Werewolf Therapeutics, Inc. · NASDAQ:HOWL
Werewolf Therapeutics — Investor Presentation (December 2025)
41 slides from Werewolf Therapeutics's investor presentation, Dec 18, 2025
Slide 1: Corporate Presentation December 2025
Exhibit 99.1 Corporate Presentation December 2025 1 | ©2025 WEREWOLF THERAPEUTICS ©2025 WEREWOLF THERAPEUTICS
Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and in the development of product candidates, including the conduct of research activities uncertainties. All statements, other than statements of historical fact
Slide 3: Clinically Validated Technology to Solve the Limitations of Potent Cancer Immunotherapies
Clinically Validated Technology to Solve the Limitations of Potent Cancer Immunotherapies PREDATOR® platform leverages differentiated masking and linker technology to create two classes of TM TM novel, conditionally activated biologics – INDUKINE (inducible cytokine) and INDUCER (inducible T cell en
Slide 4: Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies
Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine and T Cell Engager Therapies The Challenge: Our Solution: Off-Tumor Toxicity Limits Conditionally Activated Therapeutic Index Immunotherapy Suboptimal Pharmaceutical Properties With Optimized Therapeutic Index Tumor Activated Thera
Slide 5: Next-Generation Conditionally Activated Biologics
Targeted Antitumor Immunity Next-Generation Conditionally Activated Biologics INDUKINE and INDUCER molecules are designed with differentiated masking and protease linker technology INDUKINE Molecules INDUCER Molecules Inducible cytokines Inducible T cell engagers Proprietary Masking Technology Propr
Slide 6: PREDATOR Masking and Linker Technology Validated by Clinical Data
PREDATOR Masking and Linker Technology Validated by Clinical Data Optimized therapeutic index observed in patients On-target immune activation in tumors After 2 doses of WTX-124 Pretreatment DAPI CD8 GrzB Increased CD8 T cell infiltration/activation in the tumor of a 65- year-old woman with cutaneou
Slide 7: Clinical Stage Company Building a Pipeline of Conditionally Activated Biologics
Clinical Stage Company Building a Pipeline of Conditionally Activated Biologics MODALITY PROGRAM TARGET INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 1b Advanced/Metastatic WTX-124 IL-2 Cancers Advanced/Metastatic WTX-330 IL-12 Cancers JZP898 IFNα Cancer Globally licensed to Jazz Pharmaceuticals
Slide 8: WTX-124 IL-2 INDUKINE Molecule
WTX-124 IL-2 INDUKINE Molecule 8 8 | | © ©2025 WER 2025 WERE EWOLF WOLF THER THERA AP PEUTICS EUTICS
Slide 9: WTX-124: Potential Best-in-Class Molecule Serves as Foundational IL-2 Therapy
WTX-124: Potential Best-in-Class Molecule Serves as Foundational IL-2 Therapy WTX-124, an IL-2 INDUKINE Molecule • Systemically administered • Fully potent, alpha-binding IL-2 • Selectively activated in the tumor microenvironment via proprietary linker technology • Designed to deliver a tolerable, f
Slide 10: WTX-124: Safely Administered in Outpatient Setting Without Restriction
WTX-124: Safely Administered in Outpatient Setting Without Restriction Safety profile supports combinability of WTX-124 with ICI or other SOC in earlier lines of therapy Treatment-Emergent Adverse Events (TEAEs) in > 10% of patients Key safety findings at active dose levels (12, 18mg): • No evidence
Slide 11: WTX-124: Regression of SOC Refractory Solid Tumors Observed in One-Third of Patients
WTX-124: Regression of SOC Refractory Solid Tumors Observed in One-Third of Patients Data labels indicate best overall response per RECIST 1.1, tumor type Abbreviations: SOC–standard of care; IO–immuno-oncology (immunotherapy); PD–progressive disease; SD–stable disease; PR–partial response; CR–compl
