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| Item 7.01. | Regulation FD Disclosure |
On November 12, 2024, Werewolf Therapeutics, Inc. (the “Company”) made publicly available on its website an updated corporate presentation. A copy of the presentation is furnished as Exhibit 99.1 hereto and is incorporated herein by reference.
The information furnished under this Item 7.01, 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 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Investor Presentation, dated November 2024 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
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: November 12, 2024 | By: | /s/ Timothy W. Trost | ||||
| Timothy W. Trost | ||||||
| Chief Financial Officer and Treasurer | ||||||
Exhibit 99.1 Delivering the Power of Immunotherapy CORPORATE PRESENTATION | November 2024 1 | ©2024 WEREWOLF THERAPEUTICS
Cautionary Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties inherent in the development of product candidates, including the conduct uncertainties. All statements, other than statements of historical facts, contained in this of research activities and the initiation and completion of preclinical studies and clinical presentation, including statements regarding Werewolf Therapeutics, Inc.’s trials; uncertainties as to the availability and timing of results from preclinical studies (the “Company”) strategy, future operations, prospects, plans, and objectives of and clinical trials; the timing of and the Company’s ability to submit and obtain management; the projection of the cash runway; the expected timeline for the regulatory approval for investigational new drug applications; whether results from preclinical and clinical development of product candidates and the availability of data preclinical studies will be predictive of the results of later preclinical studies and clinical from such preclinical and clinical development; the potential activity and efficacy of trials; whether preliminary or interim data from a clinical trial will be predictive of the product candidates in preclinical studies and clinical trials; the anticipated safety profile results of the trial and future clinical trials; the Company’s ability to manage cash of product candidates; and the timing and outcome of planned meetings with regulatory resources and obtain additional cash resources to fund the Company’s foreseeable and authorities, constitute forward-looking statements within the meaning of The Private unforeseeable operating expenses and capital expenditure requirements; as well as the Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “approach,” risks and uncertainties identified in the “Risk Factors” section of the Company’s most “believe,” “contemplate,” “continue,” “could,” “design,” “designed to,” “engineered,” recent Form 10-Q filed with the Securities and Exchange Commission (“SEC”) and in “estimate,” “expect,” “goal,” “intend,” “may,” “might,” “objective,” “ongoing,” subsequent filings the Company may make with the SEC. In addition, the forward- “opportunity,” “plan,” “potential,” “predict,” “project,” “promise,” “should,” “target,” looking statements included in this presentation represent the Company’s views as of “will,” or “would,” or the negative of these terms, or other comparable terminology are the date of this presentation. The Company anticipates that subsequent events and intended to identify forward-looking statements, although not all forward-looking developments will cause its views to change. However, while the Company may elect to statements contain these identifying words. The Company may not actually achieve the update these forward-looking statements at some point in the future, it specifically plans, intentions or expectations disclosed in these forward-looking statements, and you disclaims any obligation to do so. These forward-looking statements should not be relied should not place undue reliance on these forward-looking statements. Actual results or upon as representing the Company’s views as of any date subsequent to the date of this events could differ materially from the plans, intentions and expectations disclosed in presentation. these forward-looking statements as a result of various important factors, including: ® ® WEREWOLF , the WEREWOLF logo, PREDATOR , INDUKINE and other Werewolf trademarks, service marks, graphics and logos are trade names, trademarks or registered trademarks of Werewolf Therapeutics, Inc., in the United States or other countries. All rights reserved. Note: Certain graphics contained in this presentation are created with BioRender.com. 2 | ©2024 WEREWOLF THERAPEUTICS
Who we are Our mission is to unlock the promise of cytokines as effective immunotherapies Werewolf is developing next generation cytokine therapies designed to harness their innate immunological potential to transform the lives of patients with cancer and other serious diseases. 3 | 3 | © ©2024 2024 W WE ER RE EW WOL OLF F T TH HER ERA AP PEU EUT TIIC CS S
