Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Investor Presentation (January 2023)
39 slides from Xilio Therapeutics's investor presentation, Jan 9, 2023
Slide 1: Unleashing the Potential of Immuno-Oncology Therapies
1 Unleashing the Potential of Immuno - Oncology Therapies January 9, 2023 © 2023 Xilio Therapeutics, Inc.
Slide 2: Forward-Looking Statements
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: the initiation of patient enr
Slide 3: Clinical-Stage Company Positioned for Multiple Anticipated Milestones in 2023
3 Xilio is a Clinical - Stage Company, Well - Positioned for Multiple Anticipated Milestones Across 3 Clinical Programs in 2023 * Patient dosing and evaluation in Phase 1 monotherapy dose - escalation cohort is ongoing. Plan to explore opportunities for str ategic collaborations to advance XTX101 an
Slide 4: The Promise and Pitfalls of Immuno-Oncology Therapy
4 The Promise and Pitfalls of Immuno - Oncology Therapy • Immuno - oncology (IO) therapies have transformed the treatment landscape and long - term outlook for some patients with advanced cancer - IO treatments are primarily available for “hot” tumors, while “warm” and “cold” tumors continue to make
Slide 5: Xilio believes the next revolution in IO cancer therapies
5 Xilio ( ex - il - ee - oh) believes the next revolution in IO cancer therapies will trick tumors into activating their own treatments , while simultaneously sparing healthy tissues and cells We are here to pursue that promise for patients 2016 XLO ~100 3 Founded NASDAQ Employees Clinical Stage Pro
Slide 6: Pioneering Tumor-Activated Immuno-Oncology Therapies
6 Pioneering Tumor - Activated Immuno - Oncology Therapies to Pursue Positive Outcomes for More Patients Mission Design and deliver tumor - activated immuno - oncology therapies that provide effective, tolerable and durable therapeutic options for patients with solid tumors Vision We envision a futu
Slide 7: Leveraging Our Deep Expertise to Build a Transformational IO Company
7 Leveraging Our Deep Expertise to Build a Transformational Immuno - Oncology Company • Intentionally built team with significant breadth and depth of biotech and big pharma experience including cytokines such as IL - 12 • Team has collectively contributed to: - >15 IND applications - >25 NDAs, sNDA
Slide 8: Xilio's Tumor-Activated Precision Immuno-Oncology
8 Xilio’s Tumor - Activated Precision Immuno - Oncology • We are passionate about harnessing and focusing the power of the immune system to treat cancer • We have developed a novel approach designed to outsmart tumors by using the tumor’s growth activities against itself - Tumor proteases activate a
Slide 9: Building a Transformative Immuno-Oncology Pipeline
9 Building a Transformative Immuno - Oncology Pipeline 1. Plan to initially evaluate XTX202 as a monotherapy and as a combination therapy for the treatment of renal cell carcinoma (RC C) and melanoma prior to potential expansion into additional cancer indications. 2. Plan to initially evaluate XTX30
Slide 10: Xilio Designed, Tumor Activated
10 Xilio Designed, Tumor Activated Seeking to Develop a Transformational IO Approach
Slide 11: Tumor-Activated Design Components – XTX202 (IL-2)
11 Xilio’s Tumor - Activated Design Components – XTX202 (IL - 2) Inactive State Cleavage Site Half - Life Extension Domain Effector Domain Masking Domain Active State Half - Life Extension Domain Effector Domain MMP activation MMP: matrix metalloproteases
Slide 12: Molecules are Activated by Dysregulated Tumor Proteases (MMPs)
12 Xilio’s Molecules are Activated by Dysregulated Tumor Proteases (MMPs) Xilio’s optimized substrate sequences enable efficient activation of the molecule by MMPs Xilio molecules are readily activated by human tumors ex vivo Xilio molecules demonstrated tumor - specific activation in vivo In vitro
Slide 13: First Demonstration of Clinical Platform Validation in Patients
13 First Demonstration of Clinical Platform Validation and Tumor - Selective Activation in Patients Patient Details (n=2) XTX202 treated tumors featured increased stromal TIL and robust increases in CD8+ T cells compared to pre - treatment XTX202 treatment resulted in minimal pharmacodynamic changes
