HOWL 8-K
Werewolf Therapeutics, Inc. (HOWL)
8-K
2025-08-14
For: 2025-08-14
View Original
Added on
April 06, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
______________________
FORM 8-K
______________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): August 14, 2025
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(Exact name of registrant as specified in its charter)
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Registrant’s telephone number, including area code: (617 ) 952-0555
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
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Securities registered pursuant to Section 12(b) of the Act: | ||||||||||||||
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
Item 2.02. Results of Operations and Financial Condition.
On August 14, 2025, Werewolf Therapeutics, Inc., a Delaware corporation (the “Company”), issued a press release announcing financial results for the quarter ended June 30, 2025. A copy of the press release is being furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information contained in Item 2.02 in this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 7.01. Regulation FD Disclosure.
On August 14, 2025, the Company made publicly available on its website an updated corporate presentation. A copy of the presentation is furnished as Exhibit 99.2 hereto and is incorporated herein by reference.
The information furnished under this Item 7.01, including Exhibit 99.2, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01. Financial Statements and Exhibits.
| Exhibit No. | Description | |||||||
Press release issued by the Company on August 14, 2025 | ||||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
Cautionary Note Regarding Forward-Looking Statements
Any statements in this Current Report on Form 8-K about the Company’s future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to substantial risks and uncertainties and actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include statements regarding the Company’s strategy, future operations, prospects, plans, objectives of management, 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. 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: 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 may make with the SEC. In addition, the forward-looking statements included in this Current Report on Form 8-K represent the Company’s views as of the date of this Current Report on Form 8-K. 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 Current Report on Form 8-K.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| WEREWOLF THERAPEUTICS, INC. | ||||||||
Date: August 14, 2025 | By: | /s/ Timothy W. Trost | ||||||
| Timothy W. Trost | ||||||||
| Chief Financial Officer and Treasurer | ||||||||
Exhibit 99.1
Werewolf Therapeutics Reports Second Quarter 2025 Financial Results and Provides Business Update
– WTX-124 Phase 1/1b clinical trial on track for interim data readout in the fourth quarter of 2025, including patients in both the monotherapy and combination expansion arms of cutaneous melanoma and renal cell carcinoma –
– Planning to engage with U.S. Food & Drug Administration (FDA) in the second half of 2025 to discuss potential registrational pathways for WTX-124 in advanced or metastatic cutaneous melanoma –
– Phase 1b/2 clinical trial of WTX-330 is actively enrolling, with anticipated determination of dosing regimen by the end of 2025 –
– Company announces WTX-1011, its first INDUCERTM T-cell engager development candidate, targeting STEAP1 –
Watertown, Mass., August 14, 2025 (GLOBE NEWSWIRE) – 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, today provided a business update and reported financial results for the second quarter ended June 30, 2025.
“We continue to advance the differentiated technology born out of our PREDATOR® platform and capitalize on the strong foundation of clinical data from our lead INDUKINETM asset, WTX-124,” said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. “For WTX-124, we remain on track for an interim data readout of our Phase 1/1b clinical trial in the fourth quarter of 2025. The readout is expected to include patients with cutaneous melanoma and renal cell carcinoma, where there exist significant unmet therapeutic needs and which represent large commercial opportunities in oncology. We also anticipate meeting with the FDA later this year to discuss potential registrational pathways. Further, we are excited to introduce WTX-1011, our first INDUCER T-cell engager candidate, targeting STEAP1 for prostate cancer. Utilizing novel anti-CD3 PREDATOR masking technology, our WTX-1011 preclinical data have shown anti-tumor activity while reducing peripheral activity to prevent cytokine release syndrome. Given the broad potential of our approach with INDUCER molecules, we plan to nominate an additional candidate before year-end.”
Recent Highlights and Upcoming Milestones
Clinical-Stage INDUKINE Molecules:
•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.
◦All expansion arms are actively enrolling patients in the ongoing Phase 1/1b clinical trial at a recommended dose of 18 mg administered intravenously every two weeks (IV Q2W).
◦During the fourth quarter of 2025, Werewolf plans to release interim data from the monotherapy and combination expansion arms, including tolerability, response rate, and durability 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.
•WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.
◦Actively enrolling in a Phase 1b/2 clinical trial (WTX-330x2102) in locally advanced or metastatic solid tumors. Anticipate determination of dosing regimen by the end of 2025.
Preclinical-Stage INDUCER Molecules:
•WTX-1011: a potential first-in-class conditionally activated anti-STEAP1 T-cell engager to provide an improved therapeutic index.
◦STEAP1 is a promising prostate cancer target with limited expression in normal tissues, but notable toxicities are associated with existing anti-STEAP1 T-cell engager therapy.
◦Preclinical data demonstrated that PREDATOR® masking technology successfully silenced peripheral activity and prevented cytokine release.
▪WTX-1011 has beneficial exposure in cynomolgus monkeys with a half-life close to 100 hours.
▪WTX-1011 is stable in the periphery, with less than 0.7% of active INDUCER molecule detected.
▪Effective masking of WTX-1011 is confirmed by low levels of cytokine production compared to a 10-fold lower dose of unmasked STEAP1 INDUCER molecule.
•Utilizing a novel and highly effective anti-CD3 masking strategy, Werewolf expects to nominate an additional candidate in the second half of 2025.
Preclinical-Stage INDUKINE Portfolio:
•Werewolf’s previously announced development candidates WTX-712, its Interleukin-21 (IL-21) INDUKINE molecule, and WTX-518, its binding protein resistant Interleukin-18 (IL-18) INDUKINE molecule, each for the treatment of cancer, and WTX-921, a first-of-its-kind Interleukin-10 (IL-10) INDUKINE molecule for the treatment of inflammatory bowel disease (IBD) and potentially other inflammatory diseases, are available for partnering.
Financial Results for the Second Quarter of 2025:
•Cash position: As of June 30, 2025, cash and cash equivalents were $77.6 million, compared to $92.0 million as of March 31, 2025. The Company believes its existing cash and cash equivalents as of June 30, 2025, will be sufficient to fund operational expenses and capital expenditure requirements into the fourth quarter of 2026.
•Research and development expenses: Research and development expenses were $13.1 million for the second quarter of 2025, compared to $15.3 million for the same period in 2024.
•General and administrative expenses: General and administrative expenses were $4.4 million for the second quarter of 2025, compared to $4.8 million for the same period in 2024.
•Net loss: Net loss was $18.0 million for the second quarter of 2025, compared to $17.2 million for the same period in 2024.
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 INDUKINETM and INDUCERTM 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 advancing WTX-124 in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor and WTX-330 in multiple solid tumor types as a single agent. 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. 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 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 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®, INDUKINETM, INDUCERTM, 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.
Werewolf Therapeutics, Inc.