Slide 12: WTX-124: Complete Regression of IO-Resistant Melanoma Metastases Observed
WTX-124: Complete Regression of IO-Resistant Melanoma Metastases Observed Resolution of metastatic deposits observed at challenging sites of disease including in the liver Data labels indicate best overall response per RECIST 1.1, tumor type Abbreviations: IO-immunotherapy; PD-progressive disease; S
Slide 13: WTX-124: Objective Responses Observed in Cutaneous Melanoma
WTX-124: Objective Responses Observed in Cutaneous Melanoma Monotherapy Combination Escalation Expansion All Escalation Expansion All Efficacy evaluable 6 14 20 5 6 11 Efficacy evaluable 4 10 14 5 2 7 (not IO primary resistant) # PR/CR 1 3 4 2 0 2 2 2 4 0 3 3 SD PD 3 9 12 3 3 6 * ** ORR /ORR17%/25 % 2
Slide 14: WTX-124: Durable Objective Responses Seen in Treatment-Refractory Melanoma Patients
WTX-124: Durable Objective Responses Seen in Treatment-Refractory Melanoma Patients Discontinued WTX-124 therapy in the setting of a complete response Patient discontinued WTX-124 with an ongoing partial response due to a carpal tunnel-like adverse event. Required no additional anticancer therapy fo
Slide 15: WTX-124: Tumor Regression and Prolonged Disease Control Observed in RCC Subjects
WTX-124: Tumor Regression and Prolonged Disease Control Observed in RCC Subjects Weeks on study • RCC expansion arms fully enrolled (n=40); updated data will be available in 1H26 • Heavily pretreated patient population; most received 3-4 prior lines, including VEGF inhibitors, or are primary IO resi
Slide 16: WTX-124: Encouraging Antitumor Activity Observed in Additional Solid Tumor Indications
WTX-124: Encouraging Antitumor Activity Observed in Additional Solid Tumor Indications Development opportunities to be informed by additional data from ongoing Ph1/1b study (final data expected in 1H26) • WTX-124 therapy demonstrated tumor regression in multiple solid tumor indications including CSC
Slide 17: Confirmed PR in NSCLC patient treated with WTX-124/pembrolizumab
Confirmed PR in NSCLC patient treated with WTX-124/pembrolizumab Baseline CT 16-week restaging CT 67-year-old woman with PD-L1+ NSCLC s/p three prior lines of systemic therapy: 1. Carboplatin/pemetrexed/bevacizumab 2. Docetaxel/selinexor 3. Atezolizumab (BOR SD) At study entry, patient had metastase
Slide 18: Complete response ongoing at 24 months in a patient with ICI-refractory cutaneous SCC
June 2023: PET-CT at time of September 2023: Baseline CT Complete response ongoing at 24 months in progression on cemiplimab performed at study entry T a patient with ICI-refractory cutaneous SCC NT 72-year-old man with metastatic cutaneous SCC who progressed on RT/cetuximab and had no response to f
Slide 19: WTX-124: Next Generation IL-2 Molecule Has Validated PREDATOR Platform
WTX-124: Next Generation IL-2 Molecule Has Validated PREDATOR Platform Key Takeaways ü WTX-124 has successfully met internally established tolerability and efficacy benchmarks ü Monotherapy WTX-124 has demonstrated activity in relapsed/refractory cutaneous melanoma comparable to high dose IL-2 but w
Slide 20: WTX-330 IL-12 INDUKINE Molecule
WTX-330 IL-12 INDUKINE Molecule 20 20 | | © ©2025 WER 2025 WERE EWOLF WOLF THER THERA AP PEUTICS EUTICS
Slide 21: WTX-330: Potential First-in-Class Molecule to Address Immunotherapy Resistant Cancers
WTX-330: Potential First-in-Class Molecule to Address Immunotherapy Resistant Cancers WTX-330, an IL-12 INDUKINE Molecule • Systemically administered • Validated masking and linker technology • Fully potent, non-half-life extended IL-12 released in tumor microenvironment • Designed to deliver a tole
