Werewolf Therapeutics, Inc. · NASDAQ:HOWL

Werewolf Therapeutics — Investor Presentation (January 2024)

31 slides from Werewolf Therapeutics's investor presentation, Jan 8, 2024

  1. Slide 1: Shifting the Balance in Cytokine Therapeutics: Corporate Overview

    Exhibit 99.2 Shifting the Balance in Cytokine Therapeutics Corporate Overview | January 2024

  2. Slide 2: Cautionary Statements

    Cautionary Statements This presentation contains forward-looking statements that involve substantial risks and important factors, including: uncertainties inherent in the development of product uncertainties. All statements, other than statements of historical facts, contained in this candidates, in

  3. Slide 3: Who we are

    Who we are Our mission is to unlock the promise of cytokines as more effective immunotherapies We are a clinical-stage biopharmaceutical company developing next generation, conditionally activated cytokine therapies for the treatment of cancer and other serious diseases We have two investigational d

  4. Slide 4: Clinical-Stage Company with Compelling Portfolio of Innovative Cytokine Therapeutics

    Clinical-Stage Company with Compelling Portfolio of Innovative Cytokine Therapeutics Designed on a platform capable of addressing broad therapeutic applications in oncology and beyond Clinical Programs Key Catalysts Robust Pipeline Scalable Platform Financial Stability Cash and cash equivalents WTX-

  5. Slide 5: Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine Therapy

    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 INDUKINE

  6. Slide 6: PREDATOR Platform

    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 spec

  7. Slide 7: INDUKINE Molecules: Targeting Cytokine Activity to Diseased Tissue

    INDUKINE Molecules: Targeting Cytokine Activity to Diseased Tissue Healthy tissue Cytokine inactive INDUKINE design Tumor tissue Cytokine activation Immune cell activation High exposure of Tumor-selective INDUKINE molecule protease activation 7 | ©2024 WEREWOLF THERAPEUTICS

  8. Slide 8: PREDATOR Platform: Disease Selective Protease (DSP) Substrate Screen

    PREDATOR Platform: Disease Selective Protease (DSP) Substrate Screen Innovative Linker Discovery Approach to Address Protease Heterogeneity Across Diseases and Patients Disease Tissue Healthy Tissue • Highly diverse substrate library • Unique protease specificities Patients & Healthy Donors • Innova

  9. Slide 9: A Balanced Portfolio of Clinical and Preclinical Drug Candidates

    A Balanced Portfolio of Clinical and Preclinical Drug Candidates PROGRAM INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 RIGHTS Advanced or Metastatic Solid Tumors WTX-124 Monotherapy & in combination IL-12 INDUKINE Molecule with Pembrolizumab Advanced or Metastatic WTX-330 Solid Tumors and Lymph

  10. Slide 10: WTX-124: Expanding the Utility of IL-2 Therapy

    WTX-124: Expanding the Utility of IL-2 Therapy Delivering IL-2 to the Tumor Microenvironment with Improved Safety and Therapeutic Index The Challenge Deliver the benefits of IL-2 therapy with less toxicity to a broader range of patients Potential WTX-124 Advantages and Opportunity • Delivery of IL-2

  11. Slide 11: WTX-124 has an Improved Therapeutic Index Compared to Native IL-2

    WTX-124 has an Improved Therapeutic Index Compared to Native IL-2 Full potency IL-2 is required for complete tumor regression in preclinical models; WTX-124 generates immune memory WTX-124 antitumor activity is substantially more potent WTX-124 activates long-term antitumor immune memory than non-al

  12. Slide 12: WTX-124 Delivers IL-2 Selectively to Tumor Tissue in Preclinical Models

    WTX-124 Delivers IL-2 Selectively to Tumor Tissue in Preclinical Models Robust expansion and activation of antitumor CD8+ T effector cells in the TME Plasma Tumor Plasma Tumor 1000 WTX-124 INDUKINE 1000 Free IL-2 100 100 WTX-124 dosed on 10 10 Day 1 and 4 (50 µg) 1 1 0.1 0.1 0.01 0.01 0 48 96 144 19

