Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Q3 2024 Earnings Presentation
50 slides from Xilio Therapeutics's earnings presentation, Nov 7, 2024
Slide 1: Unleashing the Potential of Immuno-Oncology Therapies
1 Unleashing the Potential of Immuno-Oncology Therapies November 7, 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 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 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: Positioned for Multiple Anticipated Key Clinical Milestones in Q4 2024
7 1. Evaluating vilastobart (XTX101) in combination with atezolizumab (Tecentriq®) under co-funded clinical collaboration with Roche in Phase 2 combination trial in metastatic MSS CRC. PD: pharmacodynamic; PK: pharmacokinetic; SEECR: selective effector-enhanced cell engager Positioned for Multiple A
Slide 8: Vilastobart (XTX101) Tumor-Activated, Fc-enhanced Anti-CTLA-4
8 Vilastobart (XTX101) Tumor -Activated, Fc -enhanced Anti -CTLA - 4
Slide 9: Vilastobart: Tumor-Activated, High Affinity Binding, Fc-Enhanced Anti-CTLA-4
9 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 10: Phase 2 Proof-of-Concept Trial for MSS CRC with Roche Collaboration
10 Initial data (n = ~20 total) in MSS CRC in Q4 2024 Additional data (n = ~40 total) in MSS CRC in Q1 2025 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 metastas
Slide 11: CRC Incidence Increasing; Majority of Stage 4 MSS CRC Have Liver Metastases
11 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 11 ~90,000 new
Slide 12: I-O Therapies Have Shown Little to No Efficacy in MSS CRC
12 • 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 13: Vilastobart Phase 1C Combination Dose Escalation Data
13 Vilastobart (anti-CTLA-4) Phase 1C Combination Dose Escalation Data Vilastobart + Atezolizumab
Slide 14: Vilastobart Advancing in Phase 2 Proof-of-Concept Trial for MSS CRC
14 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 15: Phase 1C Enrolled Heavily Pre-Treated Patients with Cold Tumors
15 Data cutoff date: October 7, 2024 ECOG PS: ECOG performance status Phase 1C Combination Dose Escalation for Vilastobart (anti-CTLA-4) and Atezolizumab Enrolled Heavily Pre-Treated Patients with Cold Tumors Patient Characteristics Total (n=17) Demographics Age, median (range) 69 (39, 77) Female 6
Slide 16: Combination Was Generally Well-Tolerated with Minimal irAEs
16 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 17: Combination Demonstrated Anti-Tumor Activity in Cold Tumors
17 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. 1. PR (unconfirmed), patient wit
Slide 18: Anti-Tumor Activity Including Sustained Tumor Reduction in MSS CRC
18 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 19: PR in Patient with Ampullary Carcinoma After Single Cycle
19 PR (Unconfirmed)* in Patient with Ampullary Carcinoma (Cold Tumor) After Single Cycle of Combination of Vilastobart (anti-CTLA-4) and Atezolizumab Malignant Neoplasm of Ampulla of Vater • 76 year-old male • 2 prior lines of therapy: - Gemcitabine + nab-Paclitaxel - 5-fluorouracil + Irinotecan Lip
Slide 20: PR in Ampullary Carcinoma (32% Reduction in Sum of Diameters)
20 PR (Unconfirmed)* in Ampullary Carcinoma After Single Cycle of Combination of Vilastobart (anti-CTLA-4) and Atezolizumab (32% Reduction in Sum of Diameters) Target Lesion At Screening Target Lesion After 8 weeks Data cutoff date: October 7, 2024. Patient administered vilastobart (150 mg Q6W) and
Slide 21: PR in Patient With MSS CRC, Full Resolution of Target Lesion in Liver
21 PR (Unconfirmed)* in Patient With MSS CRC, Including Full Resolution of Target Lesion in Liver • 69 year-old female • 5 prior lines of therapy: - FOLFOX-Avastin - FOLFIRI-Avastin - Cetuximab - Lonsurf - FOLFIRI-Panitumamab • Administered vilastobart (150 mg Q6W) + atezolizumab (1200 mg Q3W) MSS C