Condensed Consolidated Statements of Operations (unaudited)
(amounts in thousands, except share and per share data)
| Three Months Ended June 30, | Six Months Ended June 30, | ||||||||||||||||||||||
| 2025 | 2024 | 2025 | 2024 | ||||||||||||||||||||
| Revenue: | |||||||||||||||||||||||
| Collaboration revenue | $ | — | $ | 1,143 | $ | — | $ | 1,885 | |||||||||||||||
Operating expenses: | |||||||||||||||||||||||
Research and development | 13,143 | 15,271 | 26,263 | 28,179 | |||||||||||||||||||
General and administrative | 4,399 | 4,832 | 9,270 | 9,828 | |||||||||||||||||||
Total operating expenses | 17,542 | 20,103 | 35,533 | 38,007 | |||||||||||||||||||
Operating loss | (17,542) | (18,960) | (35,533) | (36,122) | |||||||||||||||||||
| Other (expense) income | (440) | 1,711 | (538) | 2,680 | |||||||||||||||||||
Net loss | $ | (17,982) | $ | (17,249) | $ | (36,071) | $ | (33,442) | |||||||||||||||
| Net loss per common share, basic | $ | (0.40) | $ | (0.40) | $ | (0.80) | $ | (0.79) | |||||||||||||||
| Net loss per common share, diluted | $ | (0.40) | $ | (0.43) | $ | (0.80) | $ | (0.82) | |||||||||||||||
| Weighted-average common shares outstanding, basic | 44,981,746 | 43,521,406 | 44,904,880 | 42,564,342 | |||||||||||||||||||
| Weighted-average common shares outstanding, diluted | 44,981,746 | 44,043,184 | 44,904,880 | 42,825,231 | |||||||||||||||||||
Werewolf Therapeutics, Inc.
Selected Condensed Consolidated Balance Sheet Data (unaudited)
(amounts in thousands)
| June 30, 2025 | December 31, 2024 | ||||||||||
| Cash and cash equivalents | $ | 77,596 | $ | 110,995 | |||||||
| Working capital | $ | 65,268 | $ | 97,886 | |||||||
| Total assets | $ | 92,566 | $ | 126,929 | |||||||
| Total notes payable, net of discount and issuance costs | $ | 27,105 | $ | 26,095 | |||||||
| Total stockholders’ equity | $ | 41,464 | $ | 73,390 | |||||||
Investor Contact:
Dan Ferry
LifeSci Advisors
617.430.7576
Media Contact:
Amanda Sellers
Deerfield Group
301.332.5574
Company Contact:
Tim Trost
Chief Financial Officer
Werewolf Therapeutics
©2025 WEREWOLF THERAPEUTICS1 | CORPORATE PRESENTATION | August 2025 Building a Novel Class of Conditionally Activated Immunotherapies for Patients with Cancer
©2025 WEREWOLF THERAPEUTICS2 | Cautionary Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding Werewolf Therapeutics, Inc.’s (the “Company”) strategy, future operations, prospects, plans, and objectives of management; 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; the anticipated safety profile of product candidates; and the timing and outcome of planned meetings with regulatory authorities, 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,” “opportunity,” “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 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 may make with the SEC. In addition, the forward- looking statements included in this presentation represent the Company’s views as of the date of this presentation. 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 presentation. Note: Certain graphics contained in this presentation are created with BioRender.com. 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.
©2025 WEREWOLF THERAPEUTICS3 | Investment Highlights Deep and Diversified Pipeline Utilizing Unique PREDATOR® Platform Solid FoundationTissue-Targeted Conditionally Activated Biologics with Near-Term Milestones Clinical Stage INDUKINE Molecules: • WTX-124 (IL-2 prodrug) interim Phase 1/1b data readout expected in 4Q25; Meeting with FDA planned in 2H25 to discuss potential registrational pathways • WTX-330 (IL-12 prodrug) Initiated Phase 1b/2 follow-on dose- and regimen-finding study in 1Q25; anticipated determination of dosing regimen by end of 2025 Next-Generation INDUCER Molecules: • Harness PREDATOR masking technology and novel protease linkers to overcome therapeutic index limitations seen with other T cell engagers • WTX-1011 STEAP1 INDUCER T Cell Engager for prostate cancer • Additional INDUCER development candidate nomination expected in 2H25 Developmental pipeline and customizable technology provides partnering opportunities Runway into 4Q26 with multiple potential near-term catalysts $77.6M in cash and equivalents as of June 30, 2025 Operational Expertise with Experienced Management Team
©2025 WEREWOLF THERAPEUTICS4 | Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies Suboptimal Pharmaceutical Properties Toxicity with Poor Clinical Outcomes Our Solution: Conditionally Activated Immunotherapy The Challenge: Off-Tumor Toxicity Limits Therapeutic Index With Optimized Therapeutic Index Masked Therapy (inactive) Activated Therapy Tumor Activated Therapy Activated immune cells On-Target Immune Activation Targeted Delivery to the Tumor Microenvironment
©2025 WEREWOLF THERAPEUTICS5 | Unique and Customizable Molecules with Tissue-Targeted Properties Across Multiple Indications INDUKINE Molecules INDUKINE and INDUCER molecules harness PREDATOR masking and protease linker technology INDUCER Molecules Next-Generation Conditionally Activated Molecules Designed to Improve Therapeutic Index Proprietary Masking Technology H al f-L ife Ex te ns io n Proprietary Linker Targeted Antitumor Immunity
6 | ©2025 WEREWOLF THERAPEUTICS Leveraging Positive INDUKINE Clinical Data to Advance INDUCER Development Strategy Platform Technology Validated by WTX-124 Clinical Data Abbreviation: TME-tumor microenvironment 1Nirschi CJ et al., Cancer Immunology Research 2022 10(5):581-596 2Nirschi CJ et al., SITC 2023 Poster: Optimal Antitumor Immunity is Triggered by WTX-124, a Clinical Stage Conditionally Activated INDUKINE Molecule 3Based on patient data for whom treatment biopsies were available as of February 7, 2025. 4Preliminary clinical data as of May 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. 5Preliminary clinical data as of March 26, 2025, for an ongoing, open label Phase 1/1b clinical trial. Preferential exposure of active molecule in the TME1 On-target immune activation in TME1,3 Reduction of systemic toxicity and off-tumor effects2,4 Confirmed, durable responses in multiple solid tumors4 Wide therapeutic index compatible with outpatient administration5 Proprietary Masking Technology H al f-L ife Ex te ns io n Proprietary Linker Targeted Antitumor Immunity
