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STRENGTH IN SYNERGY .POWERFUL IMPACT. Thank you for joiningOur webcast will begin shortly
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© ALX Oncology Inc. All rights reserved. NASDAQ GSALXOR&D Day 2025Jason Lettmann | Chief Executive OfficerMarch 5, 2025
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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-looking statements and includes, but is not limited to the (i) results and cost and timing of our product development activities and clinical trials; (ii) completion of the Company’s clinical trials that are currently underway, in development or otherwise under consideration; (iii) our expectations about the timing of achieving regulatory approval and the cost of our development programs; (iv) projected financial performance of the Company; (v) the expected development of the Company’s business, projects, collaborations and joint ventures; (vi) execution of the Company’s vision and growth strategy, including with respect to future M&A activity and global growth; (vii) sources and availability of third-party financing for the Company’s research and development; (viii) future liquidity, working capital, and capital requirements; and (ix) industry trends. These and other risks are described more fully in ALX Oncology’s filings with the Securities and Exchange Commission (“SEC”), including ALX Oncology’s Annual Report on Form 10-K and other documents ALX Oncology files with the SEC from time to time. Although forward-looking statements contained in this presentation are based upon what management of the Company believes are reasonable assumptions, there can be no assurance that forward-looking statements will prove to be accurate. Actual results and future events could differ materially from those anticipated in such statements. The Company undertakes no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws.This presentation concerns product candidates that are under clinical investigation, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. These product candidates are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated.This presentation also contains estimates and other statistical data made by independent parties and by ALX Oncology relating to market size and growth and other industry data. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of ALX Oncology’s future performance and the future performance of the markets in which it operates are necessarily subject to a high degree of uncertainty and risk.March 5, 2025 ALX Oncology R&D Day3 Forward-Looking Statements
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March 5, 2025 ALX Oncology R&D Day4 What We Will Cover Today 3 2 1 4Share the results of aggressive prioritization and cost-cutting resulting in additional catalysts and extending our runway into Q4 2026 Lay out a clear and focused development strategy with several pathsto FDA registration Summarize the clinical data that underpin our conviction in evorpacept’s activityProvide new guidance on upcoming data events over next ~12-18 months across multiple clinical studiesALX has now demonstrated that combining evorpacept with anti-cancer antibodies is active and is advancing several trials forward to drive the program towards approval
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5 Today’s PresentersJason LettmannCEO, ALX Oncology Alan Sandler, MDCMO, ALX Oncology Paula R. Pohlmann, MD, MS, PhDAssociate ProfessorChief, Section of Breast Cancer Clinical ResearchDepartment of Breast Medical OncologyDepartment of Investigational Cancer TherapeuticsUT MDACC Eric Van Cutsem, MD, PhD Professor Gastroenterology / Digestive OncologyUniversity Hospitals Gasthuisberg / Leuven & KU LeuvenBelgium Allison Dillon, PhDCBO, ALX Oncology Harish Shantharam, CFA CFO, ALX Oncology Jaume Pons, PhDCSO, ALX OncologyALX Oncology R&D DayMarch 5, 2025
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10Concluding RemarksJason Lettmann, Chief Executive Officer 01IntroductionJason Lettmann, Chief Executive Officer02History of Evorpacept and Preclinical RationaleJaume Pons, PhD, Chief Scientific Officer03Clinical Data in HER2+ Patient PopulationsAlan Sandler, MD, Chief Medical Officer04New Breast Cancer Program Paula Pohlmann, MD, MD Anderson Cancer Center05New Colorectal Cancer ProgramEric Van Cutsem, MD, PhD, Univ Hospitals Belgium06Antibody Combinations in Heme Malignancies Alan Sandler, MD, Chief Medical Officer07Building the Evorpacept FranchiseAllison Dillon, PhD, Chief Business Officer08ALX2004Jaume Pons, PhD, Chief Scientific Officer09Financial Updates and MilestonesHarish Shantharam, Chief Financial Officer ALX Oncology R&D Day6 March 5, 2025
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ALX Oncology R&D Day Looking Back at Our 2024 Priorities Build an A Team: Assemble world-class management team and board Focus on execution: Deliver data from five clinical studies Drive what’s next:Advance new evorpacept studies and ALX2004 into the clinicResults2024 Accomplishments•Delivered first positive randomized study in the CD47 space with the ASPEN-06 gastric data - oral presentation at ASCO GI 2025•Delivered ASPEN-07 bladder data at ASCO 2024, evorpacept + zanidatamab breast data at SABCS 2024, and NHL data at AACR 2024 •Completed enrollment of ASPEN-03, 04 and 07, and announced first patient dosed in Sanofi study with Sarclisa•Added to leadership with new CMO Dr. Alan Sandler, new CFO Harish Shantharam, new CBO Dr. Allison Dillon, and several others in < one year•Added deep clinical and oncology strength to Board of Directors with Dr. Barbara Klencke and Dr. Chris Takimoto in Q4 2024•Drove indication selection and study launch for evorpacept antibody combinations in breast and colorectal cancers•Delivered IND-ready package for ALX2004 to support Q1 2025 IND submission7March 5, 2025