Clinical-Stage Biopharma Company – Next Generation Conditionally Activated Therapies Strong Foundation Robust Discovery Engine Clinical Focus PREDATOR® Platform TM Disciplined & Experienced Novel INDUKINE molecules High-Value Opportunities Validated & Differentiated Tunable, tissue-targeted INDUKINE design WTX-124, an IL-2 prodrug, is potentially a Deep preclinical pipeline with WTX-712 $122.8M in cash and equivalents as of delivers highly potent payloads with best-in-class pipeline-in-a-product for (IL-21), WTX-518 (IL-18), WTX-910 (IL-10), September 30, 2024 improved therapeutic index over immunotherapy-sensitive tumors and IFNα INDUKINE (licensed to Jazz) recombinant counterpart molecules Runway through at least 2Q26 with • Improved tolerability over HD IL-2 Modular platform extends pipeline multiple near-term catalysts • Increased patient access to therapy Validation of conditional activation expansion and collaboration potential to • Dose expansion ongoing in priority platform demonstrated through clinical additional targets, tumor types, Experienced leadership with expertise tumor types as mono + combo and preclinical testing of multiple opportunities beyond oncology, additional advancing immunotherapy R&D INDUKINE molecules modalities 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 • Generally well tolerated with monotherapy antitumor activity • Phase 1/2 study will explore optimal dosing and assess activity in selected RDE = recommended dose for expansion indications 4 | ©2024 WEREWOLF THERAPEUTICS
Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine Therapy The Challenge: Our Solution: Off-Tumor Cytokine Toxicity Limits Conditionally Activated Therapeutic Index Immunotherapy Suboptimal Pharmaceutical Properties With Optimized Therapeutic Index Tumor Activated cytokine INDUKINEs (inactive cytokines) Activated cytokines Activated immune cells Toxicity Poor Clinical Outcomes Targeted Delivery to the On-Target Immune Tumor Microenvironment Activation 5 | ©2024 WEREWOLF THERAPEUTICS
PREDATOR Exposure Platform Half-life extension Selectivity Tumor activation Tunable, Tissue-targeted Therapeutics for Cancer Potency Native Cytokine and other Diseases INDUKINE molecules contain multiple Safety domains, each with a unique function that Peripheral inactivation can be ‘tuned’ for specific mechanisms and pharmaceutical properties necessary to treat disease 6 6 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
A Portfolio of Novel Clinical and Preclinical Drug Candidates ANTICIPATED PROGRAM INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 MILESTONES Advanced or Metastatic Solid Tumors Initial data readout from WTX-124 monotherapy expansion Monotherapy and in combination IL-2 INDUKINE Molecule expected in 1H25 with pembrolizumab Advanced or Metastatic Enrollment in Phase 1/2 WTX-330 Solid Tumors and Lymphoma dose and regimen IL-12 INDUKINE Molecule finding study expected in Monotherapy 1H25 WTX-712 Cancer Indications IND-enabling studies IL-21 INDUKINE Molecule WTX-518 IND-enabling studies Cancer Indications IL-18 INDUKINE Molecule WTX-921 Partnering opportunity Inflammatory Disease, including IBD IL-10 INDUKINE Molecule Novel INDUKINE Partnering opportunity Immuno-oncology Molecules PARTNERED PROGRAMS Phase 1/1b FIH study as Cancer Indications JZP898 monotherapy and in Exclusive global rights combination with IFNα INDUKINE Molecule licensed to Jazz Pharmaceuticals pembrolizumab 7 | ©2024 WEREWOLF THERAPEUTICS
# WTX-124 8 8 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
WTX-124: Improving the Efficacy and Tolerability of IL-2 THE CHALLENGE 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 9 | ©2024 WEREWOLF THERAPEUTICS Abbreviations: SOC-standard of care; ICI-immune checkpoint inhibitor
Goal to Significantly Expand Patient Populations Who Might Benefit from IL-2 But most patients don’t receive HD IL-2 has potential for profound HD IL-2 due to toxicity patient benefit Malignant Malignant Renal 10% Complete Response Melanoma Cell Carcinoma 9% Partial Response 8% 7% 6% 5% 80+ Months 59+ Months 4% CR Median Duration Received IL-2 Other Received IL-2 Other CR Median Duration 3% 2% 1% Large % of patients across multiple tumor types 0% currently unable to receive HD IL-2 could be treated Metastatic Renal Cell Carcinoma Metastatic Melanoma ORR = 15% ORR = 16% with a more tolerable IL-2 therapy that retains the profound clinical benefit 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 10 | ©2024 WEREWOLF THERAPEUTICS Response rate for patients treated with HD-IL-2
WTX-124 Delivers IL-2 Selectively to Tumors in Preclinical Models Released IL-2 expands and activates antitumor CD8+ T effector cells preferentially over Tregs Plasma Tumor WTX-124 INDUKINE IL-2 MC38 mice WTX-124 dosed on Day 1 and 4 (50 µg) Vehicle WTX-124 Abbreviation: TIL-tumor infiltrating lymphocytes Nirschl CJ et al., Cancer Immunology Research 2022 10(5):581-596 11 | ©2024 WEREWOLF THERAPEUTICS