©2025 WEREWOLF THERAPEUTICS7 | PROGRAM TARGET INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 STATUS WTX-124 INDUKINE Molecule IL-2 Advanced or Metastatic Solid Tumors Monotherapy & in combination with pembrolizumab Anticipate meeting with FDA in 2H25; Interim Ph1/1b monotherapy and combination data expected in 4Q25 WTX-330 INDUKINE Molecule IL-12 Advanced or Metastatic Solid Tumors and Lymphoma Monotherapy Anticipate determination of dosing regimen by the end of 2025 WTX-712 INDUKINE Molecule IL-21 Oncology IND-enabling studies ongoing; Available for partnering WTX-518 INDUKINE Molecule IL-18 Oncology IND-enabling studies ongoing; Available for partnering WTX-921 INDUKINE Molecule IL-10 Inflammatory Disease, including IBD Available for partnering WTX-1011 INDUCER Molecule STEAP1 Prostate Cancer IND-enabling studies ongoing; Available for partnering INDUCER Molecules Multiple Oncology Additional candidate nomination expected in 2H25 JZP898 INDUKINE Molecule IFNα Oncology Exclusive global rights licensed to Jazz Pharmaceuticals Phase 1/1b FIH study as monotherapy and in combination with pembrolizumab Pipeline: Novel Clinical and Preclinical Drug Candidates
©2025 WEREWOLF THERAPEUTICS8 | ©2025 WEREWOLF THERAPEUTICS WTX-124
©2025 WEREWOLF THERAPEUTICS9 | THE CHALLENGE WTX-124: Maximizing the Therapeutic Index of IL-2 Therapy in Cancer Patients Abbreviations: HD-high dose; SOC-standard of care; ICI-immune checkpoint inhibitor Approved high-dose IL-2 therapy with aldesleukin (Proleukin®) produces durable responses in patients with cutaneous melanoma and renal cell carcinoma, but its use is limited by severe toxicity Unique Advantages of WTX-124, an IL-2 INDUKINE Molecule Novel prodrug engineered with enhanced pharmaceutical properties to selectively release a fully potent IL-2 in the tumor microenvironment to stimulate antitumor immunity with reduced toxicity Key Opportunities • Provide IL-2 therapy broadly to patients with advanced or metastatic cutaneous melanoma and renal cell carcinoma who are ineligible for HD IL-2 • IL-2 therapy may have potential benefit in any of the ICI-sensitive solid tumor indications • Address an unmet medical need for ICI-relapsed/refractory patients • Safely combine IL-2 therapy with SOC agents including ICIs in earlier lines of therapy
©2025 WEREWOLF THERAPEUTICS10 | Significant Opportunity to Expand IL-2 Market Across Multiple Indications Abbreviations: HD-high dose; CR-complete response; ORR-objective response rate Proleukin (aldesleukin) injection label, Reference ID: 3165255; Proleukin (aldesleukin) injection label (fda.gov), accessed Sept. 2, 2024 Malignant Melanoma Received IL-2 Other Malignant Renal Cell Carcinoma Received IL-2 Other But most patients don’t receive HD IL-2 due to toxicity 0% 1% 2% 3% 4% 5% 6% 7% 8% 9% 10% Re sp on se ra te fo r p at ie nt s t re at ed w ith HD -IL -2 Complete Response Partial Response Metastatic Renal Cell Carcinoma ORR = 15% Metastatic Melanoma ORR = 16% 80+ Months CR Median Duration 59+ Months CR Median Duration HD IL-2 has potential for profound patient benefit Large % of patients across multiple tumor types currently unable to receive HD IL-2 could be treated with a more tolerable IL-2 therapy that retains the profound clinical benefit
©2025 WEREWOLF THERAPEUTICS11 | WTX-124 Delivers IL-2 Selectively to Tumors in Preclinical Models Wild type IL-2 released in the TME expands and activates antitumor CD8+ T effector cells preferentially over Tregs Abbreviations: TME-tumor microenvironment; TIL-tumor infiltrating lymphocytes; Tet-tetramer Nirschl CJ et al., Cancer Immunology Research 2022 10(5):581-596 Nirschl CJ et al., SITC 2023 Poster: Optimal Antitumor Immunity is Triggered by WTX-124, a Clinical Stage Conditionally Activated INDUKINE Molecule WTX-124 Vehicle Plasma Tumor IL-2 WTX-124 INDUKINE WTX-124 dosed on Day 1 and 4 (50 µg) WTX-124 antitumor activity is substantially more potent than a “non-alpha” IL-2 INDUKINE molecule in MC38 tumor model Tumor selective targeting of IL-2 exposure
©2025 WEREWOLF THERAPEUTICS12 | Trial Details mTPI-2 (Modified Toxicity Probability Interval 2) study design; enrolling ~175 patients with IO- sensitive tumors Monotherapy and combination therapy dose escalations enrolled in parallel with staggered start for combination Assessment of safety, efficacy, pharmacokinetics, biomarkers, and ADA Tumor biopsies obtained on treatment to evaluate PD biomarkers supporting proof of mechanism Abbreviations: RDE-recommended dose for expansion; IV-intravenous; Q2W-once every two weeks; Q6W-once every six weeks MTD-maximum tolerated dose; ADA-antidrug antibody; SOC-standard of care; PD-pharmacodynamic; IO-immunotherapy Note: Dose escalation completed February 4, 2025. WTX-124 Monotherapy and Combination Expansion Arms are Actively Enrolling Dose escalation completed with 65 patients having received at least one dose of WTX-124 COMBINATION THERAPY DOSE ESCALATION MONOTHERAPY DOSE ESCALATION RDE 6 mg n=43 mg n=41 mg n=3 6 mg n=43 mg n=4 12 mg n=4 18 mg n=6 18mg IV Q2W selected as WTX-124 monotherapy RDE (MTD not established)12 mg n=11 18 mg n=9 23 mg n=8 28 mg n=3 RDE clinical activity 23 mg N=5 clinical activity n=42 patients treated n=23 patients treated 18mg IV Q2W selected as WTX- 124 RDE in combination with pembrolizumab 400mg IV Q6W (MTD not established) 1. Renal cell carcinoma • Monotherapy: n=20 • Combination therapy: n=20 2. Cutaneous melanoma • Monotherapy: n=20 • Combination therapy: n=20 3. Cutaneous SCC • Monotherapy: n=10 4. NSCLC, PD-L1+ • Combination therapy: n=20 MONOTHERAPY/COMBINATION THERAPY DOSE EXPANSION
©2025 WEREWOLF THERAPEUTICS13 | WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Key Safety Findings: • Most frequent related TEAEs were arthralgia, fatigue, pruritis and eosinophilia • Majority of related TEAEs were Grade 1 and 2, Grade 3 TEAEs at ≥18mg were manageable, reversible • No evidence of VLS, ≥ Grade 2 CRS, or infusion reactions • No recurrence to date of irAEs that had previously occurred on ICI therapy • No new safety signals seen in combination with pembrolizumab Abbreviations: TEAEs-treatment-emergent adverse events; IV-intravenously; Q2W-once every two weeks; irAEs-immune related adverse events; ICI-immune checkpoint inhibitor; CRS-cytokine release syndrome; VLS-vascular leak syndrome Note: Preliminary clinical data as of May 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. Adverse event preferred terms Number of subjects Frequency of related TEAEs occurring in more than one patient N=35 patients were treated with WTX-124 monotherapy (1-28 mg IV Q2W) and evaluable for safety
