Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Investor Presentation (June 2025)
44 slides from Xilio Therapeutics's investor presentation, Jun 2, 2025
Slide 1: Unleashing the Potential of Immuno-Oncology Therapies
Unleashing the Potential of Immuno-Oncology Therapies May 31, 2025 © 2025 Xilio Therapeutics, Inc.
Slide 2: Forward-Looking Statements and Disclaimers
Forward-Looking Statements and Disclaimers This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, timing and expectations related to: development timeline
Slide 3: Immuno-Oncology Therapy Key to Curative Potential, But Limited by Systemic Toxicity
Immuno-Oncology Therapy is the Key to Curative Potential, But Continues to Be Limited by Systemic Toxicity Xilio believes the next revolution in I-O therapy will harness the power of the body’s immune system by leveraging the dysregulated biology of the tumor against itself 3 I-O: immuno-oncology
Slide 4: Xilio Exploits Dysregulated MMP Activity in Invasive Cancer
Xilio Exploits Dysregulated MMP Activity, a Hallmark of Invasive Cancer Common Across a Wide Range of Solid Tumors, to Activate Molecules in the Tumor MMPs are dysregulated broadly across solid tumors MMP mRNA expression in tumor vs. normal tissue MMPs MMPs and immune cells co-localize at the invasi
Slide 5: Xilio Platform and Capabilities
Xilio Platform and Capabilities Delivering a Portfolio of Differentiated Molecules Across Diverse Mechanisms and Architectures T Cell Antibodies Cytokines Bispecifics Engagers Vilastobart XTX301 XTX501 Tumor-Activated Cell Engagers Tumor-activated Tumor-activated IL-12 Tumor-activated PD-1/IL-2 bisp
Slide 6: Advancing Pipeline of Tumor-Activated Immunotherapies
Advancing Pipeline of Tumor-Activated Immunotherapies Leveraging Clinically-Validated Platform Technology, Including Masked T Cell Engagers Collaborations and Program Tumor Types Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Partnerships Vilastobart (1) Metastatic Tumor-activated anti-CTLA-4 MSS CR
Slide 7: Anticipated Milestones
Anticipated Milestones* Anticipated Milestone Timing Vilastobart (tumor-activated anti-CTLA-4) Reported updated Phase 2 data in combination with atezolizumab in MSS CRC May 2025 (ASCO) Report updated Phase 2 data in combination with atezolizumab in MSS CRC, including at the 150 mg Q6W dose level for
Slide 8: Vilastobart Tumor-Activated, Fc-enhanced Anti-CTLA-4
Vilastobart Tumor-Activated, Fc-enhanced Anti-CTLA-4
Slide 9: Vilastobart: Tumor-Activated, Fc-Enhanced Anti-CTLA-4
Vilastobart: Tumor-Activated, High Affinity Binding, Fc-Enhanced Anti-CTLA-4 Highlights from Previously Reported Data Inactive State ü High affinity binding, 10x potency of ipilimumab in preclinical studies(1)ü Fc mutations for enhanced effector function (ADCC), improved T cell priming and Treg Vari
Slide 10: CRC Incidence is Increasing, Particularly in Young Adults
CRC Incidence is Increasing, Particularly In Young Adults, with New Cases Typically Identified at Later Stages ~90,000 new cases of Stage 4 CRC patients ~95% of Stage 4 CRC patients have MSS CRC (1) estimated in the US per year CRC is 2nd in cancer-related deaths in the US and leading cause of cance
Slide 11: Approved I-O Therapies Show Little Efficacy in MSS CRC
Approved I-O Therapies Have Shown Little to No Efficacy in MSS CRC, While Other Anti-CTLA-4 Molecules in Development Have Been Limited by Toxicity to Date Treatment for advanced MSS CRC typically includes Current Standard of Care in 3L+ MSS CRC Provides Minimal Benefit chemotherapy combinations, (1)
