Werewolf Therapeutics Q2 2024 Financial Results and Business Update

Werewolf Therapeutics, Inc., a pioneering biopharmaceutical company based in Watertown, Massachusetts, has provided a business update and disclosed financial results for the second quarter that ended on June 30, 2024. The company is focused on developing conditionally activated therapeutics designed to stimulate the immune system for treating cancer and other immune-mediated conditions.

In June 2024, at the American Society for Clinical Oncology (ASCO) Annual Meeting, Werewolf presented promising interim data from the ongoing Phase 1/1b clinical trial of its systemically delivered, conditionally activated Interleukin-2 (IL-2) molecule, WTX-124. The data showed that WTX-124, being developed as monotherapy and in combination with pembrolizumab for multiple solid tumors, was generally well-tolerated and demonstrated clinical activity.

Key highlights from the WTX-124 data included:
- Three objective clinical responses were achieved when WTX-124 was used as monotherapy, including one durable confirmed complete response and two partial responses in patients who were relapsed/refractory to immune checkpoint inhibitor therapy.
- Patients showed 100% regression of target lesions within the first two therapy cycles.
- Mild to moderate treatment emergent adverse events were primarily manageable and reversible.
- Analysis of paired tumor biopsies by NanoString indicated robust activation and expansion of effector T cells over Tregs.
- The recommended dose for the expansion (RDE) phase as monotherapy was set at 18 mg intravenously every two weeks (IV Q2W).

Werewolf also reported that WTX-124 in combination with pembrolizumab was generally well tolerated, with biomarker activity indicating potential combination efficacy. Clinical activity was observed in two melanoma patients at the 12 mg combination dose level. Dose escalation for this combination is ongoing, with updated data and the opening of expansion arms expected in the second half of 2024.

Additionally, Werewolf announced initial safety and efficacy data from its ongoing Phase 1 clinical trial of WTX-330, an IL-12 INDUKINE molecule for advanced or metastatic solid tumors. The data revealed that WTX-330 had achieved therapeutically relevant exposure levels of IL-12 prodrug, demonstrating significantly higher systemic drug concentration compared to previous IL-12 therapeutic strategies. One patient with metastatic melanoma achieved an unconfirmed partial response, and two patients with microsatellite stable colorectal cancer achieved stable disease.

Preclinical candidates, WTX-712 and WTX-518, are also progressing. WTX-518 targets IL-18 and has shown in vitro activity unimpeded by IL-18BP, delivering BPR IL-18 to tumor environments, causing complete tumor regression in mouse models. WTX-712 targets IL-21 and demonstrated superior anti-tumor efficacy compared to IL-2 in resistant mouse tumor models.

During the American Association of Immunologists Meeting in May 2024, Werewolf also shared data on its conditionally active IL-10 INDUKINE molecules for treating inflammatory bowel disease. The data indicated these molecules were inactive in peripheral tissues but active in target tissues, preventing intestinal histological damage and inhibiting inflammatory cytokine production in mouse models of colitis.

Financially, Werewolf reported a cash position of $135.3 million as of June 30, 2024, slightly down from $139.2 million as of March 31, 2024. Collaboration revenue was $1.1 million for the second quarter, down significantly from $8.1 million in the same period in 2023, primarily due to the completion of the company's performance obligations under the collaboration agreement with Jazz Pharmaceuticals. Research and development expenses increased to $15.3 million, up from $9.6 million in the same period last year, largely due to ongoing clinical trials for WTX-124 and WTX-330. General and administrative expenses were slightly up at $4.8 million. The net loss for the second quarter was $17.2 million, compared to $5.1 million in the same period in 2023.

Werewolf Therapeutics continues to leverage its proprietary PREDATOR® platform to design conditionally activated molecules that aim to stimulate both adaptive and innate immunity, with the goal of overcoming the limitations of conventional proinflammatory immune therapies.