Slide 1: Shifting the Balance in Cytokine Therapeutics: WTX-124 Phase 1/1b Update
Exhibit 99.2 Shifting the Balance in Cytokine Therapeutics ASCO 2024 WTX-124 Phase 1/1b Clinical Trial Update Investor Webcast June 3, 2024 ©2024 WEREWOLF THERAPEUTICS
Slide 2: Cautionary Note Regarding Forward-Looking Statements and Disclaimer
Cautionary Note Regarding Forward-Looking Statements and Disclaimer 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
Slide 3: Agenda
3 • Introductory Remarks and Program Overview – Dan Hicklin, Ph.D., CEO • Walk-through of WTX-124 Data – Justin Moser, M.D. • Closing Remarks – Randi Isaacs, M.D., CMO Agenda • Q&A 3 | ©2024 WEREWOLF THERAPEUTICS
Slide 4: Overview of WTX-124 Program Objectives
Overview of WTX-124 Program Objectives A cytokine prodrug engineered to improve 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
Slide 5: WTX-124: Summary of Data to Date
WTX-124: Summary of Data to Date Establishes potential for a best-in-class IL-2 therapy SITC - Nov 2023 ASCO - June 2024 Updated monotherapy and initial combination Initial monotherapy dose-escalation data; dose-escalation data; 47 patients (1-28 mg) 16 patients (1-12 mg) • Monotherapy antitumor act
Slide 6: Justin Moser, MD
Justin Moser, MD Associate Clinical Investigator HonorHealth Research Institute 6 6 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
Slide 7: WTX-124 FIH Study Monotherapy Expansion Arms are now Open and Enrolling
WTX-124 FIH Study Monotherapy Expansion Arms are now Open and Enrolling Forty-seven patients have received at least one dose of WTX-124 (35 in monotherapy, 12 in combination) Monotherapy/Combination Dose Expansion MONOTHERAPY DOSE ESCALATION Determination Advanced or metastatic renal cell of WTX-124
Slide 8: Patient Population was Heterogeneous and Heavily Pretreated
WTX-124 Phase 1 Patient Population was Heterogeneous and Heavily Pretreated All 47 patients (monotherapy, combination) progressed on standard-of-care ICI regimens Demographics Tumor Types Prior Therapies All prior lines of therapy Enrollment restricted to solid tumor n (%) indications for which immu
Slide 9: WTX-124 Generally Well Tolerated as Monotherapy in Outpatient Setting
WTX-124 was Generally Well Tolerated as a Monotherapy in the Outpatient Setting Treatment-related adverse events were primarily mild to moderate including at clinically active doses Key Safety Findings: Frequency of related TEAEs • Most frequent related TEAEs occurring in were arthralgia, fatigue, p
Slide 10: No New Safety Signals with WTX-124 Combined with Pembrolizumab
No New Safety Signals were Observed for WTX-124 Combined with Pembrolizumab Addition of pembrolizumab did not change the character of related adverse events Frequency of related TEAEs occurring more than once for patients at 3-12 mg WTX-124 monotherapy (N=19) or combination therapy (N=12) • Majority
Slide 11: WTX-124 Demonstrated Monotherapy Antitumor Activity at Doses ≥12 mg
WTX-124 Demonstrated Monotherapy Antitumor Activity at Doses ≥12 mg Durable CR (8+ months) in a patient with CSCC; PRs in patients with melanoma and GEJ cancer Cutaneous SCC (12 mg) * NSCLC (1 mg) Melanoma (6 mg) Melanoma (18 mg) NSCLC (3 mg) NSCLC (18 mg) NSCLC (12 mg) Gastroesophageal junction (18
Slide 12: Complete Regression of Target Lesions in Responding Patients
Complete Regression of Target Lesions in Patients Responding to WTX-124 Three patients had objective responses and an additional seven had stable target lesions at potential RDE doses (n=16) *Metastatic lymph node target lesion normalized in size (<1 cm) * * Abbreviations: RDE- recommended dose for
Slide 13: Responses at Target Lesions Rapid and Durable at Potential RDE Doses