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8 2025 Strategic Imperatives Deliver BD partnership/ strategic dealsExpand and execute with existing partnersRAISE ALX PROFILE & PARTNER EXPAND INDICATIONS & DELIVER PIPELINEPursue additional studies in BC and CRCDrive ALX2004to IND clearanceOPTIMIZE BUDGET & PRIORITIESDeliver major catalysts on current cashManage budget to extend runway Deliver ASPEN-03 / ASPEN-04 dataExecute on ongoing studiesEXECUTE ON EXISTING STUDIES March 5, 2025 ALX Oncology R&D Day
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HER2CD20EGFRCD38 Nectin-4 HER2 PD(L)11A N T I - C A N C E R A N T I B O D I E S2A N T I B O D Y -D R U G C O N J U G A T E S ( A D C S )3C H E C K P O I N T I N H I B I T O R S Bold Vision for Evorpacept: Deliver First-In-Class, Universal Combination Agent ALX Oncology R&D Day9 Three Evorpacept MOAs Combinations in the Clinic Clinical StudiesASPEN-06Gastric Ph2ASPEN-01Gastric Ph1bEvo + ZaniBreast Ph1bASPEN-01NHL Ph1bMDAndersonNHL Ph1bASPEN-07Bladder Ph1bASPEN-01HNSCC Ph1b March 5, 2025
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ALX Oncology R&D Day10 Evorpacept Is Designed to Enhance the Activity of the Majority of Biologics Used in Oncology Today2023 Global Sales of Biologics in Oncology: $88B Analysis based on GlobalData sales estimates PD(L)1 inhibitors: $50BAnti-cancer antibodies: $28BADCs: $9B March 5, 2025
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S T A T U SP H A S E 3P H A S E 2P H A S E 1I N D E N A B L I N GI N D I C A T I O NP R O G R A MM O D A L I T Y/ T A R G E TE V O R P A C E P T P R O G R A M SNext steps pending FDA input2L or 3L Advanced HER2-Overexpressing Gastric/Gastroesophageal Junction (GEJ)ASPEN-06Evorpacept, Herceptin®, CYRAMZA® + Paclitaxel1Anti-cancerAntibodiesLaunching Q1 ‘25, FPI mid-year ’25ENHERTU®-Experienced HER2-Positive Breast CancerASPEN-BreastEvorpacept, Herceptin®+ chemotherapyLaunching Q1 ‘25, FPI mid-year ’252L, EGFR-Naïve Metastatic Colorectal Cancer (CRC)ASPEN-CRCEvorpacept, Erbitux®+ chemotherapyTopline results Q2 ‘251L PD-L1 Positive Advanced HNSCC (Head and Neck Squamous Cell Carcinoma)ASPEN-03Evorpacept + KEYTRUDA®2Checkpoint InhibitorsTopline results Q2 ‘251L Advanced HNSCCASPEN-04Evorpacept, KEYTRUDA®, 5FU + Platinum2 Data update Q2’ 25Urothelial CancerASPEN-07Evorpacept + PADCEV®ADCsA L X 2 0 0 4 P R O G R A MFiling IND Q1 ’25 EGFR-Expressing Solid TumorsSingle-agent dose-escalation and expansionADCMarch 5, 2025 ALX Oncology R&D Day11 ALX Oncology is Pursuing a Robust Development Plan for Evorpacept ALX Oncology retains worldwide rights to evorpacept.1. Lilly supplies CYRAMZA® for ALX Oncology’s ASPEN-06 program 2. Merck supplies KEYTRUDA® for ALX Oncology’s ASPEN-03 and ASPEN-04 programs
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S T A T U SP H A S E 3P H A S E 2P H A S E 1I N D E N A B L I N GI N D I C A T I O NP R O G R A MM O D A L I T Y/ T A R G E TE V O R P A C E P T P R O G R A M SData presented at SABCS ‘24HER2-Expressing Breast Cancer and Other CancersZanidatamab1 + EvorpaceptAnti-cancerAntibodiesFPI Q3 ‘24, Currently EnrollingRRMM (Relapsed or Refractory Multiple Myeloma)SARCLISA® + Dexamethasone2+ EvorpaceptCurrently EnrollingHER2-Positive HER2-Low Metastatic Breast CancerENHERTU® (I-SPY)3+ EvorpaceptADCsALX Oncology is Pursuing a Robust Development Plan for Evorpacept:Non-ALX Sponsored Evorpacept Trials ALX Oncology retains worldwide rights to evorpacept.1. Jazz Pharmaceuticals sponsors zanidatamab clinical trial 2.Quantum Leap Healthcare Collaborative sponsors I-SPY clinical trial 3. Sanofi sponsors SARCLISA clinical trialALX Oncology R&D Day12March 5, 2025
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March 5, 2025 ALX Oncology R&D Day13 Upcoming milestone ASPEN-03 and ASPEN-04 Phase 2 Readout: 1L HNSCC •Primary endpoint updated to be only ORR to support potential Accelerated Approval •OS, PFS, and ORR between groups are secondary endpoints•Results will be submitted to a medical meeting in 2H 2025 2:1Evorpacept + KeytrudaEvorpacept 45 mg/kg (Q3W)+ Keytruda + 5FU + cisplatin or carboplatinPrimary EndpointN≈118 N≈59Evorpacept45 mg/kg (Q3W)+ KeytrudaKeytruda (Q3W)•ORR based on BICR vs historical control of pembro alone2:1Evorpacept + Keytruda + chemoN≈108 N≈54•ORR based on BICR vs historical control of pembro + 5FU + platinumASPEN-03 Phase 2 trialASPEN-04 Phase 2 trialKeytruda + 5FU + cisplatin or carboplatin (Q3W) Primary Endpoint ASPEN-03 and ASPEN-04 TLR expected 2Q 2025 Secondary analyses will include ORR between randomized arms
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March 5, 2025 ALX Oncology R&D Day14 Unmet Need in HNSCC and Evorpacept’s Potential … are novel and bring a different mechanistic approach to target … have demonstrated efficacy in randomized settings given that single-arm trials have not consistently translated to larger pivotal trials… can address the entire 1L continuum of careincluding both pembro and pembro + chemo… are IO agents that can enable the “long tail” and ultimately benefit survivalNeed for agents in 1L HNSCC that:Drives a different MOA to cell killing via enhanced T-cell priming and activation With >300 patients enrolled, ASPEN-03/ 04 will be largest randomized trials in 1L HNSCC to read out since the LEAP studyASPEN-03/04 test evorpacept in combination with pembro +/- chemoMost advanced IO agent in development in 1L HNSCC with potential to be first IO drug approved since pembro in 2019Evorpacept’s potential