Slide 14: First Demonstration of Clinical Platform Validation in Patients
14 First Demonstration of Clinical Platform Validation and Tumor - Selective Activation in Patients Patients had an optional on - treatment tumor biopsy and were the only two patients treated with XTX202 for whom a tumor biopsy an alysis was available as of January 9, 2023. H&E: hematoxylin - eosin;
Slide 15: Robust Increases in CD8+ T Cells Observed in Patient Tumors
15 Patient #2: RCC patient treated with XTX202 at 0.53 mg/kg Q3W (dose level 3) Robust Increases in CD8+ T Cells Observed in Patient Tumors Following XTX202 Treatment Patient #1: Melanoma patient treated with XTX202 at 0.38 mg/kg Q3W (dose level 2) 0 2 4 6 8 0 2 4 6 8 Relative fold change in CD8+ T
Slide 16: Executing on Our Vision to Deliver Tumor-Activated Therapies
16 Executing on Our Vision to Deliver Tumor - Activated Immuno - Oncology Therapies Created Through Our Unique and Efficient Design Process Xilio is positioned to demonstrate clinical platform validation in 2023 NHP: non - human primate. ✓ Complete Validated activation in vitro across multiple model
Slide 17: XTX202 Tumor-Activated IL-2
17 XTX202 Tumor - Activated IL - 2
Slide 18: XTX202 (IL-2) Phase 1/2 Trial Design
18 XTX202 (IL - 2) Phase 1/2 Trial Design Provides Efficient Path to Potential Monotherapy Proof - of - Concept • Dosing patients at 1 mg/kg dose level, the target dose range for XTX202 • No signs of VLS or decreases in albumin (an early sign of VLS) observed • Preliminary analyses indicated evidenc
Slide 19: In Vivo Activity of XTX202 in Combination with Anti-PD1
19 Enhancement of In Vivo Activity and Evidence of Memory Response for XTX202 (IL - 2) in Combination with Anti - PD1 Anti - tumor activity of XTX202 as a single agent and in combination with anti - mPD - 1 was evaluated in hFcRn Tg32 transgenic mice b earing the murine MB49 bladder carcinoma model.
Slide 20: Multiple Combination Opportunities Enabled by XTX202 (IL-2)
20 Multiple Combination Opportunities Enabled by XTX202 (IL - 2) Properties: Tumor - Activated, Well - Tolerated Preclinically, Clinically - Validated Target 1. Xilio data presented at SITC 2022. 2. Gola et al., Haematologica 2003. 3. Wigginton et al., J Natl Cancer Inst 1996. 4. Go llo b et al., Jo
Slide 21: XTX202 (IL-2) Key Takeaways
21 XTX202 (IL - 2) Key Takeaways • IL - 2 has significant therapeutic potential both as monotherapy and in combination - Monotherapy tumor types include: RCC, melanoma, lung cancer - Attractive combination partners include: mAbs (e.g., anti - PD - 1), cytokines (e.g., IL - 12), cell therapies, cance
Slide 22: XTX301 Tumor-Activated IL-12
22 XTX301 Tumor - Activated IL - 12
Slide 23: The Potential of IL-12 as a Therapeutic Agent
23 The Potential of IL - 12 as a Therapeutic Agent • IL - 12 has ground - breaking potential as a potent IO therapeutic agent • Poor tolerability has limited its clinical progress for decades • No currently approved IL - 12 agents INF γ : interferon gamma; MTD: maximum tolerated dose; NK: natural ki
Slide 24: IL-12 Can Remodel Cold Tumor Microenvironment
24 IL - 12 Can Remodel Cold Tumor Microenvironment Towards a Pro - Inflammatory (Hot) State that Favors Anti - Tumor Immunity • CD8 T and NK cells are abundant in tumor • Pro - inflammatory microenvironment • Improved prognosis and effective killing of tumor cells with immunotherapy treatment • Lack
Slide 25: XTX301 – Tumor-Activated IL-12 Designed to Outsmart Tumors
25 XTX301 – Tumor - Activated IL - 12 Designed to Outsmart Tumors XTX301 custom mask designed to address unique challenges presented by the complex heterodimer structure of IL - 12 Masking Domain Half - Life Extension Domain Cleavage Site Effector Domain Inactive State Active State MMP Activation
Slide 26: mXTX301 Demonstrated Dose-Dependent Anti-Tumor Activity
26 mXTX301 ( Murine Surrogate) Demonstrated Dose - Dependent Anti - Tumor Activity Without Body Weight Loss In Vivo Tumor Growth Body Weight TGI: tumor growth inhibition. MC38 model: s.c. 0.5x106 cells; single IV dose of mXTX301 and mXTX302 on Day 0. Tumor growth data shown as mean ± SEM. Tumor volu