Slide 22: PR Including Resolution of Liver Metastatic Lesion in MSS CRC
22 PR (Unconfirmed)* Including Resolution of Liver Metastatic Lesion in Patient With MSS CRC (33% Reduction in Sum of Diameters) Target Liver Lesion – After 9 weeks Target Liver Lesion – After 27 weeks Target Liver Lesion – Baseline No visible lesion 22 Data cutoff date: October 7, 2024. Patient adm
Slide 23: Encouraging Initial Evidence of Combination Activity in Phase 1C
23 Initial data (n = ~20 total) in MSS CRC in Q4 2024 Additional data (n = ~40 total) in MSS CRC in Q1 2025 Data cutoff date: October 7, 2024 Encouraging Initial Evidence of Combination Activity Observed in Phase 1C; Anticipate Initial Phase 2 Combination Proof-of-Concept Data in Q4 2024 • Gener
Slide 24: Vilastobart (XTX101) Phase 1 Monotherapy Clinical Data
24 Vilastobart (XTX101) Phase 1 Monotherapy Clinical Data
Slide 25: Phase 1 Monotherapy Trial Patient Characteristics
25 Phase 1 Monotherapy Trial for Vilastobart (anti-CTLA-4) Included Patients With a Wide Range of Advanced/Refractory Solid Tumors Patient Characteristics Total (n=39) Demographics Age, median (range) 62 (43, 80) Female 19 (49%) ECOG PS 0 12 (31%) ECOG PS 1 27 (69%) Prior Lines of Anti-Cancer Treatm
Slide 26: Vilastobart 150 mg Q6W Generally Well-Tolerated with Minimal TRAEs
26 Data cutoff date: October 7, 2024 Vilastobart (anti-CTLA-4) 150 mg Q6W Was Generally Well-Tolerated with Minimal TRAEs AE Category / Term All TRAEs with ≥10% incidence in any category or any Grade 3 TRAE Vilastobart 150 mg Q6W (monotherapy RP2D, n=21) Any Grade 3 Diarrhea 3 (14%) 2 (10%) Colitis
Slide 27: Anti-Tumor Activity With Confirmed PR in PD-L1 Negative NSCLC
27 Data cutoff date: October 7, 2024. n=17 response-evaluable patients RCC: renal cell carcinoma Vilastobart (anti-CTLA-4) 150 mg Q6W Demonstrated Anti-Tumor Activity With Confirmed PR in PD-L1 Negative NSCLC, Including Resolution of Liver Metastases -60 -40 -20 0 20 40 60 80 100 MSS CRC - 1% Best %
Slide 28: Deep and Durable Confirmed PR in PD-L1 Negative NSCLC
28 Vilastobart (anti-CTLA-4) 150 mg Q6W Demonstrated Deep and Durable Confirmed PR in Patient with PD-L1 Negative NSCLC, Including Resolution of Innumerable Hepatic Metastases • 66 year-old female • Progressed after 1 prior line of treatment (paclitaxel and carboplatin) • Administered vilastobart at
Slide 29: Confirmed PR Through 36 Weeks in PD-L1 Negative NSCLC
29 Vilastobart (anti-CTLA-4) 150 mg Q6W Demonstrated Deep and Durable Confirmed PR Through 36 Weeks in a Patient with PD-L1 Negative NSCLC 29 9 weeks of vilastobart Baseline 18 weeks of vilastobart 52% Reduction (Sum of Diameters) Through 36 Weeks
Slide 30: Durable Resolution of Hepatic Metastases Through 36 Weeks
30 Vilastobart (anti-CTLA-4) 150 mg Q6W Demonstrated Durable Resolution of Hepatic Metastases Through 36 Weeks in a Patient with PD-L1 Negative NSCLC 9 weeks of vilastobart Baseline 30 18 weeks of vilastobart
Slide 31: XTX301 Tumor-Activated IL-12
31 XTX301 Tumor -Activated IL -12
Slide 32: The Compelling Potential of IL-12 as a Therapeutic Agent
32 • 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 33: XTX301 Designed to Overcome Limitations of Systemic IL-12
33 Inactive State XTX301: Tumor-Activated IL-12 • Activated XTX301 designed to have optimized short half-life IL-12 (half-life extension domain not retained) • Efficient activation by human tumors demonstrated ex vivo • Robust anti-tumor activity and tumor-selective PD in vivo in preclinical model •
Slide 34: Partnership with Gilead to Explore IL-12 Across Solid Tumors
34 Entered Into Partnership with Gilead in March 2024, Designed to Explore Broad Potential of IL-12 Across Solid Tumors $43.5M total upfront payments ($30M cash payment + $13.5M initial equity investment at a premium ($1.97/share) Up to $604M additional contingent payments: • Includes up to $29M pri
