Werewolf Therapeutics, Inc. · NASDAQ:HOWL
Werewolf Therapeutics — Investor Presentation (September 2023)
22 slides from Werewolf Therapeutics's investor presentation, Sep 18, 2023
Slide 1: Corporate Overview | September 2023: Shifting the Balance in Cytokine Therapeutics
Corporate Overview | September 2023 Shifting the Balance in Cytokine Therapeutics Exhibit 99.1
Slide 2: Cautionary Statements
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, Inc.’s (the “Company”) strate
Slide 3: Who we are
| ©2023 Werewolf Therapeutics We have two investigational drugs in Phase I clinical trials Our headquarters and research facilities are located in Watertown, Massachusetts Our mission is to unlock the promise of cytokines as more effective immunotherapies We are a clinical-stage biopharmaceutical co
Slide 4: 2023 Value-drivers and On-going Value Creation
WTX-124 Ongoing enrollment in monotherapy dose escalation Ongoing enrollment in combination dose escalation with pembrolizumab Initial clinical data readout expected 4Q23 On-going Value Creation 2023 Value-drivers WTX-330 Ongoing enrollment in monotherapy dose escalation JZP898 Initiating Phase I cl
Slide 5: Overcoming Off-Target Toxicity has been a Key Challenge for Cytokine Therapy
Suboptimal Pharmaceutical Properties Toxicity Our Solution: Conditionally Activated Immunotherapy The Challenge: Off-Tumor Cytokine Toxicity Limits Therapeutic Index Poor Clinical Outcomes With Optimized Therapeutic Index INDUKINEs (inactive cytokines) Activated cytokines Tumor Activated cytokine Ac
Slide 6: PREDATOR Platform
PREDATOR Platform Safety Peripheral inactivation Exposure Half-life extension Selectivity Tumor activation Potency Native Cytokine Tunable, Tissue-targeted Therapeutics for Cancer and other Diseases INDUKINE molecules contain multiple domains, each with a unique function that can be ‘tuned’ for spec
Slide 7: INDUKINE Molecules: Targeting Cytokine Activity to Diseased Tissue
INDUKINE Molecules: Targeting Cytokine Activity to Diseased Tissue Tumor tissue Cytokine activation Immune cell activation INDUKINE design High exposure of INDUKINE molecule Tumor-selective protease activation Healthy tissue cytokine inactive
Slide 8: Innovative Linker Discovery Approach to Address Protease Heterogeneity
Disease Tissue Healthy Tissue Library of novel protease substrates Highly diverse substrate library Unique protease specificities Innovative screening approach Substrates selected in the context of a globular protein Screens possible with a variety of diseased tissues Disease Selective Protease (DSP
Slide 9: A Balanced Portfolio of Clinical and Preclinical Drug Candidates
RIGHTS PROGRAM INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PHASE 2 Immuno-oncology Inflammatory Diseases Novel INDUKINE Molecules Cancer Indications WTX-712 IL-21 INDUKINE Molecule Cancer Indications Exclusive Global Rights Licensed to Jazz JZP898 IFNα INDUKINE Molecule Advanced or Metastatic Solid T
Slide 10: WTX-124: Expanding the Utility of IL-2 Therapy
The Challenge Deliver the benefits of IL-2 therapy with less toxicity to a broader range of patients CD8 Potential WTX-124 Advantages and Opportunity Delivery of IL-2 selectively to the TME to improve the therapeutic index Potential for activity beyond approved indications for rhIL2 IL-2 therapy wit
Slide 11: 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 antitumor activity in MC38 tumor model WTX-124 has an Improved Therapeutic Index Compared to Native IL-2 Improved therapeutic window compared to IL-2 cytokine Nirschl CJ et al., Cancer Immunology Research 2022
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 Free IL-2 WTX-124 INDUKINE WTX-124 dosed on Day 1 and 4 (50 mg) Robust expansion and activation of antitumor CD8+ T effector cells in the TME Time (hr) Time (hr) Tumor Plasma WTX-124 Vehicle Nirschl CJ et al., Cancer Immunology
Slide 13: WTX-124 Activates Long-term Antitumor Immune Memory in Preclinical Models
CD44 CD62L Tumor Naïve MC38 CR WTX-124 Activates Long-term Antitumor Immune Memory in Preclinical Models Nirschl CJ et al., Cancer Immunology Research 2022 10(5):581-596 Abbreviations: TME-tumor microenvironment; CR-complete regression
Slide 14: WTX-124 Phase 1 Trial Design
Determination of monotherapy MTD/RDE Patients with IO sensitive tumor types who have exhausted all SOC options or for whom SOC is not indicated Monotherapy Dose Escalation 4Q 2023: Anticipated release of initial safety, tolerability, pharmacokinetics and biomarker data Determination of combination t
Slide 15: WTX-330: Leveraging the Potential of IL-12 Therapy
CD8 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
Slide 16: IL-12 INDUKINE Delivers IL-12 Selectively to Tumor Tissue
Differential Gene Signatures Intratumoral IL-12 pathway activation Activation of multiple antigen presentation mechanisms Th1 lineage skewing Treg instability Increased chemokine expression mWTX-330 WTX-124 172 122 296 MC38 tumor model mWTX-330 Vehicle IL-12 INDUKINE Delivers IL-12 Selectively to Tu
Slide 17: IL-12 INDUKINE Inhibits Growth of Poorly Immunogenic EMT-6 Mouse Tumors
Increased TCR clonality of tumor infiltrating T cells CD103 CD11b Vehicle mWTX-330 Increase of cross-presenting DCs in tumors Efficacy in anti-PD-1 refractory EMT-6 tumors IL-12 INDUKINE Vehicle DAPI PanCK CD3 CD8 IL-12 INDUKINE Vehicle Fraction of TCR Repertoire Clone Rank Fraction of TCR repertoir
Slide 18: First-In-Human Study of WTX-330
Monotherapy expansion arms to open after determination of MTD/RDE Relapsed/refractory advanced or metastatic solid tumors failing SOC, including immune checkpoint inhibitors Bayesian study design, n~75 CPI-naïve relapsed or refractory advanced tumor indications (tumor types for which CPIs are not ap
Slide 19: Expanding Conditional-Activation Technology to New Modalities
Oncology-focused INDUKINE Therapeutics Additional proinflammatory mechanisms Cell-based therapies mRNA therapies Non-Oncology INDUKINE Therapeutics Inflammation Other diseases Expanding Conditional-Activation Technology to New Modalities Targeted antibodies, T cell engagers, ADCs Cell-based therapie
Slide 20: PREDATOR: Value Creation Engine
PREDATOR: Value Creation Engine Our protein engineering technology optimizes the design of conditionally activated cytokine therapeutics (INDUKINE molecules) to diseased tissues. Opportunity to pursue non-cancer indications such as inflammatory diseases. Shifting the Balance in Cytokine Therapeutics
Slide 21: Experienced Leadership
Experienced Leadership Cynthia Seidel-Dugan, PhD Chief Scientific Officer Daniel J. Hicklin, PhD President and CEO Randi E. Isaacs, MD Chief Medical Officer Ellen Lubman, MBA Chief Business Officer Tim Trost, CPA Chief Financial Officer Chulani Karunatilake, PhD Chief Technology Officer
Slide 22: Thank You!
THERAPEUTICS Thank You!
Werewolf Therapeutics — Investor Presentation (September 2023) on 6ix