INDUKINE Molecule Strategy Markedly Improves the Therapeutic Window for IL-2 Incorporation of wild type IL-2 in WTX-124 is required for complete tumor regressions and immune memory formation WTX-124 activates long-term antitumor immune memory Improved therapeutic window compared to recombinant IL-2 WTX-124 antitumor activity is substantially more potent than a “non-alpha” IL-2 INDUKINE in MC38 tumor model 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 12 | ©2024 WEREWOLF THERAPEUTICS
Data from Ongoing WTX-124 Phase 1/1b Study in ICI-treated Patient Population Safety Clinical Activity • Generally well tolerated in the outpatient setting • Objective responses at WTX-124 doses ≥12 mg • No evidence of vascular leak syndrome, cytokine Ø Confirmed, durable CR in patient with CSCC release syndrome (≥Grade 2) or infusion reactions Ø Confirmed, durable PRs in 2 patients with • Majority of related TEAEs were Grade 1-2 (all were metastatic melanoma (combination with pembro) reversible) • Durable regression of target lesions in patients who • No related Grade 4 or 5 TEAEs responded to therapy • No new safety signals when combined with • Dose-dependent expansion and activation of effector pembrolizumab T cells in the tumor microenvironment, further enhanced with combination therapy WTX-124 has monotherapy antitumor activity in patients refractory to SOC ICI regimens 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 May 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. 13 | ©2024 WEREWOLF THERAPEUTICS
WTX-124 Monotherapy and Combination Expansion Arms are Open and Enrolling 67 patients have received at least one dose of WTX-124 (n=47 monotherapy, n=20 combination therapy)* Monotherapy/Combination Dose Expansion MONOTHERAPY DOSE ESCALATION Advanced or metastatic (to be Determination 28 mg of WTX-124 IV enrolled): TBD 23 mg n=3 Q2W RDE/ 18 mg n=8 12 mg n=9 MTD as a • Renal cell carcinoma (n=20) 6 mg open n=11 3 mg open monotherapy n=4 1 mg RDE n=4 clinical n=3 • Cutaneous melanoma (n=20) activity • Cutaneous squamous cell COMBINATION THERAPY DOSE ESCALATION carcinoma (monotherapy only; n=10) Determination of WTX- 124 IV Q2W RDE/MTD 23 mg • Non-small cell lung cancer TBD 18 mg N=2 in combination with 12 mg (combination only; n=20) N=6 6 mg pembrolizumab IV Q6W n=4 open 3 mg n=4 RDE n=4 Other advanced or metastatic IO- clinical activity sensitive tumor types TBD mTPI-2 (Modified Toxicity Monotherapy and combination Tumor biopsies obtained on Assessment of safety, efficacy, Trial Probability Interval 2) study therapy dose escalations enrolled treatment to evaluate PD pharmacokinetics, design; enrolling ~160 patients in parallel with staggered start for biomarkers supporting proof of Details biomarkers, and ADA with IO-sensitive tumors combination 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; IO-immunotherapy; SOC-standard of care; PD-pharmacodynamic *Enrollment as of November 5, 2024 14 | ©2024 WEREWOLF THERAPEUTICS
WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Key Safety Findings: Frequency of related TEAEs • Most frequent related TEAEs occurring in were arthralgia, fatigue, pruritis more than and eosinophilia one patient • Majority of related TEAEs were Grade 1 and 2, Grade 3 TEAEs at N=35 patients were treated ≥18mg were manageable, with WTX-124 reversible monotherapy • No evidence of VLS, ≥ Grade 2 (1-28 mg IV CRS, or infusion reactions Q2W) and evaluable for • No recurrence to date of irAEs safety that had previously occurred on ICI therapy • No new safety signals seen in combination with pembrolizumab Adverse event preferred terms Number of subjects 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. 15 | ©2024 WEREWOLF THERAPEUTICS
WTX-124 Monotherapy Induced Rapid, Durable Regressions of Target Lesions All three objective responses to WTX-124 monotherapy occurred within two cycles (~8 weeks) Gastroesophageal junction * tumor (18 mg) Cutaneous squamous cell Melanoma (12 mg) carcinoma (12 mg) * Three patients had objective responses (ORR = 3/16); an additional seven had stable target lesions at potential RDE doses *Metastatic lymph node target lesion normalized in size (<1 cm) 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. 16 | ©2024 WEREWOLF THERAPEUTICS
June 2023: PET-CT at time of September 2023: Baseline CT Complete Response (CR) Ongoing at 12+ Months in a progression on cemiplimab performed at study entry Patient with ICI-Refractory Cutaneous SCC T NT 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 a b Baseline CT showed a 2.6 cm premaxillary target lesion (T) and a non- target lesion (NT) extending into the pterygopalatine fossa – panel b November 1, 2023: First November 30, 2023: Confirmatory restaging CT at 8 weeks PET-CT at 12 weeks 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 the setting of confirmed CR c d (ongoing at 12+ months) 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 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. 17 | ©2024 WEREWOLF THERAPEUTICS