Slide 12: Vilastobart Demonstrated Meaningful Clinical Activity and Differentiated Safety
Vilastobart Has Demonstrated Meaningful Clinical Activity and Differentiated Safety Profile in Combination, Supporting Opportunity in MSS CRC and a Range of Other Tumor Types 26% preliminary ORR observed in Phase 2 in heavily pre-treated patients (80% of patients 3L+) with MSS CRC without liver meta
Slide 13: Vilastobart Phase 2 Data Presented at ASCO on May 31, 2025
Vilastobart (anti-CTLA-4) Phase 2 Data for Combination of Vilastobart and Atezolizumab Presented at ASCO on May 31, 2025
Slide 14: Phase 1/2 Study Design for Vilastobart
Phase 1/2 Study Design for Vilastobart in Advanced Solid Tumors and Metastatic MSS CRC KEY PHASE 2 ELIGIBILITY PHASE 1A/B PHASE 1C PHASE 2 At least 1 prior chemotherapy Monotherapy Dose-Escalation Vilastobart + Atezolizumab Vilastobart + Atezolizumab regimen for metastatic CRC and Expansion Dose-Esc
Slide 15: Phase 2 Enrolled Heavily Pre-Treated MSS CRC Patients
Phase 2 Enrolled Heavily Pre-Treated (3L+) Patients With MSS CRC With and Without Liver Metastases, Including Patients With Peritoneal Metastases Patient Total Prior Lines of Anti-Cancer Tumor Total Treatment Total Characteristics (n=44) Treatment Types (n=44) Status (n=44) Age, median (range) 55 (2
Slide 16: Preliminary 26% ORR in MSS CRC Without Liver Metastases
Preliminary 26% ORR Reported in Patients With MSS CRC Without Liver Metastases 200% 80 Best Response  Without With Best Response Liver Metastasis Liver Metastasis 60 Partial Response Per RECIST (n = 27) (n = 17) PR 7* 0 in 41% 40% Stable Disease 40 SD 5 3 Disease Progression ORR 26% 0% lesions 30%
Slide 17: Durable Anti-Tumor Activity in MSS CRC Without Liver Metastases
Durable Anti-Tumor Activity Observed in Patients With MSS CRC Without Liver Metastases 6 out of 7 responders remain on treatment Treatment duration currently up to 37 weeks Best Response Partial response Stable disease Disease progression New lesion Treatment Status Ongoing Discontinued # Data cutof
Slide 18: Significant Reductions in Tumor Burden and Biomarkers
Significant Reductions in Tumor Burden With Meaningful Improvements in Clinical Symptoms and Decreases in Tumor Biomarkers Data cutoff date: May 12, 2025 18 CEA: carcinoembryonic antigen; ctDNA: circulating tumor DNA
Slide 19: Radiographic Responses Accompanied by ctDNA Reductions
Radiographic Responses Were Accompanied by Substantial ctDNA Reductions Changes in sum of diameters Changes in ctDNA score 200% Baseline Best Baseline % from in Diameters of ctDNA Change Change Sum % in from Best Score * Data cutoff date: May 12, 2025 Dodged waterfall plot showing best % change from
Slide 20: MSS CRC Patient With Liver Metastasis and Confirmed PR
MSS CRC Patient With Liver Metastasis and Previously Reported Confirmed PR From Phase 1C Still On Treatment After 14+ Months With Response Deepening Patient with MSS CRC and Liver Metastasis Screening 9 weeks 18 weeks 27 weeks 36 weeks 45 weeks 57 weeks Sum of diameters 98.4 mm 70.5 mm 71.0 mm 66.3
Slide 21: Differentiated Safety and Tolerability vs Other Anti-CTLA-4 Agents
Combination of Vilastobart and Atezolizumab Demonstrated Meaningfully Differentiated Safety and Tolerability Compared to Other Anti-CTLA-4 Agents All Phase 2 Patients Dose Reduction and Treatment Discontinuation TRAEs ≥10% incidence (any Grade) or (n=44) Vilastobart dose reduction due to TRAE+ 1 (2%
Slide 22: Potential Development Plan for 3L+ MSS CRC Without Liver Metastases
