Werewolf Therapeutics, Inc. · NASDAQ:HOWL

Werewolf Therapeutics — Investor Presentation (August 2025)

46 slides from Werewolf Therapeutics's investor presentation, Aug 14, 2025

Slide 1: Building a Novel Class of Conditionally Activated Immunotherapies for Patients with Cancer
©2025 WEREWOLF THERAPEUTICS1 | CORPORATE PRESENTATION | August 2025 Building a Novel Class of Conditionally Activated Immunotherapies for Patients with Cancer
Slide 2: Cautionary Statements
©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
Slide 3: Investment Highlights
©2025 WEREWOLF THERAPEUTICS3 | Investment Highlights Deep and Diversified Pipeline Utilizing Unique PREDATOR® Platform Solid FoundationTissue-Targeted Conditionally Activated Biologics with Near-Term Milestones Clinical Stage INDUKINE Molecules: • WTX-124 (IL-2 prodrug) interim Phase 1/1b data reado
Slide 4: Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies
©2025 WEREWOLF THERAPEUTICS4 | Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies Suboptimal Pharmaceutical Properties Toxicity with Poor Clinical Outcomes Our Solution: Conditionally Activated Immunotherapy The Challenge: Off-Tumor Toxicity Limits Ther
Slide 5: Unique and Customizable Molecules with Tissue-Targeted Properties Across Multiple Indications
©2025 WEREWOLF THERAPEUTICS5 | Unique and Customizable Molecules with Tissue-Targeted Properties Across Multiple Indications INDUKINE Molecules INDUKINE and INDUCER molecules harness PREDATOR masking and protease linker technology INDUCER Molecules Next-Generation Conditionally Activated Molecules D
Slide 6: Leveraging Positive INDUKINE Clinical Data to Advance INDUCER Development Strategy
6 | ©2025 WEREWOLF THERAPEUTICS Leveraging Positive INDUKINE Clinical Data to Advance INDUCER Development Strategy Platform Technology Validated by WTX-124 Clinical Data Abbreviation: TME-tumor microenvironment 1Nirschi CJ et al., Cancer Immunology Research 2022 10(5):581-596 2Nirschi CJ et al., SIT
Slide 7: Pipeline
©2025 WEREWOLF THERAPEUTICS7 | PROGRAM TARGET INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 STATUS WTX-124 INDUKINE Molecule IL-2 Advanced or Metastatic Solid Tumors Monotherapy & in combination with pembrolizumab Anticipate meeting with FDA in 2H25; Interim Ph1/1b monotherapy and combination d
Slide 9: WTX-124: Maximizing the Therapeutic Index of IL-2 Therapy in Cancer
©2025 WEREWOLF THERAPEUTICS9 | THE CHALLENGE WTX-124: Maximizing the Therapeutic Index of IL-2 Therapy in Cancer Patients Abbreviations: HD-high dose; SOC-standard of care; ICI-immune checkpoint inhibitor Approved high-dose IL-2 therapy with aldesleukin (Proleukin®) produces durable responses in pat
Slide 10: Significant Opportunity to Expand IL-2 Market Across Multiple Indications
©2025 WEREWOLF THERAPEUTICS10 | Significant Opportunity to Expand IL-2 Market Across Multiple Indications Abbreviations: HD-high dose; CR-complete response; ORR-objective response rate Proleukin (aldesleukin) injection label, Reference ID: 3165255; Proleukin (aldesleukin) injection label (fda.gov),
Slide 11: WTX-124 Delivers IL-2 Selectively to Tumors in Preclinical Models
©2025 WEREWOLF THERAPEUTICS11 | WTX-124 Delivers IL-2 Selectively to Tumors in Preclinical Models Wild type IL-2 released in the TME expands and activates antitumor CD8+ T effector cells preferentially over Tregs Abbreviations: TME-tumor microenvironment; TIL-tumor infiltrating lymphocytes; Tet-tetr
Slide 12: Trial Details
©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, efficac
Slide 13: WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting
©2025 WEREWOLF THERAPEUTICS13 | WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Key Safety Findings: • Most frequent related TEAEs were arthralgia, fatigue, pruritis and eosinophilia • Majority of related TEAEs were Grade 1 and 2, Grade 3 TEAEs at ≥18mg were manageabl