WTX-124 in Combination with Pembrolizumab Demonstrates Durable Responses in ICI-treated Patients Dose Indication Prior therapies Response Status Response DL Tumor Type Prior Therapies Dose Duration • 3w: Increased T cell activation (biopsy) • 8w: 28.7% ↓ of both TLs • Treatment ongoing >7m 1. Pembrolizumab/propranolol 12mg Melanoma • 16w: 39.4% ↓ of both TLs (RECIST uPR) • Progression-free 2. TVEC • 24w: 39.4% ↓ of both TLs (confirmed PR) 1. Pembrolizumab • Treatment ongoing >7m • 8w: 41.3% ↓ of both TLs (RECIST uPR) 12mg Melanoma 2. Ipilimumab/nivolumab • Progression-free • 16w: 46% ↓ of both TLs (confirmed PR) 3. Nivolumab • Combination dose escalation and expansion enrollment are ongoing • Early evidence of combination anti-tumor activity at clinically active WTX-124 dose Abbreviations: ICI-immune checkpoint inhibitor; TL-target lesion; uPR-unconfirmed partial response; PR-partial response Note: Preliminary clinical data as of October 25, 2024, for an ongoing, open label Phase 1/1b clinical trial. 18 | ©2024 WEREWOLF THERAPEUTICS
INDUKINE Strategy Successfully Delivers IL-2 to the TME with Low Plasma Exposures Data support the improved therapeutic index and safety profile 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 ~136-fold lower than HD Cycle 1 PK IL-2 ~136-fold profiles for WTX-124 • Across all dose levels, free and free IL-2 IL-2 levels are very low (<1.6% of prodrug exposure) • Accounts for improved tolerability profile compared to HD IL-2 Abbreviations: PK-pharmacokinetics; HD-high dose; IV-intravenous; Q2W-once every two weeks Note: Preliminary clinical data as of May 1, 2024, for an ongoing, open label Phase 1/1b clinical trial. 19 | ©2024 WEREWOLF THERAPEUTICS
WTX-124 Caused Dose Dependent Increases in Intratumoral T-cell Activation by NanoString Top 40 Key insights from tumor upregulated biomarkers: T-cell activation genes across all • Largest changes seen at 18 mg monotherapy (monotherapy) and 12 mg dose levels (combination) • Upregulation of GRZB and IL2RA signify enhanced effector T cell function • Treg genes including FOXP3 and TNFRSF4 did not increase with dose • Data indicated preferential expansion of effector T cells over Tregs • No observed carry-over effect from prior checkpoint inhibitors based on Treg genes distinct NanoString signature for monotherapy vs. combination at 3 and 6 mg Note: Data presented for patients for whom on-treatment biopsies were available as of May 1, 2024. 20 | ©2024 WEREWOLF THERAPEUTICS
Preliminary WTX-124 Clinical Data Demonstrate Potential for Best-in-Class IL-2 Therapy Key Takeaways ü Monotherapy activity and an improved tolerability profile demonstrated in heavily pretreated patients refractory to all SOC therapies, including immune checkpoint inhibitors ü Combinations with ICIs and other SOC, including in earlier lines of therapy, supported by tolerable safety profile ü Patient with primary ICI-resistant CSCC remains in complete response for > 12 months ü Durable, confirmed partial responses (> 7 months) noted in 2 melanoma patients treated with combination WTX-124 and pembrolizumab ü 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 Next Steps ü Preliminary monotherapy expansion data anticipated in 1H25 ü Engage regulators to discuss potential registrational pathways, including accelerated approval for monotherapy ü Initiate planning for registrational clinical trial in selected tumor types based on regulatory feedback ü Next potential milestone anticipated in 1 with release of preliminary monotherapy expansion da Abbreviations: SOC-standard of care; ICI-immune checkpoint inhibitor; CSCC-cutaneous squamous cell carcinoma; RDE-recommended dose for expansion 21 | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS RDE = recommended dose for expansion
Development Strategy Designed to Realize WTX-124 Commercial Opportunity Priority Indications: Engaging with FDA on potential registrational path Fast to Market for monotherapy expansion indications in 2L+ melanoma, RCC, CSCC Other IO-Sensitive Tumors: Indication Expansion Development in additional indications in expansion based on evolving data Combine with SOC in Earlier Lines: Safety profile supports combinations in earlier lines of Move Upstream therapy across multiple indications where PD-(L)1 therapy is approved Abbreviations: RCC-renal cell carcinoma; ICI-immune checkpoint inhibitor; CSCC-cutaneous squamous cell carcinoma; IO-immunotherapy; SOC-standard of care 22 | ©2024 WEREWOLF THERAPEUTICS
# WTX-330 23 23 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
WTX-330: Leveraging the Potential of IL-12 Therapy to Address IO Resistance 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 Unique Advantages of WTX-330, an IL-12 INDUKINE Molecule Novel prodrug engineered to release a fully potent, wild type IL-12 cytokine selectively in the tumor microenvironment to improve the therapeutic index 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 Abbreviations: IO-immunotherapy; SOC-standard of care 24 | ©2024 WEREWOLF THERAPEUTICS
