Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Investor Presentation (March 2026)
36 slides from Xilio Therapeutics's investor presentation, Mar 9, 2026
Slide 1: Unlocking the Potential of Immuno-Oncology Therapies
Unlocking the Potential of Immuno-Oncology Therapies March 9, 2026 © 2026 Xilio Therapeutics, Inc. ®
Slide 2: Forward-looking statements
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 timelines and anticipated milestones for Xilio’s pr
Slide 3: Leveraging our clinically-validated masking technology to develop tumor-selective I-O therapies
Leveraging our clinically-validated masking technology to develop tumor-selective I-O therapies designed to unlock the potential for durable efficacy by focusing anti-tumor activity within the tumor microenvironment without severe side effects associated with systemically active I-O agents I-O: immu
Slide 4: Xilio's Clinically-Validated Masking Technology and Capabilities
Xilio’s Clinically-Validated Masking Technology and Capabilities are Being Applied Across Diverse Mechanisms and Architectures for I-O Therapies Xilio’s masked molecules are activated in the tumor by matrix metalloproteases (MMP) and other tumor-specific proteases Proprietary masking libraries and c
Slide 5: Pipeline programs and anticipated milestones
Program Tumor Types Discovery IND Enabling Phase 1 Phase 2 Anticipated Milestones Wholly-Owned Programs XTX501 Bispecific PD-1 / masked IL-2 NSCLC and other solid tumors IND submission: mid 2026 Initial Phase 1 data: 2H 2027 (1) PSMA+STEAP1 Multi-specific, masked T cell engager with co-stimulation (
Slide 6: Strong Financial Position and Proven Capabilities to Advance Pipeline
Strong Financial Position and Proven Capabilities to Advance Pipeline of Potential Best-in-Class Masked I-O Therapies Strong financial position through AbbVie, Gilead and Roche collaborations and equity financings $137.5M in estimated cash and cash equivalents as of December 31, 2025 (1) $40M in gro
Slide 7: XTX501 Bispecific PD-1 / masked IL-2
XTX501 Bispecific PD-1 / masked IL-2
Slide 8: XTX501: Bispecific PD-1 / Masked IL-2 Designed to Enable High Potency IL-2
Targeted delivery of IL-2 to PD-1+ cells selectively expands tumor-specific CD8+ cells to increase tumor cell killing efficiency without activating peripheral T cells that drive toxicity Incorporates a high potency IL-2 variant affinity tuned with optimal receptor binding profile for IL-2 alpha / be
Slide 9: XTX501 Exhibited a Potential Best-in-Class Profile Based on Preclinical Data
XTX501 Exhibited a Potential Best-in-Class Profile Based on Preclinical Data XTX501 and XTX500 (1) Bind PD-1 With Higher Affinity Than Other PD-1 Bispecifics XTX501 was Effectively Masked and XTX500 (Unmasked XTX501) was Most Potent Activator of T Cells XTX501 Demonstrated Meaningfully Differentiate
Slide 10: XTX501 Demonstrated Antibody-Like PK and Favorable Tolerability Preclinically
XTX501 Demonstrated Antibody-Like PK and Favorable 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 PD-1/IL-2 exposure after a single equal molar dose of 9.25, 2.75 or 0.92 mg/kg intravenous injection
Slide 11: XTX501 Demonstrated Favorable Tolerability in NHP
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. Left panel: PK analysis demonstrated dose-proportional exposure and linea
