Werewolf Therapeutics presents data from ongoing Phase 1/1b trial of WTX-124

Werewolf Therapeutics announced new clinical data from the Phase 1/1b trial evaluating WTX-124, its conditionally activated Interleukin-2 INDUKINETM molecule, in patients with locally advanced or metastatic solid tumors after checkpoint inhibitor therapy. The data was presented on June 1, 2024, in a poster session at the 2024 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois. The ongoing Phase 1/1b study is evaluating WTX-124 as a monotherapy and in combination with pembrolizumab in patients with immunotherapy sensitive advanced or metastatic solid tumors who have failed standard of care treatment, including checkpoint inhibitor therapy. The presentation at ASCO captures data from 47 heavily pretreated patients: 35 patients treated with at least one monotherapy dose of WTX-124, ranging from 1 mg to 28 mg; 12 patients treated with WTX-124 at doses ranging from 3 mg to 12 mg in combination with pembrolizumab. WTX-124 as a monotherapy produced three objective clinical responses including one durable confirmed complete response and two partial responses in patients who are relapsed/refractory to immune checkpoint inhibitor therapy. Responding patients had 100% regression of target lesions with responses occurring within the first two cycles of therapy and showing durability at RDE. Related treatment emergent adverse events were primarily mild to moderate in severity, manageable and reversible; no new safety signals were identified when WTX-124 was combined with pembrolizumab. Analysis of paired tumor biopsies by NanoString suggests that WTX-124 robustly activated/expanded effector T cells preferentially over Tregs. Increased T cell activation signature for the combination suggests a potential for improved antitumor activity by combining WTX-124 with pembrolizumab. WTX-124 was clinically active and generally well tolerated in patients, not all of whom would be eligible for HD IL-2 based on age, indication or other factors. Based on these results, Werewolf has selected a WTX-124 monotherapy dose of 18 mg administered intravenously every two weeks, as the RDE to progress into the Phase 1b dose-expansion portion of the trial. The Company has thus far opened three expansion arms in advanced or metastatic renal cell carcinoma, cutaneous melanoma and cutaneous squamous cell carcinoma. Werewolf also continues to dose-escalate WTX-124 in combination with pembrolizumab and expects to select an RDE to open the combination dose-expansion portion of the study in the third quarter of 2024. In parallel, the Company also plans to engage regulators to discuss potential registrational pathways for WTX-124, including strategies for monotherapy accelerated approval in immune-checkpoint inhibitor relapsed/refractory indications.