©2025 WEREWOLF THERAPEUTICS14 | WTX-124 Monotherapy Induced Rapid, Durable Regressions of Target Lesions Abbreviations: RDE-recommended dose for expansion; BCC-basal cell carcinoma; NSCLC-non-small cell lung cancer; HCC-hepatocellular carcinoma; RCC-renal cell carcinoma; GEJ-gastroesophageal junction tumor; CSCC-cutaneous squamous cell cancer; ORR-objective response rate Note: Preliminary clinical data as of May 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. *Metastatic lymph node target lesion normalized in size (<1 cm) Three patients had objective responses (ORR = 3/16); an additional seven had stable target lesions at potential RDE doses * Cutaneous squamous cell carcinoma (12 mg) Melanoma (12 mg) Gastroesophageal junction tumor (18 mg) * All three objective responses to WTX-124 monotherapy occurred within two cycles (~8 weeks)
©2025 WEREWOLF THERAPEUTICS15 | Complete Response Ongoing at >18 Months in a Patient with ICI-Refractory Cutaneous SCC 72-year-old man with metastatic cutaneous SCC who progressed on RT/cetuximab and had no response to four doses (12 weeks) of cemiplimab (Libtayo®; anti-PD-1) – panel a Initiated treatment with WTX-124 (12 mg IV Q2W) three months after discontinuing cemiplimab Baseline CT showed a 2.6 cm premaxillary target lesion (T) and a non- target lesion (NT) extending into the pterygopalatine fossa – panel b WTX-124 TREATMENT RESPONSE • 3 weeks: On-treatment biopsy of target lesion showed no tumor • 8 weeks: restaging CT showed a partial response (PR) with a 62% decrease of target lesion, no increase of non-target lesion – panel c • 12 weeks: confirmatory PET-CT showed a complete metabolic response of target/non-target lesions, consistent with a CR – panel d Patient tolerated therapy well with only Grade 2 arthralgias, Grade 2 rash WTX-124 treatment stopped at 21 weeks in setting of confirmed CR Response ongoing at >1 year off drug June 2023: PET-CT at time of progression on cemiplimab September 2023: Baseline CT performed at study entry November 30, 2023: Confirmatory PET-CT at 12 weeks T NT November 1, 2023: First restaging CT at 8 weeks a b c d Abbreviations: SCC-squamous cell carcinoma; CT-computed tomography scan; IV-intravenous; Q2W-every two weeks; PET-positron emission tomography; ICI-immune checkpoint inhibitor Note: Preliminary clinical data as of May 12, 2025, for an ongoing, open label Phase 1/1b clinical trial.
©2025 WEREWOLF THERAPEUTICS16 | Early Evidence in Dose Escalation of Durable Antitumor Activity for Combination of WTX-124 and Pembrolizumab Abbreviations: SOC-standard of care; TL-target lesion; uPR-unconfirmed partial response; PR-partial response; CR-complete response; IV-intravenously; Q2W-once every two weeks; Q6W-once every six weeks Note: Preliminary clinical data as of May 12, 2025. • Antitumor activity demonstrated in two patients with cutaneous melanoma treated with WTX-124 (12 mg IV Q2W) in combination with pembrolizumab (400 mg Q6W) • Both patients previously received SOC immune checkpoint inhibitor therapy • Patient with CR had five liver metastases at baseline (two target, three non-target); all regressed completely • Both patients tolerated therapy well over multiple cycles Overall response per RECIST 1.1 PR (confirmed) CR (confirmed) Target lesion responses over time in cutaneous melanoma patients treated with 12mg WTX-124 (12 mg IV Q2W) plus pembrolizumab (400 mg Q6W)
©2025 WEREWOLF THERAPEUTICS17 | WTX-124 Effectively Limits Systemic Exposure of Active Cytokine Data account for the improved safety profile and therapeutic index of WTX-124 compared to HD IL-2 Preliminary PK findings: • WTX-124 dosed at 18 mg IV Q2W has a ~1.5-fold higher Cmax than HD IL-2 • Peak free IL-2 exposure after WTX-124 18 mg is ~146-fold lower than HD IL-2 • Across all dose levels, free IL-2 levels are very low (0.5%* of prodrug exposure) • WTX-124 PK is approximately dose- proportional up to 18 mg IV Q2W • Repeat dosing does not cause accumulation of WTX-124 or free IL-2 • ADA are transient, primarily low titer, and have no impact on repeat dose exposure • Pembrolizumab does not affect WTX- 124 PK Cycle 1 PK profiles for WTX-124 and free IL-2 compared to HD IL-2 Cmax (mean ± SEM) *Mean Cmax ratio (free IL-2/WTX-124 prodrug) in Cycle 1 expressed as percentage. Abbreviations: HD-high dose; IV-intravenously; Q2W-once every two weeks; PK-pharmacokinetics; ADA-antidrug antibodies Note: Preliminary clinical data as of March 26, 2025. ~146-fold Preliminary PK data as of December 3, 2025
©2025 WEREWOLF THERAPEUTICS18 | WTX-124 Treatment Causes Dose Dependent Increases in Intratumoral T-cell Activation Note: Data presented for patients for whom on-treatment biopsies were available as of February 7, 2025. Treg gene Key insights from NanoString analysis of paired tumor biopsies: • Largest changes seen at WTX-124 23 mg (monotherapy) • Increased CD3D and CD8A likely reflect increased T cells in tumors • Upregulation of IL2RA, GZMB, LAG3 and CTLA4 signify increased T cell activation and effector function • Treg genes such as FOXP3 do not vary with dose • Combination therapy causes upregulation of a distinct subset of genes not seen with monotherapy including TBX21 and IFNG Top 40 upregulated T-cell activation genes across all monotherapy dose levels Key T cell genes upregulated after combination therapy lo g2 F ol d ch an ge
©2025 WEREWOLF THERAPEUTICS19 | Preliminary WTX-124 Clinical Data Demonstrate Potential for a Best-in-class IL-2 Therapy Abbreviations: SOC-standard of care; RDE-recommended dose for expansion; IV-intravenously; Q2W-once every two weeks; CR-complete response; PR-partial response; ICI-immune checkpoint inhibitor; PK-pharmacokinetics; TME-tumor microenvironment 18 mg IV Q2W selected as RDE for both monotherapy and combination therapy based on optimal balance of clinical activity and tolerability (all expansion arms open and enrolling) Durable monotherapy activity (CR, PR per RECIST 1.1) demonstrated in heavily pretreated patients refractory to all SOC therapies, including immune checkpoint inhibitors (ICIs) Safety profile with SOC ICI pembrolizumab supports opportunities for development in earlier lines of therapy PK data notable for high WTX-124 exposure but low free IL-2 exposure in plasma, validating prodrug design On treatment biopsies show hallmarks of IL-2 activity in TME (e.g., effector CD8 T cell expansion and activation) 4Q25: Anticipate release of interim data from Phase 1/1b study of monotherapy and combination with pembrolizumab, including tolerability, response rate, and durability for patients with cutaneous melanoma and renal cell carcinoma 2H25: Plan to engage regulators to discuss potential registrational pathways in advanced or metastatic cutaneous melanoma Key Takeaways Next Steps
