Alx Oncology Holdings Inc. · NASDAQ:ALXO
Alx Oncology — Q3 2025 Earnings Presentation
39 slides from Alx Oncology's earnings presentation, Nov 7, 2025
Slide 1: Q3 2025 Results
Q3 2025 Results NASDAQ GS November 7, 2025 ALXO © ALX Oncology Inc. All rights reserved.
Slide 2: Forward-looking Statements
Forward-looking Statements Certain information set forth in this presentation contains “forward-looking information”, under applicable laws collectively referred to herein as forward-looking statements. Except for statements of historical fact, information contained herein constitutes forward-lookin
Slide 3: Q3 Highlights
01 Q3 Highlights Jason Lettmann Chief Executive Officer, ALX Oncology ALX Oncology Clinical Program Update Q3 2025 Results & 02 Evorpacept & ALX2004 Business Update Barb Klencke, MD Chief Medical Officer, ALX Oncology Evorpacept 02 Breast Cancer Potential Peter Schmid, MD FRCP, MD, PhD Barts Cancer
Slide 4: ALX Oncology Q3 2025 Key Accomplishments and Updates
ALX Oncology Q3 2025 Key Accomplishments and Updates In a new analysis from the Ph2 ASPEN-06 gastric cancer trial presented at SITC, the addition of evorpacept led to a compelling benefit in HER2+ patients with high CD47 expression ORR 65 vs. 26%; mDOR 25.5 vs. 8.4m; mPFS 18.4 vs. 7m (HR 0.39); mO
Slide 5: Research in CD47 Provides a Strong Foundation for Utilizing CD47 as a Negative Prognostic Biomarker
Research in CD47 Over the Last 10+ Years Provides a Strong Foundation for Utilizing CD47 as a Negative Prognostic Biomarker Increased CD47 expression is correlated with poor patient outcomes in many tumor types including2: Breast cancer3, 14 Oral squamous cell carcinoma4 • In a meta-analysis of
Slide 6: Topline Data Showed CD47 Expression Was a Key Predictive Biomarker
Topline Data Previously Shared Showed CD47 Expression Was a Key Predictive Biomarker Demonstrating Compelling Overall Response Rate With the Addition of Evorpacept ASPEN-06 HER2+ Gastric/GEJ Trial (ORR) CD47-High CD47-Low ITT Retained HER2+ Retained HER2+ 65.0%* Evorpacept + TRP TRP 41.3% 37.5% 26.6
Slide 7: New Data Presented at SITC Show Potential for Evorpacept Benefit
New Data Presented at SITC Today Show Potential for Evorpacept to Drive Transformational Benefit Across All Key Efficacy Parameters in Patients with High CD47 Expression ASPEN-06 Gastric / GEJ Trial Patients with CD47-High Expression and Retained HER2+ (N=43/127) ORR mDOR mPFS mOS 30 (months) (month
Slide 8: ALX Is Focused on Driving Toward Two Key Inflection Points in 2026
ALX Is Focused on Driving Toward Two Key Inflection Points in 2026 PROGRAM INDICATION AN TICIPATED MILESTONES E VO R PAC E PT ASPEN-Breast FPI Q4 2025 Evorpacept, trastuzumab ENHERTU®-Experienced HER2-Positive Breast Cancer + chemotherapy Interim data – Q3 2026 ALX2004 ALX2004 First patient dosed Au
Slide 9: ALX Oncology is Pursuing a Focused Development Plan
ALX Oncology is Pursuing a Focused Development Plan MODALITY IND /TARGET PROGRAM INDICATION ENABLING PHASE 1 PHASE 2 PHASE 3 STATUS EVORPACEPT PROGRAMS ASPEN-Breast ENHERTU®-Experienced HER2-Positive Breast Evorpacept, Trastuzumab FPI Q4’25 Cancer + chemotherapy SARCLISA® + Dose escalation RRMM Dexa
Slide 10: Clinical Program Update: Evorpacept – CD47 Blocker
Clinical Program Update Evorpacept – CD47 Blocker Ph2 ASPEN Gastric Cancer Trial Update and the Path Forward Barbara Klencke, MD CMO, ALX Oncology
