Werewolf Therapeutics’ Clinical Data for WTX-124 and WTX-330 Presented at the Society for Immunotherapy of Cancer’s (SITC) 2026 Annual Meeting
Both programs showed clinical activity in treatment-refractory cancers, with no evidence of vascular leak syndrome reported.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Werewolf Therapeutics (Nasdaq: HOWL) presented clinical results for its WTX-124 and WTX-330 cancer treatments at the SITC annual meeting.
The Phase 1/1b WTX-124 study reported data from 155 patients. Dose-expansion combination treatment with pembrolizumab produced response rates of 37.5% in previously treated non-small cell lung cancer and 15.8% in previously treated cutaneous melanoma. One monotherapy complete response remained ongoing for approximately three years without additional anticancer therapy. Werewolf aligned with the FDA on 18 mg intravenously every two weeks as the recommended Phase 2 dose, alone and with pembrolizumab.
The Phase 1b/2 WTX-330 study reported data from 24 patients, including a confirmed partial response in gallbladder cancer and fewer treatment-related adverse events than first-in-human material at equivalent doses. Werewolf continues exploring further clinical development opportunities for both programs.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Positive
- Moderate pointWTX-124 dose alignment with FDA established 18 mg intravenously every two weeks for monotherapy and pembrolizumab combinations.
- Minor pointWTX-124 monotherapy dose escalation produced three objective responses, including a complete response ongoing approximately three years without additional anticancer therapy.
- Minor pointWTX-124 plus pembrolizumab dose escalation produced confirmed complete and partial responses ongoing at study end, 24 months.
- Minor point37.5% response rate occurred with WTX-124 plus pembrolizumab in dose-expansion lung cancer patients after chemoimmunotherapy.
- Minor point15.8% response rate occurred with WTX-124 plus pembrolizumab in dose-expansion cutaneous melanoma after immunotherapy and targeted therapy.
10 minor points
- Minor point33% response rate occurred with WTX-124 plus pembrolizumab in dose-expansion patients without primary immune-checkpoint inhibitor resistance.
- Minor pointWTX-124 target-lesion regression lasted 3–13 months in additional lung cancer, mucosal melanoma and gastroesophageal junction cancer patients.
- Minor pointWTX-124 paired biopsies from 43 patients showed increased T-cell and T-cell activation gene expression.
- Minor pointBoth treatments showed no evidence of vascular leak syndrome or recurrence of prior immune-related adverse events.
- Minor pointWTX-124 was administered safely as outpatient monotherapy and with pembrolizumab; WTX-330 was well tolerated, primarily outpatient.
- Minor pointWTX-330 treatment-related adverse events were less frequent at equivalent doses than with first-in-human material.
- Minor pointWTX-330 showed high systemic exposure to its inactive precursor and low exposure to active interleukin-12.
- Minor pointWTX-330 tumor signaling was detected in 7 of 9 patients providing paired biopsies.
- Minor pointWTX-330 produced a confirmed partial response in gallbladder cancer and additional tumor regressions in treatment-refractory solid tumors.
- Minor pointFurther development opportunities remain under exploration for both WTX-124 and WTX-330.
Negative
- None.
News Explained
The presentation adds a safety observation: Werewolf reported that both WTX-124 and WTX-330 were administered in outpatient settings with no evidence of vascular leak syndrome or recurrence of prior immune-related adverse events.
Key Figures
- WTX-124 recommended Phase 2 dose
- 18 mg IV Q2W
- FDA-aligned dose for monotherapy and combination with pembrolizumab
- WTX-124 patients reported
- 155 patients
- Phase 1/1b trial data presented at SITC
- NSCLC response rate
- 37.5%
- WTX-124 combination; prior chemoimmunotherapy
- Cutaneous melanoma response rate
- 15.8%
- WTX-124 combination; prior ICI and targeted therapy
- Response rate
- 33%
- WTX-124 combination in patients with non-primary ICI-resistant disease
- WTX-330 patients reported
- 24 patients
- Phase 1b/2 trial data presented at SITC
- Paired biopsies with signaling
- 7 of 9 patients
- WTX-330 intratumoral IL-12/STAT4 signaling
- Confirmed partial response
- 1 confirmed partial response
- WTX-330 patient with gallbladder cancer
Previous Clinical trial Reports
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FDA granted WTX-124 Fast Track based on earlier melanoma activity and tolerability.