©2025 WEREWOLF THERAPEUTICS20 | Fast to Market Indication Expansion Move Upstream Priority Indications: Engage with FDA on potential registrational path for expansion indications in cutaneous melanoma, RCC, CSCC Other IO-Sensitive Tumors: Development in additional indications in expansion based on evolving data Combine with SOC in Earlier Lines: Safety profile supports combinations in earlier lines of therapy across multiple indications where PD-(L)1 therapy is approved Development Strategy Designed to Realize WTX-124 Commercial Opportunity Abbreviations: RCC-renal cell carcinoma; ICI-immune checkpoint inhibitor; CSCC-cutaneous squamous cell carcinoma; IO-immunotherapy; SOC-standard of care
©2025 WEREWOLF THERAPEUTICS21 | Market Potential in the US in Advanced/Metastatic Melanoma ~$4.1B Spanning 1L-3L US Incident Cases 14,500 1L Treatment 2L/3L Treatment ~12,800 patients PD-1 monotherapy (KEYNOTE-006) Nivolumab + Ipilimumab (CheckMate-067) Nivolumab + LAG3 (RELATIVITY-047) BRAF + MEK (40-60% pts BRAFmut) Less often 1L Sequenced after IO ~7,700 patients PD-1 monotherapy (KEYNOTE-001) BRAF +/- MEK (Sequencing based on 1L) PD-1 + CTLA-4 (Sequencing based on 1L) PD-1 + LAG-3 (Sequencing based on 1L) TILs (C-144-01) Chemotherapy $2.5B $1.6B Source: SEER; Melanoma CancerMPact Treatment Architecture 2022
©2025 WEREWOLF THERAPEUTICS22 | Source: Bluestar analysis 1 Based on disclosed 2023 revenue for PD-(L)1 $4.1B $2.6B $8.3B $8.3B Melanoma CSCC PD-L1 ≥1% NSCLC RCC Future WTX-124 Development Plan WTX-124 has opportunity to address unmet need within four priority tumor types Market Size for Melanoma, CSCC, RCC, and PD-L1 ≥1% NSCLC WTX-124 has the potential to expand into additional tumor types where PD-(L)1 is approved A total of ~20 additional tumor types with US revenue of ~$27B1 (in 2023) ~$23B Total Market Opportunity for Four Tumor Types in WTX-124 Development Plan
©2025 WEREWOLF THERAPEUTICS23 | ©2025 WEREWOLF THERAPEUTICS WTX-330
©2025 WEREWOLF THERAPEUTICS24 | Key Opportunities • Enable patients to benefit from IL-12 therapy for the first time through improved tolerability • Leverage IL-12 biology to address a significant unmet medical need for patients with poorly immunogenic tumors or tumors resistant to SOC immunotherapies • Investigate complementary combination strategies to further enhance antitumor activity THE CHALLENGE IL-12 is a potent, pleiotropic cytokine that could address a substantial unmet medical need for patients who are resistant to SOC immunotherapies. Unfortunately, systemic administration of recombinant human IL-12 therapy is associated with severe, unmanageable toxicities that have precluded its clinical development Novel prodrug engineered to release a fully potent, wild type IL-12 cytokine selectively in the tumor microenvironment to improve the therapeutic index Abbreviations: IO-immunotherapy; SOC-standard of care WTX-330: Leveraging the Potential of IL-12 Therapy to Address IO Resistance Unique Advantages of WTX-330, an IL-12 INDUKINE Molecule
©2025 WEREWOLF THERAPEUTICS25 | MC38 tumor model mWTX-330 Vehicle Vehicle mWTX-330WTX-124 -1 0 1 mWTX-330 WTX-124 172 122 296 Differential Gene Signatures Intratumoral IL-12 pathway activation Activation of multiple antigen presentation mechanisms Th1 lineage skewing Treg fragility Increased chemokine expression Therapeutic Window INDUKINE Delivers IL-12 Selectively to Tumor Tissue with an Improved Therapeutic Index Activation of antitumor CD8+ T effector cells & pleiotropic immune activation in the TME in preclinical models Nirschl CJ et al., Cancer Immunology Research, 1 July 2023; 11 (7): 962–977 Abbreviation: TME-tumor microenvironment
©2025 WEREWOLF THERAPEUTICS26 | WTX-330 Phase 1 FIH Clinical Trial – WTX-330x2101 (Completed) Twenty-five patients received at least one dose of WTX-330 to date (n=11 in escalation, n=14 in expansion) Trial Details Bayesian logistic regression model study design Monotherapy escalation followed by two basket expansion arms ICI-unapproved and ICI- resistant indications as supported by IL-12 biology and preclinical data Assessment of safety, efficacy, PK, biomarkers, and ADA On-treatment biomarker analysis (tumor, blood) evaluating proof of mechanism including conditional activation ARM A (N=5): Patients with IO-sensitive solid tumors who have been treated with a SOC ICI regimen and who have 1° or 2° resistance ARM B (N=9): Patients with tumors for which ICI therapy is not indicated/approved (IO-naïve) Dose Expansion Abbreviations: FIH-first in human; ICI-immune checkpoint inhibitor; IO-immunotherapy; IV-intravenous; Q2W-once every two weeks; SOC-standard of care; PK- pharmacokinetics; ADA-antidrug antibody 0.016 mg/kg n=3 0.024 mg/kg IV Q2W selected for dose expansion arms 0.032 mg/kg n=50.024 mg/kg n=3 Monotherapy Dose Escalation Patients with solid tumors relapsed/refractory to all SOC Clinical activity Tolerability
©2025 WEREWOLF THERAPEUTICS27 | WTX-330 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Related TEAEs were primarily mild to moderate including at clinically active doses Key safety findings: • Most frequent related TEAEs were CRS1, chills, pyrexia and elevated liver function test abnormalities • Gr3 and Gr4 related TEAEs were manageable, reversible • Toxicities were typical for systemic IL-12 therapy, less severe compared to rhIL-12 and improved with continued dosing • Expansion arms opened at 0.024 mg/kg - two DLTs observed at 0.032 mg/kg (Gr3 mucositis, Gr3 AST increase); no MTD reached 1CRS graded by ASTCT grading scale (see: Lee DW, et al. Biol Blood Marrow Transplant 2019;25(4):625–38) Abbreviations: CRS-cytokine release syndrome; TEAEs–treatment-emergent adverse events; Gr–grade; DLTs–dose limiting toxicities; AST–aspartate aminotransferase Frequency of related TEAEs occurring in more than one patient N=25 patients treated with ≥1 dose of WTX-330 across three dose levels (0.016-0.032 mg/kg IV Q2W) Number of subjects Adverse event preferred terms # of patients Note: Final data for WTX-330 FIH Phase 1 study Database lock date: March 5, 2025
©2025 WEREWOLF THERAPEUTICS28 | WTX-330 Demonstrated Monotherapy Clinical Activity Across Diverse Tumor Types One patient with a confirmed PR (RECIST 1.1) and an additional seven patients with stable target lesions (n=15)1 Abbreviations: MSS-microsatellite stable; CRC-colorectal cancer; NET-neuroendocrine tumor; SCC-squamous cell cancer; NSCLC-non-small cell lung cancer; PR-partial response Note: Preliminary clinical data as of October 7, 2024. 1An additional patient with pancreatic ductal adenocarcinoma was evaluable and had an overall response of RECIST SD, but the data were not entered at the time of the database snapshot.
