Form 8-K - Current report

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): May 8, 2025

___________________________________________

WEREWOLF THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

___________________________________________


Delaware	001-40366	82-3523180
(State or Other Jurisdiction	(Commission	(IRS Employer
of Incorporation)	File Number)	Identification No.)


200 Talcott Ave, 2nd Floor
Watertown, Massachusetts			02472
(Address of Principal Executive Offices)			(Zip Code)

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):


☐			Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐			Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐			Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐			Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class

Trading Symbol(s)

Name of each exchange on which registered

Common Stock, $0.0001 par value per share

HOWL

The Nasdaq Global Select Market

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 May 8, 2025, Werewolf Therapeutics, Inc., a Delaware corporation (the “Company”), issued a press release announcing financial results for the quarter ended March 31, 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 May 8, 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
99.1						Press release issued by the Company on May 8, 2025
99.2						Investor Presentation, dated May 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 expected timeline regarding the clinical development of product candidates, including the announcement of data, the potential activity and efficacy of product candidates in preclinical studies and clinical trials, and the timing and outcome of planned meetings with regulatory authorities. 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, 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-K 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: May 8, 2025	By:	/s/ Timothy W. Trost
		Timothy W. Trost
		Chief Financial Officer and Treasurer

Exhibit 99.1

Werewolf Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update

– WTX-124 Phase 1/1b clinical trial on track for data readouts and interactions with the FDA in the second half of the year –

– First patient dosed in the Phase 1b/2 clinical trial of WTX-330, seeking to build on the clinical activity and tolerability demonstrated in the recently completed WTX-330 first-in-human Phase 1 trial –

– Company announces development of its proprietary INDUCERTM T cell engager molecules; development candidate targeted by the end of the second quarter of 2025 –

– Updated cash guidance provides runway into the fourth quarter of 2026 –

Watertown, Mass., May 8, 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 first quarter ended March 31, 2025.

“Werewolf continues to build on our promising data and progress across our clinical-stage programs,” said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. “We remain on track in our Phase 1/1b clinical trial evaluating WTX-124 to share interim data and meet with the FDA to discuss potential registrational pathways in the second half of this year. Additionally, in recognition of Skin Cancer Awareness month, Werewolf is launching an educational campaign in May to highlight the differentiation of Werewolf’s conditionally activated therapeutics and patient experiences to date in the WTX-124 clinical trial. I am also pleased to report that we recently initiated a Phase 1b/2 clinical trial of WTX-330 to explore antitumor activity and optimize the exposure of our IL-12 INDUKINE molecule in the tumor microenvironment. Finally, Werewolf has been making significant progress towards nominating its first INDUCER T cell engager development candidate in the second quarter of 2025, with preclinical data demonstrating that PREDATOR® masking technology successfully silenced peripheral activity and prevented cytokine release. We believe that our proprietary PREDATOR masking and targeting technology distinctly positions us to build a robust pipeline of T cell engagers with potentially best-in-class potency and safety profiles, filling a gap in the current immuno-oncology landscape.”

Recent Highlights and Upcoming Milestones

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 second half of 2025, Werewolf plans to present interim data from the monotherapy and combination expansion arms, including tolerability, response rate, and durability, and to engage with regulatory authorities to discuss potential registrational pathways for WTX-124, including strategies for accelerated approval.

•The data continue to demonstrate clinically meaningful anti-tumor activity with a tolerable safety profile in patients who have previously been treated with immune checkpoint inhibitors.

•Launching a skin cancer awareness campaign educating various stakeholders on WTX-124 patient outcomes to date and the innovative science underlying Werewolf’s IL-2 cytokine therapy.

WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.

•Initiated patient dosing in a Phase 1b/2 clinical trial (WTX-330x2102) to optimize the exposure of WTX-330 in the tumor microenvironment, following the encouraging clinical activity and tolerability seen in the WTX-330x2101 first-in-human study.

Preclinical 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, 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.

•Werewolf has extended its conditional activation technology to T cell engagers, utilizing a novel and highly effective anti-CD3 masking strategy for its INDUCER T cell engager molecules. Preclinical data demonstrate that the Company’s PREDATOR masking technology successfully silenced peripheral activity and prevented cytokine release in its INDUCER molecules. The Company’s first INDUCER development candidate is expected to be nominated in the second quarter of 2025.

