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Advancing Science. Designing Hope. JPM HC Conference January 2025
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Forward-Looking Statements This presentation contains forward-looking statements. Any statements that are not solely statements of historical fact are forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward- looking statements. These forward-looking statements include statements relating to the potential benefits of our product candidates and combinations; our clinical, data generation and data presentation plans for 2025, including having data readouts from GALAXIES Lung-201, GALAXIES H&N-202, TIG-006 H&N, and EOS- 984; our expectation to submit an IND for TRM-010 in 1Q25; our expectation that the TIGIT safety profile will be further improved by updated safety protocols, aiming to reduce discontinuation rates; our market opportunities and number of patients potentially eligible for our product candidates; the potential benefits of our collaboration with GSK; intentions around trial enrollment and recruitment; and our expected cash runway through 2027. These forward-looking statements involve risks and uncertainties, many of which are beyond iTeos’ control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and early results or interim data from a clinical trial may change as more patient data become available and are subject to audit verification procedures; the data for our product candidates may not be sufficient to support regulatory approval; iTeos may encounter unanticipated costs or may expend cash more rapidly or more slowly than currently anticipated due to challenges and uncertainties inherent in product research and development and biologics manufacturing; the expected benefits and opportunities related to the agreement between iTeos and GSK may not be realized or may take longer to realize than expected due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement, challenges and uncertainties inherent in product research and development and manufacturing limitations; iTeos may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing its product candidates to market, for various reasons, some of which may be outside of iTeos’ control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, negative developments in the field of immuno-oncology, such as adverse events or disappointing results, including in connection with competitor therapies, and regulatory, court or agency decisions such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in iTeos’ Quarterly Report on Form 10-Q for the period ended September 30, 2024 filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Statements regarding the Company’s cash runway do not indicate if and when the Company may access the capital markets. Any of the foregoing risks could materially and adversely affect iTeos’ business, results of operations and the trading price of iTeos’ common stock. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. iTeos does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof. 2
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2025: Pivotal Year of Datasets 3 01 >400 PATIENTS IN 2025 OF TIGIT:PD-1 DATA 02 EMERGING PIPELINE OF FIRST-IN-CLASS OPPORTUNITIES 03 FUNDED THROUGH IMPACTFUL MILESTONES ~$684M* in Cash, Runway Through 2027GALAXIES Lung-201 GALAXIES H&N-202 TIG-006 H&N EOS-984: Restoring T Cell Proliferation EOS-215: Overcoming PD-1 Resistance H&N, head and neck cancer; *Pro forma cash, cash equivalents and short -term investments as of September 30, 2024
