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WEREWOLF THERAPEUTICS 2025 WEREWOLF THERAPEUTICS
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2025 WEREWOLF THERAPEUTICS
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
engager) molecules INDUKINE molecules WTX-124 (IL-2): Potential best-in-class efficacy and tolerability profile observed in current Phase 1/1b clinical trial as a monotherapy and in combination with ICI in outpatient setting, including
monotherapy 30% ORR in a defined subset of melanoma patients based on preliminary data Werewolf Next milestone: Final Phase 1/1b data anticipated in 1H26; seeking strategic partner for further development Therapeutics WTX-330 (IL-12):
Potential first-in-class IL-12 therapy demonstrated monotherapy anti-tumor activity and improved therapeutic index in FIH study; improved tolerability and monotherapy efficacy further supported by interim data from ongoing Phase 1b/2 clinical trial
Next milestone: Phase 1b/2 update anticipated in 1H26; seeking strategic partner for further development Building a Novel Class of Tumor-activated INDUCER T cell engager molecules Cutting-edge T cell engager platform leveraging
clinically validated PREDATOR technology that has Immunotherapies for demonstrated complete silencing and efficient tumor activation to address therapeutic index limitations of Patients with Cancer conventional T cell engagers WTX-1011
(STEAP1): Potential best-in-class molecule targeting STEAP1, a clinically validated prostate cancer antigen, designed to enhance tumor exposure and antitumor activity with an improved safety profile WTX-2022 (CDH6): Potential first-in-class
molecule targeting CDH6, a clinically validated target in ovarian cancer; designed for optimized tumor-specific activation and reduced off-tumor toxicity Next milestones: INDs for WTX-1011 and WTX-2022 anticipated in mid-2027 Abbreviations:
ICI-immune checkpoint inhibitor; ORR-overall response rate; FIH-first in human; IND-investigational new drug application 3 | 2025 WEREWOLF THERAPEUTICS
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 Therapy Masked Therapy
(inactive) Activated Therapy Activated immune cells Toxicity with Poor Clinical Outcomes Targeted Delivery to the On-Target Immune Tumor Microenvironment Activation 4 | 2025 WEREWOLF THERAPEUTICS
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 Proprietary Linker
Werewolf's innovative PREDATOR Platform offers potential for pipeline expansion and partnering opportunities with clinically proven technology 5 | 2025 WEREWOLF THERAPEUTICS Half-Life Extension
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 cutaneous melanoma
WTX-124 preliminary clinical trial data at 18 mg as of October 20, 2025. 1 Highly favorable tolerability profile Durable clinical responses (including CRs) Incidence of VLS Grade 3/4 hypotension Pretreatment After 12w of WTX-124 50% 50% Complete
response in an ICI-refractory 25% 25% CSCC patient, now off all anticancer therapy >1.5 years 0% 0% 0% 0% 2 3 4 3 HD IL-2 WTX-124 HD IL-2 WTX-124 1 3 Data presented is not from head-to-head study Preliminary clinical trial data as of October 20,
2025 2 4 Jeong et al., J Clin Med, 2019 - incidence of VLS by Atkins et al., J Clin Oncol, 1999 meta-analysis Abbreviations: CR-complete response; ICI-immune checkpoint inhibitor; 6 | 2025 WEREWOLF THERAPEUTICS CSCC-cutaneous squamous
cell carcinoma; VLS-vascular leak syndrome
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 IFN Cancer Globally licensed to Jazz Pharmaceuticals INDUKINE
(Cytokine) * Molecules WTX-712 IL-21 Cancer * Cancer WTX-518 IL-18 Inflammatory Diseases * WTX-921 IL-10 including IBD STEAP1+ Cancers WTX-1011 STEAP1 INDUCER CDH6+ Cancers (T cell engager) WTX-2022 CDH6 Molecules Undisclosed Multiple Cancer
Abbreviations: IND-investigational new drug application; IBD-irritable bowel disease 7 | * Will advance pending partnership. 2025 WEREWOLF THERAPEUTICS
WTX-124 IL-2 INDUKINE Molecule 8 8 | | 2025 WER 2025 WERE
EWOLF WOLF THER THERA AP PEUTICS EUTICS
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, full potency IL-2 mechanism as monotherapy or in combination Clinical Proof of Concept Established Potential Registration-Enabling Path Safely administered in outpatient setting with no patient FDA Fast Track designation
granted for WTX-124 restrictions (no VLS or DLT) as a monotherapy or in monotherapy in advanced cutaneous melanoma combination with SOC Positive FDA EOP1 meeting provided guidance for Objective, durable responses observed as a
monotherapy registration path in melanoma - 18 mg accepted as in melanoma, CSCC and GEJ, and in combination with CPI recommended dose in melanoma, NSCLC and RCC Phase 1/1b expansion data update expected in 1H26; Observed
monotherapy activity in heavily pretreated seeking strategic partner for further development melanoma patients (> 20% ORR) consistent with historical high-dose IL-2 activity in 1L setting Abbreviations: VLS-vascular leak syndrome;
DLT-dose-limiting toxicity; SOC-standard of care; CSCC-cutaneous squamous cell carcinoma; GEJ-gastro-esophageal junction; CPI-checkpoint inhibitor; RCC-renal cell cancer; NSCLC-non-small cell lung cancer; ORR-overall response rate; FDA-Food and Drug
Administration; EOP1-end of phase 1 9 | 2025 WEREWOLF THERAPEUTICS
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 of