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A WTX-124 trial patient with advanced skin cancer reportedly achieved complete remission.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
immune checkpoint inhibitor medical
vascular leak syndrome medical
recist 1.1 technical
interleukin-2 medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
- In a Phase 1/1b clinical trial, WTX-124 was administered safely at its recommended Phase 2 dose of 18 mg IV Q2W in the outpatient setting as monotherapy and in combination with pembrolizumab, with durable antitumor activity in patients with relapsed/refractory immunotherapy-sensitive solid tumors -
- Aligned with FDA on a recommended Phase 2 dose of 18 mg IV Q2W for WTX-124 as monotherapy and in combination with pembrolizumab -
- In a Phase 1b/2 clinical trial, WTX-330 was well tolerated using an optimized drug product and demonstrated monotherapy antitumor activity in patients with advanced, treatment refractory solid tumors -
WALTHAM, Mass., Nov. 09, 2026 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), a biopharmaceutical company that has developed conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer, today announced new clinical data from its Phase 1/1b clinical trial of WTX-124 and its Phase 1b/2 clinical trial of WTX-330, its conditionally activated Interleukin-2 (IL-2) and Interleukin-12 (IL-12) INDUKINE™ molecules, respectively, for the treatment of solid tumors, as presented by posters at the Society for Immunotherapy of Cancer’s (SITC) 2026 Annual Meeting from November 6-8, 2026.
“Werewolf is extremely proud of the team that designed the WTX-124 and WTX-330 molecules and shepherded them through their first-in-human clinical trials. The data presented at SITC demonstrated that both molecules were administered in the outpatient setting with no evidence of vascular leak syndrome or recurrence of prior immune-related adverse events, and each molecule showed evidence of clinical activity in patients with advanced, treatment refractory disease. We would like to express our gratitude to the patients who participated in both of these clinical studies, as well as to the investigators and their study teams. Werewolf continues to explore opportunities for the further clinical development of the WTX-124 and WTX-330 programs,” said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf.
The Phase 1/1b clinical trial of WTX-124 evaluated WTX-124 as a monotherapy and in combination with pembrolizumab in patients with relapsed/refractory, immunotherapy-sensitive locally advanced or metastatic solid tumors who were refractory to or intolerant of standard of care treatment. The presentation at SITC reported data from 155 patients: 65 patients treated in Part 1 (dose escalation), 42 with 1-28 mg WTX-124 IV Q2W monotherapy and 23 with WTX-124 1-23 mg IV Q2W combined with pembrolizumab 400 mg IV Q6W; and an additional 90 patients treated in Part 2 (dose expansion) with the WTX-124 recommended phase 2 dose as monotherapy (n=49) or in combination with pembrolizumab (n=41). All patients had previously received standard of care immune-checkpoint inhibitor (ICI) regimens.
monotherapy dose of WTX-124, ranging from 1 mg to 28 mg; and 64 patients treated with WTX-124 at doses ranging from 3 mg to 23 mg in combination with pembrolizumab.
Data for the Phase 1/1b clinical trial of WTX-124, as of the June 4, 2026, clinical database lock date, are summarized as follows:
- In dose escalation, WTX-124 as a monotherapy produced three objective responses in dose escalation, including one durable confirmed complete response (CR) in a patient with primary immune checkpoint inhibitor (ICI)-resistant cutaneous squamous cell carcinoma (CSCC) that has remained ongoing without any additional anticancer therapy for approximately three years, and two partial responses in patients with cutaneous melanoma and gastroesophageal junction (GEJ) adenocarcinoma per immune RECIST. Additional patients with non-small cell lung cancer (NSCLC), mucosal melanoma and GEJ adenocarcinoma showed evidence of durable target lesion regression spanning 3-13 months.
- In dose escalation, WTX-124 in combination with pembrolizumab produced a confirmed CR and a confirmed partial response ongoing at the end of the study (i.e., 24 months), in patients with cutaneous melanoma, including a patient with secondary ICI-resistant disease.
- In dose expansion, WTX-124 in combination with pembrolizumab produced a
37.5% response rate in NSCLC for patients who had prior chemoimmunotherapy, as well as a15.8% response rate in cutaneous melanoma for patients with prior ICI and targeted therapy, as well as a33% response rate in patients with non-primary ICI resistant disease. - WTX-124 was administered safely in the outpatient setting as a monotherapy or in combination with a standard-of-care immune checkpoint inhibitor. Analysis of paired tumor biopsies from 43 patients showed that WTX-124 increased expression of T cell and T cell activation genes, consistent with increased tumor-infiltrating T cells and T cell activation, while expression of the regulatory T cell marker FOXP3 did not appear to change with WTX-124 dose.
