Werewolf Therapeutics Announces Pipeline and Business Updates

Rhea-AI Summary

Werewolf Therapeutics (Nasdaq: HOWL) provided a pipeline and business update focused on its INDUKINE and new INDUCER platforms.

Key clinical data: WTX-124 showed a 21% monotherapy ORR in heavily pretreated cutaneous melanoma and a 30% ORR in melanoma patients with prior immunotherapy response; Grade 3–4 related TEAEs were 25.5% and 1.9%. The FDA accepted 18 mg as the recommended WTX-124 dose and suggested a monotherapy registration path in post-ICI relapsed/refractory melanoma. WTX-330 reported an optimized process, improved therapeutic index, and a confirmed partial response in gall bladder cancer. Data updates for both programs are expected in H1 2026, and two INDUCER INDs are planned by mid-2027, contingent on funding.

Positive

• WTX-124 30% ORR in prior-response melanoma subset
• FDA accepted 18 mg as recommended WTX-124 dose
• WTX-330 optimized manufacturing improved therapeutic index
• INDs planned for WTX-1011 and WTX-2022 by mid-2027

Negative

• Grade 3–4 related TEAEs observed in 25.5% and 1.9%
• Additional funding required to advance WTX-124 and WTX-330
• IND timelines for INDUCER programs contingent on securing funds

Key Figures

WTX-124 ORR subset 30% overall response rate Phase 1b expansion arm monotherapy in post-ICI melanoma subset

WTX-124 ORR melanoma 21% objective response rate Heavily pretreated advanced/metastatic cutaneous melanoma monotherapy

WTX-124 ORR prior responders 30% objective response rate Melanoma patients with prior response to immunotherapy

Tumor regression rate 33% of tumors Patients treated with 12 or 18 mg WTX-124

Grade 3 TEAEs 25.5% (27/106) WTX-124 related treatment-emergent adverse events

Grade 4 TEAEs 1.9% (2/106) WTX-124 related treatment-emergent adverse events

WTX-330 dose 0.024 mg/kg IV Q2W Dose level with 17-fold higher Cmax than published rhIL-12

WTX-330 PR depth 45% reduction in target lesions Confirmed partial response in metastatic gall bladder cancer by RECIST 1.1

Market Reality Check

$0.6694 Last Close

Volume Volume 467,793 is roughly in line with 20-day average 468,810. normal

Technical Price 1.07 is below 200-day MA at 1.23 and 55.04% below 52-week high.

Peers on Argus

HOWL was down 0.93% pre-news while close biotech peers were mixed, with names like APLT up 2.74% and PMVP/PRLD down over 3%, pointing to stock-specific factors rather than a broad sector move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 07	Platform data update	Positive	-4.2%	Preclinical PREDATOR and INDUKINE/INDUCER data presented at SITC 2025.
Nov 04	Earnings and update	Neutral	-7.6%	Q3 2025 financials and guidance on clinical timelines and cash runway.
Oct 08	Regulatory designation	Positive	-2.6%	FDA Fast Track designation for WTX-124 in advanced cutaneous melanoma.
Oct 03	Conference posters	Neutral	+6.8%	Announcement of multiple scientific posters at SITC’s 40th Annual Meeting.
Sep 02	Investor conference	Neutral	-0.8%	Participation in H.C. Wainwright investor conference with leadership fireside chat.

Pattern Detected

Recent history shows several positive scientific or regulatory updates followed by negative price reactions, indicating a tendency for the stock to sell off on good news.

Recent Company History

Over the last few months, Werewolf reported multiple milestones, including Fast Track status for WTX-124 on Oct 8, 2025 and Q3 2025 results with cash of $65.7M expected to fund operations into Q4 2026. Scientific visibility increased with SITC 2025 data on the PREDATOR® and INDUKINE/INDUCER platforms and several conference appearances. Despite generally constructive clinical and platform news, shares often traded lower after these events. Today’s detailed pipeline and business update extends that clinical narrative, emphasizing WTX-124, WTX-330 and the emerging INDUCER T cell engager candidates.