Slide 14: WTX-124 Monotherapy Induced Rapid, Durable Regressions of Target Lesions
©2025 WEREWOLF THERAPEUTICS14 | WTX-124 Monotherapy Induced Rapid, Durable Regressions of Target Lesions Abbreviations: RDE-recommended dose for expansion; BCC-basal cell carcinoma; NSCLC-non-small cell lung cancer; HCC-hepatocellular carcinoma; RCC-renal cell carcinoma; GEJ-gastroesophageal junctio
Slide 15: Complete Response Ongoing at >18 Months in a Patient with ICI-Refractory Cutaneous SCC
©2025 WEREWOLF THERAPEUTICS15 | Complete Response Ongoing at >18 Months in a Patient with ICI-Refractory Cutaneous SCC 72-year-old man with metastatic cutaneous SCC who progressed on RT/cetuximab and had no response to four doses (12 weeks) of cemiplimab (Libtayo®; anti-PD-1) – panel a Initiated tre
Slide 16: Early Evidence of Durable Antitumor Activity for Combination of WTX-124 and Pembrolizumab
©2025 WEREWOLF THERAPEUTICS16 | Early Evidence in Dose Escalation of Durable Antitumor Activity for Combination of WTX-124 and Pembrolizumab Abbreviations: SOC-standard of care; TL-target lesion; uPR-unconfirmed partial response; PR-partial response; CR-complete response; IV-intravenously; Q2W-once
Slide 17: WTX-124 Effectively Limits Systemic Exposure of Active Cytokine
©2025 WEREWOLF THERAPEUTICS17 | WTX-124 Effectively Limits Systemic Exposure of Active Cytokine Data account for the improved safety profile and therapeutic index of WTX-124 compared to HD IL-2 Preliminary PK findings: • WTX-124 dosed at 18 mg IV Q2W has a ~1.5-fold higher Cmax than HD IL-2 • Peak f
Slide 18: WTX-124 Treatment Causes Dose Dependent Increases in Intratumoral T-cell Activation
©2025 WEREWOLF THERAPEUTICS18 | WTX-124 Treatment Causes Dose Dependent Increases in Intratumoral T-cell Activation Note: Data presented for patients for whom on-treatment biopsies were available as of February 7, 2025. Treg gene Key insights from NanoString analysis of paired tumor biopsies: • Larg
Slide 19: Preliminary WTX-124 Clinical Data Demonstrate Potential for a Best-in-class IL-2 Therapy
©2025 WEREWOLF THERAPEUTICS19 | Preliminary WTX-124 Clinical Data Demonstrate Potential for a Best-in-class IL-2 Therapy Abbreviations: SOC-standard of care; RDE-recommended dose for expansion; IV-intravenously; Q2W-once every two weeks; CR-complete response; PR-partial response; ICI-immune checkpoi
Slide 20: Development Strategy Designed to Realize WTX-124 Commercial Opportunity
©2025 WEREWOLF THERAPEUTICS20 | Fast to Market Indication Expansion Move Upstream Priority Indications: Engage with FDA on potential registrational path for expansion indications in cutaneous melanoma, RCC, CSCC Other IO-Sensitive Tumors: Development in additional indications in expansion based on e
Slide 21: Market Potential in the US in Advanced/Metastatic Melanoma
©2025 WEREWOLF THERAPEUTICS21 | Market Potential in the US in Advanced/Metastatic Melanoma ~$4.1B Spanning 1L-3L US Incident Cases 14,500 1L Treatment 2L/3L Treatment ~12,800 patients PD-1 monotherapy (KEYNOTE-006) Nivolumab + Ipilimumab (CheckMate-067) Nivolumab + LAG3 (RELATIVITY-047) BRAF + MEK (
Slide 22: Market Size for Melanoma, CSCC, RCC, and PD-L1 ≥1% NSCLC
©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, C
Slide 24: WTX-330 Key Opportunities and the IL-12 Challenge
©2025 WEREWOLF THERAPEUTICS24 | Key Opportunities • Enable patients to benefit from IL-12 therapy for the first time through improved tolerability • Leverage IL-12 biology to address a significant unmet medical need for patients with poorly immunogenic tumors or tumors resistant to SOC immunotherapi