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Preclinical Phase 1 Phase 2 Phase 3 Status Multiple Clinical Data Readouts in 2025 4 Innovative molecules and compelling combinations ENT1, equilibrative nucleoside transporter 1; (m)NSCLC, (metastatic) non-small cell lung cancer; HNSCC, head and neck squamous cell carcinoma GALAXIES Lung-301 EOS-984: Small molecule targeting ENT1 Monotherapy |+ pembrolizumab | Advanced Malignancies Data Anticipated 2H25 Monotherapy | Advanced Malignancies EOS-215: mAb targeting TREM2 + dostarlimab | + CD96 | 1L NSCLC PD-L1high + dostarlimab | 1L HNSCC PD-L1high/low + dostarlimab | 1L NSCLC PD-LI high Belrestotug: IgG1 antibody targeting TIGIT GALAXIES Lung-201 TIG-006 Enrolling Data Anticipated 2Q25 Data Anticipated 2H25 GALAXIES Lung-301 Data Anticipated 2H25 IND in 1Q25 APT-008 + dostarlimab | + CD96 | 1L HNSCC PD-L1+ GALAXIES H&N-202 TRM-010
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Belrestotug EOS-448 / GSK4428859A iTeos and GSK are uniquely positioned to leverage the TIGIT/CD226 axis 5
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6 Advancing a Leading TIGIT:PD-1 in an Evolving Landscape GALAXIES Lung-201 Quality of Components Matters Indication Selection Importance Optimizing Trial Design
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7 POC, proof of concept; Pembro, pembrolizumab The Need for a Transformative TIGIT:PD-1 Doublet Belrestotug + dostarlimab represent potentially differentiated, high-quality therapies Dostarlimab PERLA Data8 Market Leading PD-1 Monotherapy Activity1 GAL-201 ESMO Data2 TIGIT Discontinuation3 No Pembro Comparison SKY-01 Negative4 Trials Stopped5 No Pembro Comparison Fc Silent ARC-107 No Pembro Comparison All Phase 2s Stopped6 1. iTeos AACR 2021, 2. iTeos ESMO 2024, 3. Merck KeyVibe Clinical Development Update, 4. Roche Phase 3 Skyscraper-01 Study - August 22, 2023 Release, 5. Roche SKY-01 Results, 6. BeiGene Goldman Sachs Conference 2024, 7. Arcus SITC 2024 Update, 8. ESMO 2023 – Phase 2 GSK-sponsored PERLA study in 1L NSCLC
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8 1. iTeos AACR 2021 2. doi: 10.1136/jitc-2022-SITC2022.0768 3. doi: 10.1038/s41586-024-07121-9 *Merck vibostolimab has yet to publicly show Treg depletion data; Arcus’ domvanalimab is an Fc silent TIGIT and not capable of Treg depletion 0% ITOS 20mg BGNE 1800mg Roche Merck Arcus TIGIT+ Treg Depletion in Patients Fc Silent*Undisclosed* 100% 20-30%2 Mild Treg depletion3 Unique Epitope Binding High Affinity + Potency First and only TIGIT with proven Treg depletion at all doses1 Only TIGIT to Demonstrate Phase 1 Monotherapy Activity1 80% Belrestotug: The First And Only TIGIT to Demonstrate Robust Target Engagement
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Belrestotug + Dostarlimab: Strong Efficacy and Clear Differentiation 9 Best Observed Response (Without Confirmation): PR SD PD 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Patients Dostarlimab (N=32) SD PD SD SD SD SD SD SD SD SD SD SD SD PD SD SD PR PR PR PR PR PR PR PR PR PR PR PR 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Patients B: Belrestotug 400 mg + dostarlimab (N=32) PD PD PD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR 1Numerically lowest percent change from baseline that is on or prior to date of first radiological PD and start of follow -up anticancer therapy (excluding radiotherapy and surgery); patients without assessable post -baseline scans or where all baseline target lesions are not measured at subsequent visits are not included in figure; responses shown are per RECIST 1.1 by investigator assessment witho ut confirmation. PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease. ~60% ORR, 30% ORR Separation observed at every dose vs dostarlimab monotherapy Enhanced ctDNA Reduction observed at belrestotug 400mg + 1000mg vs dostarlimab monotherapy Generally Manageable irAEs to be further improved by updated safety protocols, aiming to reduce discontinuation rates