Market Pulse Summary

The stock dropped -39.6% in the session following this news. A negative reaction despite encouraging response rates and safety data for WTX-124 and WTX-330 would fit a recent pattern in which HOWL declined after positive scientific milestones. With the stock already below its 200-day MA and far under its 52-week high, further weakness could reflect concern about the company’s stated need for additional funding and reliance on strategic partnerships to advance late-stage development, alongside recent insider selling activity reported in Form 4 filings.

Key Terms

phase 1b medical

"WTX-124 initial Phase 1b expansion arm data showed 30% overall..."

"Phase 1b" is an early stage in testing a new medical treatment or vaccine, where it is given to a small group of people to evaluate its safety and determine the right dose. For investors, this phase signals progress in development, indicating the treatment is advancing through initial safety checks, which can influence expectations for future success and potential market impact.

overall response rate medical

"WTX-124 initial Phase 1b expansion arm data showed 30% overall response rate..."

Overall response rate is the percentage of patients in a clinical study whose measurable disease shrinks or disappears after receiving a treatment. Investors watch it like a product’s “hit rate” because higher response rates can signal a drug’s effectiveness, boost chances of regulatory approval and market demand, and affect a company’s future revenue prospects, similar to how a higher batting average suggests a more reliable player.

vascular leak syndrome medical

"There was no evidence of vascular leak syndrome or recurrence of prior immune-related..."

A serious medical condition in which fluid leaks from small blood vessels into surrounding tissues, causing low blood pressure, swelling, and reduced oxygen delivery to organs. Investors should care because it is a common safety risk tracked in drug and medical-device trials and can lead to halted studies, regulatory setbacks, larger development costs, or added warnings; think of a product with a hidden defect that forces recalls or limits market use.

cmax medical

"WTX-330 had a 17-fold higher Cmax than the published Cmax of rhIL-12..."

Cmax is the highest concentration of a drug measured in the bloodstream after a dose, like the peak of a wave after a stone is dropped into water. It matters to investors because that peak helps regulators and doctors judge safety and likely effectiveness, informs dosing schedules, and is used to compare formulations or generics—data that can affect a drug’s approval, marketability, and commercial value.

recist 1.1 medical

"with a 45% reduction in tumor target lesions by RECIST 1.1."

RECIST 1.1 is a standardized set of rules used in cancer clinical trials to measure how solid tumors respond to treatment by tracking changes in size on medical scans. Think of it as a consistent ruler and scorecard that tells doctors and regulators whether a drug is shrinking tumors, keeping them stable, or allowing them to grow. Investors care because RECIST-based results are common primary endpoints that influence regulatory decisions, trial success, and a therapy’s commercial prospects.

xenografts medical

"anti-tumor activity in murine models of human tumor xenografts and excellent..."

Xenografts are tissues or tumors taken from one species and implanted into another—most commonly human tumor samples grown in mice to study disease and test treatments. For investors, they matter because results from these models help drug developers decide which therapies are likely to work or cause harm, influencing project timelines, clinical trial choices and the perceived value of a biotech program; think of them as a dress rehearsal for human trials.

cytokine release medical

"excellent prevention of cytokine release in initial non-human primate studies."

Cytokine release is the surge of small signaling proteins produced by the immune system that coordinate inflammation and other defense actions; this reaction is like an alarm system that can help fight threats but may also trigger widespread inflammation if it becomes excessive. For investors, cytokine release matters because therapies that provoke or prevent it shape a drug’s safety profile, clinical trial results, regulatory approval chances and market acceptance, all of which can materially affect a company’s valuation.

AI-generated analysis. Not financial advice.

• WTX-124 initial Phase 1b expansion arm data showed 30% overall response rate as a monotherapy in a defined subset of post-ICI advanced or metastatic cutaneous melanoma patients, with potential best-in-class tolerability profile
• WTX-330 Phase 1b/2 trial initial data demonstrated additional evidence of antitumor activity and highly favorable tolerability profile, building upon monotherapy activity demonstrated in first-in-human Phase 1 clinical trial
• Additional Phase 1/1b data update for WTX-124 and completion of Part A of Phase 1b/2 clinical trial for WTX-330 are both expected in the first half of 2026
• WTX-1011, Werewolf’s first nominated INDUCER™ T cell engager development candidate targeting advanced, relapsed/refractory STEAP1-expressing cancers, continues to progress towards IND; with the announcement of Werewolf’s second INDUCER development candidate, WTX-2022, targeting CDH6-expressing cancers, Werewolf is now planning for two INDs by mid-2027

WATERTOWN, Mass., Dec. 18, 2025 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (Nasdaq: HOWL) (the “Company” or “Werewolf”), 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, today announced a pipeline update, including a review of recent data for its INDUKINE™ programs, and a business overview of its priorities for 2026 that includes a focus on the Company’s highly differentiated INDUCER T cell engager platform. The Company is seeking strategic partnerships for further development of the promising WTX-124 and WTX-330 INDUKINE programs, informed by additional data from ongoing studies.