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March 5, 2025 ALX Oncology R&D Day15 Combining Evorpacept With Anti-Cancer Antibodies Represents the MostDe-Risked Path Forward and a Substantial Commercial Opportunity HER2CD20EGFRCD381A N T I - C A N C E R A N T I B O D I E SThree Evorpacept MOAs Combinations in the Clinic Clinical StudiesASPEN-06Gastric Ph2ASPEN-01Gastric Ph1bEvo + ZaniBreast Ph1bASPEN-01NHL Ph1bMD AndersonNHL Ph1bT O D AY ’ S F O C U S The Evorpacept + Antibody Franchise
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March 5, 2025 ALX Oncology R&D Day16 Evorpacept + Anti-Cancer Antibody Mechanism of Action M A C R O P H A G EC A N C E R C E L LEvorpaceptTumor-associated antigenAnti-cancer antibody CD47Eat MeFcγ
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ALX Oncology R&D Day17 Evidence that Evorpacept Improves Upon Anti-Tumor Activity of Standard of Care Anti-Cancer Antibodies in Solid and Hematologic Tumors25%49%Gastric(HER2+ fresh biopsy or ctDNA+1)ORRN = 49 N = 4722%56%Breast(R/R HER2+ by central assessment4)ORRN = 918%54%34%83%NHL(R/R Indolent)CR RateN = 11 N = 18ControlEvo + ControlMargenza® + Chemo Benchmark3Evo + Zanidatamab4Rituximab Benchmark2Evo + RituximabR2Benchmark2Evo + R21. ASPEN-06 Dec 2, 2024 data cutoff in fresh HER2+ biopsy or ctDNA+ patients. 2. AUGMENT study, Leonard, JCO, 2019 3. Margenza prescribing information; 4. SABCS 2024 #PS8-09; HER2+ by central assessmentORR = overall response rate; CR = complete response; IST = investigator-sponsored trialASPEN-06, randomized Ph2 ASPEN-01 Ph1band historic benchmarkISTand historic benchmarkPhase 1b/2 Collaboration4 and historic benchmarkMarch 5, 2025
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Changing landscape drives opportunityin patients whohave progressed on ENHERTU and/or other HER2-directed therapiesPositive randomized data in ASPEN-06 in gastric cancer with trastuzumabPositive data in evorpacept + zanidatamab study in HER2+ metastatic breast cancerDe-risked givenpositive data in two HER2-positive cancersSignificant peak sales potential and unique opportunity to move to earlier lines of care March 5, 2025 ALX Oncology R&D Day18 The Evorpacept Opportunity in Breast CancerActive in patients who progressed on trastuzumab in gastric cancerActive in patients who progressed on ENHERTU and 5+ HER2-directed Tx in breast cancer2L+ HER2+ mBC represents a population of ~48k* patients1L HER2+ mBC and neoadjuvant setting represents a population of an additional ~120k* patients*In 7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and Japan; Source: Clarivate Market Forecast, gastroesophageal cancer, December 2024
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E V O R P A C E P T P R O G R A M SASPEN-06 GastricEvorpacept, Herceptin®, CYRAMZA® + Paclitaxel1Anti-cancermAbsASPEN-BreastEvorpacept, Herceptin®+ chemotherapyASPEN-CRCEvorpacept, Erbitux®+ chemotherapyASPEN-03/04HNSCCEvorpacept + KEYTRUDA®2+/- 5FU + PlatinumCPIsA L X 2 0 0 4ALX2004EGFR-targeted ADCADCMarch 5, 2025 ALX Oncology R&D Day19 ALX Is Focused On Aggressively Driving Several Paths to FDA RegistrationPh3Pending FDA DiscussionsFDA Meeting On AA Pathway Q2 2025 Pot’l FDA Meeting On AA Pathway 2H 2025 FDA EOP2 2027 IND SubmissionQ1 2025FDA Type C 2027 Interim Analysis 2H 2026 Safety & Early Efficacy1H 2026 Ph3 Initiation Late 2027 Top Line Results2Q 2025 Ph3 Initiation 1H 2026 First Patient In Mid-2025 Safety Data1H 2026Ph3 Initiation Late 2027 First Patient In Mid-2025
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MECHANISM AND TARGETHistory of Evorpacept and PreclinicalRationale Jaume Pons, PhDCSO, ALX Oncology
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Evorpacept: Uniquely Designed to Offer a Differentiated Safety Profile and Robust Clinical Activity in Combination with Available Cancer TherapiesE V O R PA C E P THigher affinity CD47 bindingInactive FcdomainLower molecular weightAntibody-like pharmacokineticsR O B U S T C L I N I C A L A C T I V I T YB E S T - I N -C L A S S S A F E T Y P R O F I L ES T R O N G S O L I D T U M O R A C T I V I T YB R O A D C O M B I N A T I O N P O T E N T I A LMore potently blocks CD47 signal on cancer cellsLess “sink effect”= more targetedNo known dose-dependent cytopenia = higher dosingIncreased solid tumor penetration and higher effective dosingLong halflife = less frequent dosing and matching regimen with combinations ALX Oncology R&D Day21March 5, 2025
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ALX Oncology R&D Day22 CD47 Is the Canonical Myeloid Checkpoint and Ubiquitously Expressed in Both Healthy Tissues and Tumors CD47 as a tumor-associated antigen CD47 as a myeloid checkpointCD47 expression levels from RNA sequencing Median TPMMarch 5, 2025Tang, Z. et al, GEPIA, 2017; TPM = transcripts per million
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ALX Oncology R&D Day23 Traditional CD47 Blockers With Active FC Domains Were Limited by On-Target Cytopenias March 5, 2025
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ALX Oncology R&D Day24 Evorpacept Enables Antibody-Dependent Cellular Phagocytosis (ADCP) Without Inducing Cytopenias March 5, 2025
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25 Evorpacept (ALX148) Is Designed To Avoid the Cytopenias Caused by Traditional Approaches To Targeting CD47 Inactive Fc is the core determinant of safety profile for a CD47-targeted agentas evidenced by decreased blood counts after initial dose with active FcALX Oncology R&D DayMarch 5, 2025CD-1 mice received 30 mg/kg IV single dose***p<0.001, ****p<0.0001Kauder, et al, 2018