These findings are summarized in a poster titled, “A Phase 1/1b study of the tumor-activated IL-2 prodrug WTX-124 alone or in combination with pembrolizumab in adults with relapsed/refractory, advanced/metastatic, immunotherapy-sensitive solid tumors.” The late-breaking abstract was presented by Justin Moser, M.D., HonorHealth Research Institute, at SITC on Saturday, November 7, 2026.
Werewolf has aligned with the U.S. Food and Drug Administration (FDA) on a WTX-124 recommended phase two dose (RP2D) of 18 mg IV Q2W for both monotherapy and combination with pembrolizumab. The Company believes the data support compelling opportunities for further development of WTX-124 in non-small cell lung cancer, melanoma, CSCC and gastroesophageal junction adenocarcinoma.
The Phase 1b/2 clinical trial of WTX-330 was designed to evaluate WTX-330, administered intravenously every two weeks in fixed-dose and step-up regimens, in patients with relapsed/refractory, locally advanced or metastatic solid tumors. The presentation at SITC reported data from 24 patients treated at doses ranging from 0.016 mg/kg to 0.032 mg/kg.
Data for the Phase 1b/2 clinical trial of WTX-330 as of the May 14, 2026, clinical database lock date are summarized as follows:
- WTX-330 was well tolerated and was administered primarily in the outpatient setting.
- WTX-330 showed high systemic prodrug exposure with low exposure to free (active) IL-12.
- The frequency of treatment-related adverse events was dramatically reduced at equivalent dose levels compared to what was observed with first-in-human WTX-330 material.
- WTX-330 produced evidence of intratumoral IL-12/STAT4 signaling in 7 of 9 patients contributing paired tumor biopsies.
- WTX-330 produced a confirmed partial response per RECIST 1.1 in a patient with gallbladder cancer whose best response to all prior standard-of-care therapy had been progressive disease, as well as multiple additional tumor regressions in patients with late-line refractory solid tumors.
These findings are summarized in a poster titled, “A Phase 1b/2 study of the tumor-activated IL-12 prodrug WTX-330 in patients with relapsed/refractory solid tumors." The poster was presented at SITC on November 7, 2026.
Werewolf believes WTX-330 is poised for further development as a monotherapy, in combination with an ICI, or in a sequenced combination with WTX-124.
About Werewolf Therapeutics:
Werewolf Therapeutics, Inc., is an innovative biopharmaceutical company pioneering the development of therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions. The Company has designed conditionally activated INDUKINE™ molecules that stimulate both adaptive and innate immunity with the goal of addressing the limitations of conventional proinflammatory immune therapies. Werewolf’s INDUKINE molecules are intended to remain inactive in peripheral tissue yet activate selectively in the tumor microenvironment. The Company’s clinical stage product candidates, WTX-124 and WTX-330, are systemically delivered, conditionally activated Interleukin-2 (IL-2) and Interleukin-12 (IL-12) INDUKINE molecules, respectively, for the treatment of solid tumors. To learn more visit www.werewolftx.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Werewolf’s strategy, future operations, prospects, plans, and objectives of management, the availability of data from such clinical development; the potential activity and efficacy of product candidates in preclinical studies and clinical trials; the anticipated safety profile of product candidates; and the potential further development of WTX-124 and WTX-330, including in specific tumor types and in combination with other therapies, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “approach,” “believe,” “contemplate,” “continue,” “could,” “design,” “designed to,” “engineered,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “potential,” “predict,” “project,” “promise,” “should,” “target,” “will,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: risks and uncertainties inherent in the development of Werewolf’s product candidates, including the conduct, timing, progress and results of preclinical studies and clinical trials; Werewolf’s ability to successfully advance the clinical development of WTX-124 and WTX-330; whether preliminary or interim clinical will be predictive of final results or results from subsequent clinical trials; whether the safety, tolerability and antitumor activity observed in clinical trials of WTX-124 and WTX-330 will be observed in additional patients or with longer follow-up; Werewolf’s ability to obtain regulatory approvals for its product candidates; Werewolf’s ability to obtain sufficient funding to continue the development of its product candidates; and Werewolf’s ability to obtain and maintain intellectual property rights and regulatory exclusivities; as well as the risks and uncertainties identified in the “Risk Factors” section of the Company’s most recent Form 10-Q filed with the Securities and Exchange Commission (SEC), and in subsequent filings the Company may make with the SEC. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release.
WEREWOLF®, the WEREWOLF logo, INDUKINE™, and other Werewolf trademarks, service marks, graphics and logos are trade names, trademarks or registered trademarks of Werewolf Therapeutics, Inc., in the United States or other countries. All rights reserved.
Company Contact:
Jonathan Owen
SVP, General Counsel and Secretary
Werewolf Therapeutics
jowen@werewolftx.com
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