Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Investor Presentation (January 2025)
43 slides from Xilio Therapeutics's investor presentation, Jan 21, 2025
Slide 1: Unleashing the Potential of Immuno-Oncology Therapies
1 Unleashing the Potential of Immuno-Oncology Therapies January 21, 2025 © 2025 Xilio Therapeutics, Inc. Exhibit 99.1
Slide 2: Forward-Looking Statements
2 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: plans and anticipated milestones for vilastobart (XTX101), XT
Slide 3: Immuno-Oncology Therapy Limited by Systemic Toxicity
3 I-O: immuno-oncology Immuno-Oncology Therapy is the Key to Curative Potential, But Continues to Be Limited by Systemic Toxicity Patient Portrayal 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
Slide 4: Xilio Exploits Dysregulated MMP Activity to Activate Molecules in the Tumor
4 Left panel: Heatmap summarizing RNA expression changes of genes encoding for selected MMPs (bottom) in tumor vs. adjacent normal samples from multiple TCGA studies (x-axis). Color intensity tracks with log2-transformed fold changes (log2FC). Pre-processed TCGA data were obtained from UCSC Xena. Ri
Slide 5: Tumor-Activated Approach Applied in the Clinic Across Diverse Molecular Architectures
5 TME: tumor microenvironment Xilio’s Tumor-Activated Approach Has Been Successfully Applied in the Clinic Across Diverse Molecular Architectures Cleavage Site Half-Life Extension Domain Effector Domain Masking Domain Antibody Example Cytokine Example Masking Domain Variable Domain Variable Domain M
Slide 6: Advancing Pipeline of Tumor-Activated I-O Therapies
6 Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Partnerships Mechanism of Action Tumor Types Program Co-funded clinical collaboration with Roche anti-CTLA-4 + PD-L1 Metastatic MSS CRC Vilastobart (XTX101) (1) Exclusive global option with Gilead IL-12 Advanced Solid Tumors XTX301 (2) PD-1/IL2 bispec
Slide 7: Vilastobart (XTX101) Tumor-Activated, Fc-enhanced Anti-CTLA-4
7 Vilastobart (XTX101) Tumor-Activated, Fc-enhanced Anti-CTLA-4
Slide 8: Vilastobart: Tumor-Activated, Fc-Enhanced Anti-CTLA-4 in Phase 2 Development
8 Inactive State 1. Ipilimumab analog used for preclinical studies 2. PR (confirmed) in MSS CRC patient; PR (unconfirmed) in ampullary carcinoma patient. ADCC: antibody-dependent cell-mediated cytotoxicity; NSCLC, non-small lung cancer; PR: partial response; Treg: regulatory T cells Vilastobart: Tum
Slide 9: CRC Incidence Increasing; ~95% of Stage 4 US Patients are MSS
9 1. Siegel. CA Cancer J Clin.2023;73:233. 2. Bray. CA Cancer J Clin 2024;74:229. 3. Kawazoe. J Clin Oncol. 2024;42:2918. MSI-H: microsatellite instability-high CRC Incidence is Increasing, Particularly In Young Adults; New Cases Typically Identified at Later Stages and ~95% of Stage 4 Patients in t
Slide 10: I-O Therapies Have Shown Little to No Efficacy in MSS CRC
10 • Majority of patients diagnosed with metastatic disease are not eligible for surgery and primary treatment includes chemotherapy and/or radiation (1) • Treatment for advanced MSS CRC typically includes chemotherapy +/- TKI, (1) followed by clinical trials or late-line therapies with minimal bene
Slide 11: Initial Phase 2 Data for Vilastobart + Atezolizumab in Metastatic MSS CRC
11 Vilastobart (XTX101) Initial Phase 2 Data for Vilastobart (anti-CTLA-4) + Atezolizumab in Patients with Metastatic MSS CRC Presented at ASCO GI in January 2025
