Werewolf Therapeutics, Inc. 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. 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 April 12, 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 on 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.