Slide 25: INDUKINE Delivers IL-12 Selectively to Tumor Tissue with an Improved Therapeutic Index
©2025 WEREWOLF THERAPEUTICS25 | MC38 tumor model mWTX-330 Vehicle Vehicle mWTX-330WTX-124 -1 0 1 mWTX-330 WTX-124 172 122 296 Differential Gene Signatures  Intratumoral IL-12 pathway activation  Activation of multiple antigen presentation mechanisms  Th1 lineage skewing  Treg fragility  Increas
Slide 26: WTX-330 Phase 1 First-in-Human Clinical Trial (Completed)
©2025 WEREWOLF THERAPEUTICS26 | WTX-330 Phase 1 FIH Clinical Trial – WTX-330x2101 (Completed) Twenty-five patients received at least one dose of WTX-330 to date (n=11 in escalation, n=14 in expansion) Trial Details Bayesian logistic regression model study design Monotherapy escalation followed by tw
Slide 27: WTX-330 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting
©2025 WEREWOLF THERAPEUTICS27 | WTX-330 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Related TEAEs were primarily mild to moderate including at clinically active doses Key safety findings: • Most frequent related TEAEs were CRS1, chills, pyrexia and elevated liver function
Slide 28: WTX-330 Demonstrated Monotherapy Clinical Activity Across Diverse Tumor Types
©2025 WEREWOLF THERAPEUTICS28 | WTX-330 Demonstrated Monotherapy Clinical Activity Across Diverse Tumor Types One patient with a confirmed PR (RECIST 1.1) and an additional seven patients with stable target lesions (n=15)1 Abbreviations: MSS-microsatellite stable; CRC-colorectal cancer; NET-neuroend
Slide 29: Confirmed partial response in 76-year-old woman with ICI-refractory melanoma
©2025 WEREWOLF THERAPEUTICS29 | Confirmed partial response in 76-year-old woman with ICI-refractory melanoma Abbreviations: PR-partial response, IV-intravenous, Q2W-once every two weeks, EOT-end of treatment, RLE-right lower extremity, TL-target lesion, NTL-non-target lesion Note: Preliminary clinic
Slide 30: WTX-330 Delivered 22-fold Greater IL-12 to Patients Compared to rhIL-12 Therapy
©2025 WEREWOLF THERAPEUTICS30 | WTX-330 Delivered 22-fold Greater IL-12 to Patients Compared to rhIL-12 Therapy PK data account for the improved therapeutic index of WTX-330 compared to rhIL-12 Preliminary PK findings: • WTX-330 dosed at 0.024 mg/kg IV Q2W has a ~22-fold higher Cmax than rhIL-12 at
Slide 31: WTX-330 Increased Expression of T/NK Cell Activation & Antigen Presentation Genes
©2025 WEREWOLF THERAPEUTICS31 | WTX-330 Increased Expression of T/NK Cell Activation & Antigen Presentation Genes NanoString data show evidence of pleotropic IL-12 activities in the tumor microenvironment, including in MSS CRC Abbreviations: IFN-interferon; MSS-microsatellite stable; CRC-colorectal
Slide 32: WTX-330 Increased Intratumoral T and NK Cell Expansion and Activation in MSS CRC
©2025 WEREWOLF THERAPEUTICS32 | WTX-330 Increased Intratumoral T and NK Cell Expansion and Activation in MSS CRC Pretreatment On-treatment 102-101 MSS CRC Retroperitoneal lymph node Overall response: SD x 24wks 106-104 MSS CRC Liver metastasis Overall response: PD CD8 GRZB IFNγ NK Abbreviations: NK-
Slide 33: Decreasing Peripheral IFNγ Levels with WTX-330 Dosing Correlate with Improved Tolerability
©2025 WEREWOLF THERAPEUTICS33 | Decreasing Peripheral IFNγ Levels with WTX-330 Dosing Correlate with Improved Tolerability C1D 1 P re C1D 2 C1D 3 C2D 1 C2D 2 C2D 3 0 5000 10000 15000 20000 80000 100000 120000 140000 IFNγ IF N γ (p g/ m L) 0.016 mg/kg 0.032 mg/kg 0.024 mg/kg Analysis of plasma IFNγ l
Slide 34: WTX-330 Phase 1b/2 Clinical Trial (Actively Enrolling)
©2025 WEREWOLF THERAPEUTICS34 | WTX-330 Phase 1b/2 Clinical Trial (Actively Enrolling) This clinical trial (WTX-330x2102), is a follow-on to the WTX-330 FIH Phase 1 clinical trial (WTX-330x2101) Trial Details Part A portion to drive choice of optimal regimen Results of the Fixed Dose Finding will in