Dan Hicklin, PhD, President and CEO of Werewolf said, “Werewolf is dedicated to developing novel, tumor activated immunotherapies for the treatment of cancer. We are encouraged by the unprecedented clinical responses in conjunction with tolerability demonstrated by WTX-124 as a monotherapy and in combination with pembrolizumab in patients with cancers refractory to standard of care. We believe these data provide a rationale for further development of WTX-124 in the refractory setting as well as potential development in earlier lines of therapy. We are also pleased that recent WTX-330 data further demonstrated a very favorable tolerability profile and additional evidence of monotherapy activity in particularly difficult to treat immunotherapy resistant cancers. These clinical data from our WTX-124 and WTX-330 INDUKINE programs have provided important validation for our core PREDATOR^® platform technology. We are excited to apply this validated technology to our new INDUCER T cell engager platform where preclinical studies have demonstrated potentially best-in-class silencing and reduction of off-tumor toxicity that has the potential to address the challenges and gaps of current T cell engagers.”

Recent preliminary data for the INDUKINE programs:

• Compelling data from the Phase 1/1b clinical trial for WTX-124 as of October 30, 2025, included objective, durable responses as a monotherapy in melanoma, cutaneous squamous cell carcinoma, and gastroesophageal junction cancer, and in combination with pembrolizumab in cutaneous melanoma, non-small cell lung cancer, and renal cell carcinoma.
  • Monotherapy objective response rate of 21% seen in heavily pretreated patients with advanced or metastatic cutaneous melanoma is consistent with historic high-dose IL-2 activity.
  • For patients in this same melanoma population who had a prior response to any immunotherapy regimen (i.e., were not primary resistant to immunotherapy), a 30% objective response rate was observed.
  • Among patients treated on study with either 12 or 18 mg of WTX-124, tumor regression was seen in approximately 33% of tumors, including renal cell carcinoma, cutaneous squamous cell carcinoma, non-small cell lung cancer, and additional solid tumor indications.
  • There was no evidence of vascular leak syndrome or recurrence of prior immune-related adverse events, and with Grade 3 and 4 related TEAEs seen in 25.5% (27/106) and 1.9% (2/106), based on clinical data as of October 20, 2025.
  • In addition, at a recent End of Phase 1 meeting with the FDA, 18 mg was accepted as the recommended dose to move forward in development, and the FDA provided initial guidance for a monotherapy WTX-124 registration path in post-ICI advanced or metastatic relapsed/refractory melanoma.
• In the Phase 1b/2 clinical trial of WTX-330, additional evidence of highly favorable tolerability and antitumor activity in challenging tumor types was observed in the first twelve patients treated as of the data cutoff date of October 31, 2025. These results build upon data from the first-in-human Phase 1 clinical trial completed in the first quarter of 2025.
  • An optimized manufacturing process for WTX-330 was introduced in this study, which further improved the safety profile, pharmacokinetics, and therapeutic index.
  • At a dose of 0.024 mg/kg IV Q2W, WTX-330 had a 17-fold higher Cmax than the published Cmax of rhIL-12, and at all dose levels, free IL-12 levels were 0.12% of prodrug exposure.
  • As of December 2, 2025, there was one confirmed partial response in metastatic gall bladder cancer failing prior standard of care with a 45% reduction in tumor target lesions by RECIST 1.1.

Key Updates and 2026 Priorities

The Phase 1/1b clinical trial of WTX-124 is expected to be completed in the first half of 2026, with an additional data update planned to be provided at that time. Additional funding will be required to initiate any further development, which could include a registration-enabling trial. An update from the dose- and regimen-determining Part A of the Phase 1b/2 clinical trial of WTX-330 is expected in the first half of 2026. Additional funding will be required to further develop WTX-330, which could include sequential administration of WTX-330 and WTX-124 that may provide a novel development path in poorly immunogenic tumors. The Company is seeking strategic partners for its INDUKINE programs.