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March 5, 2025 ALX Oncology R&D Day26 Evorpacept Combined With Anti-Cancer Antibodies in a Range of Cancer Types Evorpacept unleashes macrophages to destroy cancer cells and the combined effectwith an anti-cancer antibody potentiates the innate immune system,an underexploited pathway of tumor killing Solid tumorsHematologic malignancies**CRC PDOX22420 Model OE19 HER2+ Gastric ModelRaji NOD-SCID Model MM1.R phagocytosis assayDays post implantation10 14 18 22 26ALX protein, nM (log10)-2 -1 0 1 2 3Days post implantation8 12 16 20 24 28 32 360 5 10 15 20 25 30 35 40 45Days post implantationPBSEvorpaceptCetuximabEvorpacept + cetuximabPBSEvorpaceptTrastuzumabEvorpacept + TrastuzumabPBSEvorpaceptRituximabEvorpacept + rituximabEvorpacept + daratumumabControl + daratumumabEvorpacept + isotype controlControl + isotype control * p < 0.0001 one-way ANOVA compared to antibody alone**** p < 0.0001, paired two-tailed t-test, N=10 mice/group** p <0.01, two-tailed t-test, N=10 mice/groupTrastuzumab, twice/week, 6 doses; evorpacept, twice/week, 6 doses** p =0.0051, paired two-tailed t-test, N=5 mice/groupCetuximab (3 mg/kg), every 7 days, 3 doses; evorpacept (30 mg/kg), every 4 days, 6 dosesKauder, et al, 2019; ALX unpublished research
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Increased Tumor-Associated Macrophages and Infiltrating Lymphocytes Observed After Treatment with Evorpacept Combinations in Patients Baseline tumor-infiltrating immune cells in responders and non-responders treated with evorpacept + trastuzumab, ramucirumab, and paclitaxel ALX Oncology R&D Day27March 5, 2025Chung, et al, ESMO 2021
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CLINICAL DATA IN HER2+ PATIENT POPULATIONSGastric Cancer: Trastuzumab + EvorpaceptBreast Cancer: Zanidatamab + Evorpacept A N T I - C A N C E RA N T I B O D I E SAlan Sandler, MDCMO, ALX Oncology
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March 5, 2025 ALX Oncology R&D Day29 ASPEN-06 Phase 2: Evorpacept Plus TRP in HER2+ Advanced/Metastatic GC/GEJ Adenocarcinoma Primary endpoints in both ITT and fresh biopsy populations:•Improvement in ORR** vs assumed historical control of 30% (Wilke et al, Lancet, October 2014)•Improvement in ORR** over internal control (difference ≥ 10%)Secondary endpoints•DOR, PFS, OSExploratory endpoint•ctDNAEvorpaceptTRP+ + +Key eligibility criteria•HER2+ GC or GEJ that has progressed on or after prior HER2-directed therapy•2L or 3L•Prior trastuzumab deruxtecan (ENHERTU) and/or checkpoint inhibitors allowed•Prior CD47-agent, anti-SIRPα, or ramucirumab excluded1:1VS.ITT patientsN=127 Fresh HER2+* biopsy subsetN=48ControlTRP+ + + GC- gastric cancer, GEJ- gastroesophageal junction, TRP- trastuzumab, ramucirumab, paclitaxel; selected secondary and exploratory endpoints shown.*Fresh HER2-positive is defined as biopsies that were HER2-positive after receiving prior HER2-targeted treatment **Based on investigator assessmentEvoEvorpacept (30 mg/kg IV Q2W) Trastuzumab (6 mg/kg > 4 mg/kg Q2W)TRamucirumab (8 mg/kg Q2W)RPaclitaxel (80 mg/m2on day 1, 8, 15 of 28-day cycle)PAll patients enrolled received a prior HER2-targeted therapy (e.g., trastuzumab) and were enrolled with either a HER2+ fresh or archival biopsy
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ASPEN-06 Safety: Evo-TRP Was Generally Well Tolerated and ≥Grade 3 TEAEs Were Largely Balanced Across the Two Arms •The incidence of adverse events due to any cause was comparable by arm•There were 11 Grade 5 treatment emergent adverse events (four for ETRP; seven for TRP), only two of which were deemed to be treatment related: esophageal perforation (ETRP) and pneumopathy (TRP)All causality adverse events, by gradeGrade 5Grade 4Grade 3Grade 2Grade 1100%80%60%40%20%020%40%60%80%100%All G5 TEAEs: ETRP (N=4): sepsis N=2, esophageal perforation N=1, respiratory failure N=1. TRP (N=7): sepsis N=1, pneumonia/pneumopathy/respiratory infection N=1 each, sudden death N=1, death from unknown cause N=1, esophageal hemorrhage N=1; data cutoff as of 02 Dec 2024Evorpacept’s safety profile was consistent with its prior experience in over 700 patients treated to dateEvoEvorpacept TrastuzumabTRamucirumabRPaclitaxelP N=63ControlEvoTRP+ + + N=63TRP+ + ALX Oncology R&D Day30March 5, 2025
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ALX Oncology R&D Day31 Evorpacept Demonstrated Durable Activity in Patients with HER2-Positivity Confirmed by Fresh Biopsy or ctDNAEvoTRP+ + +TRP+ +Confirmed ORR = 48.9%(95% CI: 34.1%, 63.9%)mDOR = 15.7m(95% CI: 7.7m, NR)Confirmed ORR = 24.5%(95% CI: 13.3%, 38.9%)mDOR = 9.1m(95% CI: 3.5, NR)Patients with HER2+ confirmed with fresh biopsy OR ctDNA+ (n=96) Seven patients treated with Evo+TRP and five patients treated with TRP had no post-baseline assessment or best response of NE; data cutoff as of 02 Dec 2024; NR = Not ReachedEvoEvorpacept TrastuzumabTRamucirumabRPaclitaxelPMarch 5, 2025
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ALX Oncology R&D Day32 Improved Progression-Free Survival in Patients with Fresh Biopsy or HER2+ Positive ctDNA Data cutoff as of 02 Dec 2024 Progression-free survival (PFS) based on investigator assessmentHER2+ confirmed with fresh biopsy OR ctDNA+ (n=96)Hazard Ratio: 0.64 [0.39; 1.07] Number of patients with events30 (63.8%)37 (75.5%) Evo + TRPTRP12-month rate40%21%Number of patients censored17 (36.2%)12 (24.5%)mPFS [95% CI]7.5 [5.5-14.7]6.7 [4.0-9.0]March 5, 2025
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ASPEN-06 Gastric Study: Potential Lead Indication in a Biomarker-Selected Patient Population FDA meeting scheduled in Q2 to discuss ASPEN-06 results and possible path to Accelerated Approval; update planned in Q2 ALX Oncology R&D Day33 Robust and Durable Clinical Activityin HER2+ PatientsValidated Mechanismof Action with a Clear BiomarkerConsistently Well-Tolerated with a Multidrug RegimenActive in Patients Who Have Progressedon Conventional HER2-Directed TherapyEvorpacept + TRP Compares Favorably to Benchmarks in >2L TreatmentMarch 5, 2025