Financial Results for the First Quarter of 2025:

•Cash position: As of March 31, 2025, cash and cash equivalents were $92.0 million, compared to $111.0 million as of December 31, 2024. Based on updated forecasting, the Company now believes its existing cash and cash equivalents as of March 31, 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 first quarter of 2025, compared to $12.9 million for the same period in 2024.

•General and administrative expenses: General and administrative expenses were $4.9 million for the first quarter of 2025, compared to $5.0 million for the same period in 2024.

•Net loss: Net loss was $18.1 million for the first quarter of 2025, compared to $16.2 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 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 tumor types or Non-Hodgkin Lymphoma as a single agent. 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 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-K 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 March 31,
	2025		2024
Revenue:
Collaboration revenue	$	—	$	742
Operating expenses:
Research and development	13,120		12,908
General and administrative	4,871		4,996
Total operating expenses	17,991		17,904
Operating loss	(17,991)		(17,162)
Other (expense) income	(98)		969
Net loss	$	(18,089)	$	(16,193)

Net loss per common share, basic and diluted	$	(0.40)	$	(0.39)

Weighted-average common shares outstanding, basic and diluted	44,827,159		41,607,279

Werewolf Therapeutics, Inc.

Selected Condensed Consolidated Balance Sheet Data (unaudited)

(amounts in thousands)


	March 31, 2025		December 31, 2024
Cash and cash equivalents	$	92,042	$	110,995
Working capital	$	82,788	$	97,886
Total assets	$	107,236	$	126,929

Total notes payable, net of discount and issuance costs	$	26,585	$	26,095
Total stockholders’ equity	$	57,307	$	73,390

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

©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 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-K 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 | Clinical-Stage Biopharma Company – Next Generation Conditionally Activated Therapies Robust Discovery Engine Novel INDUKINETM and INDUCERTM molecules Clinical Focus High-Value Opportunities PREDATOR® Platform Validated & Differentiated Tunable, tissue-targeted INDUKINE design delivers highly potent payloads with improved therapeutic index over recombinant counterpart molecules Validation of conditional activation platform demonstrated through clinical and preclinical testing of multiple INDUKINE molecules Strong Foundation Disciplined & Experienced WTX-124, an IL-2 prodrug, is potentially a best-in-class pipeline-in-a-product for immunotherapy-sensitive tumors WTX-330, an IL-12 prodrug, has the potential to be a first-in- class molecule to address poorly immunogenic cancers as a monotherapy or in combination with standard of care Deep preclinical pipeline with WTX-712 (IL-21), WTX-518 (IL- 18), WTX-921 (IL-10), and IFNα INDUKINE (licensed to Jazz) Modular platform extends pipeline expansion and collaboration potential to additional targets, tumor types, opportunities beyond oncology, additional modalities, including conditionally activated T cell engagers (INDUCER molecules) $92.0M in cash and cash equivalents as of March 31, 2025 Runway into 4Q26 with multiple near-term catalysts Experienced leadership with expertise advancing immunotherapy R&D

©2025 WEREWOLF THERAPEUTICS4 | Suboptimal Pharmaceutical Properties Toxicity Our Solution: Conditionally Activated Immunotherapy The Challenge: Off-Tumor Cytokine Toxicity Limits Therapeutic Index Poor Clinical Outcomes With Optimized Therapeutic Index INDUKINEs (inactive cytokines) Activated cytokines Tumor Activated cytokine Activated immune cells On-Target Immune Activation Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine Therapy Targeted Delivery to the Tumor Microenvironment

©2025 WEREWOLF THERAPEUTICS5 | PREDATOR Platform Blocking Domain: Safety Peripheral inactivation Anti-HSA: Exposure Half-life extension Linker: Selectivity Proprietary tumor activation Native Cytokine: Potency antitumor immune response Tunable, Tissue-targeted Therapeutics for Cancer and other Diseases INDUKINE molecules contain multiple domains, each with a unique function that can be ‘tuned’ for specific mechanisms and pharmaceutical properties necessary to treat disease ©2025 WEREWOLF THERAPEUTICS