Slide 35: XTX301 Phase 1 Monotherapy Dose Escalation Initial Data
35 XTX301 Phase 1 Monotherapy Dose Escalation Initial Data
Slide 36: XTX301 Monotherapy Phase 1 Ongoing: No DLTs Reported To Date
36 DL1: 5 μg/kg Q3W DL2: 15 μg/kg Q3W As of August 5, 2024 * Q6W dosing schedule evaluated at DL3 based on emerging PK data for XTX301 half-life in inactive state ** Preceded by a single priming dose of XTX301 at 15 μg/kg DL1: dose level 1; DL2: dose level 2; DL3: dose level 3; DL4: dose level 4; MT
Slide 37: XTX301 Phase 1 Monotherapy Data Anticipated in Q4 2024
37 XTX301 Phase 1 Monotherapy Data Anticipated in Q4 2024 • Demonstrated dose-dependent anti-tumor activity without significant body weight loss in vivo • Preferentially activated in tumors vs. plasma in vivo and patient tumors vs. plasma ex vivo • Generally well-tolerated with no DLTs observed to d
Slide 38: XTX501 PD1/IL2 Bispecific
38 XTX501 PD1/IL2 bispecific
Slide 39: XTX501: Tumor-Activated PD1/IL2 Bispecific
39 Inactive State NHP: non-human primate; VHH: variable heavy domain of heavy chain. XTX501: Tumor-Activated PD1/IL2 Bispecific • 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+ T cells and
Slide 40: XTX501 Designed to Induce Differentiated Immune Response
40 XTX501 Designed to Induce a Differentiated, Enhanced Immune Response to Cancer Compared to PD-(L)1 Monotherapy or PD-(L)1 + IL-2 Combination Figure adapted from Deak et al., OncoImmunology, 2023. Figure generated using BioRender.com. • Targeted delivery of IL-2 to PD1+ cells selectively enhances
Slide 41: XTX501 Demonstrated Differentiated Pharmacology vs PD1 or PD1+XTX202
41 Vehicle PD1 +XTX202 PD1/IL2 Bispecific 0 2 4 6 8 10 15 20 Tumor CD8+GranzymeB+ T cells Fold-Change Over Vehicle XTX501 Increased Intra-tumoral Cytotoxic and TCF1+ Stem-like T cells Robust Preclinical Monotherapy Activity Beyond XTX202 + PD1 Combination XTX501 Demonstrated Differentiated Pharmacol
Slide 42: Cell Engager Programs
Cell Engager Programs xilid
Slide 43: Tumor-Activated Cell Engagers Built on Validated Masking Approach
43 Selective Effector-Enhanced Cell EngageR (SEECR molecules) Xilio is Developing Tumor-Activated Cell Engagers Built on Our Validated Masking Approach and Conditional Half-Life Optimization Advanced Tumor-Activated Cell EngageR (“ATACR” molecules) Illustrations generated using Biorender.com Design
Slide 44: Masking Technology Enabled Efficient Masking of CD3 Binding Domain
44 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 45: SEECR Molecule Drove Sustained Serial Tumor Cell Killing
45 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 46: SEECR Antibody-Like PK and Enhanced Activity and Survival
46 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 47: Management Overview and Recent Financial Results
47 Management Overview and Recent Financial Results
Slide 48: Experienced Leadership Team with Proven Track Record
48 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 CHRIS FRANKENFIELD Chief Financial and Operating Officer UL
Slide 49: Q3 2024 Financial Results; Cash Runway Through End of Q2 2025
49 Q3 2024 Financial Results Anticipate Cash Runway Through End of Q2 2025 Balance Sheet September 30, 2024 (1) December 31, 2023 Cash and Cash Equivalents $61.3M $44.7M 1. Unaudited Statement of Operations Three Months Ended September 30 2024 (1) 2023 (1) License Revenue $2.3M $— Research & Develop
Slide 50: Xilio is a Differentiated I-O Company with Proprietary Tumor-Activated Platform
50 Xilio is working to deliver highly potent, localized immunotherapies in cancer and beyond Xilio Therapeutics is a Differentiated I-O Company with a Proprietary Tumor-Activated Platform and the Team to Deliver