WTX-124 / Werewolf Therap - LARVOL DELTA

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. (GlobeNewswire) - "During the fourth quarter of 2025, Werewolf plans to release interim data...for patients with cutaneous melanoma and renal cell carcinoma; Werewolf expects to engage with regulatory authorities in the second half of 2025 to discuss potential registrational pathways for WTX-124 in advanced or metastatic cutaneous melanoma."

P1 data • Cutaneous Melanoma • Renal Cell Carcinoma

Werewolf Therapeutics to Participate in the KidneyCAN 7th Annual Kidney Cancer Research Summit (Werewolf Therapeutics) - "The presentation will focus on Werewolf’s innovative approach to harnessing conditionally-activated cytokines designed to selectively activate immune responses within tumors. It will cover early clinical findings from the development of WTX-124, a tumor-activated IL-2 INDUKINE molecule. While high-dose IL-2 is a proven therapy for renal cell carcinoma (RCC), among other solid tumors, its use is limited by severe toxicity. Dr. Isaacs will highlight how the WTX-124 strategy aims to improve the therapeutic index, maximizing anti-tumor activity in immunotherapy-sensitive tumors like RCC while reducing systemic side effects."

Preclinical • Renal Cell Carcinoma • Solid Tumor

KEYNOTE-D17: Dose Escalation and Expansion Study of WTX-124 as Monotherapy and in Combination With Pembrolizumab (Pembro) in Patients With Selected Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Werewolf Therapeutics, Inc. | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

HonorHealth Research Institute patient with advanced skin cancer in remission for more than a year following clinical trial of Werewolf Therapeutics' investigational novel conditionally activated IL-2 pro-drug WTX-124 (GlobeNewswire) - "The investigational drug is an engineered derivative of the long-proven, but highly toxic, anti-cancer drug known as Interleukin-2 (IL-2). The drug is designed to remain inactive in the periphery until it selectively releases fully potent IL-2 in the tumor microenvironment to stimulate antitumor immunity with reduced toxicity...The clinical trial (NCT05660384) is evaluating the investigational drug 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."

Clinical • Solid Tumor

Werewolf Therapeutics to Participate in Hanson Wade’s 6th Annual Cytokine-Based Drug Development Summit (GlobeNewswire) - "The presentation will highlight how data from patients treated with IL-2 and IL-12 INDUKINE molecules in first-in-human clinical trials have successfully validated Werewolf’s unique approach to engineering differentiated, tumor-activated immunotherapies."

Clinical data • Solid Tumor

Werewolf Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "The cutaneous melanoma monotherapy dose-expansion arm of the Phase 1/1b clinical trial evaluating WTX-124 in a more homogeneous, less heavily pre-treated patient population is expected to be fully enrolled in the first half of 2025, and the cutaneous melanoma dose-expansion arm evaluating WTX-124 in combination with pembrolizumab is expected to be fully enrolled by the end of 2025. The Company expects to use the monotherapy and combination data to engage with regulators to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval, in the second half of 2025. Anticipated presentation of interim data from monotherapy and combination expansion arms in the fourth quarter of 2025....On track to initiate a Phase 1/2 dose- and regimen-finding clinical trial by the end of the first quarter of 2025 to optimize the exposure of WTX-330 in the tumor microenvironment."

New P1/2 trial • P1 data • Trial status • Cutaneous Melanoma • Oncology • Solid Tumor

Werewolf Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - P1 | N=150 | NCT05479812 | Sponsor: Werewolf Therapeutics, Inc. | "WTX-124 has shown promising monotherapy activity and an improved tolerability profile versus high dose IL-2 in heavily pretreated patients refractory to all standard-of-care therapies, including immune checkpoint inhibitors....Of the five previously disclosed objective responses, one monotherapy and two combination responses continue to demonstrate no evidence of disease progression, with the monotherapy complete response ongoing at greater than one year off therapy, one combination response improving from a confirmed partial response to a complete response, and both combination responses ongoing at greater than eight months."

P1 data • Melanoma • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma

Werewolf Therapeutics Provides Business Update and Highlights 2025 Strategic Outlook (GlobeNewswire) - "Data from expansion arms in Phase 1/1b clinical trial evaluating WTX-124 as monotherapy expected in first half of 2025 to guide regulatory engagement on potential registrational pathways; Data from expansion arms in Phase 1/1b clinical trial evaluating WTX-124 in combination with pembrolizumab anticipated in fourth quarter of 2025."

P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Skin Cancer

WTX-124: “WTX-124 was generally well tolerated as a monotherapy in the outpatient setting”; Cutaneous squamous cell carcinoma (Werewolf Therapeutics) - Corporate Presentation: “WTX-124 monotherapy induced rapid, durable regressions of target lesions”

P1 data • Cutaneous Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma

Werewolf Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "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....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."