Slide 22: WTX-330: Phase 1b/2 Dose- and Regimen-Optimization Study
WTX-330: Phase 1b/2 Dose- and Regimen-Optimization Study WTX-330x2102 Part A: Dose and Regimen Finding (ongoing) Part B: Expansion (potential) Population: Relapsed/refractory metastatic GI WTX-330 IV Q2W 28-day cycle malignancies including microsatellite stable (MSS) colorectal cancer, GEJ, gastric,
Slide 23: WTX-330: Dramatic Improvement in Safety Profile Due to Optimized Manufacturing Process
WTX-330: Dramatic Improvement in Safety Profile Due to Optimized Manufacturing Process x2101 trial (Process 1) x2102 trial (Process 2) N=20 pts N=12 pts 0.016, 0.024 mg/kg 0.016, 0.024, 0.016→0.024 mg/kg Each adverse event is counted once per patient based on the highest grade Abbreviation: AE-adver
Slide 24: WTX-330: 17-Fold Greater IL-12 Compared to Recombinant Human IL-12 Therapy at its MTD
WTX-330: 17-Fold Greater 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 First-dose PK profiles for WTX-330 and free IL-12 compared to Preliminary PK findings: rhIL-12 Cmax at its MTD (mean ± SEM) • WTX-33
Slide 25: WTX-330: Preliminary Efficacy Data from Phase 1b/2 Initial Cohorts
WTX-330: Preliminary Efficacy Data from Phase 1b/2 Initial Cohorts Showed Further Evidence of Antitumor Activity in Challenging Tumor Types Abbreviations: PDAC-pancreatic ductal adenocarcinoma; STS-soft tissue sarcoma; CRC-colorectal cancer; MEL-melanoma; GC-gastric cancer; NSCLC-non-small cell lung
Slide 26: Objective response in a patient with refractory gallbladder cancer
Objective response in a patient with Baseline CT refractory gallbladder cancer 57-year-old woman with MSS, TMB-low gallbladder cancer whose BOR was PD to each of two prior lines of SOC therapy: 1. Cisplatin/gemcitabine/durvalumab 2. 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) 8-week restaging CT
Slide 27: Addressing IO Resistance with Novel WTX-330 & WTX-124 Combination Therapy
Addressing IO Resistance with Novel WTX-330 & WTX-124 Combination Therapy In preclinical study, mWTX-330 pretreatment sensitized EMT-6 tumors to WTX-124 mWTX-330 Day 1 WTX-124 mWTX-330 + WTX-124 Days 8, 11 Vehicle DAPI CD8 Hypothesis: WTX-330 enhances adaptive antitumor immune recognition and activa
Slide 28: INDUCER Molecules Inducible T Cell Engagers
INDUCER Molecules Inducible T Cell Engagers 28 28 | | © ©2025 WER 2025 WERE EWOLF WOLF THER THERA AP PEUTICS EUTICS
Slide 29: INDUCER Molecules: Next Generation Conditionally Activated T Cell Engagers
INDUCER Molecules: Next Generation Conditionally Activated T Cell Engagers Proprietary masking technology and clinically validated pan-cancer linker to improve therapeutic index INDUCER Molecules Differentiating Features ✓ Proprietary and optimized anti-CD3 masking technology to reduce off-tumor tox
Slide 30: INDUCER Masking Designs Enhance Exposure and Tolerability in Preclinical Studies
INDUCER Masking Designs Based on Target Selectivity Enhance Exposure and Tolerability in Preclinical Studies Robust, Reversible Masking Improved Plasma Exposure Reduction in CRS 80 600 60 400 40 200 20 0 0 -4 -2 0 2 4 Log (nM) Anti-CD3 Masked 1x Unmasked Control WTX-1011: Intact INDUCER Molecule 10x
Slide 31: INDUCER Molecules Selectively Target Active TCE Exposure to the Tumor Microenvironment
INDUCER Molecules Selectively Target Active TCE Exposure to the Tumor Microenvironment INDUCER PK: Selective Unmasking in Tumor Systemic Exposure Antitumor Efficacy of αCD3+αTAA Masked INDUCER Molecule in a Humanized CDX Model AUC : 0.6% Free/Total AUC : 7.5% Tumor/Plasma Intratumoral Exposure AUC :
Slide 32: WTX-1011: STEAP1 INDUCER Molecule for Prostate Cancer