Slide 35: WTX-330 Clinical Data Summary
©2025 WEREWOLF THERAPEUTICS35 | Abbreviations: MTD-maximum tolerated dose; TEAE-treatment-emergent adverse events; AE-adverse event; MSS-microsatellite stable; CRC-colorectal cancer; PR-partial response; TME-tumor microenvironment ©2025 WEREWOLF THERAPEUTICS  First systemically administered IL-12 t
Slide 37: INDUCER Molecules Utilize Werewolf's PREDATOR Platform for Optimal TCE Design
37 | ©2025 WEREWOLF THERAPEUTICS INDUCER Molecules Utilize Werewolf’s PREDATOR Platform for Optimal TCE Design INDUCER: Inducible T cell engager Cytokine Release Syndrome (CRS) Various "on-target, off-tumor" organ adverse effects (dose-limiting toxicity) Poor tumor exposure leading to sub-optimal th
Slide 38: INDUCER Molecules: Next Generation Conditionally Activated T Cell Engager Design
38 | ©2025 WEREWOLF THERAPEUTICS INDUCER Molecules: Next Generation Conditionally Activated T Cell Engager Design Harnessing proprietary masking technology and clinically validated pan-cancer linker to improve therapeutic index Proprietary and optimized anti-CD3 masking technology to reduce systemic
Slide 39: INDUCER Masking Technology is Highly Differentiated
39 | ©2025 WEREWOLF THERAPEUTICS In Vitro Cell Killing In Vivo Cytokine Release INDUCER Masking Technology is Highly Differentiated -6 -5 -4 -3 -2 -1 0 1 2 0 10 20 30 40 50 TCE (Log nM) % C el l D ea th Unmasked αCD3 Masked αCD3+αTAA Masked -5 -4 -3 -2 -1 0 1 2 0 10 20 30 40 50 INDUCER (Log nM) % C
Slide 40: INDUCER Molecules Provide Potent Antitumor Activity While Improving Tolerability
40 | ©2025 WEREWOLF THERAPEUTICS In vitro Killing of Target Cells 0 10 20 30 40 -20 -10 0 10 20 Days After Initiation of Dosing % W ei gh t C ha ng e Vehicle 1x Unmasked INDUCER Molecule 10x Masked INDUCER Molecule Improved Tolerability in a Mouse Model With a Cross-Reactive TAA Antitumor Efficacy I
Slide 41: WTX-1011: STEAP1 INDUCER Molecule for Prostate Cancer
41 | ©2025 WEREWOLF THERAPEUTICS Key Opportunities • WTX-1011 is a potential first-in-class masked anti-STEAP1 T cell engager with an improved therapeutic index • Potential to provide STEAP1 T cell engager therapy broadly to patients with metastatic castration-resistant prostate cancer • Potential o
Slide 42: WTX-1011 is Unmasked by Human Tumors and Demonstrates Antitumor Activity
42 | ©2025 WEREWOLF THERAPEUTICS In Vitro Processing/Activation of WTX-1011 by Dissociated Tumors In Vivo Efficacy of WTX-1011 in LNCaP CDX Tumor Model WTX-1011 is Unmasked by Human Tumors and Demonstrates Antitumor Activity 0 10 20 30 40 100 200 300 Days After Dosing Tu m or V ol um e (m m 3 ) Vehi
Slide 43: WTX-1011 Exposure and Cytokine Release in Non-Human Primates
43 | ©2025 WEREWOLF THERAPEUTICS • WTX-1011 showed beneficial exposure in cynomolgus monkeys with a half–life close to 100 hours • WTX-1011 was stable in the periphery, with less than 0.7% of active INDUCER detected • Effective masking of WTX-1011 was confirmed by low levels of cytokine production c
Slide 44: Investment Highlights
44 | ©2025 WEREWOLF THERAPEUTICS Investment Highlights Deep and Diversified Pipeline Utilizing Unique PREDATOR® Platform Solid FoundationTissue-Targeted Conditionally Activated Biologics with Near-Term Milestones Clinical Stage INDUKINE Molecules: • WTX-124 (IL-2 prodrug) interim Phase 1/1b data rea
Slide 45: Experienced Leadership
©2025 WEREWOLF THERAPEUTICS45 | Experienced Leadership Daniel J. Hicklin, PhD President and CEO Randi E. Isaacs, MD Chief Medical Officer Steven Bloom Chief Business Officer Tim Trost, CPA Chief Financial Officer Chulani Karunatilake, PhD Chief Technology Officer William Winston, PhD Senior Vice Pre