©2025 WEREWOLF THERAPEUTICS29 | Confirmed partial response in 76-year-old woman with ICI-refractory melanoma Abbreviations: PR-partial response, IV-intravenous, Q2W-once every two weeks, EOT-end of treatment, RLE-right lower extremity, TL-target lesion, NTL-non-target lesion Note: Preliminary clinical data as of October 7, 2024, for an ongoing, open label Phase 1/1b clinical trial. Pretreatment: Patient had diffuse in-transit metastases of R lower leg (a, b), a melanomatous ulcer (b) and strong FDG uptake on PET (c) Treatment history: • Progressed while receiving adjuvant pembrolizumab • Presented with diffuse in-transit metastases of the R lower leg, a non-healing melanomatous ulcer and an enlarged R inguinal lymph node Timeline of response to 0.024 mg/kg WTX-330 IV Q2W: • 3 weeks: On-treatment biopsy showed no tumor • 8 weeks: 47% ↓ in TL and no increase in NTL (RECIST PR); punch biopsies showed no active melanoma • 10 weeks: Reduced tumor metabolic activity on PET-CT • 16 weeks: RECIST PR confirmed but patient discontinued WTX-330 due to a related anemia 12 weeks after stopping WTX-330, patient noted to have an ongoing response at a subset of lesions On-/post-treatment: Many nodules have regressed (d, e), ulcer has healed (e) and tumor metabolic activity is markedly decreased (f) Transverse section of R leg visualized by PET-CTa b c d e f Decreased FDG uptake in R leg on PET-CT
©2025 WEREWOLF THERAPEUTICS30 | WTX-330 Delivered 22-fold Greater IL-12 to Patients Compared to rhIL-12 Therapy PK data account for the improved therapeutic index of WTX-330 compared to rhIL-12 Preliminary PK findings: • WTX-330 dosed at 0.024 mg/kg IV Q2W has a ~22-fold higher Cmax than rhIL-12 at its MTD (500 ng/kg; Atkins MB et al. 1997) • Peak free IL-12 exposure after 0.024 mg/kg WTX-330 is ~5-fold lower than rhIL-12 at its MTD • Across all dose levels, free IL-12 levels are very low (<1.6% of prodrug exposure) • WTX-330 PK is approximately dose- proportional from 0.016 to 0.032 mg/kg • PK exposure generally preserved upon repeat dosing Abbreviations: MTD-maximum tolerated dose; PK-pharmacokinetic; IV-intravenous; Q2W-once every two weeks Note: Preliminary PK data as of June 21, 2024. PK profiles for WTX-330 and free IL-12 compared to rhIL-12 Cmax at its MTD (mean ± SEM) ~22-fold ~5-fold LOQ 0.47 nM
©2025 WEREWOLF THERAPEUTICS31 | WTX-330 Increased Expression of T/NK Cell Activation & Antigen Presentation Genes NanoString data show evidence of pleotropic IL-12 activities in the tumor microenvironment, including in MSS CRC Abbreviations: IFN-interferon; MSS-microsatellite stable; CRC-colorectal cancer; Cholangio-cholangiocarcinoma; SCC-squamous cell cancer; PD-pharmacodynamic * Indicates that biopsied lesion was a liver metastasis; # representative multiplexed immunofluorescence analyses shown on next slide for these patients Note: Preliminary clinical data as of October 7, 2024; figure does not include data from responding melanoma patients as biopsies showed no tumor Changes in gene expression caused by WTX-330 demonstrating IL-12 activity: • Increased expression of IFNG, IL12RB2, CD8A, GRZMB and PRF1 associated with T cell activation and/or cytolytic function • Increased expression of CD274, CXCL10 and CXCL9 consistent with an IFN response • Upregulation of genes involved with antigen processing and presentation Log2 fold change Gene N=9 patients contributing paired tumor biopsies * # *, # *
©2025 WEREWOLF THERAPEUTICS32 | WTX-330 Increased Intratumoral T and NK Cell Expansion and Activation in MSS CRC Pretreatment On-treatment 102-101 MSS CRC Retroperitoneal lymph node Overall response: SD x 24wks 106-104 MSS CRC Liver metastasis Overall response: PD CD8 GRZB IFNγ NK Abbreviations: NK-natural killer; MSS-microsatellite stable; CRC-colorectal cancer; SD-stable disease; PD-progressive disease; wks-weeks, GrzB-granzyme B; scrn-screening (i.e., baseline/pretreatment) Note: Preliminary clinical data as of October 7, 2024. SCRN C1D22 0 50 100 150 CD8+ Cell Density C D 8+ /m m 2 1.5X SCRN C1D22 0 2 4 6 8 GrzB+CD8+ Cell Density G rz B + C D 8+ /m m 2 1.75X SCRN C1D22 0.0 0.5 1.0 1.5 GrzB+ NK Cell Density G rz B + N K /m m 2 SCRN C1D22 0 50 100 150 200 CD8+ Cell Density C D 8+ /m m 2 3.4X SCRN C1D22 0 2 4 6 8 10 GrzB+CD8+ Cell Density G rz B + C D 8+ /m m 2 8X SCRN C1D22 0 10 20 30 40 50 GrzB+ NK Cell Density G rz B + N K /m m 2
©2025 WEREWOLF THERAPEUTICS33 | Decreasing Peripheral IFNγ Levels with WTX-330 Dosing Correlate with Improved Tolerability C1D 1 P re C1D 2 C1D 3 C2D 1 C2D 2 C2D 3 0 5000 10000 15000 20000 80000 100000 120000 140000 IFNγ IF N γ (p g/ m L) 0.016 mg/kg 0.032 mg/kg 0.024 mg/kg Analysis of plasma IFNγ levels after WTX-330 dosing showed: • Dose-related IL-12 induction of IFNγ after the first dose • IFNγ “tachyphylaxis” beyond the first dose (levels were not measured after 2nd dose) Implications: • Elevated IFNγ levels likely account for early WTX-330 adverse events, like CRS • Decreased IFNγ levels with peripheral IL- 12 exposure could potentially be leveraged to improve WTX-330 tolerability and maximize tumor IL-12 exposure Abbreviations: IFN-interferon; CRS-cytokine release syndrome Note: Preliminary clinical data as of October 7, 2024. *Note that peripheral IFNγ levels were not measured after C1D15 dose *