Slide 27: mXTX301 Preferentially Activated in Tumors vs. Plasma In Vivo
27 mXTX301 (Murine Surrogate) was Preferentially Activated in Tumors vs. Plasma In Vivo mXTX301 demonstrated tumor - specific activation in vivo mXTX301 treatment resulted in cleavage - dependent enhancement in activity vs. non - activatable control Left panel: Mice bearing MC38 syngeneic colorectal
Slide 28: mXTX301 Induced Memory Responses in Murine Model
28 mXTX301 Induced Memory Responses in Murine Model Enabling Tumor Rejection Upon Rechallenge of Complete Responders mXTX301 treatment resulted in complete regressions in 9 out of 12 mice Majority of mXTX301 complete responders rejected tumors upon rechallenge 0 5 10 15 20 25 16 32 64 128 256 512 10
Slide 29: XTX301 (IL-12) Preclinical Data Support Broad Therapeutic Index
29 XTX301 (IL - 12) Preclinical Data Support Potential for Broad Therapeutic Index • XTX301 was tolerated at doses up to 2.0 mg/kg Q1W x4 in NHP (HNSTD) • mXTX301 induced tumor regressions in murine model following a single dose of 0.13 mg/kg HNSTD: highest non - severely toxic dose; NHP: non - huma
Slide 30: XTX301 (IL-12) Trial Designed to Enable Monotherapy and Combination Opportunities
30 XTX301 (IL - 12) Trial Designed to Enable Multiple Monotherapy and Combination Opportunities for Expansion in Both Hot and Cold Solid Tumors • IND cleared in November 2022 • Anticipate initiating enrollment in monotherapy dose - escalation in planned Phase 1 trial in Q1 2023 • Initial dose level
Slide 31: XTX301 (IL-12) Key Takeaways
31 XTX301 (IL - 12) Key Takeaways • IL - 12 has significant therapeutic potential across both “hot” and “cold” tumor types - “Hot” tumors include lung, bladder, head & neck, kidney, liver, melanoma, MSI high CRC - “Cold” tumors include prostate, ovarian, breast, pancreatic, brain, MSS CRC • No appro
Slide 32: XTX101 Tumor-Activated aCTLA-4
32 XTX101 Tumor - Activated aCTLA - 4
Slide 33: XTX101 (aCTLA4) Phase 1 Trial
33 XTX101 (aCTLA4) Phase 1 Trial • Announced encouraging preliminary Part 1A data in August 2022 • Preliminary PK analyses demonstrated dose - proportional drug exposure, with limited active (unmasked) XTX101 in peripheral circulation consistent with PK data observed in preclinical studies* • Comple
Slide 34: XTX101 Anti-CTLA-4 Key Takeaways
34 XTX101 Anti - CTLA - 4 Key Takeaways • Next generation anti - CTLA - 4 molecules seek to improve upon the efficacy and tolerability of existing molecules, such as ipilimumab • XTX101 is an Fc - enhanced, tumor - activated, anti - CTLA - 4 currently being studied in a Phase 1 clinical trial for ad
Slide 35: Looking Ahead: Platform Opportunities are Broad
35 Looking Ahead Xilio’s Tumor - Activated Platform Opportunities are Broad
Slide 36: Potential to Deliver Locally-Activated Immunotherapies Beyond Cancer
36 Looking Ahead: Potential to Deliver Highly Potent, Locally - Activated Immunotherapies Beyond Cancer Masked Cytokines Masked Antibodies Pro - and Anti - Inflammatory Processes Proteases in Diseases of Immune Dysregulation Actively pursuing the next generation of tumor - activated platform capabil
Slide 37: Third Quarter 2022 Financial Results
37 Third Quarter 2022 Financial Results Balance Sheet September 30, 2022* December 31, 2021 Cash and Cash Equivalents $139.1M $198.1M Statement of Operations Three Months Ended September 30, 2022* 2021* Research & Development Expenses $13.0M $10.5M General & Administrative Expenses $7.2M $5.5M Net L
Slide 38: Clinical-Stage Company Positioned for Multiple Anticipated Milestones in 2023
38 Xilio is a Clinical - Stage Company, Well - Positioned for Multiple Anticipated Milestones Across 3 Clinical Programs in 2023 * Patient dosing and evaluation in Phase 1 monotherapy dose - escalation cohort is ongoing. Plan to explore opportunities for str ategic collaborations to advance XTX101 a
Slide 39: Differentiated IO Company with a Proprietary Tumor-Activated Platform
39 Xilio is working to deliver highly potent, localized immunotherapies in cancer and beyond Xilio Therapeutics is a Differentiated IO Company with a Proprietary Tumor - Activated Platform and the Team to Deliver Patient Portrayal
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