vascular leak syndrome (of any grade) or recurrence of prior immune-related adverse events Grade 3 and 4 related TEAEs seen in 25.5% (27/106) and 1.9% (2/106) of patients, respectively, and were all manageable and reversible Most
frequent related TEAEs included arthralgias, fatigue, pruritis, pyrexia Combination Monotherapy (12 and 18 mg No excess toxicity or new safety (12 and 18 mg IV Q2W) IV Q2W) signals seen when WTX-124 was n=47 n=59 combined with pembrolizumab
Abbreviations: ICI-immune checkpoint inhibitor; SOC-standard of care; AE-adverse event ; IV-intravenous; Q2W-every two weeks Notes: Preliminary clinical data as of October 20, 2025. Each related TEAE is counted once per patient based on the highest
grade. 10 | 2025 WEREWOLF THERAPEUTICS
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-complete response; MEL-melanoma; BCC-basal cell carcinoma; UV-uveal melanoma; URO-urothelial cancer; MUC-mucosal melanoma; MSI-H-microsatellite instability high (small bowel adenocarcinoma);
NSCLC-non-small cell lung cancer; CHOL- cholangiocarcinoma; H&N-head and neck cancer (paranasal sinus adenocarcinoma); RCC-renal cell cancer; HCC-hepatocellular carcinoma; GEJ-gastroesophageal junction tumor;
CSCC-cutaneous squamous cell carcinoma Note: Preliminary clinical data as of October 30, 2025. 11 | 2025 WEREWOLF THERAPEUTICS
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; SD-stable
disease; PR-partial response; CR-complete response Note: Preliminary clinical data as of October 30, 2025. 12 | 2025 WEREWOLF THERAPEUTICS
WTX-124: Objective Responses Observed in Cutaneous Melanoma Monotherapy
Combination Escalation Expansion All Escalation Expansion All E cacy 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 % 21%/30%
20%/28.6%40 %/40%0 % 18%/28.6% 112 97.3 393.5 393.5 DOR, 53 n/a mean days (STD) (48.9) (49.6) (78.5) (78.5) # Unconfirmed, PD on confirmatory scan *PR/CR divided by number of efficacy evaluable patients treated with active doses of WTX-124 (12 or 18
mg) **PR/CR divided by number of efficacy evaluable patients who were not primary IO resistant, defined as no response to any prior IO regimen Abbreviations: PR-partial response; CR-complete response; SD-stable disease; PD-progressive disease
ORR-overall response rate; DOR-duration of response; IO-immunotherapy; 13 | STD-standard deviation 2025 WEREWOLF THERAPEUTICS Note: Preliminary clinical data as of October 30, 2025.
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 for 7 months
Discontinued WTX-124 due to a single progressing target lesion. Subsequently received radiation therapy with curative intent Note: Preliminary clinical data as of October 30, 2025. 14 | 2025 WEREWOLF THERAPEUTICS
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 resistant
Analyzing data to understand drivers of response Results support further consideration of WTX-124 in an earlier line of therapy Abbreviations: RCC-renal cell carcinoma; PD-progressive disease; SD-stable disease; PR-partial response;
VEGF-Vascular Endothelial Growth Factor Note: Preliminary clinical data as of October 30, 2025. 15 | 2025 WEREWOLF THERAPEUTICS
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 CSCC, NSCLC and
GEJ cancer Data suggest multiple development opportunities in addition to melanoma Complete Phase 1/1b data expected in 1H26 Data labels indicate best overall response per RECIST 1.1, tumor type Abbreviations: PD-progressive
disease; SD-stable disease; PR-partial response; CR-complete response; MEL-melanoma; BCC-basal cell carcinoma; UV-uveal melanoma; URO-urothelial cancer; MUC- mucosal melanoma;
MSI-H-microsatellite instability high (small bowel adenocarcinoma); NSCLC-non-small cell lung cancer; CHOL- cholangiocarcinoma; H&N-head and neck cancer (paranasal sinus adenocarcinoma); HCC-hepatocellular carcinoma;
GEJ-gastroesophageal junction tumor; CSCC-cutaneous squamous cell carcinoma Note: Preliminary clinical data as of October 30, 2025. 16 | 2025 WEREWOLF THERAPEUTICS
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 metastases to the
adrenal gland, bone and multiple lymph nodes Top: CT images showed DAPI Timeline of response to WTX-124/pembrolizumab: marked regression of a CD8 large paraaortic lymph GrzB 8 weeks: 50.4% in TLs (uncon rmed PR) node target
lesion 16 weeks: 65.6% in TLs (con rmed PR) Right: Baseline 24 weeks: 65.6% in TLs (ongoing PR) biomarkers were notable for high PD-L1 (IHC) Patient soon to start Cycle 5 of combination therapy and a
T-cell-inflamed PD-L1 TME (multiplexed IF) Related AEs include rash, arthralgia and myalgia (all manageable in outpatient setting) Abbreviations: PR-partial response; NSCLC-non-small cell lung cancer; s/p-status post; TL-target lesion; BOR-best
overall response; SD-stable disease; AE-adverse event; IHC- immunohistochemistry; IF-immunofluorescence; TME-tumor microenvironment; CT-computed tomography Note: Preliminary clinical data as of October 30, 2025. 17 | 2025 WEREWOLF
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 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 ab 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 setting of confirmed CR cd Response ongoing at >1.5 year off drug with no additional
therapy Abbreviations: SCC-squamous cell carcinoma; CT-computed tomography scan; IV-intravenous; Q2W-every two weeks; PET-positron emission tomography; ICI-immune checkpoint inhibitor; CR- complete response 18 | Note: Preliminary clinical data as of