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1 Xilio Therapeutics Corporate Update Call February 12, 2025
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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 to the timing and expectations related to the receipt of contingent milestones and payments; the success of Xilio’s collaborations and partnerships; the anticipated timing of milestones and the sufficiency and availability of cash to fund activities related thereto; development timelines for Xilio’s product candidates; the potential benefits of any of Xilio’s current or future product candidates; the potential for Xilio to leverage its research platform to develop bispecific and cell engager molecules; and Xilio’s strategy, goals and anticipated financial performance, milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “seek,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, general market conditions, risks and uncertainties related to ongoing and planned research and development activities, including initiating, conducting or completing preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned preclinical studies or clinical trials or the development of Xilio’s current or future product candidates; Xilio’s ability to obtain and maintain sufficient preclinical and clinical supply of current or future product candidates; Xilio’s advancement of multiple early-stage immune cell engager programs, including tumor-activated immune cell engagers and tumor-activated effector-enhanced immune cell engagers; initial, preliminary or interim preclinical or clinical data or results, which may not be replicated in or predictive of future preclinical or clinical data or results; Xilio’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; results from preclinical studies or clinical trials for Xilio’s product candidates, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of Xilio’s current or future clinical trials; Xilio’s ability to obtain, maintain and enforce patent and other intellectual property protection for current or future product candidates; Xilio’sability to obtain and maintain sufficient cash resources to fund its operations; the impact of international trade policies on Xilio’s business, including U.S. and China trade policies; Xilio’s ability to maintain its collaborations or partnerships with Roche, Gilead and AbbVie. These and other risks and uncertainties are described in greater detail in the sections entitled “Risk Factor Summary” and “Risk Factors” in Xilio’s filings with the U.S. Securities and Exchange Commission (SEC), including Xilio’s most recent Quarterly Report on Form 10-Q and any other filings that Xilio has made or may make with the SEC in the future. Any forward-looking statements contained in this presentation represent Xilio’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except asrequired by law, Xilio explicitly disclaims any obligation to update any forward-looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Xilio’s own internal estimates and research. While Xilio believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, Xiliohas not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of Xilio’s internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners. TECENTRIQ is a registered trademark of Genentech USA Inc., a member of the Roche Group. Forward-Looking Statements and Disclaimers
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3 Today’s Agenda René Russo, Pharm.D. Chief Executive Officer and President Uli Bialucha, Ph.D. Chief Scientific Officer Chris Frankenfield Chief Financial and Operating Officer Introduction René Russo, Pharm.D. Collaboration and Option Agreement with AbbVie Chris Frankenfield Masked T Cell Engager Programs Uli Bialucha, Ph.D. Concluding Remarks René Russo, Pharm.D. Q&A
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4 Introduction René Russo, Pharm.D. Chief Executive Officer and President
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5 Program Tumor Types Discovery IND-Enabling Phase 1 Phase 2 Phase 3 Collaborations and Partnerships Vilastobart (1) Masked anti-CTLA-4 Metastatic MSS CRC Co-funded clinical collaboration with Roche XTX301 (2) Masked IL-12 Advanced Solid Tumors Option to license XTX501 Masked PD-1/IL-2 Advanced Solid Tumors PSMA Masked T cell engager Prostate CLDN18.2 Masked T cell engager Gastric, Pancreatic, Esophageal, Lung STEAP1 Masked T cell engager Prostate, Lung Colorectal Undisclosed Masked T cell engagers (3) Undisclosed Collaboration and option 1. Evaluating vilastobart (XTX101) in combination with atezolizumab (Tecentriq®) in patients with metastatic MSS CRC under co-funded clinical collaboration with Roche. 2. Evaluating XTX301 in Phase 1 monotherapy dose escalation and dose expansion for the treatment of advanced solid tumors under exclusive global partnership with Gilead. 3. Advancing an initial masked T cell engager program in collaboration with AbbVie, and AbbVie has the right to nominate up to two additional masked T cell engager programs. CRC: colorectal cancer; MSS: microsatellite stable Advancing Pipeline of Tumor-Activated Immunotherapies, Including Masked T Cell Engagers, Leveraging Clinically-Validated Platform Technology