©2025 WEREWOLF THERAPEUTICS6 | PROGRAM INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 ANTICIPATED MILESTONES Cancer Indications Cancer IndicationsWTX-712 IL-21 INDUKINE Molecule Cancer Indications Exclusive global rights licensed to Jazz Pharmaceuticals JZP898 IFNα INDUKINE Molecule Advanced or Metastatic Solid Tumors and Lymphoma Monotherapy WTX-330 IL-12 INDUKINE Molecule Advanced or Metastatic Solid Tumors Monotherapy and in combination with pembrolizumab A Portfolio of Novel Clinical and Preclinical Drug Candidates Cancer Indications WTX-518 IL-18 INDUKINE Molecule T Cell Engagers INDUCER Molecules WTX-124 IL-2 INDUKINE Molecule Anticipate meeting with FDA and providing interim P1/1b mono/combo data in 2H25 Inflammatory Disease, including IBD WTX-921 IL-10 INDUKINE Molecule PARTNERED PROGRAMS Actively enrolling in P1b/2 clinical trial IND-enabling studies IND-enabling studies Available for partnering First Development Candidate to be nominated in 2Q25 Phase 1 FIH study as monotherapy and in combination with pembrolizumab

©2025 WEREWOLF THERAPEUTICS8 | THE CHALLENGE WTX-124: Improving the Efficacy and Tolerability of IL-2 Abbreviations: SOC-standard of care; ICI-immune checkpoint inhibitor Approved high-dose IL-2 therapy (HD IL-2) 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 THERAPEUTICS9 | Goal to Significantly Expand Patient Populations Who Might Benefit from IL-2 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 THERAPEUTICS10 | 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 IL-2 WTX-124 INDUKINE WTX-124 Vehicle Abbreviations: TME-tumor microenvironment; TIL-tumor infiltrating lymphocytes; Tet-tetramer Nirschl CJ et al., Cancer Immunology Research 2022 10(5):581-596 Plasma Tumor WTX-124 dosed on Day 1 and 4 (50 µg) MC38 syngeneic tumor model

©2025 WEREWOLF THERAPEUTICS11 | Incorporation of wild type IL-2 in WTX-124 is required for complete tumor regressions and immune memory formation WTX-124 Produces Complete Responses with an Improved Therapeutic Window vs. IL-2 WTX-124 activates long-term antitumor immune memory Improved therapeutic window compared to recombinant IL-2 Abbreviations: TW-therapeutic window; CR-complete regression Nirschl CJ et al., SITC 2023 Poster: Optimal Antitumor Immunity is Triggered by WTX-124, a Clinical Stage Conditionally Activated INDUKINE Molecule WTX-124 antitumor activity is substantially more potent than a “non-alpha” IL-2 INDUKINE molecule in MC38 tumor model

©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 | Data from Ongoing WTX-124 Phase 1/1b Study in ICI-treated Patient Population Safety • Generally well tolerated in the outpatient setting • No evidence of vascular leak syndrome, cytokine release syndrome (≥Grade 2) or infusion reactions • Majority of related TEAEs were Grade 1-2 (all were reversible) • No related Grade 4 or 5 TEAEs • No new safety signals when combined with pembrolizumab Abbreviations: TEAE-treatment-emergent adverse events; CR-complete response; CSCC-cutaneous squamous cell carcinoma; PR-partial response; SOC-standard of care; ICI-immune checkpoint inhibitor Note: Preliminary clinical data as of October 25, 2024, for an ongoing, open label Phase 1/1b clinical trial. Clinical Activity • Confirmed, durable responses and antitumor activity noted at WTX-124 doses ≥12 mg in multiple solid tumors with both monotherapy WTX-124 and in combination with pembrolizumab • Durable regression of target lesions in patients who responded to therapy • Dose-dependent expansion and activation of effector T cells in the tumor microenvironment, further enhanced with combination therapy WTX-124 has monotherapy antitumor activity in patients refractory to SOC ICI regimens

©2025 WEREWOLF THERAPEUTICS14 | 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; 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 THERAPEUTICS15 | 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 THERAPEUTICS16 | 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 12 mg WTX-124 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 October 25, 2024, for an ongoing, open label Phase 1/1b clinical trial.