Slide 12: XTX501 Demonstrated Differentiated Preclinical Pharmacology
XTX501 Demonstrated Differentiated Preclinical Pharmacology Compared to PD-1 and Combination of PD-1 + IL-2, Suggesting Enhanced Anti-Tumor Immunity XTX501 Demonstrated Increased Intra-Tumoral Cytotoxic and TCF1+ Stem-Like T Cells Vehicle PD1+Fc-IL-2 XTX501 Vehicle PD1+Fc-IL-2 XTX501 Left panel: Fem
Slide 13: XTX501 Has Potential for Increased Therapeutic Index
1. Clinical data reported by Innovent Biologics, Inc. for IBI363, a PD-1/IL-2 α-bias bispecific antibody fusion protein (non-masked), in immunotherapy-resistant NSCLC and cold tumors such as acral, mucosal melanoma and MSS CRC. MSS CRC: microsatellite stable colorectal cancer XTX501 Has Potential fo
Slide 14: Masked T Cell Engagers
Masked T Cell Engagers THERAPEUTICS*
Slide 15: Xilio's Modular Architecture Enables Optimal T Cell Engager Designs
SEECR: selective effector-enhanced cell engager (masked T cell engager with co-stimulation); TAA: tumor-associated antigen Xilio’s Modular Architecture Enables Optimal T Cell Engager Designs Tailored to Maximize Tumor Exposure While Minimizing T Cell Engagement in Healthy Tissue Highly effective CD3
Slide 16: PSMA+STEAP1 Dual-TAA targeted, masked T cell engager with co-stimulation (SEECR)
PSMA+STEAP1 Dual-TAA targeted, masked T cell engager with co-stimulation (SEECR)
Slide 17: PSMA+STEAP1 (SEECR): Best-in-Class Potential for Prostate Cancer
By targeting PSMA+STEAP1, designed to avoid resistance due to antigen escape and sub-clonal selection Dual-TAA targeting designed to address heterogeneity of PSMA and STEAP1 expression across prostate tumors Significant opportunity, with PSMA and/or STEAP1 expressed in ~95% of metastatic CRPC Co-sti
Slide 18: Dual-TAA Targeting Supported by Heterogeneous PSMA and STEAP1 Expression
PSMA and STEAP1 are validated T cell engager targets in prostate cancer However, a significant proportion of advanced stage prostate tumors display heterogenous PSMA or STEAP1 expression Heterogenous expression patterns could allow for resistance to T cell engagers targeting a single antigen Dual-TA
Slide 19: PSMA+STEAP1 (SEECR): Target-Dependent Activity and Effective Masking
Left panel: Isogenic cells lines engineered to either express PSMA or STEAP1 (or remain target-negative) were co-cultured with primary human T cells. Target cell killing in response to indicated titrations of test articles was evaluated using a luciferase-based cell viability readout. Right panel: T
Slide 20: PSMA+STEAP1 (SEECR) Robust Anti-Tumor Activity with Favorable Tolerability and PK
Left panel: C4-2 prostate cancer tumor cells were inoculated in NSG mice engrafted with human T cells. Anti-tumor activity in response to indicated test articles was evaluated over time. Two-way ANOVA followed by Dunnett's multiple comparisons test was used for statistical analysis (**P < 0.01). Rig
Slide 21: PSMA+STEAP1 (SEECR) additional preclinical data
Left panel: Human T cells were incubated over five consecutive rounds with indicated test articles and A431 cancer cells and percent tumor cell killing was assessed using a luminescence readout. Middle panel: C4-2 prostate cancer tumor cells were inoculated in NSG mice engrafted with human T cells.
