Werewolf Therapeutics Presents Initial Safety and Efficacy Data from Phase 1 Trial of WTX-330 in Advanced Tumors or Non-Hodgkin Lymphoma

Werewolf Therapeutics, Inc., a biopharmaceutical company based in Watertown, MA, has announced initial results from its Phase 1 clinical trial of WTX-330. This trial evaluates the use of WTX-330, a conditionally activated interleukin-12 (IL-12) INDUKINE™ molecule, as a monotherapy in patients with immunotherapy-resistant or insensitive locally advanced or metastatic solid tumors, or non-Hodgkin lymphoma.

According to Daniel J. Hicklin, Ph.D., President and CEO of Werewolf Therapeutics, the company's mission is to advance a pipeline of next-generation immuno-stimulatory medicines. The preliminary clinical data for WTX-330 reveals promising tolerability and signs of efficacy in heavily pretreated patients with late-stage solid tumors. The company looks forward to continuing the development of WTX-330 and gaining a deeper understanding of its potential clinical benefits.

IL-12 therapy is considered highly promising for immune-resistant cancer patients but has been historically limited due to severe toxicity. Werewolf's innovative approach involves developing a novel, conditionally activated IL-12, WTX-330, which aims to overcome these limitations using systemically administered, tissue-targeted technology. This approach optimizes the therapeutic index, allowing for efficacious doses to be delivered with clinical impact.

As of June 12, 2024, eleven patients had been dosed with WTX-330 in the dose-escalation phase of the study. These patients had solid tumors that were relapsed or refractory to all standard care therapies. The dosing occurred across three escalation cohorts: 0.016 mg/kg (three patients), 0.024 mg/kg (three patients), and 0.032 mg/kg (five patients). Additionally, two patients were dosed in the expansion phase at 0.024 mg/kg.

Preliminary results indicate that clinical benefits have been observed with the full-potency, systemically delivered IL-12 molecule at therapeutically relevant doses, with fewer severe toxicity-related events in an outpatient setting. Randi Isaacs, M.D., Chief Medical Officer of Werewolf, expressed optimism about these early results and looks forward to presenting more safety, biomarker, and anti-tumor activity data from patients enrolled in the expansion arms at a medical meeting in the fourth quarter of 2024.

Interleukin-12 (IL-12) is recognized for its promising antitumoral therapeutic properties, including activating natural killer (NK) cells, NK T cells, and CD8+ T cells, promoting dendritic cell antigen presentation, and producing IFN-γ. However, native IL-12 is highly toxic, and previous methods of administration at efficacious doses have resulted in unmanageable systemic toxicities or lack of efficacy. To utilize IL-12's potent therapeutic properties, it's necessary to develop treatment approaches that are locally active but systemically blocked.

WTX-330 is designed as a systemically dosed prodrug capable of delivering fully active IL-12 selectively into the tumor microenvironment via targeted intratumoral activation of the INDUKINE molecule. This design potentially broadens the therapeutic window and promotes local activation and immune response against the tumor.

Werewolf Therapeutics, Inc. is an innovative biopharmaceutical company dedicated to developing therapeutics that stimulate the body's immune system to treat cancer. The firm leverages its proprietary PREDATOR® platform to design conditionally activated molecules that stimulate both adaptive and innate immunity. Their goal is to address the limitations of conventional proinflammatory immune therapies. Their INDUKINE™ molecules aim to remain inactive in peripheral tissue but activate selectively in the tumor microenvironment. Werewolf's leading clinical-stage product candidates, WTX-124 and WTX-330, are designed for the treatment of solid tumors. The company is advancing 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.