©2025 WEREWOLF THERAPEUTICS17 | WTX-124 in Combination with Pembrolizumab Demonstrated Durable Responses in ICI-treated Patients Dose DL Indication Prior therapies Response Status 12mg Melanoma 1. Pembrolizumab/propranolol 2. TVEC • 3w: Increased T cell activation (biopsy) • 8w: 28.7% ↓ of target lesions (TLs) • 16w: 39.4% ↓ of TLs (unconfirmed PR) • 22w: 39.4% ↓ of TLs (confirmed PR) • 30w: 39.4% ↓ of TLs (ongoing PR) • 43w: 40.4% ↓ of TLs (ongoing PR) • Treatment ongoing >8m • Progression-free 12mg Melanoma 1. Pembrolizumab 2. Ipilimumab/nivolumab 3. Nivolumab • 8w: 41.3% ↓ of TLs (unconfirmed PR) • 16w: 45.9% ↓ of TLs (confirmed PR) • 25w: 66.1% ↓ of TLs (ongoing PR) • 36w: 100% ↓ of TLs with resolution of all non-target lesions (CR) • Treatment ongoing >8m • Progression-free Abbreviations: ICI-immune checkpoint inhibitor; TL-target lesion; uPR-unconfirmed partial response; PR-partial response; CR-complete response Note: Preliminary clinical data as of March 10, 2025. Dose Tumor Type Prior Therapies Response (RECIST 1.1) Duration • Early evidence of combination antitumor activity at clinically active WTX-124 dose • All arms in both monotherapy and combination dose expansion are actively enrolling

©2025 WEREWOLF THERAPEUTICS18 | 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 ~146-fold Preliminary PK data as of December 3, 2025 Note: Preliminary clinical data as of March 26, 2025

©2025 WEREWOLF THERAPEUTICS19 | 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 THERAPEUTICS20 | Preliminary WTX-124 Clinical Data Demonstrate Potential for Best-in-Class IL-2 Therapy ©2025 WEREWOLF THERAPEUTICS Abbreviations: SOC-standard of care; ICI-immune checkpoint inhibitor; CSCC-cutaneous squamous cell carcinoma; RDE-recommended dose for expansion  Monotherapy activity and an improved tolerability profile demonstrated in heavily pretreated patients refractory to all SOC therapies, including immune checkpoint inhibitors  Combinations with ICIs and other SOC, including in earlier lines of therapy, supported by tolerable safety profile  Patient with primary ICI-resistant CSCC remains in complete response for > 12 months off therapy  Durable, confirmed partial and complete responses in 2 melanoma patients during dose escalation treated with combination WTX- 124 and pembrolizumab with durability > 8 months  WTX-124 18 mg was selected as both the monotherapy and combination RDE based on clinical activity and outpatient safety profile, all expansion arms now open for enrollment  Interim data from Phase 1/1b monotherapy and combination with pembrolizumab anticipated to be released in 2H25  Engage regulators to discuss potential registrational pathways, including accelerated approval, in 2H25 Key Takeaways Next Steps

©2025 WEREWOLF THERAPEUTICS21 | Fast to Market Indication Expansion Move Upstream Priority Indications: Engaging with FDA on potential registrational path for monotherapy expansion indications in 2L+ 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 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 for Four Tumor Types in WTX-124 Development Strategy