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GALAXIES Lung-201 - Phase 2 in 1L NSCLC Status Enrolling Masking Open label PDL1 Expression ≥50% Lines of Therapy No prior systemic therapy Delivery IV Infusion 10 Study Design Objectives Evaluate belrestotug + dostarlimab safety, efficacy, PK/PD Primary Endpoint ORR Secondary Endpoint PFS, OS, DOR Clinical Trials Listing NCT05565378 Largest TIGIT Phase 2 in PD-L1 high 1L NSCLC NSCLC, non-small cell lung cancer; PK/PD, pharmacokinetic/pharmacodynamic, ORR, overall response rate; PFS, progression free sur vival; OS, overall survival; DOR, duration of response LUNG-201 Estimated Enrollment 340 R Key R Subjects Randomization Dostarlimab 500mg + Belrestotug 400mg + Nelistotug (CD96) n=60 Pembrolizumab 200mg n=60 Dostarlimab 500mg n=100 Dostarlimab 500mg + Belrestotug 100mg n=30 Dostarlimab 500mg + Belrestotug 400mg n=60 Dostarlimab 500mg + Belrestotug 1000mg n=30
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Response measure in mITT Dostarlimab N=32 A: Belrestotug 100 mg + dostarlimab N=30 B: Belrestotug 400 mg + dostarlimab N=32 C: Belrestotug 1000 mg + dostarlimab N=30 Median follow-up, months (range)1 7.0 (0.2–16.6) 8.5 (0.3–14.3) 8.5 (0.4–16.2) 6.7 (2.4–9.7) ORR,2,3 % n (95% CI) 37.5% n=12 (21.1–56.3) 63.3% n=19 (43.9–80.1) 65.6% n=21 (46.8–81.4) 76.7% n=23 (57.7–90.1) Complete response, n (%) 0 0 0 0 Partial response, n (%) 12 (37.5%) 19 (63.3%) 21 (65.6%) 23 (76.7%) Stable disease, n (%) 14 (43.8%) 5 (16.7%) 4 (12.5%) 5 (16.7%) Progressive disease, n (%) 2 (6.3%) 4 (13.3%) 3 (9.4%) 2 (6.7%) Not evaluable/no assessment,4 n (%) 4 (12.5%) 2 (6.7%) 4 (12.5%) 0 Confirmed ORR,3,5 % n (95% CI) 28.1% n=9 (13.7–46.7) 60.0% n=18 (40.6–77.3) 59.4% n=19 (40.6–76.3) 63.3% n=19 (43.9–80.1) Clinically Meaningful ORR Observed at Every Dose vs Dostarlimab Monotherapy 11 1As of data cut 7 Jun 2024, 65% of patients remained in ongoing follow -up; 2unconfirmed ORR; 3PD-L1 high (TPS ≥50%) was determined locally or centrally by DAKO 22C3 or VENTANA SP263 assay; 4patients who only had "not evaluable" post-baseline assessments, those who had a best response of "not evaluable" per RECIST 1.1 by investigator assessment, or those where no post -baseline tumour assessment was performed; 5complete or partial response confirmed by repeat imaging ≥4 weeks after response criteria first met . CI, confidence interval; mITT, modified intention-to-treat; ORR, objective response rate; PD-L1, programmed death ligand-1; RECIST, Response Evaluation Criteria in Solid Tumours; TPS, tumour positive score.
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Belrestotug + Dostarlimab Consistently Increased Depth of Response vs Dostarlimab Monotherapy 12 Best Observed Response (Without Confirmation): PR SD PD 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90- 100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Patients Dostarlimab (N=32) SD PD SD SD SD SD SD SD SD SD SD SD SD PD SD SD PR PR PR PR PR PR PR PR PR PR PR PR 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90- 100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Patients A: Belrestotug 100 mg + dostarlimab (N=30) PDPD PD PD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR SD 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90- 100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Patients B: Belrestotug 400 mg + dostarlimab (N=32) PD PD PD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR 100 90 80 70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90- 100 Maximum percentage change from baseline1 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 30 Patients C: Belrestotug 1000 mg + dostarlimab (N=30) PD PD SD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR 28 29 PR PR 1Numerically lowest percent change from baseline that is on or prior to date of first radiological PD and start of follow -up anticancer therapy (excluding radiotherapy and surgery); patients without assessable post -baseline scans or where all baseline target lesions are not measured at subsequent visits are not included in figure; responses shown are per RECIST 1.1 by investigator assessment witho ut confirmation. PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease.
