WTX-124 demonstrated high tumor selectivity and generated significant anti-tumor activity in a CD8+ T cell-dependent manner WTX-330 surrogate demonstrated significant expansion of the therapeutic window, compared to recombinant IL-12, and generated potent
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- Published on Sunday, 10 April 2022 09:38
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CAMBRIDGE, MA, USA I April 08, 2022 I Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics, today announced it presented promising preclinical data on its IL-2 and IL-12 INDUKINE™ molecules, WTX-124 and WTX-330, respectively, in posters at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 8-13, 2022, at the Ernest N. Morial Convention Center in New Orleans.
“Our conditionally activated, novel prodrug INDUKINE molecules continue to demonstrate targeted anti-tumor responses that reflect their design and engineering, remaining inactive in peripheral tissue, then unleashing an immune response within the tumor microenvironment,” said Cynthia Seidel-Dugan, Ph.D., Chief Scientific Officer of Werewolf. “IL-2 and IL-12 are proinflammatory cytokines with great potential to treat people with cancer, but systemic toxicities and poor pharmaceutical properties have limited their clinical application. These data suggest our approach may overcome these limitations and address the shortcomings associated with current cytokine treatments.”
Dr. Seidel-Dugan will discuss Werewolf’s innovative PREDATOR™ protein engineering platform, in a talk entitled, “Transforming Powerful Proinflammatory Mechanisms Into Novel Therapies for Cancer Patients,” during AACR session “New Developments in Immunotherapy: Targeting and Localizing Cytokine Activity,” on Tuesday, April 12 at 12:30 PM CDT, in the Great Hall AD, Convention Center.
Both data posters are now available online to AACR Annual Meeting attendees, and can be viewed in person between 1:30-5:00 PM CDT on Monday, April 11, during the AACR session PO.IM02.13, “Immune Response to Therapies 1”, Poster Section 37.
The WTX-124 data are summarized in a poster entitled, “WTX-124 is a Novel IL-2 Prodrug that is Conditionally Activated in Tumors and Drives Anti-Tumor Immunity by Activating Tumor Infiltrating CD8+ T Cells” (Abstract #2054). These preclinical data demonstrate WTX-124:
- is tumor-selective and generates significant anti-tumor activity in a CD8+ T Cell-dependent manner;
- has a better therapeutic window than recombinant human IL-2 (rhIL-2) or half-life extended rhIL-2;
- significantly shifts the transcriptional profile of the tumor microenvironment towards activation of various immune cell populations in both the MC38 and B16F10 models; and
- preferentially activates tumor infiltrating CD8+ and CD4+ T cells, with limited evidence of systemic T cell activation.
The WTX-330 data are summarized in a poster entitled, “WTX-330 is a Conditionally Activated IL-12 Prodrug that Fundamentally Reprograms Tumor Infiltrating CD8+ T Cells and Drives Tumor Regression” (Abstract #2055). These preclinical data demonstrate that a surrogate WTX-330:
- generates potent anti-tumor immunity in multiple syngeneic tumor models in a cleavage-dependent manner;
- displays a significant expansion of the therapeutic window compared to recombinant IL-12;
- induces an anti-tumor immune memory response;
- fundamentally shifts the transcriptional profile within the tumor and activates tumor infiltrating cytolytic effector cells in the MC38, B16-F10, and EMT6 tumor models
WTX-124 and WTX-330 INDUKINE molecules consist of wild-type IL-2 and IL-12 cytokines, respectively, tethered to an inactivation domain to prevent activation in peripheral tissue, a tumor protease-sensitive linker to allow for activation in the tumor microenvironment, and a half-life extension domain to improve tumor exposure.
Werewolf is developing WTX-124 as a potential monotherapy or in combination with checkpoint inhibitors in multiple tumor types. The Company has entered into a clinical trial collaboration agreement with Merck, known as MSD outside the United States and Canada, to evaluate WTX-124 as a monotherapy and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with solid tumors.
Werewolf is developing WTX-330 as a single agent for the treatment of relapsed or refractory advanced or metastatic solid tumors, or lymphoma failing standard of care.
The Company expects to file an Investigational New Drug Application (IND) for WTX-124 in the second quarter of 2022, and for WTX-330 in the third quarter of 2022.
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 are continuing preclinical studies for both WTX-124 and WTX-330 and expect to advance each candidate in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor.
To learn more visit www.werewolftx.com.
SOURCE: Werewolf Therapeutics
