Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Investor Presentation (December 2024)
42 slides from Xilio Therapeutics's investor presentation, Dec 19, 2024
Slide 1: Unleashing the Potential of Immuno-Oncology Therapies
1 Unleashing the Potential of Immuno-Oncology Therapies December 19, 2024 © 2024 Xilio Therapeutics, Inc.
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 in Solid Tumors
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 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 Clinical and Preclinical Tumor-Activated Molecules
6 Program Tumor Types Mechanism of Action Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Partnerships Vilastobart (XTX101) in combination with atezolizumab (1) Metastatic MSS CRC anti-CTLA-4 + PD-L1 Clinical collaboration with Roche (with co-funding) XTX301 (2) Advanced Solid Tumors IL-12 Exclusive
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, High Affinity Binding, Fc-Enhanced Anti-CTLA-4
8 Inactive State * Ipilimumab analog used for preclinical studies ADCC: antibody-dependent cell-mediated cytotoxicity; NSCLC, non-small lung cancer; PR: partial response; Treg: regulatory T cells Vilastobart: Tumor-Activated, High Affinity Binding, Fc-Enhanced Anti-CTLA-4 Masking Peptide Variable Do
Slide 9: Vilastobart Advancing in Phase 2 Proof-of-Concept Trial for MSS CRC
9 Q3W: once every three weeks; Q6W: once every six weeks Vilastobart (anti-CTLA-4) Advancing in Phase 2 Proof-of-Concept Trial for MSS CRC in Co-Funded Clinical Collaboration with Roche Metastatic MSS CRC patients with and without liver metastases vilastobart at 100 mg Q6W + atezolizumab at 1200 mg
Slide 10: CRC Incidence Increasing; Most Stage 4 MSS CRC Patients Have Liver Metastases
10 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: Majority of Patients with Stage 4 MSS CRC Have Liver Metastases 10 ~90,000 new
Slide 11: I-O Therapies Have Shown Little to No Efficacy in MSS CRC
11 • 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 12: Vilastobart Phase 1C Combination Dose Escalation Data
12 Vilastobart (anti-CTLA-4) Phase 1C Combination Dose Escalation Data Vilastobart + Atezolizumab
Slide 13: Vilastobart Phase 2 Trial in Co-Funded Collaboration with Roche
13 Vilastobart (anti-CTLA-4) Advancing in Phase 2 Proof-of-Concept Trial for MSS CRC in Co-Funded Clinical Collaboration with Roche Currently enrolling Phase 2 Combination Proof-of-Concept Advanced solid tumors vilastobart at 75, 100 and 150 mg Q6W + atezolizumab at 1200 mg Q3W Metastatic MSS CRC pa
Slide 14: Combination Generally Well-Tolerated with Minimal irAEs
14 Data cutoff date: October 7, 2024 1. Of the 10 patients with infusion related reactions, 4 experienced reactions related to vilastobart, 3 experienced reactions related to atezolizumab and 3 experienced reactions related to the combination. 2. Reflects discontinuation of both vilastobart and atez
Slide 15: Combination Demonstrated Anti-Tumor Activity in Cold Tumors
15 Data cutoff date: October 7, 2024. n=12 response-evaluable patients. 1. PR (unconfirmed), patient withdrew consent prior to confirmatory scan. 2. PR confirmed after the data cutoff date. Combination of Vilastobart (anti-CTLA-4) and Atezolizumab Demonstrated Anti-Tumor Activity in Cold Tumors, Inc
Slide 16: Sustained Tumor Reduction in MSS CRC Patient with Liver Disease
16 Combination of Vilastobart (anti-CTLA-4) and Atezolizumab Demonstrated Anti-Tumor Activity in Cold Tumors, Including a Sustained Tumor Reduction in a MSS CRC Patient with Metastatic Liver Disease Data cutoff date: October 7, 2024. n=12 response-evaluable patients. BOR: best overall response MSS C
Slide 17: Confirmed PR in MSS CRC Patient
17 Data cutoff date: October 7, 2024 PR confirmed at 36 weeks, after the data cutoff. Confirmed PR in MSS CRC Patient, Including Full Resolution of Metastatic Liver Lesion MSS CRC and Liver Metastasis • 69 year-old female • 5 prior lines of therapy: - FOLFOX-Avastin - FOLFIRI-Avastin - Cetuximab - L
Slide 18: Confirmed PR with Full Resolution of Liver Lesion
18 Confirmed PR in MSS CRC Patient, Including Full Resolution of Metastatic Liver Lesion Target Liver Lesion – Baseline Target Liver Lesion – After 9 Weeks No visible lesion 15.6 mm 6.8 mm 5.8 mm Target Liver Lesion – After 18 Weeks Target Liver Lesion – After 27 and After 36 Weeks Data cutoff date:
Slide 19: PR in Patient with Ampullary Carcinoma After Single Cycle
19 Data cutoff date: October 7, 2024 * Patient withdrew consent prior to confirmatory scan. C1D1: cycle 1, day 1 PR (Unconfirmed)* in Patient with Ampullary Carcinoma (Cold Tumor) After Single Cycle of Combination of Vilastobart (anti-CTLA-4) and Atezolizumab • 76 year-old male • 2 prior lines of th
Slide 20: Unconfirmed PR in Ampullary Carcinoma Patient
