Benzinga | Dec 1, 2021 08:15AM EST

Werewolf Therapeutics To Present Preclinical Data On INDUKINE Molecules At 63rd American Society Of Hematology Annual Meeting

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 the Company will present preclinical data demonstrating interleukin-12 (IL-12) and interferon-? (IFN?) INDUKINETM molecules inhibited syngeneic lymphoma tumor growth in mice, induced anti-tumor immune responses and were tolerated in non-human primates. These data will be presented in a poster presentation during the 63rd American Society of Hematology ("ASH") Annual Meeting, taking place December 11-14, 2021.



The detailed data will be shared in a poster entitled, "Conditionally Activated IL-12 or IFN? INDUKINE(tm) Molecules Inhibit Syngeneic Lymphoma Tumor Growth in Mice, Induce Anti-tumor Immune Responses and Are Tolerated in Non-human Primates," Abstract 2258, during the Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II session on Sunday, December 12, 2021 at 6:00 pm EST.

"Systemic therapy with proinflammatory immune modulators holds promise for treating cancer, but poor pharmacokinetic properties and dose-limiting toxicities such as inflammation, cytokine release syndrome, and tissue damage have prevented or limited the clinical use of cytokines such as IL-12 and interferon-?," said Cynthia Seidel-Dugan, Ph.D., Chief Scientific Officer of Werewolf and one of the poster's authors. "We are excited about the potential of these data for the activity of our INDUKINE molecules, which are designed to include fully potent cytokines, high affinity blockade elements that allow for systemic circulation among non-tumor tissues, proprietary tumor-selective protease activation, and half-life extension for optimal tumor exposure."

WTX-330 and WTX-613 are systemically delivered, conditionally activated IL-12 and IFN? INDUKINE molecules, respectively, for the potential treatment of solid tumors. The study used surrogate WTX-330 and WTX-613 INDUKINE(tm) molecules, consisting of a mouse/human chimeric IL-12 or a mouse IFN?1, to explore anti-tumor responses in syngeneic hematologic cancer models, as human IL-12 and IFN?2b are not active in mice.

The WTX-330 surrogate showed dose-dependent anti-tumor activity with four out of ten tumor-free mice at the top dose in the subcutaneously A20 B cell lymphoma model, and inhibited tumor growth during the dosing period. The WTX-613 surrogate demonstrated tumor stasis lasting beyond the treatment phase, and efficiently blocked tumor growth, utilizing the subcutaneous EG7.OVA T lymphoblast line. Both treatments were well tolerated by the mice at active dose levels.

The WTX-330 and WTX-613 surrogates also strongly activated NK and CD8+ cell responses and induced antigen-presenting cell and effector cell markers in the MC38 syngeneic tumor model, supporting a mechanism of action as described for wild-type IL-12 and IFN?. Pharmacokinetic analysis in mice revealed extended half-life (T1/2) for both WTX-330 and WTX-613 surrogates compared to the short T1/2 of native IL-12 or IFN?1. WTX-330 and WTX-613 were well tolerated in non-human primates (NHP), resulting in plasma exposure levels for INDUKINE(tm) molecules that exceeded those needed for anti-tumor activity in mice. In addition, plasma levels of free IL-12 after dosing with WTX-330 were very low compared to tolerated levels of wild-type IL-12.