On November 7, 2024 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 and other immune-mediated conditions, reported a business update and announced financial results for the third quarter ended September 30, 2024 (Press release, Werewolf Therapeutics, NOV 7, 2024, View Source [SID1234647951]).
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"Werewolf continues to progress our pipeline of INDUKINE therapeutics, led by WTX-124 and WTX-330, which have together provided preliminary clinical validation of our innovative design. To date, initial datasets from both programs have highlighted well-tolerated monotherapy activity in the outpatient setting, establishing WTX-124’s potential best-in-class profile among next-generation approaches to IL-2 and WTX-330’s potential first-in-class design which enables a wider exposure and therapeutic window of IL-12 than previously achieved," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We continue to progress WTX-124, with both monotherapy and combination expansion arms enrolling in multiple indications. We anticipate sharing monotherapy expansion data in the first half of 2025, which we expect will guide the next steps for the development program. In addition, we look forward to presenting interim data from our Phase 1 WTX-330 clinical trial at SITC (Free SITC Whitepaper) this weekend, including the emerging tolerability and clinical activity profile for WTX-330."
Recent Highlights and Upcoming Milestones
WTX-124: a systemically delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE molecule being developed as monotherapy and in combination with pembrolizumab in multiple solid tumor types.
•Werewolf continues to progress the ongoing Phase 1/1b clinical trial evaluating WTX-124 as a monotherapy and in combination with pembrolizumab.
◦Following the selection of 18 mg WTX-124 administered intravenously every two weeks (IV Q2W) as the monotherapy recommended dose for expansion (RDE), the Company has opened monotherapy expansion arms and is actively enrolling patients with metastatic melanoma, renal cell carcinoma (RCC) and cutaneous squamous cell carcinoma (CSCC) who have failed immune checkpoint inhibitor therapy.
◦The Company has also selected 18 mg WTX-124 administered IV Q2W as its RDE for the combination with pembrolizumab and has opened combination expansion arms in metastatic melanoma, RCC, and non-small cell lung cancer (NSCLC).
◦Previously, the Company disclosed that two patients with metastatic melanoma treated in the 12 mg combination dose escalation cohort had partial and near-partial responses observed in preliminary data. Both patients now have confirmed partial responses, and both patients have remained progression free on study for more than 7 months.
◦The Company also previously disclosed that one patient with advanced CSCC treated in the 12 mg monotherapy dose escalation cohort had a documented complete response and then discontinued study drug at 21 weeks. This patient has remained in complete remission for over twelve months.
◦Cumulative biomarker data from tumor biopsies continue to provide evidence that baseline CD8+ effector T cells are relevant to clinical responses and that there is no evidence of Treg activation with treatment.
•In the first half of 2025, Werewolf expects to provide an update on the WTX-124 clinical development program, including data from the monotherapy expansion arms that are evaluating WTX-124 in more homogenous, less heavily pre-treated patient populations to inform future development priorities.
•Pending additional insight into the clinical profile, Werewolf intends to engage with regulators to discuss potential registrational pathways for WTX-124, including strategies for monotherapy accelerated approval.
WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.
•Werewolf plans to present updated interim safety and efficacy data from its ongoing Phase 1 clinical trial of WTX-330 in patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held November 6-10, 2024, in Houston, Texas. Presentation details are as follows:
◦Title: The tumor-activated IL-12 prodrug WTX-330 expanded/activated tumor infiltrating lymphocytes and caused tumor regression in patients with refractory solid tumors: Interim data from an ongoing Ph1 study
◦Abstract Number: 672
◦Session Date and Time: Saturday, Nov. 9, 2024; 9:00 a.m.–8:30 p.m. CT.
◦Location: George R. Brown Convention Center – Exhibit Halls A B
•In June 2024, the Company shared a preliminary program update, reflecting the same June 12, 2024, data cut-off as captured in the SITC (Free SITC Whitepaper) abstract, showing an improved therapeutic index with systemic administration of WTX-330, producing clinical activity at generally well-tolerated doses, with a 22-fold higher systemic prodrug exposure compared to recombinant IL-12 at its maximum tolerated dose.
•The data to be presented at SITC (Free SITC Whitepaper) will expand on this initial update, further characterizing safety, pharmacokinetics (PK), biomarkers and clinical activity and capturing additional patients treated since this data cut-off.
Preclinical Portfolio: includes development candidates WTX-712 and WTX-518, INDUKINE molecules targeting IL-21 and IL-18, respectively, for treatment of cancer and WTX-921, an INDUKINE molecule delivering IL-10 for treatment of inflammatory diseases.
•In October 2024, Werewolf announced the addition of WTX-921, a novel IL-10 INDUKINE development candidate for the treatment of inflammatory bowel disease and potentially other inflammatory diseases, to its pipeline, thereby increasing the breadth of the PREDATOR platform approach in therapeutic areas outside of oncology.
•At SITC (Free SITC Whitepaper), the Company plans to present a poster highlighting the distinct mechanisms by which IL-2, IL-12, binding protein resistant IL-18, and IL-21 accomplish antitumor immunity in mice. Presentation details are as follows:
◦Title: INDUKINE Molecules Delivering Various Cytokines Utilize Unique Mechanisms of Action to Drive Anti-Tumor Efficacy in Murine Syngeneic Tumor Models
◦Abstract Number: 955
◦Session Date and Time: Friday, Nov. 8, 2024; 9:00 a.m. – 8:30 p.m. CT.
◦Location: George R. Brown Convention Center – Exhibit Halls A B
Financial Results for the Third Quarter of 2024:
•Cash position: As of September 30, 2024, cash and cash equivalents were $122.8 million, compared to $135.3 million as of June 30, 2024. The Company believes its existing cash and cash equivalents as of September 30, 2024, will be sufficient to fund operational expenses and capital expenditure requirements through at least the second quarter of 2026.
•Collaboration revenue: No collaboration revenue was recognized during the third quarter of 2024 due to the fact that Werewolf substantially completed its performance obligations under the collaboration agreement with Jazz Pharmaceuticals (Jazz) during the second quarter of 2024. Comparatively, collaboration revenue was $5.9 million for the third quarter of 2023, which includes fixed payments received from Jazz, plus costs incurred for research services to be reimbursed by Jazz.
•Research and development expenses: Research and development expenses were $12.5 million for the third quarter of 2024, compared to $10.8 million for the same period in 2023. The increase in research and development expenses was primarily due to the Company’s development efforts for WTX-124 and WTX-330, which continue to progress through their respective clinical trials, resulting in higher clinical trial costs and higher manufacturing costs to support those trials.
•General and administrative expenses: General and administrative expenses were $4.6 million for the third quarter of 2024, compared to $4.3 million for the same period in 2023.
•Net loss: Net loss was $16.7 million for the third quarter of 2024, compared to $8.3 million for the same period in 2023.