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6 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 toxicity limitations • TCEs simultaneously bind to CD3 on T cells and tumor-associated antigens (TAAs) on tumor cells forming a synapse that induces T cell-mediated killing of tumor cells • Selective activation in the tumor via masking has been shown clinically to meaningfully improve the therapeutic index • Masking has the potential to enable opportunities for many TAA targets previously thought to be undruggable • Adding co-stimulatory signaling can further enhance sustained T cell-mediated killing
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7 Illustrations generated using Biorender.com ATACR: advanced tumor-activated cell engager; SEECR: selective effector-enhanced cell engager 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 differentiation + speed and simplicity “SEECR” Format (masked cell engager + co-stimulatory domain) Builds on the ATACR format and adds a co-stimulatory domain designed to further enhance potency and durability of T cell response Optimized for differentiation + enhanced activity Added in SEECR format only
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8 Collaboration, License and Option Agreement with AbbVie Chris Frankenfield Chief Financial and Operating Officer
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9 Initial programs for tumor-activated immunotherapies (1) 1. Masked T cell engager program: Xilio responsible for advancing through opt-in by AbbVie prior to IND submission 2. Masked antibody-based program: Xilio responsible for advancing through early preclinical development 1. Subject to the terms of the agreement, AbbVie has the right to nominate up to two additional masked T cell engager programs (option programs). IND: investigational new drug application Collaboration, License and Option Agreement with AbbVie to Develop Novel Tumor- Activated Immunotherapies, Including Masked T Cell Engagers $52.0M total upfront payments ($42M cash upfront payment + $10M equity investment) Up to ~$2.1B total contingent payments: • option-related fees for masked T cell engager programs • development, regulatory and sales-based milestones across all programs Tiered royalties: mid to high single-digits
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10 Masked T Cell Engager Programs Uli Bialucha, Ph.D. Chief Scientific Officer
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11 Illustrations generated using Biorender.com ATACR: advanced tumor-activated cell engager; SEECR: selective effector-enhanced cell engager Masked T Cell Engagers are Designed to Optimize Therapeutic Index by Maximizing Tumor Exposure and Minimizing Peripheral Activity and Off-Tumor Cytotoxicity Added in SEECR format only “ATACR” Format (masked cell engager) Designed to release a potent, short half-life T cell engager upon tumor-selective activation Optimized for differentiation + speed and simplicity “SEECR” Format (masked cell engager + co-stimulatory domain) Builds on the ATACR format and adds a co-stimulatory domain designed to further enhance potency and durability of T cell response Optimized for differentiation + enhanced activity
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12 Xilio’s Masked T Cell Engagers Incorporate Our Validated Masking Approach, Conditional Half-Life Optimization +/- Co-Stimulation • Potential best-in-class anti-tumor activity and masking profile • Designed with CD3 masking to release active molecule with short half-life • Protease-dependent activity validated in vitro and in vivo Target: PSMA (ATACR Format) 1. Milestones starting in Q2 2026 are subject to raising sufficient additional capital. PK: pharmacokinetics Q4 2025: nominate development candidate Q2 2027: IND submission Q3 2025: nominate development candidate Q1 2027: IND submission Target: CLDN18.2 (ATACR Format) • First-in-class potential as masked T cell engager for CLDN18.2 • Design incorporates preclinically validated ATACR platform components and high-affinity CLDN18.2 binding domain 1H 2026: nominate development candidate 2H 2027: IND submission Target: STEAP1 (SEECR Format) • First-in-class potential as masked T cell engager for STEAP1 • Preclinical studies demonstrated enhanced activity with antibody-like PK and favorable tolerability in vivo • Preclinical validation of multiple co- stimulatory domains Prostate cancer Gastric, esophageal, pancreatic and lung cancers Prostate, colorectal and lung cancers Anticipated Milestones: (1) Tumor Types:
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13 ATACR Format for PSMA Demonstrated Potential for Improvement in Therapeutic Index In Vitro and Anti-Tumor Activity with Favorable Tolerability In Vivo Left panel: Primary human T cells were co-cultured with LNCAP prostate cancer cells. Tumor cell killing in response to indicated titrations of test articles was evaluated using a luciferase- based cell viability readout. Right panel: A375 tumor cells were inoculated in NSG mice engrafted with human T cells. Anti-tumor activity and tolerability by body weight change 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 < 0.001) # JANX007 analogue generated in-house ATACR Format for PSMA Elicited Significant Protease- Dependent Anti-Tumor Activity In Vivo • ATACR Format for PSMA Demonstrated Potential for Meaningful Improvement in Therapeutic Index In Vitro T Cell Activation 0 5 10 15 20 0 500 1000 1500 2000 2500 Days post-treatment initiation Tumor volume (mm³ + SEM) Vehicle TAA-ATACR Non-activatable Control TAA-ATACR *** 0 5 10 15 20 -20 -10 0 10 20 Days post-treatment initiation Body weight % change ( + SEM) Vehicle TAA-ATACR Non-activatable Control TAA-ATACR Anti-Tumor Activity Tolerability 0.01 1 100 10000 -20 0 20 40 60 80 100 Concentration (pM) %Normalized Killing PSMA-ATACR PSMA-ATACR + MMP JANX007# (PSMA) + MMP JANX007# (PSMA)
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14 SEECR Format Demonstrated Unique Ability to Drive Sustained, Serial Tumor Cell Killing Over Multiple Rounds of Stimulation in Preclinical Model 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. Addition of co-stimulatory signaling resulted in sustained activity enabling more durable T cell responses Longitudinal Target Cell Killing 1 2 3 4 5 0 50 100 % Target Cell Killing 1st Round 2nd Round 3rd Round 4th Round 5th Round Control TCE Non-masked TCE SEECR
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15 Prototype SEECR Molecules Demonstrated Differentiated Activity Compared to Unmasked T Cell Engagers In Vivo Left and middle panel: Immunophenotyping (flow cytometry) of tumor-infiltrating T cells from A375 tumor model treated with indicated test articles. Right panel: HCC70 tumor cells were inoculated in NSG mice engrafted with human T cells. Anti-tumor activity of indicated test articles was evaluated over time. Two-way ANOVA followed by Dunnett's multiple comparisons test was used for statistical analysis (*P < 0.05; **P < 0.005; ***P < 0.001) Control TCE Non-masked TCE SEECR 0 5 10 15 20 25 Fold-change CD3 T cells vs. control TCE (live) ✱ Control TCE Non-masked TCE SEECR 0 20 40 60 80 100 Percent Ki67+ CD8 T cells (CD3+) ✱ SEECR Enabled Superior Anti-Tumor Activity in Multiple Mouse Models 0 10 20 30 0 400 800 1200 Days post-engraftment Tumor volume (mm³ + SEM) TGI%=58 TGI%=110 ** **** *** Breast Cancer Model SEECR Drove Enhanced Tumor T Cell Infiltration and Proliferation vs Non-Masked TCE Vehicle Control TCE Non-masked TCE SEECR
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16 Advancing Pipeline of Differentiated Masked T Cell Engagers 1. Milestones starting in Q2 2026 are subject to raising sufficient additional capital. Anticipated Milestones (1) Program Tumor Types Masked T Cell Engager Format Lead Discovery Lead Optimization Candidate Selection IND Submission PSMA Prostate ATACR Q3 2025 Q1 2027 CLDN18.2 Gastric, Pancreatic, Esophageal, Lung ATACR Q4 2025 Q2 2027 STEAP1 Prostate, Lung Colorectal SEECR 1H 2026 2H 2027 Advancing additional masked T cell engager programs in collaboration with
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17 Concluding Remarks René Russo, Pharm.D. Chief Executive Officer and President
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18 Anticipated Milestones Milestone Anticipated Timing (1) Vilastobart (masked anti-CTLA-4) Report additional Phase 2 data in combination with atezolizumab in MSS CRC Mid 2025 XTX301 (masked IL-12) Development milestone ($17.5M) prior to potential Phase 1/2 opt-in Undisclosed XTX501 (masked PD-1/IL-2) IND submission Mid 2026 PSMA Program (masked T cell engager) Nominate development candidate Q3 2025 IND submission Q1 2027 CLDN18.2 Program (masked T cell engager) Nominate development candidate Q4 2025 IND submission Q2 2027 STEAP1 Program (masked T cell engager) Nominate development candidate 1H 2026 IND submission 2H 2027 1. Milestones starting in Q2 2026 are subject to raising sufficient additional capital.
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19 Q&A