WTX-1011: STEAP1 INDUCER Molecule for Prostate Cancer Background and Rationale STEAP1 INDUCER Molecule • STEAP1 is overexpressed in prostate tumors with limited expression in normal tissues • Clinically validated prostate cancer target with potential in other indications STEAP1 is Overexpressed in P
Slide 33: WTX-1011: Unmasked by Human Prostate Tumors and Demonstrated Antitumor Activity
WTX-1011: Unmasked by Human Prostate Tumors and Demonstrated Antitumor Activity in Preclinical Studies In Vitro Cell Killing Assay Expression of STEAP1 on Prostate CDX In Vivo Efficacy of WTX-1011 in LNCaP and PDX Tumors CDX Tumor Model LNCaP CDX Prostate PDX T cell-dependent cellular cytotoxicity w
Slide 34: WTX-1011: Favorable PK, Limited Peripheral Activation, and Negligible Cytokine Release in NHP
WTX-1011: Favorable PK, Limited Peripheral Activation, and Negligible Cytokine Release in NHP PK of WTX-1011 in NHP Cytokine Release in NHP 600 1x Unmasked Control 400 10x WTX-1011 200 0 Plasma levels of WTX-1011 and activated INDUCER molecule Plasma IL-6 levels 4 hours after IV administration of no
Slide 35: Trispecific INDUCER Molecules for Prostate Cancer
Trispecific INDUCER Molecules for Prostate Cancer Background and Rationale • Targeting multiple tumor antigens may overcome intra- and interpatient TAA heterogeneity to provide improved efficacy • STEAP1, PSMA, and KLK2 are selectively overexpressed and exhibit heterogeneous expression in prostate c
Slide 36: WTX-2022: CDH6 INDUCER Molecule for Kidney and Ovarian Cancer
WTX-2022: CDH6 INDUCER Molecule for Kidney and Ovarian Cancer Background and Rationale CDH6 INDUCER Molecule • CDH6 is overexpressed in renal and ovarian cancer with lower expression in normal kidney, brain, and gallbladder • Clinical validation established in ovarian cancer CDH6 is Overexpressed in
Slide 37: WTX-2022: Masking αCD3 and αCDH6 for Optimal Tumor Exposure
WTX-2022: Masking αCD3 and αCDH6 for Optimal Tumor Exposure Highly Effective, Reversible Anti-CDH6 Mask Prevented Binding to CDH6+ Cells WTX-2022 Was Unmasked by anti-CD3/CDH6 Masking Human Ovarian Tumors 100 80 60 40 20 0 Functional readout of INDUCER T cell-dependent cellular cytotoxicity with CDH
Slide 38: CDH6 INDUCER Molecules Demonstrated Tolerable Antitumor Efficacy In Vivo
CDH6 INDUCER Molecules Demonstrated Tolerable Antitumor Efficacy In Vivo Efficacy of CDH6 INDUCER CDH6 INDUCER Masking Prevents Unmasked Control CDH6 INDUCER in OVCAR-3 Tumor Model Off-tumor Toxicity 140 120 Jaundice and Normal 100 rough coat appearance 80 60 40 010 20 30 Inflamed Non-inflamed gallb
Slide 39: WTX-2022: Masking Prevented Cytokine Release and Improved Exposure in Cynomolgus Monkeys
WTX-2022: Masking Prevented Cytokine Release and Improved Exposure in Cynomolgus Monkeys Differentiated Exposure of Masked Cytokine Release in NHP INDUCER Molecule vs Unmasked Control 10000 150 1x Unmasked Control 10x WTX-2022 100 5000 50 LLOQ 0 0 0 204060 020 40 60 Pre-Dose Pre-Dose Hours Post Dose
Slide 40: Opportunity to Combine INDUCER T Cell Engager Therapy with INDUKINE Molecules
Opportunity to Combine INDUCER T Cell Engager Therapy with INDUKINE Molecules IL-2 Expands CD8 Effector T Cells and Promotes TCEs Upregulate CD25 Effector Molecule Expression in Cell Killing Assay + Total CD8+ T Cells 5 2.5×10 13.2x 5 2×10 ** 5 1.5×10 GZMB, IFNγ, 5 1×10 • IL-2 (WTX-124) expands the
Slide 41: INDUCER Molecules: Raising the Bar for T Cell Engagers
INDUCER Molecules: Raising the Bar for T Cell Engagers Key Takeaways ü Addressing Key Challenges: engineered to overcome the limitations of current T-cell engager therapies, including on-target/off-tumor toxicity and dose-limiting Cytokine Release Syndrome (CRS) ü Breakthrough Masking Technology: in
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