Slide 11: Evorpacept Blocks the CD47-SIRPα Interaction, Enhancing Targeted ADCP
Evorpacept Blocks the CD47-SIRPα Interaction, Enhancing the Targeted ADCP of Cancer Cells when Given in Combination with Anti-Cancer Antibodies SIRP⍺ Don’t SIRP⍺ Don’t SIRP⍺ Evorpacept Eat M e Eat M e MACROPHAGE MACROPHAGE MACROPHAGE CD47 CD47 CD47 CANCER CELL CANCER CELL CANCER CELL Eat M e Eat M e
Slide 12: Evorpacept Is the Only CD47 Blocker with an Inactive Fc
Evorpacept Is the Only CD47 Blocker with an Inactive Fc Designed to Avoid Toxicities Seen with Conventional Anti-CD47 Conventional anti-CD47 with active Fc Evorpacept with inactive Fc SIRP⍺ Fcγ R MACROPHAGE Red Blood Eat me Cell CD47 Fcγ R Fcγ Conventional Anti-CD47 Due to CD47’s expression on red b
Slide 13: ASPEN-06 Phase 2: Evorpacept Plus TRP in HER2+ GC/GEJ
ASPEN-06 Phase 2: Evorpacept Plus Trastuzumab + Ramucirumab + Paclitaxel (TRP) in HER2+ Advanced/Metastatic GC/GEJ Adenocarcinoma ASPEN-06 Trial Design Study Flow Diagram ITT Patients enrolled with either a HER2+ fresh or archival biopsy Key eligibility criteria N=127 • HER2+ GC or GEJ that has Evor
Slide 14: CD47 Expression Acts as a Predictive Biomarker for Durable Patient Benefit
CD47 Expression Acts as a Predictive Biomarker for Durable Patient Benefit from Evorpacept in the ASPEN-06 Trial ORR in retained HER2+ (n=95) ORR by CD47 expression level in retained HER2+ 100 100 Evorpacept + TRP TRP 90 90 80 80 Confirmed ORR, % 70 70 65.0 60 60 48.9 By CD47 50 expression 50 40 40
Slide 15: Median DOR in Patients with CD47-High Expression was Longer
Median DOR in Patients with CD47-High Expression was Longer for Evorpacept + TRP vs TRP Median Duration of Response Evorpacept + 15.7 TRP All Retained TRP HER2+ 9.1 By CD47 Expression 25.5 CD47-High (IHC3+ ≥10%) 8.4 11.2 CD47-Low (IHC3+ <10%) 12.0 0 5 10 15 20 25 30 Months Wainberg et al., The 2025
Slide 16: Evorpacept Reduced Risk of Disease Progression or Death by 61%
The Addition of Evorpacept Reduced Risk of Disease Progression or Death by 61% for Patients with Retained HER2+ Disease and High CD47 Expression Patients with CD47-High Expression and Retained HER2+ Progression-Free Survival A. Progression-Free Survival Hazard Ratio = 0.39 (95% CI: 0.17, 0.86) Evorp
Slide 17: Evorpacept Led to Improved Overall Survival in CD47-High Patients
The Addition of Evorpacept Led to Improved Overall Survival for Patients with Retained HER2+ and High CD47 Expression Patients with CD47-High Expression and Retained HER2+ Overall Survival Hazard Ratio = 0.63 (95% CI: 0.30, 1.31) Evorpacept + TRP TRP Median OS (95% CI) Evo + TRP 17.0 mos (8.5, NE) T
Slide 18: Consistent Benefit Across Multiple CD47 Cut-Points in ASPEN-06
Evorpacept + TRP Showed Consistent Benefit Across Multiple CD47 Cut-Points in Retained HER2+ and CD47+ Patients in the ASPEN-06 Study % of HER2+ ORR CD47 PFS HRb OS HRb Subgroup Evorpacept + Cut-offa TRP (95% CI) (95% CI) (n=95) TRP 49% 25% 0.72 0.95 No cut-off 100% (n=47) (n=48) (0.44, 1.18) (0.58,
Slide 19: Efficacy in CD47 High Patients Compares Favorably to Benchmark Trials
Evorpacept + TRP Efficacy Data in CD47 High Patients Compares Favorably to Benchmark Trials in HER2+ Gastric Cancer ORR mDOR (months) mPFS (months) mOS (months) ASPEN-06 DESTINY-G04 ASPEN-06 DESTINY-G04 ASPEN-06 DESTINY-G04 ASPEN-06 DESTINY-G04 70% 65% 30 25.5 60% 25 50% 44% 20 18.4 17.0 40% 14.7 Mo