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Consistent Deep Tumor Reduction with Ongoing Responses by Belrestotug + Dostarlimab vs Dostarlimab Monotherapy 13 Ongoing – in follow-up Died Ongoing – on study treatment Withdrawn 1Investigator assessed percentage change from baseline per RECIST 1.1 by investigator assessment. RECIST, Response Evaluation Criteria in Solid Tumors. 32 Days 64 96 128 160 192 224 256 288 320 352 384 416 448 Dostarlimab (N=32) 80 60 40 20 0 -20 -40 -60 -80 -100 0 Percentage change from baseline1 32 Days 64 96 128 160 192 224 256 288 320 352 384 416 448 B: Belrestotug 400 mg + dostarlimab (N=32) 80 60 40 20 0 -20 -40 -60 -80 -100 0 Percentage change from baseline1 32 Days 64 96 128 160 192 224 256 288 320 352 384 416 448 A: Belrestotug 100 mg + dostarlimab (N=30) 80 60 40 20 0 -20 -40 -60 -80 -100 0 Percentage change from baseline1 32 Days 64 96 128 160 192 224 256 288 320 352 384 416 448 C: Belrestotug 1000 mg + dostarlimab (N=30) 80 60 40 20 0 -20 -40 -60 -80 -100 0 Percentage change from baseline1
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Numerically Greater Reduction of ctDNA Associated with Belrestotug 400mg and 1000mg + Dostarlimab Cohorts 14 1000 700 500 300 200 100 0 -50 -80 -90 -95 -98 -100 ctDNA % change at Week 71 Dostarlimab (N=19) A: Belrestotug 100 mg + dostarlimab (N=18) B: Belrestotug 400 mg + dostarlimab (N=22) C: Belrestotug 1000 mg + dostarlimab (N=20) Kruskal-Wallis, p=0.073 Molecular response threshold2 1Mean variant allele frequency change from baseline to Week 7; 2molecular response threshold defined as having at least 50% reduction of ctDNA levels. Responses shown are per RECIST 1.1 by investigator assessment without confirmation. ctDNA, circulating tumour DNA; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease. Best Observed Response (Without Confirmation): PR SD PD Molecular Response Rate (>-50% from Baseline) Median ctDNA % Change -65% 11/19 (58%) -55% 9/18 (50%) -94% 15/22 (68%) -97% 18/20 (90%)
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Belrestotug + Dostarlimab Is Broadly Consistent with Known Safety Profile of Checkpoint Inhibitor Combinations 15 Increase in immune-related adverse events with belrestotug + dostarlimab vs dostarlimab Event, n (%) Dostarlimab (N=32) A: Belrestotug 100 mg + dostarlimab (N=30) B: Belrestotug 400 mg + dostarlimab (N=32) C: Belrestotug 1000 mg + dostarlimab (N=30) TEAE 29 (91%) 29 (97%) 31 (97%) 30 (100%) Grade 3+ TEAE 14 (44%) 19 (63%) 16 (50%) 16 (53%) TRAE 19 (59%) 24 (80%) 27 (84%) 29 (97%) Grade 3+ TRAE 5 (16%) 10 (33%) 7 (22%) 13 (43%) Serious TRAE 3 (9%) 10 (33%) 8 (25%) 11 (37%) Grade 5 serious TRAE 0 2 (7%) 1 (3%) 0 TRAE leading to discontinuation 2 (6%) 7 (23%) 5 (16%) 12 (40%) Grade 1/2 TR-irAE leading to discontinuation 0 (0%) 2 (7%) 3 (10%) 2 (7%) TR-irAE1 6 (19%) 20 (67%) 18 (56%) 22 (73%) Grade 3+ TR-irAE 4 (13%) 9 (30%) 5 (16%) 11 (37%) Infusion-related reactions2 4 (13%) 8 (27%) 3 (9%) 7 (23%) • The most common TRAEs overall (≥15%) were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%) • The most common TEAEs leading to discontinuation were skin and subcutaneous tissue disorders (6%) and respiratory, thoracic and mediastinal disorders (6%) • Fatal serious TRAEs include immune-mediated pneumonitis (N=1), immune-mediated hepatitis (N=1) and immune-mediated myocarditis (N=1) 1Immune-related AEs are events of potential immunologic aetiology, including irAEs; irAEs are identified as any Grade 2+ AEs (or AEs of unknown grade) based on a prespecified search list of preferred terms using the most recent MedDRA version identified by a custom MedDRA query (CMQ) using GSK Terms of Interest codes; 2infusion-related reactions are drug component–related AEs which occurred ≤1 day after drug component infusion and are identified based on a prespecified se arch list of preferred terms and most recent MedDRA version. AE, adverse event; irAE, immune-related AE; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event; TR, treatment -related; TRAE, treatment-related treatment-emergent adverse event.