Slide 22: CLDN18.2 Masked T cell engager
CLDN18.2 Masked T cell engager
Slide 23: CLDN18.2: Potential First-in-Class Masked T Cell Engager for GI Cancers
Xilio design uses high affinity CLDN18.2 isoform- selective binder CLDN18.2 is a validated target expressed across gastrointestinal cancers (gastric, pancreatic, esophageal) and lung cancer Potential for significantly expanded therapeutic index with masking – non-masked T cell engagers targeting CLD
Slide 24: CLDN18.2 (ATACR) Protease-Dependent CD3 Binding and Tumor Cell Killing
Left panel: CLDN18.2 ATACR molecule binding to recombinant human CD3 delta/epsilon either in intact form or pre-activated using recombinant MMP. Analysis performed using ELISA. Right panel top: Human T cell/cancer cell line co-culture assay evaluating tumor cell killing by either intact CLDN18.2 ATA
Slide 25: CLDN18.2 (ATACR) Robust, Dose-Dependent Anti-Tumor Activity
Left panel: GSU cells were inoculated in NSG mice engrafted with human T cells. Anti-tumor activity change in response to indicated test articles was evaluated over time. Two-way ANOVA followed by Dunnet’s multiple comparisons test was used for statistical analysis: p<0.05(*). Right panel: OE19 cell
Slide 26: Positive Exposure-Based Therapeutic Index in Preclinical Studies
Well-tolerated in NHP at 1 mg/kg No evidence of CRS Liver function markers within reference range Antibody-like PK of intact molecule No evidence of peripheral cleavage Percent cleaved molecule below LLOQ Integration of Murine Activity and NHP Tolerability Data for CLDN18.2 (ATACR) Indicative of Fav
Slide 27: Efarindodekin Alfa Masked IL-12
Efarindodekin Alfa Masked IL-12
Slide 28: Efarindodekin Alfa Designed to Overcome Limitations of Systemic IL-12
Efarindodekin alfa: masked IL-12 Efarindodekin Alfa Designed to Overcome Limitations of Systemic Recombinant Human IL-12 HNSCC: head and neck squamous cell carcinoma; INFγ: interferon gamma; NK: natural killer; TNBC: triple-negative breast cancer Half-Life Extension Domain Cleavage Site Effector Dom
Slide 29: Efarindodekin Alfa Promising Monotherapy Clinical Efficacy in Phase 1
Responses represent decrease in sum of diameters by RECISTv1.1 * Patient discontinued treatment due to Grade 3 immune system activation AE that subsequently resolved. There was no evidence of further tumor growth through the 90-day follow-up, suggesting duration of response of at least 2 months. HPV
Slide 30: Advancing Efarindodekin Alfa in Partnership with Gilead
Delivery of Phase 1/2 option data package to Gilead anticipated in 1H 2027 Xilio will receive a $75M option fee if Gilead exercises its option to the IL-12 program Data cutoff date: September 2, 2025. All doses and schedules (n=62) and RP2D (n=13). * 1 confirmed PR, 1 unconfirmed PR AE: adverse even
Slide 31: Vilastobart Masked, Fc-enhanced anti-CTLA-4
Vilastobart Masked, Fc-enhanced anti-CTLA-4
Slide 32: Vilastobart is a Next Generation anti-CTLA-4
1. Ipilimumab analog used for preclinical studies. ADCC: antibody-dependent cell-mediated cytotoxicity Vilastobart is a Next Generation anti-CTLA-4 With Meaningful Clinical Efficacy and Differentiated Safety Supporting a Significant Opportunity in MSS mCRC and Other Tumors ADCC-enhanced Fc Masking D
Slide 33: Vilastobart in Combination with Atezolizumab in MSS mCRC
Actively seeking a partner to advance development – well-suited for combinations, including PD-(L)1, PD-1/IL-2, PD1-VEGF and/or ADCs Data cutoff date: May 12, 2025. ~55% of non-MSI-H CRC patients were plasma TMB high (>10 mut/Mb) based on an analysis of the GuardantINFORM real-world clinical-genomic
Slide 34: Corporate Summary
Corporate Summary THERAPEUTICS*
Slide 35: Strong Financial Position and Proven Capabilities to Advance Pipeline
Strong Financial Position and Proven Capabilities to Advance Pipeline of Potential Best-in-Class Masked I-O Therapies Strong financial position through AbbVie, Gilead and Roche collaborations and equity financings $137.5M in estimated cash and cash equivalents as of December 31, 2025 (1) $40M in gro
Slide 36: Deep Expertise to Build a Transformational Immuno-Oncology Company
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 Luptakov
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