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 MC38 tumor model Vehicle mWTX-330 Vehicle WTX-124 mWTX-330 Therapeutic Window WTX-124 Differential Gene Signatures 172 ü Intratumoral IL-12 pathway activation ü Activation of multiple antigen 296 presentation mechanisms ü Th1 lineage skewing 122 ü Treg fragility ü Increased chemokine expression mWTX-330 -1 0 1 Nirschl CJ et al., Cancer Immunology Research, 1 July 2023; 11 (7): 962–977 Abbreviation: TME-tumor microenvironment 25 | ©2024 WEREWOLF THERAPEUTICS
WTX-330 FIH study: Study Design and Status Update Twenty-five patients have received at least one dose of WTX-330 to date (n=11 in escalation, n=14 in expansion) Monotherapy Dose Escalation Dose Expansion Patients with solid tumors relapsed/refractory to all SOC ARM A: Patients with IO-sensitive solid tumors who have been treated with a SOC ICI regimen and have primary or secondary resistance 0.032 mg/kg 0.024 mg/kg IV Q2W 0.024 mg/kg n =5 selected for dose 0.016 mg/kg n =3 ARM B: Patients with tumor types for which ICI expansion arms n =3 therapy is not indicated/approved (IO-naïve) Bayesian logistic regression On-treatment biomarker ICI-unapproved and ICI- model study design Assessment of safety, analysis (tumor, blood) Trial resistant indications as efficacy, PK, biomarkers, evaluating proof of Monotherapy escalation supported by IL-12 biology Details and ADA mechanism including followed by two basket and preclinical data conditional activation expansion arms Abbreviations: FIH-first in human; SOC-standard of care; IV-intravenous; Q2W-once every two weeks; IO-immunotherapy; ICI-immune checkpoint inhibitor; PK-pharmacokinetics; ADA-antidrug antibody Note: Preliminary clinical data as of June 12, 2024, in an ongoing, open label Phase 1 clinical trial. 26 | ©2024 WEREWOLF THERAPEUTICS
WTX-330 FIH Patient Population was Heterogeneous and Heavily Pretreated Demographics Tumor Types Prior Therapies 1 Prior lines for metastatic disease Eligible patients had relapsed solid n (%) tumors refractory to all SOC AGE (years) Mean (SD) 64.4 (9.4) 0 3 (12.0%) n (%) 1 3 (12.0%) Median 64.0 CRC (MSS) 9 (36.0%) 2 3 (12.0%) Melanoma 4 (16.0%) SEX, n (%) Female 12 (48.0%) 3 5 (20.0%) PDAC 3 (12.0%) Male 13 (52.0%) ≥4 11 (44.0%) NSCLC 2 (8.0%) Black/African- Cholangiocarcinoma 1 (4.0%) RACE, n (%) 2 (8.0%) Prior lines of immunotherapy American n (%) Endometrial (MSS) 1 (4.0%) White 21 (84.0%) 0 11 (44.0%) Urothelial (bladder) 1 (4.0%) 1 9 (36.0%) Soft tissue sarcoma 1 (4.0%) Other/ 2 (8.0%) Unknown 2 3 (12.0%) Other 3 (12.0%) 3 0 (0.0%) ≥4 2 (8.0%) 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, in an ongoing Phase 1 clinical trial 1 Adjuvant treatment regimens were not included 27 | ©2024 WEREWOLF THERAPEUTICS
WTX-330 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Key safety findings: Frequency of related TEAEs • Most frequent related TEAEs were 1 occurring in CRS , pyrexia, chills, fatigue, and elevated liver function test more than abnormalities one patient • Gr3 and Gr4 related TEAEs were N=25 patients manageable, reversible treated with at least one dose • Toxicities were typical for systemic of WTX-330 IL-12 therapy, less severe across three compared to rhIL-12, and improved dose levels with continued dosing (0.016-0.032 mg/kg IV Q2W) • Expansions opened at 0.024 mg/kg - two DLTs observed at 0.032 mg/kg (Gr3 mucositis, Gr3 AST increase); no MTD reached Adverse event preferred terms Number of subjects Abbreviations: TEAEs-treatment-emergent adverse events; CRS-cytokine release syndrome; Gr-grade; DLTs-dose limiting toxicities; AST-aspartate aminotransferase; MTD-maximum tolerated dose Note: Preliminary clinical data as of October 7, 2024, for an ongoing, open label Phase 1 clinical trial 1 CRS graded by ASTCT grading scale (see: Lee DW, et al. Biol Blood Marrow Transplant 2019;25(4):625–38) 28 | ©2024 WEREWOLF THERAPEUTICS
Decreasing Peripheral IFNγ Levels with WTX-330 Dosing Correlate with Improved Tolerability Analysis of plasma IFNγ levels after IFNγ WTX-330 dosing showed: 0.016 mg/kg 0.024 mg/kg • Dose-related IL-12 induction of IFNγ after 140000 the first dose 0.032 mg/kg 120000 • IFNγ “tachyphylaxis” beyond the first dose 100000 nd (levels were not measured after 2 dose) 80000 20000 Implications: 15000 • Elevated IFNγ levels likely account for 10000 early WTX-330 adverse events, like CRS 5000 • Decreased IFNγ levels with peripheral IL- 0 12 exposure could potentially be leveraged to improve WTX-330 tolerability * and maximize tumor IL-12 exposure *Note that peripheral IFNγ levels were not measured after C1D15 dose Abbreviations: IFN-interferon; CRS-cytokine release syndrome Note: Preliminary clinical data as of October 7, 2024, from an ongoing, open label Phase 1 clinical trial 29 | ©2024 WEREWOLF THERAPEUTICS C1D1 Pre C1D2 C1D3 C2D1 C2D2 C2D3 IFNγ (pg/mL)