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Belrestotug + Dostarlimab Is Broadly Consistent with Known Safety Profile of Checkpoint Inhibitor Combinations 16 Most common TR-irAE were skin and subcutaneous tissue disorders • The majority of Grade 2+ irAEs were skin and subcutaneous tissue disorders across all combination cohorts and were considered generally manageable with steroids (topical or oral). Adaptions to skin toxicity management are ongoing. • Immune-mediated lung disease and myocarditis were more frequent in the belrestotug 1000 mg + dostarlimab cohort 1Immune-related AEs are events of potential immunologic aetiology, including irAEs; irAEs are identified as any Grade 2+ AEs (or AEs of unknown grade) based on a prespecified search list of preferred terms using the most recent MedDRA version identified by a custom MedDRA query (CMQ) using GSK Terms of Interest codes; 2infusion-related reactions are drug component–related AEs which occurred ≤1 day after drug component infusion and are identified based on a prespecified se arch list of preferred terms and most recent MedDRA version. AE, adverse event; irAE, immune-related AE; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event; TR, treatment -related; TRAE, treatment-related treatment-emergent adverse event. Event, n (%) Dostarlimab N=32 A: Belrestotug 100 mg + dostarlimab (N=30) B: Belrestotug 400 mg + dostarlimab (N=32) C: Belrestotug 1000 mg + dostarlimab (N=30) TR-irAE1 by preferred terms (≥10% incidence in any cohort2), Grade 2+ Grade 3+ Immune-mediated dermatitis 0 0 5 (17%) 1 (3%) 0 0 6 (20%) 3 (10%) Pruritus 0 0 3 (10%) 0 5 (16%) 0 4 (13%) 0 Rash 0 0 2 (7%) 0 4 (13%) 0 2 (7%) 1 (3%) Immune-mediated hypothyroidism 1 (3%) 0 1 (3%) 0 3 (9%) 0 4 (13%) 0 ALT increase 1 (3%) 1 (3%) 3 (10%) 2 (7%) 0 0 1 (3%) 1 (3%) Immune-mediated lung disease 0 0 1 (3%) 0 1 (3%) 0 3 (10%) 1 (3%) Immune-mediated myocarditis 0 0 1 (3%) 1 (3%) 0 0 3 (10%) 1 (3%)
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GALAXIES Lung-301 - Phase 3 in 1L NSCLC Status Enrolling Masking Double-blind PDL1 Expression ≥50% Lines of Therapy No prior systemic therapy Delivery IV Infusion 17 Study Design Objectives Evaluate belrestotug + dostarlimab safety, efficacy vs placebo + pembrolizumab Primary Endpoint PFS, OS Secondary Endpoint ORR, MRR, DOR Clinical Trials Listing NCT06472076 Dostarlimab 500mg + Belrestotug 400mg Pembrolizumab + Placebo NSCLC, non-small cell lung cancer; PFS, progression free survival; OS, overall survival; ORR, overall response rate; MRR, molecular response rate; DOR, duration of response LUNG-301 Estimated Enrollment 1,000 Key R Subjects Randomization R
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GALAXIES H&N-202 - Phase 2 in 1L HNSCC Status Enrolling Masking Open label PDL1 Expression PDL1+ Lines of Therapy No prior systemic therapy Delivery IV Infusion 18 Study Design Objectives Evaluate antitumor activity, safety of dostarlimab + novel IOs Primary Endpoint ORR Secondary Endpoint PFS, OS, DOR Clinical Trials Listing NCT06062420 Dostarlimab n=72 Dostarlimab + Belrestotug n=72 Dostarlimab + Nelistotug (CD96) n=72 Dostarlimab + Belrestotug + Nelistotug (CD96) n=72 H&N or HNSCC, head and neck squamous cell carcinoma; ORR, overall response rate; PFS, progression free survival; OS, overall survival; DOR, duration of response Estimated Enrollment 360 H&N-202 R Key R Subjects Randomization Dostarlimab + PVRIG (GSK4381562) n=72
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TIG-006 – Phase 2 in 1L HNSCC PDL1High/Low Status Enrolling Masking Open label PDL1 Expression PDL1+ Lines of Therapy No prior systemic therapy Delivery IV Infusion 19 Study Design Objectives Evaluate belrestotug + dostarlimab in two CPS populations Primary Endpoint ORR Secondary Endpoint PFS, OS, DOR Clinical Trials Listing NCT05060432 CPS High ≥ 20 Dostarlimab + Belrestotug (Dose B) CPS Low < 20 Dostarlimab + Belrestotug (Dose B) Estimated Enrollment 40 R Key R Subjects Randomization