Slide 20: Evorpacept Plus Zanidatamab in Heavily Pretreated Breast Cancer
Previously Reported Robust Activity for Evorpacept Plus Zanidatamab (HER2-Targeted Agent) from a Ph1b/2 Trial of Patients With Heavily Pretreated Breast Cancer Who Had Progressed on Prior HER2 Therapies Key eligibility criteria: 100% Confirmed ORR in patients treated with Cohort 1 evorpacept + zanid
Slide 21: Compelling Clinical Evidence from Two Studies in HER2+ Disease
Compelling Clinical Evidence from Two Studies in HER2+ Disease Support Evorpacept’s Breast Cancer Trials E V O R PA C E P T Robust and Durable Clinical Activity in HER2+ Gastric/GEJ and Breast Cancer Validated Mechanism of Action with a Biomarker Consistently Well-Tolerated with HER2-Targeted
Slide 22: The Evorpacept Opportunity in Breast Cancer
The Evorpacept Opportunity in Breast Cancer Positive randomized data in ASPEN-06 in High De-risked path given gastric cancer with trastuzumab, and Probability positive data in two Ph1b/2 in combination with zanidatamab of Success HER2-positive cancers (HER2-bispecific) in HER2+ breast cancer Changin
Slide 23: Professor Peter Schmid, FRCP, MD, PhD
Professor Peter Schmid, FRCP, MD, PhD Chair, ESMO breast cancer faculty Clinical Expert for UK NICE, nominated by the Royal College of Physicians International breast cancer guidelines panel member Steering Committee member for ASPEN-09 • A multi-national single arm Ph2 study evaluating evorpacept i
Slide 24: As ENHERTU May Move to First Line, Second Line Plus Is an Unknown
As ENHERTU May Move to First Line, Second Line Plus Is an Unknown Given That There Are No HER2-Targeted Agents With Data in a Post-ENHERTU Population Future HER2+ metastatic cancer treatment paradigm 1L T-DXd (Enhertu) • Significant unmet need exists and will increase for patients that have progress
Slide 25: Unmet Need in Metastatic Breast Cancer and Evorpacept's Potential
Unmet Need in Metastatic Breast Cancer and Evorpacept’s Potential Need for agents in the HER2+ BC space that: Evorpacept’s Potential • Need for Drives a different MOA to cell killing via … are novel and bring a different mechanistic enhanced ADCP vs payload-based ADCs approach to target HER2 express
Slide 26: CD47 Protein Expression in HER2+ Breast Cancer is Over-Expressed at Diagnosis
Several Studies Have Found that CD47 Protein Expression in HER2+ Breast Cancer is Over-Expressed at the Time of Initial Diagnosis % BC % HER2+ BC Definition of Clone Ref CD47 High CD47 High High 89/200 (45%) 32/58 (55%) IRS 7-12 A1838 Alhanafy, 2024 • CD47 expression in breast cancer has 84/137 (61%
Slide 27: CD47 Expression in Breast Cancer is Higher in HER2+ Patients
CD47 Expression in Breast Cancer is Higher in HER2+ Patients and More Common in Resistant Cancer CD47 expression is higher on … CD47-high cells are more HER2+ BC cells vs HER2- and… common in recurrent HER2+ BC Candas-green, et al, Nature Communications 2020 27 ALX Oncology Corporate Presentation
Slide 28: CD47 is Upregulated in Response to T-DXd Treatment
CD47 is Upregulated in Response to T-DXd (Enhertu) Treatment in HER2- Positive Breast Cancer Cell Lines T-DXd (Enhertu) exposure increases CD47 expression • As our ASPEN-09 breast study will target post-Enhertu patients, these data provides validation that CD47 is a key mode of ADC evasion in the re