Commercial • P1 data • Oncology • Solid Tumor

Werewolf Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Upcoming Milestones...Dose escalation is ongoing for WTX-124 in combination with pembrolizumab, with updated data and opening of expansion arms anticipated in the second half of 2024; WTX-330: Werewolf anticipates sharing additional results from the checkpoint inhibitor-resistant or -naïve relapsed or refractory advanced tumor patient expansion arms in the fourth quarter of 2024."

P1 data • Hematological Malignancies • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Skin Cancer • Solid Tumor

A phase 1/1b study of the IL-2 prodrug WTX-124 in patients with locally advanced or metastatic solid tumors after checkpoint inhibitor therapy: Initial results of the combination dose escalation with pembrolizumab. (ASCO 2024) - P1 | "WTX-124 administered as a monotherapy IV Q2W in the outpatient setting is well tolerated and clinically active in patients with relapsed/refractory solid tumors after checkpoint inhibitor therapy. Preliminary results from the ongoing combination dose escalation with pembrolizumab show no new safety signals. Updated data on safety, biomarkers, and preliminary clinical activity for the combination will be presented."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P1 data • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Melanoma • Musculoskeletal Pain • Non-melanoma Skin Cancer • Oncology • Pain • Pruritus • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • IL2 • PD-L1

Werewolf Therapeutics to Present Data from Ongoing Phase 1/1b Clinical Trial of WTX-124 as Monotherapy and in Combination with Pembrolizumab in Solid Tumors (GlobeNewswire) - P1/1b | N=150 | NCT05479812 | Sponsor: Werewolf Therapeutics, Inc. | "Werewolf Therapeutics, Inc...announced new clinical data from the Phase 1/1b trial evaluating WTX-124...WTX-124 as a monotherapy produced three objective clinical responses including one durable confirmed complete response (CR) and two partial responses (PRs) in patients who are relapsed/refractory to immune checkpoint inhibitor therapy....Based on these results, Werewolf has selected a WTX-124 monotherapy dose of 18 mg administered intravenously every two weeks (IV Q2W), 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."

P1 data • Trial status • Cutaneous Melanoma • Genito-urinary Cancer • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

Werewolf Therapeutics to Present Updated Data from Phase 1/1b Clinical Trial of WTX-124 as Monotherapy and in Combination with Pembrolizumab in Solid Tumors at 2024 ASCO Annual Meeting (GlobeNewswire) - "Werewolf Therapeutics, Inc...announced the upcoming presentation of clinical data from dose-escalation arms of the Phase 1/1b trial evaluating WTX-124, its conditionally activated Interleukin-2 (IL-2) INDUKINE molecule, as monotherapy and in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors after checkpoint inhibitor therapy. Highlights from the data as of January 28, 2024, were published today in an abstract for the upcoming poster presentation, which will include additional data from a May 1, 2024, cut-off date, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31 - June 4 in Chicago, Illinois."

P1 data • Solid Tumor

Werewolf Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "At the American Society for Clinical Oncology (ASCO) Annual Meeting, the Company will present additional interim data from the monotherapy dose-escalation arm and preliminary dose-escalation data from the combination arm of its ongoing Phase 1/1b clinical trial of WTX-124....Werewolf remains on track to select a recommended dose for expansion and initiate monotherapy dose expansion arms in the first half of 2024....In the second quarter of 2024, Werewolf plans to present interim first-in-human data from Study WTX-330x2101, its Phase 1, multi-center, open-label clinical trial evaluating WTX-330 as a monotherapy in patients with immunotherapy insensitive or resistant advanced or metastatic solid tumors or non-Hodgkin lymphoma."

P1 data • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Werewolf Therapeutics Announces WTX-124 Clinical Abstract Accepted for Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Werewolf Therapeutics, Inc...today announced that an abstract providing an update of the Company’s ongoing monotherapy and combination Phase 1/1b study of WTX-124, its interleukin 2 (IL-2) INDUKINE molecule, has been accepted for poster presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31 - June 4 in Chicago, Illinois."

P1 data • Solid Tumor

Werewolf Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "In the first half of this year, we plan to present additional clinical data from our Phase 1/1b clinical trial of WTX-124, including updated monotherapy data and initial combination data, which we anticipate will build on the promising signals of antitumor activity and improved therapeutic index that we observed in the data presented at SITC last year. In addition, we plan to share data further demonstrating the performance of our platform in our preclinical programs at AACR. We also plan to share initial clinical data from WTX-330, our second clinical candidate, in the second quarter of 2024."