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On Track for 3 Robust TIGIT Datasets in 2025 20 Data readouts with >400 patients from TIGIT:PD-1 trials in 1L NSCLC and 1L HNSCC Topline Data in 2Q25 Interim Data in 2025 GALAXIES Lung-201 GALAXIES H&N-202 TIG-006 HNSCC ESMO 2024 New Patients 2025 2025 Dostarlimab 32 30 40 - Belrestotug 100mg + Dostarlimab 30 - - - Belrestotug 400mg + Dostarlimab 32 30 40 42 Belrestotug 1000mg + Dostarlimab 30 - - - Pembrolizumab - 30 - - Dostarlimab + Nelistotug - - 40 Belrestotug 400mg + Dostarlimab + Nelistotug - 30 40 - No. of Patients 124 120 >150 42 Total Patients in Dataset >240 >150 42 Endpoints ORR PFS Safety ctDNA ORR Safety ctDNA ORR Safety ORR PFS Safety NSCLC, non-small cell lung cancer; H&N or HNSCC, head and neck squamous cell carcinoma; ORR, overall response rate; PFS, progression free survival; ctDNA, circulating tumor DNA
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EOS-984 Potential first-in-class small molecule targeting ENT1 21
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Tumor cell Tumor cell proliferation 4 Immunosuppressed T cell T-cell proliferation T-cell suppression 3 A2AR Adenosine activation of A2AR 2 Adenosine High levels of extracellular adenosine Cell death and inflammation1 • The Pro-Tumoral Role of Adenosine A2A Receptor (A2AR) Intracellular Adenosine: the Key Driver of Immunosuppression 22 ENT1 plays a central role in adenosine regulation beyond conventional targets TME adenosine is a key issue for T cell activating therapies, limiting potency and persistence Industry focused on mitigating extracellular adenosine by targeting adenosine production (e.g. CD73, CD39) and blocking final endpoint (i.e. A2AR) Intracellular adenosine, regulated by ENT1, plays a pivotal role in T cell metabolism, signaling, and function – integral processes for effective immune responses TME, tumor microenvironment; ENT1, equilibrative nucleoside transporter 1 Tumor cell Tumor cell proliferation 4 Immunosuppressed T cell T cell suppression 3 ENT1 Intracellular adenosine uptake 2 Adenosine High levels of extracellular adenosine Cell death and inflammation1 • The Pro-Tumoral Role of Equilibrative Nucleoside Transporter 1 (ENT1)
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EOS-984: Enhancing T Cell Proliferation in the Hostile TME 23 Potential cornerstone to revive T cell activating therapies The Opportunity to Restore T Cell Proliferation • Blocking ENT1 restores T cell proliferation vs revival of immune cells by blocking A2AR, which is insufficient for robust antitumor response • EOS-984 is the first program to address how intracellular adenosine transports into T cells and inhibits proliferation • T cell effector function • T cell survival The Role of ENT1 • Dominant transporter of adenosine on lymphocytes effecting: • T cell metabolism • T cell expansion TME, tumor microenvironment; ENT1, equilibrative nucleoside transporter 1 Apoptosis Cytokines Activated T cell Tumor cell Tumor cell death and enhanced anti-tumor activity 4 T cell proliferation 3 T cell ENT1 Inhibition of adenosine uptake 2 EOS-984 Adenosine High levels of extracellular adenosine Cell death and inflammation1 Mechanism of Equilibrative Nucleoside Transporter 1 (ENT1) Inhibitor EOS-984