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This study provides clinical data supporting further development of evorpaceptwith HER2-targeted agents in patients with breast cancer March 5, 2025 ALX Oncology R&D Day34 Phase 1b/2 Trial Evaluating Safety and Efficacy of Evorpacept Plus Zanidatamab in Patients Who Have Progressed on Prior HER2-Directed Therapy Summary of baseline characteristics in Cohort 1•Population represented heavily pretreated R/R population •Median of six prior therapies including multiple HER2-targeted therapies •Notably, 100% of patients had received prior ENHERTU•Local assessment of HER2 in archived tumor samples was used for enrollment; when unavailable, patients could be enrolled based on central assessment•Data were analyzed for all patients enrolled and based on central assessment•Of the 20/21 patients with local HER2 assessment, eight (40%) were confirmed HER2-positive by central assessment (one centrally HER2-positive patient did not have local assessment) Key eligibility criteriaUnresectable, locally advanced and/or metastatic HER2-expressing cancer•HER2-positive breast cancer (IHC 3+ or IHC 2+/FISH-positive)•≥3 prior regimens, must include trastuzumab, pertuzumab and either T-DM1, tucatinib, or T-DXd•Data were analyzed for all patients enrolled and based on central assessmentTreatment1Expansion Cohort 11. Mandatory IRR prophylactic treatment included corticosteroids, antihistamines, and acetaminophen. Study conducted by Jazz PharmaceuticalsEvorpaceptZanidatamab+30 mg/kg Q2W 1200 mg (<70 kg) OR1600 mg (≥ 70kg) Q2WHER2-positive mBC (n=21)
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March 5, 2025 ALX Oncology R&D Day35 The Combination of Evorpacept and Zanidatamab was Well-Tolerated With a Manageable Safety Profile that is Consistent With Prior Experience With Each Agent •Most treatment-related adverse events were grade 1 or 2 (related to zanidatamab and/or evorpacept)•TRAEs of special interest included:one (1.9%) patient with grade 3 ejection fraction decreased and 12 (23.1%) patients with IRRs – all IRRs resolved; one patient had an IRR event after the dosing order was reversed to zanidatamab followed by evorpacept •No non-infectious pulmonary toxicities occurred •There were no treatment-related deathsData cutoff date 1 August 2024.a. TRAEs defined as events with an onset during or after receipt of the first dose of study treatment within 30 days after the last dose and were determined as related to zanidatamab and/or evorpacept by the investigators.b. Two additional events (diarrhea and LVEF decreased) occurred outside the 30-day window for TRAEs. c. Both events were grade 3 IRRs that resolved following treatment discontinuation. d. Defined as LVEF <50% with absolute decrease of ⩾10 percentage points below pretreatment baseline and/or grade ⩾2 heart failure. e.Grades 1-3 occurring in ⩾20% of patients or ⩾2 patients.AESI, adverse event of special interest; IRR, infusion-related reaction; LVEF, left ventricular ejection fraction; TRAE, treatment-related adverse event.Montero. et. al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007 All Patients (N=52)45 (86.5)Any TRAE, n (%)38 (73.1)Grade 1-27 (13.5)Grade 30 (0)Grade 4-53 (5.8)bSerious TRAEs, n (%)2 (3.8)cTRAEs leading to treatment discontinuation, n (%)0 (0)TRAEs leading to dose reductions, n (%)Treatment-related AESI, n (%)1 (1.9)Left ventricular dysfunctional12 (23.1)IRR0 (0)Non-infectious pulmonary toxicitiesGrade 3Grade 2Grade 1Most common TRAEs* n (%)3 (5.8)9 (17.3)20 (38.5)Diarrhea1 (1.9)7 (13.5)9 (17.3)Fatigue0 (0)3 (5.8)11 (21.2)Nausea2 (3.8)7 (13.5)3 (5.8)IRR
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March 5, 2025 ALX Oncology R&D Day36 Breast Cancer Patients With Confirmed HER2-Positivity Had the Greatest Benefit From Evorpacept + Zanidatamab Strongest efficacy in confirmed HER2+•ORR of 55.6% (5/9) •mDOR NE (range: 5.5-25.9m)•mPFS = 7.4m (95% CI: 0.6, NE)Compares favorably to benchmark•SOPHIA study (n=536) of margetuximab + chemo vs. trastuzumab + chemo (ORR: 22% vs. 16%)0%10%20%30%40%50%60%70%80%90%100%Confirmed ORRConfirmed ORR in patients treated with evorpacept + zanidatamab in Cohort 133%N=21Cohort 1All patients56%N=9Confirmed HER2+ bycentral assessment 17%N=12HER2-low or ultralow by central assessmentMedian follow-up (range) was 9.6 (0.6, 29.7) months, with six patients on treatment at data cutoff as of August 1, 2024; HER2-Low/Ultralow = IHC1+, IHC2+ / ISH-, IHC 01. JAMA Oncol. 2021;7(4):573-584. doi:10.1001/jamaoncol.2020.7932 Montero. et. al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007
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Two Studies Demonstrate the Power of Evorpacept Engaging the Innate Immune Response and Further Validate Its Mechanism With Anti-Cancer Antibodies, Particularly in HER2+ Tumors ALX Oncology R&D Day37 Robust and Durable Clinical Activityin HER2+ Gastric/GEJ and Breast CancerValidated Mechanism of Action with a Clear BiomarkerConsistently Well-Tolerated withHER2-Targeted AgentsActive in Patients Who Have Progressedon Conventional HER2-Directed TherapyE V O R PA C E P T March 5, 2025
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NEW BREAST CANCER PROGRAMASPEN-BreastPaula R. Pohlmann, M., MS., PhDAssociate ProfessorChief, Section of Breast Cancer Clinical ResearchDepartment of Breast Medical OncologyDepartment of Investigational Cancer TherapeuticsUT MDACC
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March 5, 2025 ALX Oncology R&D Day39 Breast Cancer Remains an Area of High Unmet Need Despite Recent Advancements in Early Metastatic Lines of Therapy 31.9%0%25%50%75%100%Localized Regional Distant Unknown5-year relative survival in breast cancerAmerican Association for Cancer Research: Head and Neck Cancers; SEER cancer stat facts accessed February 2025; CRC = colorectal cancer; NHL = non-Hodgkin lymphoma US top 10 types of cancer by estimated new cases in 2024 (thousands)(311)(299)(235)(153)(101)(83)(82)(81)(71)(68)42 35 125 53 8 17 14 20 16 13 400 300 200 100 0 100 200BreastProstateLung and bronchusCRCMelanomaBladderKidneyNHLHNSCCUterine Breast cancer represents 15.5% of all new cancer cases in the US and rates are rising New cases in 2024Deaths in 20241001101201301401501975 1985 1995 2005 2015 2025Rate per 100,000