Potential Development Plan for 3L+ MSS CRC in Patients Without Liver Metastases 3L+ MSS CRC Current Standard of Care in 3L+ MSS CRC Without Liver Metastases Provides Minimal Benefit Patient population Eligible for 3L+ therapy Median OS Investigational Arm Vilastobart + anti-PD-(L)1 Treatment Line OR
Slide 23: Broad Opportunity for Vilastobart Across Tumor Types
Broad Opportunity for Vilastobart Across a Range of Tumor Types Where Approved Therapies Have Insufficient Efficacy or Limited by Safety and Tolerability Issues “Cold Tumors” with Rationale Clinical Activity Demonstrated Potential to Replace Currently for Fc-Enhanced, for Anti-CTLA-4, But No Current
Slide 24: XTX301 Tumor-Activated IL-12
XTX301 Tumor-Activated IL-12
Slide 25: XTX301: Tumor-Activated IL-12
XTX301: Tumor-Activated IL-12 XTX301 Designed to Overcome the Limitations of Inactive State Systemic Recombinant Human IL-12 Half-Life Extension Domain Activated XTX301 designed to have optimized short half-life IL-12 (half-life extension domain not retained) Potential for broad therapeutic index su
Slide 26: XTX301 Advancing in Partnership with Gilead
XTX301 Advancing in Partnership with Gilead, Designed to Explore Broad Potential of IL-12 Across Solid Tumors with $75M Option Fee at Phase 1/2 Data Package $55.0M Gilead received an exclusive global total received to date ($30M cash upfront payment + license to develop and commercialize $25M in tot
Slide 27: XTX501 PD-1/IL-2 bispecific
XTX501 PD-1/IL-2 bispecific
Slide 28: XTX501: Tumor-Activated PD-1/IL-2 Bispecific
XTX501: Tumor-Activated PD-1/IL-2 Bispecific Designed to Enable High Potency, PD-1 Antibody-Like PK and Tolerability Demonstrated Synergistic Anti-Tumor Activity, Antibody-Inactive State Like PK and Favorable Tolerability in NHP Full potency alpha-optimized IL-2 with affinity-tuned, VHH-based mask A
Slide 29: Tumor-Activated Design of XTX501 Demonstrated Optimal PK and Tolerability
Tumor-Activated Design of XTX501 Demonstrated Optimal PK and Tolerability Preclinically Non-Masked PD-1/IL-2 Bispecific Was Rapidly XTX501 Achieved Antibody-Like Exposures and Cleared and Poorly Tolerated Was Well-Tolerated Even at High Doses Non-masked PD1/IL2 Bispecific Non-masked PD1/IL2 Bispecif
Slide 30: XTX501 Demonstrated Tumor-Specific Pharmacology
XTX501 Demonstrated Tumor-Specific Pharmacology with Peripheral Effects Limited to Increases in Antigen-Specific/Memory Cells Peripheral Expansion of T Cells in Response to XTX501 XTX501 Treatment Demonstrated Robust Increases in Was Limited to Antigen-Specific/Memory Cells Activated T Cell Populati
Slide 31: XTX501 Differentiated Pharmacology vs PD1 and PD1+IL-2
XTX501 Demonstrated Differentiated Pharmacology vs PD1 and Combination of PD1+IL-2 in Tumor Model, Suggesting Enhanced Anti-Tumor Immunity Preclinically Robust Preclinical Monotherapy Activity Beyond XTX501 Demonstrated Increased Intra-Tumoral Cytotoxic Fc-IL-2 + PD1 Combination was Observed with XT
Slide 32: XTX501 Demonstrated Favorable Tolerability in NHP
XTX501 Demonstrated Favorable Tolerability in NHP Single Dose PK Study in NHP Minimal Effects of XTX501 on Serum Albumin Tolerable Up to 30 mg/kg (i.e., No Signs of Vascular Leak Syndrome) XTX501 Concentration Over Time Serum Albumin Concentration Over Time 1000 6 100 5 10 (g/dL) 4 3 g/mL 1 ¼ 3 mg/k
Slide 33: Development Strategy: Focus on Tumor Types Responding to PD-1/IL-2
Development Strategy: Focus Phase 1 on Tumor Types with Demonstrated Responses to a Non-Masked PD-1/IL-2, Including Post-PD-1 and PD-L1 Low/Negative Tumors PD-(L)1 Monotherapy ORR: Lung adenocarcinoma 17% Clinical data for PD-(L)1 monotherapy and Lung SCC 17% for IBI363 (non-masked PD-1/IL-2) guide
