
  • mWTX-330 treatment substantially increases mitochondrial activity in tumor infiltrating CD8+ T cells and NK Cells while reducing signs of exhaustion on CD8+ T cells.
  • The fully human WTX-330 INDUKINETM molecule is preferentially activated by primary human tumors.

Werewolf is currently recruiting patients for a first-in-human, multi-center, open-label Phase 1 clinical trial that will evaluate WTX-330 in patients with advanced or metastatic solid tumors or lymphoma resistant to checkpoint inhibitors or for which checkpoint inhibitors are not approved. For additional information about the trial, please visit using the Identifier: NCT05678998

WTX-330 was designed to maximize clinical benefit and minimize the severe toxicities that have been observed with recombinant IL-12 therapy by including high affinity blockade of IL-12 – IL-12R interaction in systemic circulation and non-tumor tissues, half-life extension for optimal tumor exposure and proprietary tumor-selective protease activation.

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. We expect to advance clinical studies for WTX-124 in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor and WTX-330 in multiple tumor types or Non-Hodgkin Lymphoma as a single agent. To learn more visit

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Company Contact:
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Werewolf Therapeutics