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ALX Oncology R&D Day40 Recent Advancements in 1L and 2L Treatment Have Increased the Need for Effective Therapies in T-DXd Experienced Patients •Current SOC is 1stline THP followed by Enhertu for patients with no or stable CNS disease•Options for patients that progress on T-DXd are increasingly important•Current therapies used in the post T-DXd setting are approved based on pre T-DXd era trials•Ongoing DESTINY-Breast09 Phase 3 trial of 1L T-DXd +/- pertuzumab could change treatment paradigmTrastuzumab + pertuzumab + taxane (known as THP or Cleopatra regimen)1LT-DXd (ENHERTU) 2LT-DM1Tucatinib + trastuzumab + capecitabine3L+Trastuzumab + chemoTrastuzumab + HER2 TKIOther HER2-targeted therapyToday’s HER2+ metastatic cancer treatment paradigm March 5, 2025Adapted from NCCN guidelines v1.2025
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41 Established THP as the Standard of Care in First-Line Metastatic Diseasein HER2+ Breast Cancer Progression-Free SurvivalOverall Survival •CLEOPATRA study (n=808) established docetaxel + trastuzumab + pertuzumab (THP) as 1L standard of careALX Oncology R&D DayMarch 5, 2025Baselga J et al. NEJM 2012; Swain S et al. NEJM 2015; Swain S et al. Lancet Oncol 2020
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42 DESTINY-Breast 09 Is an Ongoing Challenge to 1L CLEOPATRA and May Establish T-DXd (ENHERTU) as the New 1L Standard of Care Cleopatra regimenALX Oncology R&D DayMarch 5, 2025Tolaney et al, SABCS 2021
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ALX Oncology R&D Day43 Why Do We Need More Novel Anti-HER2 Treatment Options? •Regardless of ENHERTU in 1L or 2L, patients will still progress and need new options in later lines•Lack of post-ENHERTU data supporting the effectiveness of KADCYLA and/or TUKYSA® potentially creates a new, large market opportunity with no standard of care With Destiny Breast03, ENHERTU was established as SOC in 2L mBC but … ~25% of patients progressed at 1 year and ~50% progressed at 2 yearsMarch 5, 2025Adapted from 1. Cortes J, et al N Engl J Med 2022; 2. Hurvitz et al, GS2-02 SABCS 2022.From: Pohlmann PR Spotlight Discussion SABCS 2022
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March 5, 2025 ALX Oncology R&D Day44 There Are No IO Agents Currently Approved With a Broad Label for HER2-Positive mBC There are no IO agents currently approved with a broad label for HER2-positive mBC •Currently approved•Trastuzumab•Pertuzumab•Margetuximab•In development•ZanidatamabMAbs/Bispecifics •Currently approved•T-DXd•T-DM1•In development•ARX-788ADCs •Currently approved•Lapatinib•Neratinib•Tucatinib•In development•AST-1306TKIs •Currently approved•Pembrolizumab/ dostarlimab(only approved for MSI-H or dMMR patients)•In development•EvorpaceptIO Adapted from Pohlmann PR et al. CCR Focus
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ALX Oncology Corporate Presentation45 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 •Significant unmet need exists and will increase for patients that have progressed on T-DXd•Evorpacept has demonstrated activity in post-Enhertu patients •Evorpacept + zanidatamab showed promising antitumor activity in patients with heavily pretreated HER2-positive mBC including after progression on prior T-DXd1LNo Standard of Care Exists In Patients Post-Enhertu2LT-DM1Tucatinib + trastuzumab + capecitabine3L+Adapted from NCCN guidelines v1.2025Trastuzumab + chemoTrastuzumab + HER2 TKIOther HER2-targeted therapyFuture HER2+ metastatic cancer treatment paradigmT-DXd (Enhertu)
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Dotted lines indicate 20% increase and 30% decrease in sum of diameters of target tumors. Treated patients without a post-baseline assessment are not shown (1/21 patient in cohort 1).BOR, best overall response; PR, confirmed partial response; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; PD, progressive disease; PR, partial response; SD, stable disease; T-DXd, trastuzumab deruxtecan.Data cut off date 1 August 2024.March 5, 2025 ALX Oncology R&D Day46 Evorpacept + Zanidatamab Had an ORR of 55.6% in Patients Who Had Confirmed HER2-Positivity and All Had Prior ENHERTU •Patients with heavily pre-treated HER2-positive breast cancer had benefit from evorpacept + zanidatamab•Patients had a median of six prior lines of therapy •Allpatients had received prior ENHERTUand prior trastuzumab HER2+ metastatic breast cancerCohort 1 HER2-positive by central assessmentMontero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007
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•Need for ALX Oncology R&D Day47 Unmet Need in mBC and Evorpacept’s Potential … are novel and bring a different mechanistic approach to target HER2 expression… have demonstrated activity in post-HER2-directed tx settings following both ADCs and mAbs… can supplement and enhance standard of care rather than replace the backbone therapies… are safer than ADCs, which can have off-target payload-driven toxicities … are IO agents that can enable the “long tail” and ultimately benefit survival Need for agents in the HER2+ BC space that:Drives a different MOA to cell killing via enhanced ADCP vs payload-based ADCs or kinase-driven mAbs/ bispecificsDemonstrated activity post-tras in gastric and following 4+ lines of HER2-directed therapy in breastDesigned to work synergistically with central therapies in BC like HerceptinSafety profile is differentiated versus both approved and emerging ADCs Potential to be 1stand only IO therapeutic for all HER2+ BC patients Evorpacept’s Potential March 5, 2025