Slide 34: Masked T Cell Engager Programs
Masked T Cell Engager Programs
Slide 35: Masked T Cell Engagers Have Untapped Potential in Solid Tumors
Masked T Cell Engagers (TCE) Have Untapped Potential in Solid Tumors TCEs are a promising new modality for cancer immunotherapy with meaningful clinical activity However, many compelling TCE targets have remained out of reach due to toxicity limitations TCEs simultaneously bind to CD3 on T cells and
Slide 36: Masked T Cell Engagers Designed to Optimize Therapeutic Index
Masked T Cell Engagers are Designed to Optimize Therapeutic Index by Maximizing Tumor Exposure and Minimizing Peripheral Activity and Off-Tumor Cytotoxicity “ATACR” Format (masked cell engager) Designed to release a potent, short half-life T cell engager upon tumor-selective activation Optimized for
Slide 37: Xilio's Masked T Cell Engagers: PSMA, CLDN18.2, STEAP1
Xilio’s Masked T Cell Engagers Incorporate Our Validated Masking Approach, Conditional Half-Life Optimization +/- Co-Stimulation Target: PSMA Target: CLDN18.2 Target: STEAP1 (ATACR Format) (ATACR Format) (SEECR Format) Potential best-in-class anti-tumor First-in-class potential as masked T First-in-
Slide 38: ATACR Format for PSMA Improved Therapeutic Index
ATACR Format for PSMA Demonstrated Potential for Improvement in Therapeutic Index In Vitro and Anti-Tumor Activity with Favorable Tolerability In Vivo ATACR Format for PSMA Demonstrated Potential for ATACR Format for PSMA Elicited Significant Protease-Meaningful Improvement in Therapeutic Index In V
Slide 39: SEECR Format Drives Sustained, Serial Tumor Cell Killing
SEECR Format Demonstrated Unique Ability to Drive Sustained, Serial Tumor Cell Killing Over Multiple Rounds of Stimulation in Preclinical Model Longitudinal Target Cell Killing 100 Killing 50 Addition of co-stimulatory signaling Cell resulted in sustained activity enabling Target more durable T cell
Slide 40: Prototype SEECR Molecules Demonstrated Differentiated Activity In Vivo
Prototype SEECR Molecules Demonstrated Differentiated Activity Compared to Unmasked T Cell Engagers In Vivo SEECR Drove Enhanced Tumor T Cell SEECR Enabled Superior Anti-Tumor Activity Infiltration and Proliferation vs Non-Masked TCE in Multiple Mouse Models vs . 25 Breast Cancer Model 1 (CD3+) 100
Slide 41: Collaboration, License and Option Agreement with AbbVie
Collaboration, License and Option Agreement with AbbVie to Develop Novel Tumor-Activated Immunotherapies, Including Masked T Cell Engagers $52.0M total received to date ($42M cash upfront payment + $10M equity investment) Initial programs for tumor-activated immunotherapies Up to ~$2.1B 1. Masked T
Slide 42: Recent Financial Results and Management Overview
Recent Financial Results and Management Overview
Slide 43: Q1 2025 Financial Results
Q1 2025 Financial Results (1) Anticipate Cash Runway Into Q1 2026 Balance Sheet March 31, 2025 Cash and Cash Equivalents $89.1M Statement of Operations Three Months Ended March 31, 2025 Collaboration and License Revenue $2.9M Research & Development Expenses $8.3M General & Administrative Expenses $8
Slide 44: Deep Expertise to Build a Transformational Immuno-Oncology Company
Deep Expertise to Build a Transformational Immuno-Oncology Company ULI BIALUCHA, PH.D. SCOTT COLEMAN, PH.D. Chief Scientific Officer Chief Development Officer CHRIS FRANKENFIELD CAROLINE HENSLEY Chief Financial and Operating Officer Chief Legal Officer KATARINA LUPTAKOVA, M.D. RENÉ RUSSO, PHARM.D. C
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