©2025 WEREWOLF THERAPEUTICS23 | Market Potential in the US in Advanced/Metastatic Melanoma ~$4.1B Spanning 1L-3L US Incident Cases 14,500 1L Treatment (12,800 pts) 2L/3L Treatment (7,700) ~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 THERAPEUTICS25 | 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 THERAPEUTICS26 | 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 THERAPEUTICS27 | 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; SOC-standard of care; PK-pharmacokinetics; ADA-antidrug antibody; Q2W-once every two weeks 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 THERAPEUTICS28 | WTX-330x2101 FIH Patient Population was Heterogeneous and Heavily Pretreated AGE (years) Mean (SD) 64.4 (9.4) Median 64.0 SEX, n (%) Female 12 (48.0%) Male 13 (52.0%) RACE, n (%) Black/African- American 2 (8.0%) White 21 (84.0%) Other/ Unknown 2 (8.0%) Demographics Tumor Types n (%) CRC (MSS) 9 (36.0%) Melanoma 4 (16.0%) PDAC 3 (12.0%) NSCLC 2 (8.0%) Cholangiocarcinoma 1 (4.0%) Endometrial (MSS) 1 (4.0%) Urothelial (bladder) 1 (4.0%) Soft tissue sarcoma 1 (4.0%) Other 3 (12.0%) Abbreviations: FIH-first-in-human; CRC-colorectal cancer; MSS-microsatellite stable; PDAC-pancreatic ductal adenocarcinoma; NSCLC-non-small cell lung cancer Note: Preliminary clinical data as of October 7, 2024. 1Adjuvant treatment regimens were not included Prior Therapies Prior lines for metastatic disease1 Prior lines of immunotherapy n (%) 0 11 (44.0%) 1 9 (36.0%) 2 3 (12.0%) 3 0 (0.0%) ≥4 2 (8.0%) Eligible patients had relapsed solid tumors refractory to all SOC n (%) 0 3 (12.0%) 1 3 (12.0%) 2 3 (12.0%) 3 5 (20.0%) ≥4 11 (44.0%)

©2025 WEREWOLF THERAPEUTICS29 | 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 THERAPEUTICS30 | Microsatellite-stable colorectal cancer (MSS CRC) and other GI malignancies • 50-year-old man who had progressed on seven prior lines of therapy including investigational immunotherapies had stable disease for 24 weeks • 61-year-old woman who had progressed on SOC chemotherapy combined with bevacizumab had stable disease for 16 weeks • 74-year-old man with pancreatic ductal adenocarcinoma who had progressed on SOC chemotherapy and radiation therapy demonstrated no growth of the target lesion and no increase in the non- target lesion on the first restaging scan at 8 weeks (patient ongoing) Early Signs of Clinical Antitumor Activity Across Solid Tumor Indications Metastatic cutaneous melanoma • 76-year-old woman with diffuse melanoma in- transit metastases who had progressed on adjuvant pembrolizumab achieved a confirmed PR (RECIST 1.1) for 16 weeks • 77-year-old woman with melanoma who had discontinued ipilimumab and nivolumab due to toxicity had a 24% target lesion decrease (ongoing at 12 weeks) Abbreviation: PR-partial response; MSS-microsatellite stable; CRC-colorectal cancer; GI-gastrointestinal; SOC-standard of care

©2025 WEREWOLF THERAPEUTICS31 | 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 THERAPEUTICS32 | Treatment Response in Melanoma Patient with a Confirmed RECIST PR 76-year-old woman with a BRAF wild type metastatic in-transit melanoma who progressed while receiving adjuvant pembrolizumab Patient had diffuse RLE cutaneous metastases, a non-healing melanomatous ulcer and an enlarged right inguinal lymph node Initiated treatment with 0.024 mg/kg WTX-330 IV Q2W more than two months after discontinuing pembrolizumab Timeline of response to WTX-330: • 3 weeks: On-treatment excisional biopsy of RLE skin nodules showed no tumor • 7-8 weeks: 47% decrease of TL (cluster of RLE skin nodules); no increase in NTLs (=unconfirmed PR). Punch biopsies of two pigmented lesions showed no active melanoma • 10 weeks: PET-CT showed reduced tumor metabolic activity • 16 weeks: RECIST PR confirmed with ongoing TL response, complete resolution of one NTL and no increase in second NTL. Patient discontinued therapy due to a related anemia 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. March 2024 (pretreatment): Patient progressing at melanoma in-transit metastases of RLE May 2024: After three doses of WTX-330, many nodules have flattened and/or regressed January 2024 (pretreatment): PET-CT shows progression of melanoma in-transit metastases during adjuvant pembrolizumab May 2024: After three doses of WTX-330, repeat PET-CT shows markedly decreased tumor metabolic activity in RLE Shown are two different transverse sections of RLE at each timepoint

©2025 WEREWOLF THERAPEUTICS33 | Evidence of Durable Treatment Effect in Melanoma Patient with Confirmed PR Pretreatment Post-treatment Medial RLE Lateral RLE At 28 weeks, approximately 12 weeks after discontinuing WTX-330, the patient was noted to have an ongoing response at a subset of lesions (off all therapy) • Pretreatment (March 2024): Prior to initiating treatment with WTX-330, the patient was progressing at a melanomatous ulcer (medial RLE) and at numerous in-transit metastases (medial, lateral RLE) • Post-treatment (September 2024): After a total of four doses of WTX-330, the ulcer had healed and a subset of nodules showed durable regression despite the overall mixed response Abbreviations: PR-partial response; RLE-right lower extremity Note: Preliminary clinical data as of October 7, 2024.