Responses at Target Lesions Occurred Rapidly and were Durable at Potential RDE Doses All three objective responses to WTX-124 monotherapy occurred within two cycles (~8 weeks) *Metastatic lymph node target lesion normalized in size (<1 cm) Gastroesophageal junction * tumor (18 mg) Cutaneous squamous
Slide 14: Ongoing Complete Response at 8+ Months in ICI-Refractory Cutaneous SCC
June 2023: PET-CT at time of September 2023: Baseline CT Confirmed Complete Response (CR) Ongoing at 8+ progression on cemiplimab performed at study entry Months in a Patient with ICI-Refractory Cutaneous SCC T NT 72-year-old man with metastatic cutaneous SCC who progressed on RT/cetuximab and had n
Slide 15: Partial Response in Melanoma Patient with Secondary ICI Resistance
July 2023: Baseline PET-CT at July 2023: Baseline CT shows the Partial Response (PR) in a Cutaneous Malignant time of progression on Opdualag 1.4 cm target liver lesion Melanoma Patient with Secondary ICI Resistance 78-year-old man with metastatic BRAF wild type cutaneous melanoma who discontinued a
Slide 16: Partial Response in Gastroesophageal Junction Tumor Patient
Partial Response (PR) in a Gastroesophageal Junction Tumor Patient with Secondary ICI Resistance October 2023: 63-year-old man with a metastatic gastroesophageal junction (GEJ) Baseline CT adenocarcinoma who previously progressed on FOLFOX/nivolumab and shows a 1.6 cm nivolumab/BMS986253 (anti-IL-8)
Slide 17: PK Data Continue to Demonstrate Proof of Concept for INDUKINE Strategy
PK Data Continue to Demonstrate Proof of Concept for the INDUKINE Strategy Data support the improved safety profile and therapeutic index of WTX-124 compared to HD IL-2 Cycle 1 PK profiles for WTX-124 and free IL-2 compared to Preliminary PK findings: high-dose IL-2 Cmax (mean ± SEM) • WTX-124 dosed
Slide 18: Dose Dependent Increases in Intratumoral T-cell Activation by NanoString
WTX-124 Caused Dose Dependent Increases in Intratumoral T-cell Activation by NanoString Top 40 Key insights from tumor upregulated biomarkers: T-cell activation genes across all • Largest changes seen at 18 mg monotherapy (monotherapy) and 12 mg dose levels (combination) • Upregulation of GRZB and I
Slide 19: T-cell Inflamed Tumor Microenvironment Associated with Clinical Activity
T-cell Inflamed Tumor Microenvironment Associated with WTX-124 Clinical Activity Findings in baseline tumor biopsies were consistent with the known mechanism of action of IL-2 Baseline biopsies showed trends toward greater Fresh tumor biopsies acquired prior to starting WTX-124 treatment CD8+ T cell
Slide 20: Summary of Data from Ongoing WTX-124 Phase 1/1b Study
Summary of Data from Ongoing WTX-124 Phase 1/1b Study Safety Clinical Activity • Generally well tolerated in the outpatient setting • Objective responses at monotherapy doses ≥12 mg • No evidence of vascular leak syndrome, cytokine • Confirmed, durable CR in patient with CSCC release syndrome (≥Grad
Slide 21: Randi Isaacs, MD, Chief Medical Officer
Randi Isaacs, MD Chief Medical Officer Werewolf Therapeutics, Inc. 21 21 | | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS
Slide 22: Preliminary Clinical Data Demonstrate Potential for Best-in-class IL-2 Therapy
Preliminary WTX-124 Clinical Data Demonstrate Potential for a Best-in-class IL-2 Therapy ü Monotherapy activity demonstrated in heavily pretreated patients who were refractory to all SOC therapies including checkpoint inhibitors ü Clinical activity observed in patients ineligible for approved HD IL-
Slide 23: WTX-124 Program Next Steps
WTX-124 program next steps ü WTX-124 dose of 18 mg IV Q2W has been selected as recommended dose for expansion (RDE) ü Monotherapy expansion arms in advanced or metastatic renal cell carcinoma (n=20), cutaneous melanoma (n=20), and cutaneous squamous cell carcinoma (n=10) now open for enrollment ü Do
Slide 24: Thank You
Thank You 24 | ©2024 WEREWOLF THERAPEUTICS ©2024 WEREWOLF THERAPEUTICS