Early Signs of Clinical Antitumor Activity Across Solid Tumor Indications Metastatic cutaneous melanoma Microsatellite-stable colorectal cancer (MSS CRC) and other GI malignancies • 76-year-old woman with diffuse melanoma in- transit metastases who had progressed on adjuvant • 50-year-old man who had progressed on seven prior pembrolizumab achieved a confirmed PR (RECIST lines of therapy including investigational 1.1) for 16 weeks immunotherapies had stable disease for 24 weeks • 77-year-old woman with melanoma who had • 61-year-old woman who had progressed on SOC discontinued ipilimumab and nivolumab due to chemotherapy combined with bevacizumab had stable toxicity had a 24% target lesion decrease (ongoing disease for 16 weeks at 12 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) Abbreviation: PR-partial response; MSS-microsatellite stable; CRC-colorectal cancer; GI-gastrointestinal; SOC-standard of care 30 | ©2024 WEREWOLF THERAPEUTICS
WTX-330 Demonstrated Monotherapy Clinical Activity Across Diverse Tumor Types 1 One patient with a confirmed PR (RECIST 1.1) and an additional seven patients with stable target lesions (n=15) 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, for an ongoing, open label Phase 1 clinical trial 1 An 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 31 | ©2024 WEREWOLF THERAPEUTICS
Treatment Response in Melanoma Patient with a Confirmed RECIST PR March 2024 (pretreatment): May 2024: After three doses of 76 76- -ye yea ar r- -o old ld w wo om ma an with a n with a B BRA RAF F wild ty wild type pe m me et ta as st ta atic tic in in- -tr tra ans nsiit t Patient progressing at melanoma WTX-330, many nodules have m me ela lano nom ma a who who pr pro og gr re ess sse ed d whil while e r re ec ce eiv ivin ing g a adj djuv uva an nt t in-transit metastases of RLE flattened and/or regressed pe pem mbr bro olliz izu um ma ab b P Pa atie tien nt ha t had d dif diff fuse use RL RLE E c cu ut tan ane eo ou us s m me et tas ast tas ase es s,, a n a no on n- -h he ea aling ling m me ela lano nom ma at to ous us ulc ulce er r a and nd a an n e enla nlar rg ge ed d rig righ ht ing t ingui uin na all ly lym mph ph no node de I Initia nitiat te ed d tr tre ea atm tme en nt with t with 0. 0.024 024 m mg g/k /kg g W WT TX X- -330 I 330 IV V Q2 Q2W W m mo ore re tha than n tw two o m mo on nths a ths af ft te er r disc disco on nti tin nu uiin ng g pe pem mbr bro olliz izu um ma ab b Ti Tim me elliine ne o of f r re es spo pons nse e t to o W WTX TX- -330: 330: • • 3 3 w week eeks s: : On On- -tr tre ea atm tme en nt e t ex xc cisio isiona nal bio l biop ps sy y o of f RL RLE E skin no skin nodul dule es s January 2024 (pretreatment): May 2024: After three doses of sho show we ed d no no tum tumo or r PET-CT shows progression of WTX-330, repeat PET-CT shows melanoma in-transit metastases markedly decreased tumor • • 7 7- -8 8 w week eeks s:: 47% 47% d de ec cr re eas ase e o of f T TL L (c (cllu us st te er r o of f RL RLE E skin no skin nodul dule es s) ); ; during adjuvant pembrolizumab metabolic activity in RLE no no inc incr re ea ase se in in N NT TLs Ls ( (= =unc unco on nf fir irm me ed d P PR R) ). . P Punc unch bio h biop psi sie es s o of f tw two o pig pigm me en nt te ed d le lesio sions ns sho show we ed no d no a ac ctiv tive e m me ela lano nom ma a • • 1 10 0 w week eeks s: : P PET ET- -C CT T sho show we ed r d re educ duce ed d tum tumo or r m me et ta abo bolic lic a ac ctiv tivity ity • • 1 16 6 w week eeks s: : R RE ECI CIS ST T P PR R c co on nf firm irme ed with o d with ong ngo oin ing g T TL L r re espo spon ns se e,, c co om mple plet te e r re eso solu luti tio on n o of f o one ne N NT TL a L and nd no no inc incr re ea as se e in se in sec co ond nd N NT TL L.. P Pa atie tien nt disc t disco on nti tin nu ue ed d the ther ra ap py y due due t to o a a r re ella at te ed d a an ne em miia a Shown are two different transverse sections of RLE at each timepoint 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 32 | ©2024 WEREWOLF THERAPEUTICS Note: Preliminary clinical data as of October 7, 2024, for an ongoing, open label Phase 1 clinical trial
Evidence of Durable Treatment Effect in Melanoma Patient with Confirmed PR Pretreatment Post-treatment At 28 weeks, approximately 12 weeks after discontinuing WTX-330, the patient was noted to have an ongoing response at a subset of lesions Medial (off all therapy) RLE • 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 Lateral healed and a subset of nodules showed RLE durable regression despite the overall mixed response ;; Abbreviations: PR-partial response; RLE-right lower extremity Note: Preliminary clinical data as of October 7, 2024, for an ongoing, open label Phase 1 clinical trial 33 | ©2024 WEREWOLF THERAPEUTICS
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 Log2 fold change 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 Gene Abbreviations: IFN-interferon; MSS-microsatellite stable; CRC-colorectal cancer; Cholangio-cholangiocarcinoma; SCC-squamous cell cancer; PD-pharmacodynamic N=9 patients contributing * Indicates that biopsied lesion was a liver metastasis; # representative multiplexed immunofluorescence analyses shown on next slide for these patients paired tumor biopsies Note: Preliminary clinical data as of October 7, 2024, from an ongoing, open label Phase 1 clinical trial; figure does not include data from responding melanoma patients as biopsies showed no tumor 34 | ©2024 WEREWOLF THERAPEUTICS