©2025 WEREWOLF THERAPEUTICS34 | 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 THERAPEUTICS35 | 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 THERAPEUTICS36 | 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 THERAPEUTICS37 | 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 THERAPEUTICS38 | 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 Phase 1 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-2 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 THERAPEUTICS39 | 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  Exploring antitumor activity and anticipate opening expansion arms in locally advanced or metastatic cutaneous melanoma, locally advanced or metastatic microsatellite stable (MSS) colorectal cancer and advanced non-Hodgkin’s lymphoma (NHL) Key Takeaways Next Steps WTX-330 is a Potentially First-in-Class Systemically Administered IL-12 Therapy

41 | ©2025 WEREWOLF THERAPEUTICS Applying Innovative Protein Therapeutics Design to Inflammatory DiseasesINDUCER Molecules Employ Werewolf’s PREDATOR Platform for TCE Design TCE Challenges • Cytokine Release Syndrome (CRS) and various "on-target, off- tumor" organ adverse effects (dose- limiting toxicity) • Poor tumor exposure leading to sub- optimal therapeutic effect • Current T cell engagers (TCEs) lack sufficient safety to be broadly used across solid tumor indications • Application of conditional activation technologies using Werewolf’s PREDATOR Platform (masking and tumor-selective activation) are showing early promise • Werewolf has deployed its clinically validated design platform to build a pipeline of TCEs, INDUCER molecules, with potentially best-in-class potency and safety • Improved CD3 masking strategy to reduce CRS • Novel, proprietary, tumor protease sensitive linkers to increase the therapeutic Index • Optimizing target engagement and TCE exposure in the tumor through target specific protein selection Werewolf's Solution INDUCER = Inducible T cell engager

©2025 WEREWOLF THERAPEUTICS42 | Werewolf’s Proprietary αCD3 Masking Provides TCEs with Differentiated Silencing In Vivo Cytokine Release Assay (IL-6) Tumor Antigen A Tumor Antigen B Tumor Antigen C In Vitro Cell Killing Assays αCD3 masking prevents cytokine release in mouse models αCD3 masking of T cell engagers consistently and dramatically silences peripheral activity when targeting various tumor associated antigens

©2025 WEREWOLF THERAPEUTICS44 | WTX-712: Expanding the Utility of IL-21 Therapy Potential WTX-712 Advantages • IL-21 is a differentiated, pleiotropic cytokine that drives effective antitumor response by activating multiple immune cell types • Recombinant IL-21 has shown clinical antitumor activity but has not been developed due to dose- limiting toxicities • Preclinical data demonstrated that IL-21 is active in ICI-resistant models • WTX-712 is designed to deliver IL-21 to the TME and improve the therapeutic index Status • IND-enabling studies Sullivan JM et al., AACR 2023 Poster: Generation of IL-21 INDUKINETM Molecules for the Treatment of Cancer Sullivan JM et al., SITC 2023 Poster: Development of WTX-712, a Conditionally Active IL-21 INDUKINETM Molecule for the Treatment of Cancer Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINETM Molecule, Induces a Strong antitumor Phenotype Through a Differentiated Mechanism Abbreviations: ICI-immune checkpoint inhibitor; CTL-cytotoxic T lymphocyte IL-21 activates multiple immune cell types, inhibiting Tregs and promoting M1 macrophage function. By driving a less terminally differentiated stage of CD8+ T cells, IL-21 results in sustained CTL expansion and activity in tumors. From IL-21 Signaling in Immunity | F1000Research