Slide 29: Ongoing Ph 2 Breast Cancer Study in CD47-High and HER2+ Patients
Ongoing Ph 2 Breast Cancer Study Aims to Deliver Strong Benefit in CD47- High and HER2+ Patients who Progress on ENHERTU Key eligibility criteria Key objectives HER2+ mBC (IHC3+ or Primary IHC2+/ISH+) Evorpacept ORR in HER2 ctDNA+ subpopulation Measurable disease per N=80 RECIST 1.1 + Trastuzu
Slide 30: HER2+ and CD47-High 2L+ BC Represents a Significant Commercial Opportunity
HER2+ and CD47-High 2L+ BC Represents a Significant Initial Commercial Opportunity with Potential to Move into Earlier Lines of Therapy 2L+ HER2+ 48K1 Confirmed HER2+ 60-80%2 ~20K addressable patients are CD47-high CD47 High Represents $2-4B 50-70%3 market opportunity in CD47- high, HER2+ 2L+ BC4 An
Slide 31: Clinical Program Update: ALX2004 – EGFR ADC
Clinical Program Update ALX2004 – EGFR ADC Barbara Klencke, MD CMO, ALX Oncology
Slide 32: ALX2004 Designed to Maximize the Therapeutic Window
ALX2004 was Designed to Maximize the Therapeutic Window and Has the Potential to Establish Proof-of-Concept Early in Development Cycle EGFR antibody: Matuzumab-derived EGFR antibody selected to minimize off-tumor skin toxicity and to maximize therapeutic window Epitope distinct from that of FDA-appr
Slide 33: Preclinical Data Support Dose Dependent Activity and Differentiated Safety
Preclinical Data Support Dose Dependent Activity and Differentiated Safety Profile A N T I -T U M O R A C T I V I T Y SAFETY • Dose-dependent activity Safety profile in NHP toxicity across a range of tumors, studies support clinical EGFR expression levels, and development plans mutations • Does not
Slide 34: ALX2004 Shows Potent Anti-Tumor Activity Across Multiple Tumor Types
ALX2004 Shows Potent Anti-Tumor Activity Across Multiple Tumor Types, Varying Levels of EGFR Expression and Mutational Status HCC827 (NSCLC) NCI-H1975 (NSCLC) COLO205 (CRC) HCT116 (CRC) EGFRdel19 mt EGFR L858R/T790M mt, wt EGFR, BRAF V600E wt EGFR, KRAS G12D EGFR: 145,000/cell surface EGFR: 50,000/c
Slide 35: Safety Profile Findings in NHP Toxicity Support Clinical Development
Safety Profile Findings in NHP Toxicity Support Clinical Development Plans GLP NHP Toxicology Study Design Key Findings 10 mg/kg dose (n=10) NOAEL (No Observed Adverse Effect Level) 6-week repeat dose (Q3W dosing) with 6-week 20 mg/kg dose (n=10) recovery period at 5, 10 and HNSTD (Highest Non Sever
Slide 36: Phase 1 Clinical Development Plan in EGFR-Expressing Tumors
Phase 1 Clinical Development Plan in EGFR-Expressing Tumors Dose Finding (Phase 1a) ALX2004 IV Q3W in Dose Expansion (Phase 1b) NSCLC, HNSCC, CRC, and ESCC n = up to 80 Dose Escalation Dose Level 5 n=3+ 1 or 2 tumor types selected from Dose Level 4 Dose Escalation at up to 2 BOIN Dose Escalation n=3
Slide 37: Concluding Remarks
Concluding Remarks Jason Lettman CEO, ALX Oncology
Slide 38: Today's Key Messages
Today’s Key Messages ALX is focused on driving toward multiple inflection points in 2026 across both our 1 programs – Evorpacept and ALX2004 The addition of Evorpacept led to a compelling benefit for patients with high CD47 2 expression and retained HER2+ gastric cancer with the potential to transla
Slide 39: ALXO
NASDAQ GS ALXO © ALX Oncology Inc. All rights reserved.
ALX Oncology Holdings — Q3 2025 Earnings Presentation on 6ix