  13. Slide 13: First-In-Human Study of WTX-124 Monotherapy and in Combination with Pembrolizumab

    First-In-Human Study of WTX-124 Monotherapy and in Combination with Pembrolizumab Patients with IO sensitive tumor types who have exhausted all SOC options or for whom SOC is not indicated Monotherapy/Combination Dose Expansion Monotherapy Dose Escalation Determination of Advanced or metastatic rena

  14. Slide 14: Patient Demographics from Early Monotherapy Dose Escalation Cohorts (n=16)

    Patient Demographics from Early Monotherapy Dose Escalation Cohorts (n=16) Prior lines of systemic therapy, Tumor type Demographics (including immunotherapy) AGE (years) Mean (SD) 66.9 (10.62) n (%) n (%) Median 66.0 Melanoma* 8 (50.0%) 1 2 (12.5%) SEX, n (%) Female 8 (50.0%) NSCLC 5 (31.3%) 2 4 (25

  15. Slide 15: WTX-124 was Generally Well-Tolerated in the Outpatient Setting at Relevant Doses

    WTX-124 was Generally Well-Tolerated in the Outpatient Setting at Relevant Doses Sixteen patients in four dose escalation cohorts (1-12 mg IV Q2W) were evaluable for safety Frequency of related treatment-emergent AEs Key safety findings to date: Abdominal distension Abdominal pain Arthralgia • Drug

  16. Slide 16: Plasma PK Data Show an Extended WTX-124 Half-Life with Low Free IL-2 Exposure

    Plasma PK Data Show an Extended WTX-124 Half-Life with Low Free (Active) IL-2 Exposure Preliminary PK data validate INDUKINE design and support improved therapeutic index and safety profile of WTX-124 Cycle 1 PK profiles for WTX-124 and free (active) IL-2 compared to high-dose IL-2 Cmax (mean ± SEM)

  17. Slide 17: Immunofluorescence Staining of Tumor Biopsies from Patients Treated with WTX-124

    Immunofluorescence Staining of Tumor Biopsies from Patients Treated with WTX-124 Tumor-specific expansion and activation of CD8 T cells and NK cells differentiate WTX-124 among next-gen IL-2 molecules 65yo F with melanoma (6mg) 50yo F with melanoma (12mg) 61yo F with uveal melanoma (6mg) Pre-treatme

  18. Slide 18: WTX-124 Induced Dose-Dependent Changes in Immune Gene Expression

    WTX-124 Induced Dose-Dependent Changes in Immune Gene Expression Consistent with IL-2 Activity in the Tumor Microenvironment T-cell activation genes T-cell activation genes increased by ≥2.5-fold (172 genes) 102-004 (melanoma) – Cohort 3, 6 mg NanoString nCounter® 20 PanCancer immune panel 15 (770 g

  19. Slide 19: WTX-124 Demonstrated Monotherapy Antitumor Activity in Patients Refractory to ICI Therapy

    WTX-124 Demonstrated Monotherapy Antitumor Activity in Patients Refractory to ICI Therapy At 12 mg dose level, WTX-124 shrank treatment-refractory tumor metastatic deposits (3/5 patients) 2. Patient 102-006: unconfirmed PR (RECIST 1.1) 1. Patient 107-002: unconfirmed PR (RECIST 1.1) • 72-year-old ma

  20. Slide 20: Proof of Mechanism for WTX-124 and Proof of Concept for INDUKINE Design

    Proof of Mechanism for WTX-124 and Proof of Concept for INDUKINE Design Established Monotherapy WTX-124 administered in an outpatient setting has been well tolerated and has reached exposures associated with clinical responses in dose escalation Majority of patients treated would not have been eligi

  21. Slide 21: WTX-330: Leveraging the Potential of IL-12 Therapy

    WTX-330: Leveraging the Potential of IL-12 Therapy The Challenge Develop a tolerable IL-12 therapy to stimulate innate and adaptive antitumor immune responses Potential WTX-330 Advantages and Opportunity • Delivery of IL-12 mechanism selectively to the TME with an improved therapeutic index • Potent