©2025 WEREWOLF THERAPEUTICS45 | IL-21 Elicits a Highly Effective CD8+ T Cell Response in ICI-Refractory Preclinical Models Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINETM Molecule, Induces a Strong antitumor Phenotype Through a Differentiated Mechanism Abbreviations: ICI-immune checkpoint inhibitor IL-21 treatment results in a sustained intratumoral polyfunctional CD8+ T cell response optimally suited to cell killing IL-21 is active in several ICI refractory models and can provide greater antitumor activity than IL-2 Induction of effector molecules in CD8+ T cells *Analytes quantified: IFN-𝞬𝞬, TNF, GzmA, GzmB, Prf1 Increased CD8+ T cell polyfunctionality* EMT-6 Renca

©2025 WEREWOLF THERAPEUTICS46 | WTX-712 Tumor Selective Activity Results in Robust Antitumor Immune Activation in Preclinical Models Sullivan JM et al., AACR 2023 Poster: Generation of IL-21 INDUKINETM Molecules for the Treatment of Cancer Sullivan JM et al., SITC 2023 Poster: Development of WTX-712, a Conditionally Active IL-21 INDUKINETM Molecule for the Treatment of Cancer Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINETM Molecule, Induces a Strong antitumor Phenotype Through a Differentiated Mechanism Abbreviation: TW-therapeutic window WTX-712 specifically induces IFNγ in the tumor WTX-712 antitumor activity in MC38 tumor model with an improved therapeutic window compared to IL-21 cytokine IL-21 INDUKINE treatment transforms the tumor microenvironment with robust and rapid effector CD8+ T cell response to drive tumor regressions Tumor Cell CD11c CD8 Granzyme B Perforin Vehicle IL-21 INDUKINE

©2025 WEREWOLF THERAPEUTICS48 | WTX-518: Regulating Multiple Immune Cell Types to Drive Antitumor Immunity Potential WTX-518 Advantages • IL-18 elicits an antitumor immune response by promoting the collaboration of multiple immune cell types and increasing stem-like CD8+ T cells • WTX-518 is designed to uniquely eliminate the ability of IL-18BP to inhibit IL-18 and systemically deliver IL- 18 within the TME • Potential to complement WTX-330 based on the known synergy of IL-18 and IL-12 to drive T cell activation Status • IND-enabling studies Morris KR et al., AACR 2024 Poster: Discovery of WTX-518, an IL-18 pro-drug that is conditionally activated within the tumor microenvironment and induces regressions in mouse tumor models Abbreviations: TME-tumor microenvironment; BP-binding protein IL-18 activates innate and adaptive immune cells promoting IFN-γ production by antigen-experienced T cells and favoring Th1 differentiation of naïve T cells

©2025 WEREWOLF THERAPEUTICS49 | WTX-518 is Resistant to IL-18 Binding Protein with Improved Antitumor Activity Abbreviations: BPR-binding protein resistant; TME-tumor microenvironment WTX-518 retains potency while preventing binding to IL-18BP BPR mIL-18 INDUKINE provides greater efficacy than wild-type IL-18 INDUKINE in the MC38 tumor model and increased density of polyfunctional and stem-like CD8+ T cells Vehicle WT mIL-18 INDUKINE BPR mIL-18 INDUKINE Tumor cells Polyfunctional CD8+ Stem-like CD8+ BPR mIL-18 INDUKINE triggers tumor cytotoxicity and transforms the TME

©2025 WEREWOLF THERAPEUTICS50 | Veh icl e BPR IL -18 IN DUKINE 0 20 40 60 80 100 Polyfunctional NK Cells N K C el l % P ro du ci ng ≥ 3 Ef fe ct or C yt ok in es ✱✱✱✱ BPR mIL-18 INDUKINE increases density of polyfunctional effector cells Veh icl e BPR m IL-18 IN DUKINE 0 500 1000 1500 Polyfunctional CD8+ T cells C el ls /m m 2 *** BPR mIL-18 INDUKINE triggers the formation of immune cell hubs, including stem-like CD8+ T cells, driving the regression of established tumors CD11c CD8 TCF1 CD4 Nkp46Tumor Cell CD11c CD8 Granzyme B Perforin Abbreviation: BPR-binding protein resistant BPR mIL-18 INDUKINE Treatment Promotes Robust Effector Activation and Immune Cell Interactions