©2025 WEREWOLF THERAPEUTICS34 | WTX-330 Phase 1b/2 Clinical Trial (Actively Enrolling) This clinical trial (WTX-330x2102), is a follow-on to the WTX-330 FIH Phase 1 clinical trial (WTX-330x2101) Trial Details Part A portion to drive choice of optimal regimen Results of the Fixed Dose Finding will inform the step-up dose(s) to be explored Criteria for advancement of a specific regimen includes: • Total WTX-330 exposure delivered to patients • Frequency of related toxicities and associated peripheral IFNγ • Extent/frequency of IL-12 pharmacodynamic activity observed in on-treatment tumor biopsies • antitumor activity ARM A (n~20): Locally advanced or metastatic cutaneous melanoma (1⁰ or 2⁰ resistance to SOC CPIs) ARM B (n~20): Locally advanced or metastatic microsatellite stable (MSS) colorectal cancer (r/r to SOC but naïve to immunotherapy) ARM C (n~10): Advanced NHL (r/r to SOC but CPI naïve) Expansion in Selected Indications (n~50) Abbreviations: FIH-first in human; PD-pharmacodynamics; IV-intravenous; Q2W-once every two weeks; r/r-relapsed/refractory; SOC-standard of care; CPI-checkpoint inhibitor; NHL-Non-Hodgkin’s Lymphoma; IFNγ – interferon gamma STEP-UP DOSE FINDING Patients with r/r advanced/metastatic solid tumors Regimen Determining (n~50) FIXED DOSE FINDING Patients with r/r advanced/metastatic solid tumors WTX-330 IV Q2W 28-day cycle
©2025 WEREWOLF THERAPEUTICS35 | Abbreviations: MTD-maximum tolerated dose; TEAE-treatment-emergent adverse events; AE-adverse event; MSS-microsatellite stable; CRC-colorectal cancer; PR-partial response; TME-tumor microenvironment ©2025 WEREWOLF THERAPEUTICS First systemically administered IL-12 therapy with monotherapy clinical activity and a generally tolerable safety profile Increased therapeutic window: WTX-330 delivered 22-fold more IL-12 on a molar basis than rhIL-12 therapy at its MTD INDUKINE design proof-of-concept: Second clinical program validating the INDUKINE design for delivery of toxic immune payloads with improved tolerability and clinical benefit Safety and tolerability profile: Related TEAEs were primarily mild to moderate in severity and consistent with known IL-12 safety profile; severe AEs were manageable and reversible Antitumor Activity: Demonstrated by a confirmed RECIST PR and target lesion shrinkage in two melanoma patients and stable disease for 16 and 24 weeks in two MSS CRC patients NanoString data showed evidence of pleotropic IL-12 activity in the TME Tumor biopsies from four patients with MSS CRC showed immune activation, including in liver metastases Actively enrolling in Phase 1b/2 clinical trial to optimize WTX-330 exposure in the TME Anticipated determination of dosing regimen by end of 2025 Key Takeaways Next Steps WTX-330 is a Potentially First-in-Class Systemically Administered IL-12 Therapy
©2025 WEREWOLF THERAPEUTICS36 | ©2025 WEREWOLF THERAPEUTICS INDUCER Molecules
37 | ©2025 WEREWOLF THERAPEUTICS INDUCER Molecules Utilize Werewolf’s PREDATOR Platform for Optimal TCE Design INDUCER: Inducible T cell engager Cytokine Release Syndrome (CRS) Various "on-target, off-tumor" organ adverse effects (dose-limiting toxicity) Poor tumor exposure leading to sub-optimal therapeutic effect Optimized CD3 masking strategy to reduce CRS Novel, proprietary, tumor protease sensitive linkers to increase the therapeutic Index Improved exposure of active INDUCER molecule in tumors TCE Challenges Werewolf’s Solution Tumor cell Tumor target Masked in circulation On-target, off-tumor Excess cytokines Poor tumor exposure Systemic toxicity Active in tumor Enhanced tumor exposure Pan-cancer linkers cleaved Tumor T cell T cell receptor Abbreviation: TCE-T cell engager
38 | ©2025 WEREWOLF THERAPEUTICS INDUCER Molecules: Next Generation Conditionally Activated T Cell Engager Design Harnessing proprietary masking technology and clinically validated pan-cancer linker to improve therapeutic index Proprietary and optimized anti-CD3 masking technology to reduce systemic toxicity and off-tumor effects Novel Pan-cancer Linker acts as tumor-specific switch, enabling precise unmasking and conditional activation in the TME Novel anti-CD3 Ab optimized for developability Tumor-associated antigen binding domain selected for optimal immune cell engagement Tumor targeting mask utilized when target has more extensive expression in normal tissues Proprietary anti-HSA VHH for half-life extension & increased tumor exposure Tumorprotease cleavable linkers Anti-CD3 mask Anti-CD3 Tumorantigen binding domain Anti-HSA VHH for half-life extension T cell Tumor Tumortargeting mask Abbreviation: TME-tumor microenvironment
39 | ©2025 WEREWOLF THERAPEUTICS In Vitro Cell Killing In Vivo Cytokine Release INDUCER Masking Technology is Highly Differentiated -6 -5 -4 -3 -2 -1 0 1 2 0 10 20 30 40 50 TCE (Log nM) % C el l D ea th Unmasked αCD3 Masked αCD3+αTAA Masked -5 -4 -3 -2 -1 0 1 2 0 10 20 30 40 50 INDUCER (Log nM) % C el l D ea th αCD3 Masked Unmasked Targeted cell killing of SKOV3 tumor cells by TCEs with conventional peptide or Werewolf anti-CD3 masking strategies In vivo cytokine release in humanized NSG mice following administration of bivalent CD3 antibodies with conventional peptide or Werewolf anti-CD3 masking strategies When compared to conventional anti-CD3 masking in preclinical studies: • INDUCER anti-CD3 masking produced molecules with a greater range of inducibility, even when compared to a molecule with both anti-CD3 and anti-TAA conventional peptide masking • INDUCER anti-CD3 masking approach completely prevented CRS in humanized mice, outperforming conventional masking 0 8 16 24 32 40 48 0 500 1000 1500 2000 2500 Time (Hours) IF N γ (p g/ m l) 13X αCD3 Masked 1X Unmasked 1X αCD3 Masked 0 8 16 24 32 40 48 0 500 1000 1500 2000 2500 Time (Hours) IF N γ (p g/ m l) 13X αCD3 Masked 1X Unmasked 1X αCD3 Masked Conventional Masked TCE INDUCER Molecule Conventional Anti-CD3 Mask INDUCER Mask Abbreviations: TCE-T cell engager; CRS-cytokine release syndrome
