Werewolf Therapeutics(HOWL) Newsfilter·2024-06-25 11:00Core Insights - Werewolf Therapeutics, Inc. announced initial results from a Phase 1 clinical trial evaluating WTX-330, a conditionally activated interleukin-12 (IL-12) INDUKINE™ molecule, as a monotherapy for patients with immunotherapy-insensitive or resistant locally advanced or metastatic solid tumors or non-Hodgkin lymphoma [18] Group 1: Clinical Trial Results - WTX-330 demonstrated therapeutically relevant exposure levels of systemically delivered IL-12 prodrug with improved tolerability compared to historical data for rhIL-12 [2][20] - Early dose-escalation data showed encouraging clinical activity, including an unconfirmed partial response in a metastatic melanoma patient and stable disease in two patients with microsatellite stable colorectal cancer [14][20] - The study had dosed eleven patients in dose escalation with three cohorts: 0.016 mg/kg (n=3), 0.024 mg/kg (n=3), and 0.032 mg/kg (n=5) [14] Group 2: Mechanism and Technology - WTX-330 is designed to deliver fully active IL-12 selectively into the tumor microenvironment through targeted intratumoral activation, potentially broadening the therapeutic window [4][7] - The INDUKINE™ technology allows for the stimulation of both adaptive and innate immunity while remaining inactive in peripheral tissues [7] Group 3: Safety and Tolerability - Patients exhibited mild to moderate treatment-related toxicities, primarily associated with the first dose, with no Grade 4 or Grade 5 adverse events reported [20] - Two patients experienced reversible dose-limiting toxicities at the 0.032 mg/kg dose level, indicating a manageable safety profile [20] Group 4: Future Developments - The company plans to present further safety, biomarker, and antitumor activity results from patients enrolled in expansion arms at a medical meeting in the fourth quarter of 2024 [3][19] - Expansion arms have been opened to evaluate 0.024 mg/kg of WTX-330 in patients with immune checkpoint inhibitor-sensitive solid tumors [20]