20 PR (Unconfirmed)* in Patient with Ampullary Carcinoma (Cold Tumor) After Single Cycle of Combination of Vilastobart (anti-CTLA-4) and Atezolizumab Data cutoff date: October 7, 2024. Patient administered vilastobart (150 mg Q6W) and atezolizumab (1200 mg Q3W). 20 * PR (unconfirmed) at week 8 (32%
Slide 21: Encouraging Initial Evidence; Phase 2 Data Planned at ASCO GI January 2025
21 ❑ Plan to report initial Phase 2 data (n = ≥20 total) in MSS CRC at ASCO GI in January 2025 ❑ Plan to report additional Phase 2 data (n = ~40 total) in MSS CRC in mid 2025 Data cutoff date: October 7, 2024 PR confirmed after data cutoff date. Encouraging Initial Evidence of Combination Activity i
Slide 22: XTX301 Tumor-Activated IL-12
22 XTX301 Tumor -Activated IL -12
Slide 23: The Compelling Potential of IL-12 as a Therapeutic Agent
23 • 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 antiproliferative, pro-apoptotic and antitumor mechanisms. Th1-t
Slide 24: XTX301: Tumor-Activated IL-12
24 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. IFNɣ: interferon gamma XTX301: Tumor-Activated I
Slide 25: XTX301 Advancing in Partnership with Gilead
25 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 26: XTX501 PD1/IL2 Bispecific
26 XTX501 PD1/IL2 bispecific
Slide 27: XTX501 Has Potential to be Best-in-Class PD1/IL2 Bispecific
27 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 28: XTX501: Tumor-Activated PD1/IL2 Bispecific
28 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 29: XTX501 Designed to Overcome Limitations of Non-Masked PD1/IL2 Bispecifics
29 Figure generated using BioRender.com. XTX501 is Designed to Overcome Limitations of Non-Masked PD1/IL2 Bispecifics Periphery Tumor
Slide 30: Tumor-Activated Design Enabled Optimal PK and Tolerability
30 XTX501 exposure after a single 10, 3 or 1 mg/kg intravenous (i.v) 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 intravenous (i.v) injection in non-tumor bearing C57BL/6-hFcRn mice. Body weight data are di
Slide 31: XTX501 Demonstrated Tumor-Specific Pharmacology
31 XTX501 Demonstrated Tumor-Specific Pharmacology with Peripheral Effects Limited to Increases in Antigen-Specific/Memory Cells CD8 Effector Memory Granz B IFNγ TCF1 Antigen- specific 0 1 2 3 4 20 40 60 80 100 Fold change Over Vehicle Vehicle XTX501 Spleen XTX501 Treatment Induced Robust Increases
Slide 32: XTX501 Differentiated Pharmacology vs PD1 and PD1+Fc-IL-2 Combination
32 XTX501 Increased Intra-Tumoral Cytotoxic and TCF1+ Stem-Like T Cells XTX501 Demonstrated Differentiated Pharmacology vs PD1 and PD1+Fc-IL-2 Combination in MB49 Mouse Tumor Model, Indicating Enhanced Anti-Tumor Immunity -100 -80 -60 -40 -20 0 20 40 60 80 100 500 1000 Tumor Volume Change from Basel
Slide 33: XTX501 Demonstrated Favorable Tolerability in NHP
33 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 elimination across all doses tested. (B) Albumin rema
Slide 34: Tumor-Activated Cell Engager Programs
34 Tumor-Activated Cell Engager Programs
Slide 35: ATACR Format Designed to Optimize Therapeutic Index of T Cell Engagers
35 Illustrations generated using Biorender.com ATACR Format Designed to Optimize Therapeutic Index of T Cell Engagers by Maximizing Tumor Exposure and Minimizing Healthy Tissue Binding “ATACR”: Advanced Tumor-Activated Cell EngageR Design Goals: • Potent tumor-selective T cell engagement with condit
Slide 36: Tumor-Activated SEECR Molecules Deliver T Cell Activation and Co-Stimulation
36 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 37: Masking Technology Enabled Efficient Masking of CD3 Binding Domain
37 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 killing in co-culture assay. A375 tumor cells were cultured overnight before addition of expanded T cells at a 5:1
Slide 38: SEECR Drove Sustained, Serial Tumor Cell Killing
38 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 Molecule Demonstrated Unique Ability to Drive Sustained, Serial Tumor Cell Killing Over Multiple Rounds of
Slide 39: SEECR Antibody-Like PK and Enhanced Activity and Survival
39 SEECR Featured Antibody-Like PK and Tolerability Comparable to Control SEECR Showed Significantly Enhanced Activity and Survival Compared to Standard TCE PK, tolerability, and anti-tumor activity of SEECR-T molecules were evaluated in the human A375 melanoma model in NSG mice engrafted with human
Slide 40: Management Overview and Recent Financial Results
40 Management Overview and Recent Financial Results
Slide 41: Deep Expertise to Build a Transformational Immuno-Oncology Company
41 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 42: Q3 2024 Financial Results
42 Q3 2024 Financial Results Anticipate Cash Runway Into Q3 2025* Balance Sheet September 30, 2024 (1) December 31, 2023 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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