40 | ©2025 WEREWOLF THERAPEUTICS In vitro Killing of Target Cells 0 10 20 30 40 -20 -10 0 10 20 Days After Initiation of Dosing % W ei gh t C ha ng e Vehicle 1x Unmasked INDUCER Molecule 10x Masked INDUCER Molecule Improved Tolerability in a Mouse Model With a Cross-Reactive TAA Antitumor Efficacy In a Humanized CDX Model 0 5 10 15 20 0 500 1000 1500 2000 2500 Study Day Tu m or v ol um e (m m 3) Vehicle 1x µg Unmasked INDUCER Molecule 3x ug αCD3 Masked INDUCER Molecule -6 -4 -2 0 2 4 0 20 40 60 80 INDUCER (Log nM) % C el l D ea th αCD3 Masked INDUCER Molecule: Intact αCD3 Masked INDUCER Molecule: Protease Cleaved Healthy Tissue Inhibition of Off-Tumor Toxicity Tumor Tumor Selective Activation INDUCER Molecules Provide Potent Antitumor Activity While Improving Tolerability
41 | ©2025 WEREWOLF THERAPEUTICS Key Opportunities • WTX-1011 is a potential first-in-class masked anti-STEAP1 T cell engager with an improved therapeutic index • Potential to provide STEAP1 T cell engager therapy broadly to patients with metastatic castration-resistant prostate cancer • Potential opportunities in other solid tumor types, including lung and colorectal Unique Advantages of WTX-1011, a STEAP1 INDUCER Molecule Potential for highly effective silencing of activity in the periphery and selective release of active T cell engager in tumors THE CHALLENGE STEAP1 is a promising prostate cancer target with limited expression in normal tissues, but toxicities are associated with anti-STEAP1 T cell engager therapy STEAP1 trimer (PDB 6y9b) STEAP1 is Overexpressed in Prostate Cancer WTX-1011: STEAP1 INDUCER Molecule for Prostate Cancer ST EA P1 G en e Ex pr es sio n
42 | ©2025 WEREWOLF THERAPEUTICS In Vitro Processing/Activation of WTX-1011 by Dissociated Tumors In Vivo Efficacy of WTX-1011 in LNCaP CDX Tumor Model WTX-1011 is Unmasked by Human Tumors and Demonstrates Antitumor Activity 0 10 20 30 40 100 200 300 Days After Dosing Tu m or V ol um e (m m 3 ) Vehicle 10X WTX-1011 1X Unmasked STEAP1 INDUCER • WTX-1011 was broadly unmasked by human prostate tumors specimens, and prostate PDX and CDX tumors • WTX-1011 controlled tumor growth in the LNCaP CDX tumor model WTX-1011 processing by dissociated human prostate tumors, patient derived xenograft (PDX) prostate tumors, and LNCaP cell-line derived xenograft (CDX) tumors Efficacy of unmasked STEAP1 INDUCER and WTX-1011 in the human T cell engrafted NSG mice LNCaP CDX tumor model Expression of STEAP1 on Prostate CDX and PDX Tumors A FFPE PDX prostate tumor or LNCAP CDX tumors were stained with an anti-human STEAP1 antibody and imaged using the Lunaphore COMET IF Imaging system STEAP1DAPI LNCAP CDX Prostate PDX Human PDX LNCaP 0 50 100 150 % P ro ce ss in g Human tumors, n=9 PDX tumor, n=8 LNCaP tumor, n=4
43 | ©2025 WEREWOLF THERAPEUTICS • WTX-1011 showed beneficial exposure in cynomolgus monkeys with a half–life close to 100 hours • WTX-1011 was stable in the periphery, with less than 0.7% of active INDUCER detected • Effective masking of WTX-1011 was confirmed by low levels of cytokine production compared to a 10-fold lower dose of unmasked STEAP1 INDUCER molecule 0 200 400 600 IL -6 (p g/ m L) 1x Non-masked STEAP1 INDUCER Molecule 10x WTX-1011 0 24 48 72 96 120 144 168 0 1000 2000 3000 4000 5000 Elapsed Time (hr) Pl as m a TC E Co nc en tr at io n (n g/ m L) Activated WTX-1011 WTX-1011 AUC0-168h Processed/ Intact: 0.62% Plasma levels of WTX-1011 and activated (unmasked) INDUCER molecule after IV administration of WTX-1011 in NHP Plasma IL-6 levels 4 hours after IV administration of non-masked STEAP1 INDUCER molecule or 10x greater dose of WTX-1011 Cytokine Release in NHPPK of WTX-1011 in NHP WTX-1011 has Favorable PK, Limited Peripheral Activation, and Negligible Cytokine Release in NHP Abbreviations: PK-pharmacokinetics; NHP-non-human primate; IV-intravenous
44 | ©2025 WEREWOLF THERAPEUTICS Investment Highlights Deep and Diversified Pipeline Utilizing Unique PREDATOR® Platform Solid FoundationTissue-Targeted Conditionally Activated Biologics with Near-Term Milestones Clinical Stage INDUKINE Molecules: • WTX-124 (IL-2 prodrug) interim Phase 1/1b data readout expected in 4Q25; Meeting with FDA planned in 2H25 to discuss potential registrational pathways • WTX-330 (IL-12 prodrug) Initiated Phase 1b/2 follow-on dose- and regimen-finding study in 1Q25; anticipated determination of dosing regimen by end of 2025 Next-Generation INDUCER Molecules: • Harness PREDATOR masking technology and novel protease linkers to overcome therapeutic index limitations seen with other T cell engagers • WTX-1011 STEAP1 INDUCER T Cell Engager for prostate cancer • Additional INDUCER development candidate nomination expected in 2H25 Developmental pipeline and customizable technology provides partnering opportunities Runway into 4Q26 with multiple potential near-term catalysts $77.6M in cash and equivalents as of June 30, 2025 Operational Expertise with Experienced Management Team
©2025 WEREWOLF THERAPEUTICS45 | Experienced Leadership Daniel J. Hicklin, PhD President and CEO Randi E. Isaacs, MD Chief Medical Officer Steven Bloom Chief Business Officer Tim Trost, CPA Chief Financial Officer Chulani Karunatilake, PhD Chief Technology Officer William Winston, PhD Senior Vice President, Research
©2025 WEREWOLF THERAPEUTICS46 | Thank you!