P1 data • Preclinical • Non-Hodgkin’s Lymphoma • Solid Tumor

Werewolf Therapeutics Provides Business Update and Highlights 2024 Strategic Outlook (GlobeNewswire) - "WTX-124: In the first half of 2024, Werewolf plans to: Report updated interim data from the monotherapy dose-escalation arm of the Phase 1/1b study; Select a recommended dose for expansion (RDE) and initiate monotherapy dose expansion arms; and Report initial data from the combination dose escalation cohorts of the Phase 1/1b study."

P1 data • Trial status • Oncology • Solid Tumor

WTX-124: “WTX-124 administered as a monotherapy IV Q2W has been well tolerated and reached exposures associated with intratumoral IL-2 pharmacodynamic activity and clinical responses despite enrollment of a heterogeneous patient population and small patient numbers“; Solid tumors (Werewolf Therapeutics) - Conference Call Presentation

P1 data • Oncology • Solid Tumor

Werewolf Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Update (Yahoo Finance) - "Research and development expenses: Research and development expenses were $10.8 million for the third quarter of 2023, compared to $13.1 million for the same period in 2022. The decrease in research and development expenses was primarily due to a decrease in contract manufacturing costs associated with WTX-124 and WTX-330. The decline in contract manufacturing costs was partially offset by an increase in clinical trial costs for WTX-124 and WTX-330."

Commercial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

PK/RO modeling of WTX-124, a tumor-activated IL-2 prodrug, highlights the potential for a substantially improved therapeutic index compared to other IL-2 molecules (SITC 2023) - P1 | "The models also show that substantially higher doses of the tumor-activated non-alpha IL-2 molecule are required to attain the same RO on TILs as WTX-124. A first-in-human clinical trial of WTX-124 is presently underway (NCT05479812)."

Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8

Spatial analysis of tumor infiltrating lymphocyte populations in syngeneic mouse tumor models after treatment with IL-12 (mWTX-330) and IL-2 (WTX-124) INDUKINETM molecules (SITC 2023) - "This phenomenon was further amplified by combination treatment with blockers of the PD-1 pathway, highlighting the potential for INDUKINETM treatments to amplify the effects of checkpoint inhibitors. Conclusions Treatment of murine tumor bearing mice with either mWTX-330 or WTX-124 resulted in significant remodeling of immune cell populations found within the tumor tissue, simultaneously increasing immune cell infiltration, and generating a potent activation of effector cells."

IO biomarker • Preclinical • Tumor-infiltrating lymphocyte • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • GZMB • IL12A • IL2

Optimal antitumor immunity triggered by WTX-124, a clinical stage conditionally activated INDUKINETM molecule that releases fully potent IL-2 in the tumor microenvironment (SITC 2023) - P1 | "This data corroborates recent publications demonstrating that IL-2 non-alpha molecules fail to take full advantage of the positive antitumor biology generated by IL-2. WTX-124 is currently in Phase I clinical testing (NCT05678998)."

Biomarker • Clinical • Tumor microenvironment • Oncology • CD4 • CD8 • FOXP3 • IFNG • IL2

A phase 1/1b study of the tumor-activated IL-2 prodrug WTX-124 alone or in combination with pembrolizumab in patients with immunotherapy-sensitive locally advanced or metastatic solid tumors (SITC 2023) - P1 | "PK data show sustained prodrug exposure in plasma with low levels of active IL-2. The data demonstrate the potential of WTX-124 to safely deliver a fully potent, wild-type IL-2 to the TME in patients with solid tumors."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Cutaneous Melanoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • PD-L1

Werewolf Therapeutics Presents Preliminary Monotherapy Data from Phase 1/1b Clinical Trial Establishing Proof of Mechanism for WTX-124 at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting (GlobeNewswire) - P1 | N=75 | NCT05678998 | Sposnor: Werewolf Therapeutics, Inc. | "Werewolf Therapeutics, Inc...announced preliminary first-in-human clinical data from initial monotherapy dose-escalation cohorts in the Company’s lead clinical program, WTX-124x2101....WTX-124 showed expected pharmacokinetics with evidence of wide therapeutic index allowing for continued dose escalation. WTX-124 demonstrated both translational biomarker activity and early evidence of monotherapy antitumor activity at 6 mg and 12 mg doses. CD8+ T and NK cell proliferation and activation in the tumor microenvironment and immune cell gene expression changes were seen at 6 mg and 12 mg dose levels....Dose escalation is ongoing in the monotherapy and combination therapy arms of the trial with additional data from monotherapy dose-escalation cohorts informing declaration of recommended dose for expansion (RDE) and opening of the monotherapy expansion arms expected in the first half of 2024."

P1 data • PK/PD data • Trial status • Oncology • Solid Tumor