Additional Evidence of Increased T/NK cell Expansion and Activation in MSS CRC Pretreatment On-treatment CD8+ Cell GrzB+CD8+ Cell GrzB+ NK Cell Density Density Density 102-101 150 8 1.5 1.75X 1.5X MSS CRC 6 100 1.0 Retroperitoneal lymph node 4 50 0.5 2 Overall response: 0 SD x 24wks 0 0.0 SCRN C1D22 SCRN C1D22 SCRN C1D22 CD8+ Cell GrzB+CD8+ Cell GrzB+ NK Cell Density Density Density 200 10 50 106-104 8X 3.4X 8 40 MSS CRC 150 6 30 Liver metastasis 100 4 20 Overall response: 50 2 10 PD 0 0 0 SCRN C1D22 SCRN C1D22 SCRN C1D22 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, from an ongoing, open label Phase 1 clinical trial 35 | ©2024 WEREWOLF THERAPEUTICS 2 2 CD8+/mm CD8+/mm GrzB+ CD8+/mm2 GrzB+ CD8+/mm2 2 GrzB+ NK/mm2 GrzB+ NK/mm
WTX-330 Delivered 22-fold > IL-12 Compared to Recombinant Human IL-12 Therapy at its MTD PK data account for the improved therapeutic index of WTX-330 compared to rhIL-12 PK profiles for WTX-330 and free IL-12 compared to Preliminary PK findings: rhIL-12 Cmax at its MTD (mean ± SEM) • 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) ~22-fold • Peak free IL-12 exposure after 0.024 mg/kg WTX-330 is ~5-fold lower than LOQ 0.47 nM rhIL-12 at its MTD ~5-fold • 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, from an ongoing, open label Phase 1 clinical trial 36 | ©2024 WEREWOLF THERAPEUTICS
WTX-330 is a Potentially First-in-Class Systemically Administered IL-12 Therapy Key Takeaways ü First systemically administered IL-12 therapy with monotherapy clinical activity and a generally tolerable safety profile ü Increased therapeutic window: WTX-330 delivered 22-fold more IL-12 on a molar basis than rhIL-12 therapy at its MTD ü INDUKINE design proof-of-concept: Second clinical program validating the INDUKINE design for delivery of toxic immune payloads with improved tolerability and clinical benefit ü 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 ü 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 Next Steps ü Planning underway for Phase 1/2 dose- and regimen-finding study to optimize WTX-330 exposure in TME – expected to begin enrolling 1H25 ü Exploring antitumor activity in selected tumor types Abbreviations: MTD-maximum tolerated dose; TEAE-treatment-emergent adverse events; AE-adverse event; MSS-microsatellite stable; CRC-colorectal cancer; PR-partial response; 37 | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS TME-tumor microenvironment RDE = recommended dose for expansion
# WTX-712 38 38 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
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 From IL-21 Signaling in Immunity | F1000Research IL-21 activates multiple immune cell types, inhibiting Tregs and promoting M1 macrophage function. Status By driving a less terminally differentiated stage of CD8+ T cells, IL-21 results in sustained CTL expansion and activity in tumors. • IND-enabling studies TM Sullivan JM et al., AACR 2023 Poster: Generation of IL-21 INDUKINE Molecules for the Treatment of Cancer TM Molecule for the Treatment of Cancer Sullivan JM et al., SITC 2023 Poster: Development of WTX-712, a Conditionally Active IL-21 INDUKINE TM Molecule, Induces a Strong Anti-tumor Phenotype Through a Differentiated Mechanism Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINE Abbreviations: ICI-immune checkpoint inhibitor; CTL-cytotoxic T lymphocyte 39 | ©2024 WEREWOLF THERAPEUTICS
IL-21 Elicits a Highly Effective CD8+ T Cell Response in ICI-Refractory Preclinical Models EMT-6 Renca 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 Increased CD8+ T cell polyfunctionality* IL-21 treatment results in a sustained intratumoral polyfunctional CD8+ T cell response optimally suited to cell killing *Analytes quantified: IFN-���� , TNF, GzmA, GzmB, Prf1 TM Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINE Molecule, Induces a Strong Anti-tumor Phenotype Through a Differentiated Mechanism 40 | ©2024 WEREWOLF THERAPEUTICS Abbreviations: ICI-immune checkpoint inhibitor
WTX-712 Tumor Selective Activity Results in Robust Antitumor Immune Activation in Preclinical Models WTX-712 antitumor activity in MC38 tumor model with an IL-21 INDUKINE treatment transforms the tumor improved therapeutic window compared to IL-21 cytokine microenvironment with robust and rapid effector CD8+ T cell response to drive tumor regressions Vehicle WTX-712 specifically induces IFNγ in the tumor IL-21 INDUKINE Tumor Cell CD11c CD8 Granzyme B Perforin TM Sullivan JM et al., AACR 2023 Poster: Generation of IL-21 INDUKINE Molecules for the Treatment of Cancer TM Sullivan JM et al., SITC 2023 Poster: Development of WTX-712, a Conditionally Active IL-21 INDUKINE Molecule for the Treatment of Cancer TM Sullivan JM et al., AACR 2024 Poster: WTX-712, a Conditionally Active IL-21 INDUKINE Molecule, Induces a Strong Anti-tumor Phenotype Through a Differentiated Mechanism Abbreviation: TW-therapeutic window 41 | ©2024 WEREWOLF THERAPEUTICS
