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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
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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
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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
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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
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 IFN 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 IFN INDUKINE Molecule licensed to Jazz Pharmaceuticals pembrolizumab 7 | 2024 WEREWOLF THERAPEUTICS
# WTX-124 8 8 | | 2024 WEREWOLF THERAPEUTICS 2024 WEREWOLF
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
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 g) 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 Confirmed, durable CR in patient
with CSCC release syndrome ( Grade 2) or infusion reactions 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