Werewolf’s INDUCER molecules incorporate several differentiating features to address the limitations of other T-cell engager approaches by improving the therapeutic index, enhancing INDUCER exposure in the target tissue, and careful selection of tumor associated antigens that have the potential for preferential tumor association compared to normal tissue. We believe these qualities could establish Werewolf as the leading T cell engager company. INDUCER molecules utilize a proprietary masking approach and the same novel linker technology that has been clinically validated in the WTX-124 and WTX-330 programs. The preliminary preclinical data on the Company’s first development candidate, WTX-1011, targeting STEAP1 were consistent with preclinical data from the second, newly announced development candidate, WTX-2022, that targets the CDH6 tumor associated antigen. Preclinical data for each candidate demonstrated the power of the INDUCER technology with robust silencing, reversible masking and highly efficient activation in human tumor tissue. Additionally, these data showed potent, consistent and compelling preclinical anti-tumor activity in murine models of human tumor xenografts and excellent prevention of cytokine release in initial non-human primate studies. Cell line development has been initiated for each program and IND-enabling studies are underway, with IND filings planned for mid-2027, pending additional funding.

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 is leveraging its proprietary PREDATOR platform to design conditionally activated INDUKINE and INDUCER 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 most advanced 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. Werewolf is leveraging positive data from its INDUKINE molecules to advance the development of INDUCER molecules. Werewolf’s first INDUCER development candidate, WTX-1011, targets STEAP1 for prostate cancer, and its second INDUCER candidate, WTX-2022, targets CDH6 for ovarian and kidney cancer.

To learn more visit www.werewolftx.com or follow us on LinkedIn.

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, including potential strategic partnerships; the projection of the cash runway; the expected timeline for the preclinical and clinical development of product candidates and the availability of data from such preclinical and clinical development; the timing of anticipated regulatory engagement; the potential activity and efficacy of product candidates in preclinical studies and clinical trials; and the anticipated safety profile of product candidates constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “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: uncertainties inherent in the development of product candidates, including the conduct of research activities, and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and the Company’s ability to submit and obtain regulatory approval for investigational new drug applications; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether preliminary or interim data from a clinical trial will be predictive of the future results of the trial and future clinical trials; the Company’s ability to manage cash resources and obtain additional cash resources to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; 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 has made and 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, PREDATOR^®, INDUKINE™, INDUCER™, 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.

Investor Contact:
Dan Ferry
LifeSci Advisors
617.430.7576
daniel@lifesciadvisors.com

Media Contact:
Amanda Sellers
Deerfield Group
301.332.5574
amanda.sellers@deerfieldgroup.com

Company Contact:
Tim Trost
Chief Financial Officer
Werewolf Therapeutics
ttrost@werewolftx.com

FAQ

What clinical response did Werewolf report for WTX-124 (HOWL) in December 2025?

WTX-124 showed a 21% monotherapy ORR in heavily pretreated cutaneous melanoma and 30% ORR in patients with prior immunotherapy response.

What dose did the FDA accept for WTX-124 and what does it mean for HOWL?

The FDA accepted 18 mg as the recommended dose to move forward and provided initial guidance for a monotherapy registration path in post-ICI relapsed/refractory melanoma.

When will Werewolf provide additional WTX-124 and WTX-330 data updates?

Additional data updates for both WTX-124 and the Part A readout of WTX-330 are expected in the first half of 2026.

What material safety figures did Werewolf disclose for WTX-124?

Werewolf reported Grade 3 related TEAEs in 25.5% of patients and Grade 4 related TEAEs in 1.9% as of the cited data cutoff.

What progress did Werewolf report for its INDUCER T cell engager programs (HOWL)?

Preclinical INDUCER candidates WTX-1011 (STEAP1) and WTX-2022 (CDH6) showed robust silencing, reversible masking, activation in tumor tissue, and IND filings are planned by mid-2027 pending funding.

How will Werewolf fund further development of WTX-124 and WTX-330?

Werewolf stated that additional funding will be required and it is seeking strategic partners for further development.