  22. Slide 22: IL-12 INDUKINE Delivers IL-12 Selectively to Tumor Tissue

    IL-12 INDUKINE Delivers IL-12 Selectively to Tumor Tissue with an Improved Therapeutic Index Robust activation of antitumor CD8+ T effector cells and pleiotropic immune activation in the TME in preclinical models Tumor Peripheral Blood MC38 tumor model Vehicle 2000 ns ✱ ✱ mWTX-330 (7µg/dose) 60 16 V

  23. Slide 23: IL-12 INDUKINE Inhibits Growth of Poorly Immunogenic EMT-6 Mouse Tumors

    IL-12 INDUKINE Inhibits Growth of Poorly Immunogenic EMT-6 Mouse Tumors Increased Clonality of Tumor Infiltrating CD8+ T Cells in preclinical models Efficacy in anti-PD-1 refractory EMT-6 tumors Increase of cross-presenting DCs in tumors Ratio Vehicle mWTX-330 3000 Vehicle 15 ** mWTX-330 anti-PD1 20

  24. Slide 24: First-In-Human Study of WTX-330 Evaluating Safety, Tolerability and Clinical Activity

    First-In-Human Study of WTX-330 Evaluating Safety, Tolerability and Clinical Activity Monotherapy Dose Escalation Monotherapy Dose Expansion CPI-naïve relapsed or refractory advanced tumor indications (tumor types for which CPIs are not Relapsed/refractory Monotherapy approved, including NHL and mCR

  25. Slide 25: WTX-712: Expanding the Utility of IL-21 Therapy

    WTX-712: Expanding the Utility of IL-21 Therapy Potential WTX-712 Advantages and Opportunity • IL-21 distinctively leads to an effective anti-tumor response driven by activation and differentiation of multiple anti-tumor cell types including Tfh cells, B cells, and cytotoxic effector cells (CD8+ T c

  26. Slide 26: WTX-712 has an Improved Therapeutic Index Compared to Native IL-21

    WTX-712 has an Improved Therapeutic Index Compared to Native IL-21 Tumor selective activity results in robust anti-tumor immune activation in preclinical studies WTX-712 antitumor activity in MC38 tumor model with an WTX-712 treatment transforms the tumor microenvironment improved therapeutic window

  27. Slide 27: WTX-518: Overcoming the Limitations of IL-18 Therapy

    WTX-518: Overcoming the Limitations of IL-18 Therapy Potential WTX-518 Advantages and Opportunity • IL-18 activates innate (strong NK activator) and adaptive immune cells promoting production of IFN-γ from antigen experienced T cells and favoring Th1 differentiation of naïve T cells • IL-18 activity

  28. Slide 28: Expanding Conditional-Activation Technology to New Modalities

    Oncology-focused INDUKINE PREDATOR Therapeutics Platform • Additional proinflammatory mechanisms • Cell-based therapies • mRNA therapies Non-Oncology INDUKINE Werewolf’s innovative PREDATOR Therapeutics • Inflammation Platform offers value creation through • Other diseases pipeline expansion and par

  29. Slide 29: Shifting the Balance in Cytokine Therapeutics

    Shifting the Balance WTX-124 WTX-330 in Cytokine Therapeutics Phase 1 Phase 1/1b • Two lead programs in Phase 1 development Clinical Trial Clinical Trial are wholly owned by Werewolf in Advanced and in Advanced Metastatic • Collaboration is central to our growth strategy and Metastatic Solid Tumors

  30. Slide 30: Experienced Leadership

    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 Cynthia Seidel-Dugan, PhD Tim Trost, CPA Chief Business Officer Chief Scientific Officer Chief Financial Officer 30 | ©2024 W

  31. Slide 31: Thank You!

    Thank You! 31 | ©2024 WEREWOLF THERAPEUTICS

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