Werewolf Therapeutics — Investor Presentation (August 2025) on 6ix

Werewolf Therapeutics — Investor Presentation (August 2025)

Slide 1: Building a Novel Class of Conditionally Activated Immunotherapies for Patients with Cancer

Slide 2: Cautionary Statements

Slide 3: Investment Highlights

Slide 4: Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies

Slide 5: Unique and Customizable Molecules with Tissue-Targeted Properties Across Multiple Indications

Slide 6: Leveraging Positive INDUKINE Clinical Data to Advance INDUCER Development Strategy

Slide 7: Pipeline

Slide 8: WTX-124

Slide 9: WTX-124: Maximizing the Therapeutic Index of IL-2 Therapy in Cancer

Slide 10: Significant Opportunity to Expand IL-2 Market Across Multiple Indications

Slide 11: WTX-124 Delivers IL-2 Selectively to Tumors in Preclinical Models

Slide 12: Trial Details

Slide 13: WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting

Slide 14: WTX-124 Monotherapy Induced Rapid, Durable Regressions of Target Lesions

Slide 15: Complete Response Ongoing at >18 Months in a Patient with ICI-Refractory Cutaneous SCC

Slide 16: Early Evidence of Durable Antitumor Activity for Combination of WTX-124 and Pembrolizumab

Slide 17: WTX-124 Effectively Limits Systemic Exposure of Active Cytokine

Slide 18: WTX-124 Treatment Causes Dose Dependent Increases in Intratumoral T-cell Activation

Slide 19: Preliminary WTX-124 Clinical Data Demonstrate Potential for a Best-in-class IL-2 Therapy

Slide 20: Development Strategy Designed to Realize WTX-124 Commercial Opportunity

Slide 21: Market Potential in the US in Advanced/Metastatic Melanoma

Slide 22: Market Size for Melanoma, CSCC, RCC, and PD-L1 ≥1% NSCLC

Slide 23: WTX-330

Slide 24: WTX-330 Key Opportunities and the IL-12 Challenge

Slide 25: INDUKINE Delivers IL-12 Selectively to Tumor Tissue with an Improved Therapeutic Index

Slide 26: WTX-330 Phase 1 First-in-Human Clinical Trial (Completed)

Slide 27: WTX-330 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting

Slide 28: WTX-330 Demonstrated Monotherapy Clinical Activity Across Diverse Tumor Types

Slide 29: Confirmed partial response in 76-year-old woman with ICI-refractory melanoma

Slide 30: WTX-330 Delivered 22-fold Greater IL-12 to Patients Compared to rhIL-12 Therapy

Slide 31: WTX-330 Increased Expression of T/NK Cell Activation & Antigen Presentation Genes

Slide 32: WTX-330 Increased Intratumoral T and NK Cell Expansion and Activation in MSS CRC

Slide 33: Decreasing Peripheral IFNγ Levels with WTX-330 Dosing Correlate with Improved Tolerability

Slide 34: WTX-330 Phase 1b/2 Clinical Trial (Actively Enrolling)

Slide 35: WTX-330 Clinical Data Summary

Slide 36: INDUCER Molecules

Slide 37: INDUCER Molecules Utilize Werewolf's PREDATOR Platform for Optimal TCE Design

Slide 38: INDUCER Molecules: Next Generation Conditionally Activated T Cell Engager Design

Slide 39: INDUCER Masking Technology is Highly Differentiated

Slide 40: INDUCER Molecules Provide Potent Antitumor Activity While Improving Tolerability

Slide 41: WTX-1011: STEAP1 INDUCER Molecule for Prostate Cancer

Slide 42: WTX-1011 is Unmasked by Human Tumors and Demonstrates Antitumor Activity

Slide 43: WTX-1011 Exposure and Cytokine Release in Non-Human Primates

Slide 44: Investment Highlights

Slide 45: Experienced Leadership

Slide 46: Thank you!