Slide 12: Phase 2 Enrolled Heavily Pre-Treated MSS CRC Patients
12 Data cutoff date: January 13, 2025 ECOG PS: Eastern Cooperative Oncology Group Performance Status Phase 2 Enrolled Heavily Pre-Treated MSS CRC Patients With and Without Liver Metastases Total (N=40) Patient Characteristics Demographics Age, median (range) 55 (25 - 82) Female 20 (50%) ECOG PS 0 17
Slide 13: Combination Well-Tolerated With Highly Differentiated Safety Profile
13 Data cutoff date: January 13, 2025. Patients were administered combination of vilastobart (100 mg Q6W) and atezolizumab (1200 mg Q3W). 1. Dose reduction of atezolizumab is not permitted per protocol. 2. Reflects discontinuation of both vilastobart and atezolizumab. 3. Non-laboratory Grade 3 TRAEs
Slide 14: Preliminary ORR in MSS CRC Patients Without Liver Metastases
14 Data cutoff date: January 13, 2025. Patients were administered combination of vilastobart (100 mg Q6W) and atezolizumab (1200 mg Q3W). 1. Includes 2 confirmed PRs (Patient A and Patient B vignettes) and 1 unconfirmed PR (Patient C vignette, based on initial assessment by investigator at 9 weeks w
Slide 15: Anti-Tumor Activity in MSS CRC Patients, Including 2 Confirmed PRs
15 Anti-Tumor Activity in MSS CRC Patients, Including 3 PRs (2 Confirmed), Demonstrated for Combination of Vilastobart (anti-CTLA-4) and Atezolizumab Data cutoff date: January 13, 2025. One patient was found to have new brain metastases (progressive disease per RECIST) but did not yet undergo imagin
Slide 16: Confirmed PRs Deepening Through Up to 18 Weeks
16 Confirmed PRs in MSS CRC Patients Without Liver Metastases Deepening Through Up to 18 Weeks To Date Data cutoff date: January 13, 2025. One patient was found to have new brain metastases (progressive disease per RECIST) but did not yet undergo imaging of target lesions. This patient is evaluable
Slide 17: Patients Ongoing on Treatment With Combination
17 23 Patients Ongoing on Treatment with Combination of Vilastobart (anti-CTLA-4) and Atezolizumab, Including 13 Patients Who Have Not Yet Had a First Response Assessment Data cutoff date: January 13, 2025 EOT: end of treatment Treatment Duration from Cycle 1, Day 1 (Weeks)
Slide 18: Patient A: Confirmed PR in MSS CRC Without Liver Metastases
18 Patient A: Confirmed PR in Patient with MSS CRC Without Liver Metastases (47% Reduction), With Decreased CEA and ctDNA and Improvement in Clinical Symptoms • 50 year-old male • 4 prior lines of therapy: - FOLFOXIRI + bevacizumab - FOLFIRI + panitumumab - FOLFOX + bevacizumab - Regorafenib • PR (c
Slide 19: Patient B: Confirmed PR in MSS CRC Without Liver Metastases
19 Lung Lesion #1 – Baseline Lung Lesion #2 – Baseline Lung Lesion #1 – 9 Week Follow-Up (1st Scan) Patient B: Confirmed PR in Patient with MSS CRC Without Liver Metastases (57% Reduction), With Undetectable ctDNA and CEA Normalized • 63 year-old female • 2 prior lines of therapy: - FOLFOX - 5FU and
Slide 20: Patient C: Unconfirmed PR in MSS CRC Without Liver Metastases
20 Lung Lesions – 9 Week Follow-Up (1st Scan) Patient C: PR (Unconfirmed) in Patient with MSS CRC Without Liver Metastases (35% Reduction), With Decreased CEA and ctDNA and Improvement in Clinical Symptoms • 67 year-old female • 6 prior lines of therapy: - FOLFOX - Capecitabine + bevacizumab - 5FU +
Slide 21: Significant Decreases in ctDNA Observed in Phase 2 MSS CRC Patients