# WTX-518 42 42 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
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 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 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 43 | ©2024 WEREWOLF THERAPEUTICS
WTX-518 is Resistant to IL-18 Binding Protein with Improved Antitumor Activity BPR mIL-18 INDUKINE triggers tumor cytotoxicity and transforms the TME WTX-518 retains potency while BPR mIL-18 INDUKINE provides greater efficacy than wild-type IL-18 preventing binding to IL-18BP INDUKINE in the MC38 tumor model and increased density of polyfunctional and stem-like CD8+ T cells Tumor cells Polyfunctional CD8+ Stem-like CD8+ Vehicle WT mIL-18 INDUKINE BPR mIL-18 INDUKINE Abbreviations: BPR-binding protein resistant; TME-tumor microenvironment 44 | ©2024 WEREWOLF THERAPEUTICS
BPR mIL-18 INDUKINE Treatment Promotes Robust Effector Activation and Immune Cell Interactions BPR mIL-18 INDUKINE BPR mIL-18 INDUKINE triggers the formation of immune increases density of cell hubs, including stem-like CD8+ T cells, driving the polyfunctional effector cells regression of established tumors Polyfunctional Polyfunctional CD8+ T cells NK Cells ✱ ✱✱✱ *** 1500 100 80 1000 60 40 500 20 0 0 Tumor Cell CD11c CD8 CD11c CD8 TCF1 CD4 Nkp46 Granzyme B Perforin 45 | ©2024 WEREWOLF THERAPEUTICS Abbreviation: BPR-binding protein resistant Vehicle BPR IL-18 INDUKINE Vehicle BPR mIL-18 INDUKINE 2 Cells/mm NK Cell % Producing ≥3 Effector Cytokines
# WTX-921 46 46 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
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 Adapted from Current Opinion in Immunology 2024, 91:102495 TM Sullivan J et al., AAI 2024 Poster: Development of Conditionally Active IL-10 INDUKINE Molecules for the Treatment of Inflammatory Bowel Disease 47 | ©2024 WEREWOLF THERAPEUTICS
WTX-921 Treatment Inhibits Disease in Mouse ACT Model of IBD IL-10 INDUKINE treatment blocks disease as measured by multiple metrics Disease Activity Index 4 No colitis Vehicle WTX-921 3 Weight Change 2 **** 115 No colitis 1 Vehicle WTX-921 110 0 10 20 30 40 Days post transfer 105 Cytokines in the Colon 100 IL-1β IFN-γ Dosing✱✱✱ 0.20 0.08 ✱✱✱ 95 0.06 0.15 ✱ 0 5 10 15 20 25 30 35 40 Days post transfer 0.04 0.10 0.02 0.05 0.00 0.00 48 | ©2024 WEREWOLF THERAPEUTICS Abbreviations: ACT-adoptive cell transfer; IBD-inflammatory bowel disease % Weight Change pg/μg tissue Score pg/μg tissue
WTX-921 Treatment Inhibited Disease in Mouse ACT Model of IBD IL-10 INDUKINE treatment prevents immune cell expansion/activation and tissue destruction Control-No Colitis Disease Induced-Vehicle Treated Disease Induced-INDUKINE Treated H&E IF DAPI CD45 iNOS MUC2 Abbreviations: ACT-adoptive cell transfer; IBD-inflammatory bowel disease; H&E-hematoxylin and eosin; IF-immunofluorescence 49 | ©2024 WEREWOLF THERAPEUTICS
PREDATOR Platform Offers Value Creation through Pipeline Expansion and Partnering Oncology-focused INDUKINE Therapeutics • Additional proinflammatory mechanisms • Cell-based therapies • mRNA therapies Expanding Conditional-Activation Technology to New Modalities • T cell engagers • Antibody drug conjugates Non-Oncology INDUKINE Therapeutics • Cell-based therapies • Inflammation • Other diseases 50 | ©2024 WEREWOLF THERAPEUTICS
Shifting the Balance in Cytokine Therapeutics PREDATOR Platform: Value Creation Engine WTX-124 WTX-330 Our protein engineering technology optimizes the design Phase 1 of conditionally activated cytokine therapeutics (INDUKINE Phase 1/1b molecules) to diseased tissues. Clinical Trial Clinical Trial in Advanced and in Advanced Opportunity to pursue other modalities and non-cancer indications such as inflammatory diseases. Metastatic and Metastatic Solid Tumors Solid Tumors and Lymphoma Strong Cash Position Deep Pipeline* Strategic Clinical Development WTX-712, an IL-21 INDUKINE molecule, in Approximately $122.8M in cash and cash Two lead programs in Phase 1 development preclinical development for the treatment of equivalents (as of September 30, 2024) are wholly owned by Werewolf cancer Runway through at least WTX-518, an IL-18 INDUKINE molecule, in Collaboration is central to our growth strategy 2Q26 with multiple value-enhancing preclinical development for the treatment of with Jazz global partnership on JZP898 catalysts in the near term cancer Approximately 44.6M shares outstanding WTX-921, an IL-10 INDUKINE molecule with (as of November 1, 2024) selective delivery of IL-10 to inflamed tissues for inflammatory/autoimmune diseases *JZP898, an IFNα INDUKINE molecule, in Phase 1 clinical trials with Jazz Pharmaceuticals 51 | ©2024 WEREWOLF THERAPEUTICS
Experienced Leadership Daniel J. Hicklin, PhD Randi E. Isaacs, MD Chulani Karunatilake, PhD Chief Medical Officer President and CEO Chief Technology Officer Ellen Lubman, MBA Tim Trost, CPA William Winston, PhD Chief Business Officer Chief Financial Officer Senior Vice President, Research 52 | ©2024 WEREWOLF THERAPEUTICS
Thank you! 53 | ©2024 WEREWOLF THERAPEUTICS