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Now Advancing Two Clinical Studies in Breast Cancer: Evorpacept + Herceptin in 2L+ BC Post-ENHERTU and Evo + ENHERTU in Late-Line mBC Ph2 Randomized mBCStudy of Evorpacept + Trastuzumab + Chemo Treatment First Patient Will be Dosed Mid-year 2025 TreatmentEvorpacept 30 mg/kg every two weeks (Q2W) or 45 mg/kg every three weeks (Q3W)+ENHERTU (trastuzumab deruxtecan) 5.4 mg/kg every three weeks (Q3W)Ph 1b Single-Arm mBCStudy of Evorpacept + ENHERTU Locally advanced or metastatic HER-2 positive breast cancer following prior ENHERTU Unresectable or metastatic HER2-positive or HER2-low breast cancerCurrently Enrolling, Update Expected by EOYALX Oncology R&D Day48 Pre-ISPYNCT05868226ASPEN – BreastN=30Evorpacept + Trastuzumab +Physician’s Choice ChemotherapyMarch 5, 2025
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Proposed Randomized Phase 2 Trial of Evorpacept and Trastuzumab and Chemotherapy in Patients With HER2+ Metastatic Breast Cancer Primary Endpoints•ORR by BICRSecondary Endpoints•PFS•DOR•OSKey eligibility criteriaHER2+ mBC (IHC3+ or IHC2+/ISH+) with measurable disease per RECIST 1.1Prior T-DXdAll approved treatments are allowed post T-DXd therapy No CNS metastases or previously treated and stable CNS metastasesPoster Enhertu biopsyECOG 0-1n=60n=601:1EvorpaceptTrastuzumab+Chemotherapy+TrastuzumabChemotherapy+Vs.ALX Oncology R&D Day49March 5, 2025
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ALX Oncology R&D Day50 Path to Registration in Breast Cancer Randomized Ph2 FPI anticipated mid-year 2025Interim analysis anticipated 2H26 Potential Accelerated Approval based on ORR/DOR(n=60)(n=60) Primary EndpointORR by BICR(N ~300)(N ~300) Primary Endpoint PFSEvorpaceptTrastuzumab+Chemotherapy+TrastuzumabChemotherapy+ EvorpaceptTrastuzumab+Chemotherapy+TrastuzumabChemotherapy+ASPEN-Breast Ph2 ASPEN-Breast Ph3 March 5, 2025
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NEW COLORECTAL CANCER PROGRAMASPEN-CRC Eric Van Cutsem, MD, PhD Professor Gastroenterology / Digestive OncologyUniversity Hospitals Gasthuisberg / Leuven & KULeuvenBelgium
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CRC Is the Second Highest Cause of Cancer Deaths in the US 15.7%0%25%50%75%100%Localized Regional Distant Unknown5-year relative survival in CRCUS top 10 types of cancer by estimated new cases in 2024 (thousands)(311)(299)(235)(153)(101)(83)(82)(81)(71)(68)42 35 125 53 8 17 14 20 16 13 400 300 200 100 0 100 200BreastProstateLung and bronchusCRCMelanomaBladderKidneyNHLHNSCCUterineNew cases in 2024Deaths in 2024 Nearly a quarter of patients have metastatic disease at diagnosisDistantStage at diagnosisRegionalLocalizedALX Oncology R&D Day52March 5, 2025SEER cancer stat facts accessed February 2025; CRC = colorectal cancer; NHL = non Hodgkin lymphoma
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53 Standards of Care for Metastatic CRC Without Actionable Biomarkers Is Largely Unchanged Since the Approvals of Cetuximab and Bevacizumab •Anti-EGFR therapy is standard-of-care in patients with left-sided, RAS/BRAF wildtype tumors•In 2L treatment, mPFS is ~4 months•In RAS and BRAF-mutated tumors, EGFR is still expressed, but the ERK pathway is activated downstream of EGFR•EGFR is also expressed in right-sided tumors, but anti-EGFR treatment is ineffective1LAdvanced/Metastatic Colorectal CancerAnti-EGFRor bevacizumab + chemotherapy2L Current treatment paradigm for metastatic patientsLeft-sidedRight-sidedAnti-EGFRor bevacizumab + Chemotherapy2L or 3L Encorafenib + cetuximabAdagrasib + cetuximab/ Sotarasib + Pani (KRAS G12C-mutated)HER2-targeted therapy (HER2 IHC3+)NTRK gene fusion-positiveAnti-EGFRor bevacizumab + chemotherapyBevacizumab + chemotherapyBevacizumab + chemotherapyEncorafenib + anti-EGFR+ FOLFOXRAS and BRAF wildtypeRAS mutatedBRAF V600E mutateddMMR/MSI-HPembrolizumab orNivolumab + ipilimumabALX Oncology R&D DayMarch 5, 2025NCCN guidelines v1.2025; ESMO Metastatic Colorectal Cancer Living Guidelines; Cunningham, et al, NEJM 2004
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ALX Oncology R&D Day54 March 5, 2025
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ALX Oncology R&D Day55 March 5, 2025
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ALX Oncology R&D Day56 Evorpacept May Benefit Patients With CRC by Blocking CD47, Given That CD47 Expression Is a Negative Prognostic Factor for Patients With mCRC •CD47 is overexpressed in CRC cells compared to heathy tissue•Decreased CD47 expression is prognostic for improved survival in patients with CRC based on data showing that patients withCD47-positive CRC had significantly worse survival than patients with CD47-negative disease1 March 5, 20251. Sugimura-Nagata et al., Int J. Mol Sci. 2021:22(2690)
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ALX Oncology R&D Day57 Macrophages Are Highly Present in Colon Cancer, but Are Inhibited by CD47 •Current immune checkpoint inhibitors target T cells, which are largely absent in colorectal cancer•Evorpacept targets CD47, the checkpoint for macrophages that is overexpressed in CRC compared to heathy tissue•Macrophages are generally the most abundant immune cell type in cancers and the most profuse leukocyte in the colon•By targeting CD47, evorpacept may show activity in tumors historically classified as “cold” due to the absence of T cells MacrophageCD11bT helperCD4T cytotoxicCD8Healthy colonColorectal cancerMarch 5, 2025Tape, Trends in Cancer, 2017
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March 5, 2025 ALX Oncology R&D Day58 Evorpacept + Cetuximab Mechanism of Action in CRC M A C R O P H A G EC A N C E R C E L LEvorpaceptEGFRCetuximab CD47Eat MeFcγ