©2025 WEREWOLF THERAPEUTICS52 | WTX-921: IL-10 INDUKINE Therapy for Inflammatory Bowel Disease Potential WTX-921 Advantages • Selective delivery of IL-10 to inflamed tissues to minimize systemic toxicity • Multipronged effect by inhibiting disease driving innate and adaptive immune cell populations • Targeted delivery of IL-10 can potentially block several disease driving effector molecules and cytokines Status • Available for partnership Sullivan J et al., AAI 2024 Poster: Development of Conditionally Active IL-10 INDUKINETM Molecules for the Treatment of Inflammatory Bowel Disease Adapted from Current Opinion in Immunology 2024, 91:102495

©2025 WEREWOLF THERAPEUTICS53 | WTX-921 Treatment Inhibits Disease in Mouse ACT Model of IBD Abbreviations: ACT-adoptive cell transfer; IBD-inflammatory bowel disease IL-10 INDUKINE treatment blocks disease as measured by multiple metrics 0 5 10 15 20 25 30 35 40 80 90 100 110 120 Weight Change Days post transfer % w ei gh t c ha ng e no colitis vehicle WTX-921 Dosing 0.00 0.05 0.10 0.15 0.20 0.25 IL-1β pg /μ g tis su e ✱✱✱ ✱✱✱ 0.00 0.02 0.04 0.06 0.08 IFN-γ pg /μ g tis su e ✱✱ ✱✱✱ Cytokines in the Colon 10 20 30 40 0 1 2 3 4 5 6 Disease Activity Index Days post transfer Sc or e no colitis vehicle WTX-921 ****

©2025 WEREWOLF THERAPEUTICS54 | WTX-921 Treatment Inhibited Disease in Mouse ACT Model of IBD IL-10 INDUKINE treatment prevents immune cell expansion/activation and tissue destruction Abbreviations: ACT-adoptive cell transfer; IBD-inflammatory bowel disease; H&E-hematoxylin and eosin; IF-immunofluorescence H&E IF Control-No Colitis Disease Induced-Vehicle Treated Disease Induced-INDUKINE Treated DAPI CD45 iNOS MUC2

©2025 WEREWOLF THERAPEUTICS55 | Shifting the Balance in Cytokine Therapeutics PREDATOR Platform: Value Creation Engine Our protein engineering technology optimizes the design of conditionally activated cytokine therapeutics (INDUKINE molecules) to diseased tissues. Opportunity to pursue other modalities and non-cancer indications such as inflammatory diseases. Strategic Clinical Development Two lead programs in clinical development are wholly owned by Werewolf Collaboration is central to our growth strategy with Jazz global partnership on JZP898* WTX-124 WTX-330 Strong Cash Position Deep Preclinical Pipeline WTX-712, an IL-21 INDUKINE molecule, for the treatment of cancer WTX-518, an IL-18 INDUKINE molecule, for the treatment of cancer WTX-921, an IL-10 INDUKINE molecule for inflammatory/autoimmune diseases INDUCER molecules, T cell engagers, for the treatment of cancer Approximately $92.0M in cash and cash equivalents (as of March 31, 2025) Runway into the fourth quarter of 2026 with multiple value-enhancing catalysts expected in the near term Approximately 44.9M shares outstanding (as of May 2, 2025) Phase 1/1b Clinical Trial in Advanced and Metastatic Solid Tumors Phase 1b/2 Clinical Trial in Advanced and Metastatic Solid Tumors and Lymphoma *JZP898, an IFNα INDUKINE molecule, in a Phase 1 clinical trial with Jazz Pharmaceuticals

©2025 WEREWOLF THERAPEUTICS56 | 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

Cover Page Document	May 08, 2025
Cover [Abstract]
Document Type	8-K
Document Period End Date	May 08, 2025
Entity Registrant Name	WEREWOLF THERAPEUTICS, INC.
Entity Incorporation, State or Country Code	DE
Entity File Number	001-40366
Entity Tax Identification Number	82-3523180
Entity Address, Address Line One	200 Talcott Ave
Entity Address, Address Line Two	2nd Floor
Entity Address, City or Town	Watertown
Entity Address, State or Province	MA
Entity Address, Postal Zip Code	02472
City Area Code	(617
Local Phone Number	952-0555
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Title of 12(b) Security	Common Stock, $0.0001 par value per share
Trading Symbol	HOWL
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	true
Entity Ex Transition Period	true
Entity Central Index Key	0001785530
Amendment Flag	false