21 Available blood plasma samples (baseline and on-treatment) were analyzed with an analytically validated next generation sequencing ctDNA assay (Guardant Infinity, a multi-omic assay), that identifies somatic alterations across >750 cancer-related genes and measuring thousands of differentially me
Slide 22: Initial Data Highlight Potential for Vilastobart in Combination
22 1. Includes 2 confirmed PRs (see Patient A and Patient B vignettes) and 1 unconfirmed PR (pending confirmation, see Patient C vignette). Initial Data Highlight Potential for Vilastobart (anti-CTLA-4) in Combination in MSS CRC and a Range of Tumor Types, Including “Cold” Tumors Historically Resist
Slide 23: XTX301 Tumor-Activated IL-12
23 XTX301 Tumor-Activated IL-12
Slide 24: The Compelling Potential of IL-12 as a Therapeutic Agent
24 The Compelling Potential of IL-12 as a Therapeutic Agent • IL-12 has significant potential as a potent I-O therapeutic agent in cold tumors • Poor tolerability has limited its clinical progress for decades • No currently approved IL-12 agents INFγ is a pleiotropic molecule with associated antipro
Slide 25: XTX301: Tumor-Activated IL-12
25 XTX301: Tumor-Activated IL-12 Inactive State 1. As of November 25, 2024. Treatment-related AEs most commonly consisted of flu-like symptoms, cytokine release syndrome, increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased blood cell counts. • Activated XTX301
Slide 26: XTX301 Advancing in Partnership with Gilead
26 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 total received to date ($30M cash upfront payment + $25M in total equity investments) Up to $592.5M additional contingent payments: •
Slide 27: XTX501 PD1/IL2 bispecific
27 XTX501 PD1/IL2 bispecific
Slide 28: XTX501 Has Potential to be Best-in-Class PD1/IL2 Bispecific
28 XTX501 Has Potential to be Best-in-Class PD1/IL2 Bispecific • Targeted delivery of IL-2 to PD1+ cells selectively enhances IL-2 signaling on tumor-reactive, stem-like T cells, endowing progeny T cells with enhanced effector function and fitness • XTX501 designed to optimize each component of the
Slide 29: XTX501: Tumor-Activated PD1/IL2 Bispecific
29 Inactive State NHP: non-human primate; VHH: variable heavy domain of heavy chain. XTX501: Tumor-Activated PD1/IL2 Bispecific • Full potency alpha-optimized IL-2 with affinity-tuned, VHH-based mask • Non-masked PD1 in Fc-silenced heterodimeric IgG1 backbone • XTX501 designed to direct IL-2 to PD1+
Slide 30: XTX501 Designed to Overcome Limitations of Non-Masked PD1/IL2 Bispecifics
30 Figure generated using BioRender.com. XTX501 is Designed to Overcome Limitations of Non-Masked PD1/IL2 Bispecifics Periphery Tumor
Slide 31: XTX501 Demonstrated Optimal PK and Tolerability Preclinically
31 Tumor-Activated Design of XTX501 Demonstrated Optimal PK and Tolerability Preclinically XTX501 exposure after a single 10, 3 or 1 mg/kg intravenous injection in non-tumor bearing C57BL/6-hFcRn mice. Non-masked PD1/IL2 exposure after a single equal molar dose of 9.25, 2.75 or 0.92 mg/kg intravenou
Slide 32: XTX501 Demonstrated Tumor-Specific Pharmacology
32 XTX501 Demonstrated Tumor-Specific Pharmacology with Peripheral Effects Limited to Increases in Antigen-Specific/Memory Cells Spleen XTX501 Treatment Demonstrated Robust Increases in Activated T Cell Populations in Tumor CD8 Effector Memory Granz B IFN γ TCF1 Antigen-specific 0 1 2 3 4 20 40 60 8
Slide 33: XTX501 Demonstrated Differentiated Pharmacology vs PD1 and PD1+IL-2