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Anti-PD-1 Activity Enhanced by Restoration of T Cell Proliferation by EOS-984 24 aPD-1 inactive in high adenosine aPD-1 enhances tumor killing High adenosine No adenosine % Specific killing activity 40 30 20 10 0 Peptide + IL-2/IL-7 + + + + + + ATP - - + + + + αPD-1 - + - + - + EOS-984 - - - - + + EOS-984 + aPD-1 combination maximizes tumor killing by functional memory T cells 180 µM Tumor volume (mm3) 0 200 400 600 800 1000 0 20 40 60 Days post-graft P < 0.0001 P = 0.0035P < 0.0001 P < 0.0001 Vehicle Anti-PD-1 EOS301984 EOS301984 + anti-PD-1 Humanized TNBC model (MDA-MB-231) containing high adenosine
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EOS-984: Phase 1 in Advanced Solid Tumors Status Enrolling Masking Open Label PDL1 Expression PDL1+ (all %) Lines of Therapy All-comers Delivery Oral 25 Study Design Objectives Evaluate safety/tolerability of EOS-984 as a monotherapy and in combination with pembrolizumab Primary Endpoint Safety/tolerability, PK/PD Secondary Endpoint ORR, PFS, OS, DOR EOS-984 (15mg) EOS-984 (10mg) EOS-984 (22.5mg) EOS-984 (Dose B) + Pembrolizumab (200mg) EOS-984 (5mg) EOS-984 (30mg) RP2D EOS-984 (Dose C)+ Pembrolizumab (200mg) EOS-984 (Dose A) + Pembrolizumab (200mg) Evaluation of target engagement and impact on T cells in TME TME, tumor microenvironment; RP2D, recommended Phase 3 dose; PK/PD, pharmacokinetic/pharmacodynamic; ORR, overall response rate; PFS, progression free survival; OS, overall survival; DOR, duration of response Estimated Enrollment 84
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EOS-215 Potential best-in-class anti-TREM2 antagonist 26
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EOS-215: Reprogramming the Hostile TME 27 Targeting TREM2 addresses an overlooked immune axis, overcoming PD-1 resistance TREM2, triggering receptor expressed on myeloid cells 2; MOA, mechanism of action; NK, natural killer; TAM, tumor-associated macrophage. The Opportunity to Remodel the TME with EOS-215 • Creates a hospitable TME amenable to a T cell response by reprogramming TAMs • Potential early clinical signals due to macrophages accumulation after each line of treatment The Role of TREM2 • TREM2 regulates myeloid cells to maintain tissue homeostasis by controlling inflammation and promoting tissue repair • When cancer hijacks the TREM2 signaling, it enables: • Tumor growth via angiogenesis • Immune system evasion and survival via fibrosis • Drives metabolic reprogramming + efferocytosis • Cancer treatment resistance via TAMS Tumor cell Apoptosis Tumor cell apoptosis and decrease in metastasis4 Angiogenesis Fibrosis Metabolic adaptation and immune exhaustion Pro-inflammatory signaling Wound healing mechanisms CD8+ T cell Immunostimulatory tumor microenvironment 3 Effective PD-1 inhibitor Active CD8+ T cell B cell Active NK cell Immune cell recruitment, activation, and proliferation 2 Pro-inflammatory macrophage TAM TREM2 EOS006215 Inhibition + reprogramming of TREM2+ cells 1 Mechanism of Anti-Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Antagonist EOS-215
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28 2025: Pivotal Year of Data Generation Innovative portfolio leveraging deep tumor immunology expertise TIGIT ~$684M As of Sept. 30, 2024 Runway through 2027 Pro forma cash, cash equivalents and investments Emerging Pipeline 1L NSCLC Phase 2 GALAXIES Lung-201 interim data Continued global expansion of Phase 3 GALAXIES Lung-301 ENT1 Phase 1 APT-008 topline monotherapy + combination data Funded Through Significant Milestones NSCLC, non-small cell lung cancer; HNSCC, head and neck squamous cell carcinoma; ENT1, equilibrative nucleoside transporter 1; TREM2, triggering receptor expressed on myeloid cells 2; MOA, mechanism of action 1L HNSCC Phase 2 GALAXIES H&N-202 interim data Phase 1/2 TIG-006 HNSCC topline data TREM2 Preclinical data TREM-010 Phase 1 initiation
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Thank You