33 XTX501 Demonstrated Differentiated Pharmacology vs PD1 and Combination of PD1+IL-2 in Tumor Model, Suggesting Enhanced Anti-Tumor Immunity Preclinically XTX501 Increased Intra-Tumoral Cytotoxic and TCF1+ Stem-Like T Cells -100 -80 -60 -40 -20 0 20 40 60 80 100 500 1000 Vehicle XTX501 Fc-IL-2 + PD
Slide 34: XTX501 Demonstrated Favorable Tolerability in NHP
34 XTX501 Demonstrated Favorable Tolerability in NHP Female cynomolgus monkeys were given a single 30-minute intravenous infusion of XTX501 at 3, 10, and 30 mg/kg and samples were collected for PK and clinical pathology analysis. (A) PK analysis demonstrated dose-proportional exposure and linear eli
Slide 35: Tumor-Activated Cell Engager Programs
35 Tumor-Activated Cell Engager Programs
Slide 36: ATACR Format Designed to Optimize Therapeutic Index of T Cell Engagers
36 ATACR Format Designed to Optimize Therapeutic Index of T Cell Engagers by Maximizing Tumor Exposure and Minimizing Healthy Tissue Binding Figure generated using BioRender.com. “ATACR”: Advanced Tumor-Activated Cell EngageR Design Goals: • Potent tumor-selective T cell engagement with conditional
Slide 37: Tumor-Activated SEECR Molecules for T Cell Activation and Co-Stimulation
37 Xilio’s Tumor-Activated SEECR Molecules are Designed to Deliver Potent T Cell Activation and Co-Stimulation Specifically to Tumors “SEECR”: Selective Effector-Enhanced Cell EngageR Design Goals: • Potent tumor-selective T cell engagement and co-stimulation • Minimal peripheral activity and off-tu
Slide 38: Masking Technology Enabled Efficient Masking of CD3 Binding Domain
38 Xilio’s Masking Technology Enabled Efficient Masking of the CD3 Binding Domain of Cell Engagers Preclinically Left panel: Protease dependent CD3-binding demonstrated via TAA-TCEs bound to immobilized CD3 in an ELISA. Right panel: Protease-dependent tumor cell killing. Active TAA-TCEs led to killi
Slide 39: SEECR Format Drove Sustained, Serial Tumor Cell Killing
39 Human T cells were incubated over three consecutive rounds with indicated test articles and A431 cancer cells and percent tumor cell killing was assessed using a luminescence readout. SEECR Format Demonstrated Unique Ability to Drive Sustained, Serial Tumor Cell Killing Over Multiple Rounds of St
Slide 40: Prototype SEECR Molecules Exhibited Antibody-Like PK and Increased Survival
40 Prototype SEECR Molecules Exhibited Antibody-Like PK, Were Well-Tolerated and Increased Survival in Murine Models SEECR Featured Antibody-Like PK and Tolerability Comparable to Control SEECR Showed Significantly Enhanced Survival Compared to Standard TCE Pharmacokinetics (PK), tolerability, and a
Slide 41: Management Overview and Recent Financial Results
41 Management Overview and Recent Financial Results
Slide 42: Deep Expertise to Build a Transformational Immuno-Oncology Company
42 Deep Expertise to Build a Transformational Immuno-Oncology Company Experienced Leadership Team with Proven Track Record in Biotech and Pharma Developing Novel Therapies RENÉ RUSSO, PHARM.D. Chief Executive Officer and President, Director ULI BIALUCHA, PH.D. Chief Scientific Officer KATARINA LUPTA
Slide 43: Q3 2024 Financial Results
43 Q3 2024 Financial Results Anticipate Cash Runway Into Q3 2025* Balance Sheet September 30, 2024 December 31, 2023 (1) Cash and Cash Equivalents $61.3M $44.7M 1. Unaudited * After giving effect to remaining $8.2M equity investment by Gilead on December 18, 2024. Statement of Operations Three Month
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