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•Need for ALX Oncology R&D Day59 Unmet Need in Metastatic CRC and Evorpacept’s Potential … are novel and bring a different mechanistic approach by combining with EGFR-targeted antibodies… leverage the importance of macrophages in CRC vs. prior T-cell driven approaches … can improve the efficacy of cetuximab, the SOC for CRC… have a manageable, well-tolerated safety profile which could be used earlier in 1L or 2L EGFR-naïve patients… are IO agents that can provide long-term survival benefit Need for agents in the CRC space that:Potential to build on promising ASPEN-06 gastric data in a similar tumor typeUniquely designed to activate macrophages that are highly abundant in CRCDesigned to work synergistically and add ADCP on top of cetuximab’s ADCC-driven tumor killingSafety profile allows for combining with multiple therapeutic options and in earlier lines Potential to be a novel IO drug for 2L CRC patients Evorpacept’s Potential March 5, 2025
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March 5, 2025 ALX Oncology R&D Day60 ASPEN-CRC: Evorpacept + Cetuximab + FOLFIRI in Patients With 2L Metastatic Colorectal Cancer Primary Objectives•Safety and tolerability•Recommended Phase 2 dose (RP2D)•Recommended regimenSecondary Objectives•Anti-tumor activity including ORR, DCR, DOR, PFS, and OSDosing: Cetuximab; QW 400 mg/m2loading -> 250 mg/m2 or Q2W 500 mg/m2 FOLFIRI; irinotecan + leucovorin + 5FUORR = objective response rate, DCR = disease control rate, DOR = duration of response, PFS = progression-free survival, OS = overall survival Key eligibility criteria•Histologically-confirmed left-sided metastatic CRC•KRAS/NRAS/BRAF wild type•pMMR/MSS•Progression on or after first-line oxaliplatin-based SOC therapy•No prior anti-EGFR treatment•No prior irinotecan-based therapy•ECOG 0 or 1Dose escalation and optimization (N~ 40-60)Evorpacept 10 mg/kg QW Regimen ARegimen BEvorpacept 15 mg/kg QW +Cetuximab QWEvorpacept 20 mg/kg Q2W Evorpacept 30 mg/kg Q2W +FOLFIRI Q2W+Cetuximab QW+FOLFIRI Q2W+Cetuximab Q2W+FOLFIRI Q2W+Cetuximab Q2W+FOLFIRI Q2W
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ALX Oncology R&D Day61Ph1b/2 FPI anticipated mid-year 2025Safety and initial efficacy anticipated 1H ‘26 ASPEN-CRC Phase 1b/2Evorpacept+Cetuximab+FOLFIRI Primary endpoints•Safety•Tolerability•RP2D•Dosing regimenASPEN-CRC Phase 3(N~40-60)EvorpaceptCetuximabFOLFIRICetuximabFOLFIRI Primary endpoint•OS(N~500)+++ Path to Registration in Previously Treated Colorectal Cancer March 5, 2025
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ANTIBODY COMBINATIONS IN HEME MALIGNANCIES NHL: Rituxan + EvorpaceptMultiple Myeloma: SARCLISA + EvorpaceptAlan Sandler, MDCMO, ALX Oncology
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63 SIRPα-Positive Macrophages Increase at Time of Progression After R2in Patients With Follicular Lymphoma (FL) •Rituximab + lenalidomide (R2) is the standard-of-care therapy for patients with relapsed FL, with a 34% CR rate•RELEVANCE (N=517) trial demonstrated activity of R2 in frontline FL was similar to standard-of-carerituximab + chemotherapy CSF1-R+ SIRPα+ M before R2CSF1-R+ SIRPα+ M after R2Marques-Piubelli M et al, Blood Adv 2022; Strati, et al, AACR 2024 #10285; Leonard, et al, JCO 2019; Morschhauser, et al, NEJM 2018 CSF1-R+ SIRPα+ MCD163+ SIRPα+ M ALX Oncology R&D DayMarch 5, 2025
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March 5, 2025 ALX Oncology R&D Day64 ASPEN-01 Phase 1b Clinical Trial of Evorpacept + the CD20-Targeted Antibody Rituximab in Aggressive and Indolent NHL In indolent NHL, evorpacept + rituximab achieved:•ORR = 72% (8/11)•CR = 54% (6/11)•Evorpacept + rituximab demonstrated favorable impact when compared to single-agent rituximab benchmarks of 18% CR and 53% ORR from AUGMENT pivotal study of rituximab + lenalidomide in indolent NHLEvorpacept (10 mg/kg QW) + RituximabData cutoff: October 1, 2020; Response evaluable patients; responses include metabolic response per Lugano Response Criteria.Leonard, et al, JCO, 2019100 200 300 400 5000-100-80-60-40-20020406080100Change from Baseline (%)Time from Initiation of Treatment (Days)Aggressive NHLIndolent NHL500 100 200150 250 350300 400-100-50050100Change from Baseline (%)Time from Initiation of Treatment (Days)Evorpacept (15 mg/kg QW) + RituximabAggressive NHLIndolent NHL TreatmentCohortsRelapsed/refractory NHL, prior regimen with Rituximab Evorpacept10 or 15 mg/kg once a week (QW)+Rituximab375 mg/m2once a week for four weeks, once monthly for eight monthsPhase 1b clinical trial of evorpacept + rituximab in patients with aggressive or indolent NHL
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March 5, 2025 ALX Oncology R&D Day65 Phase 1/2 IST of Evorpacept + R2 in Indolent and Aggressive Relapsed or Refractory B-cell Non-Hodgkin Lymphoma Primary Outcomes•Phase 1: Safety and RP2D•Phase 2: CR rateSecondary Outcomes•ORR•PR•DoR•PFS•OS•AEsEvoEvorpacept RituximabRLenalidomideLInvestigator Sponsored Trial. P. Strati. AACR 2024, Oral Presentation. Abstr #CT037; Indolent = Follicular Lymphoma and Marginal Zone Lymphoma; Aggressive = Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma; CR = Complete response; PR = Partial response; ORR = Objective response rate; DoR= Duration of response; PFS = Progression free survival; AEs = Adverse events; IST = Investigator Sponsored Trial; RP2D = recommended phase 2 dose Key eligibility criteriaPhase 1•Adult patients with relapsed refractory B-NHL•≥2 prior lines of systemic therapy for patients with aggressive B-NHL or 1 for patients with indolent B-NHL•No prior lenalidomidePhase 2•Adult patients with previously untreated indolent B-NHLN=3 Evo30 mg/kg (Q2W)Day 1-21 on cycles 1-6L+Weekly on cycle 1 & Q4W on cycles 2-6R+Phase 1 (R/R)Presented at AACR 2024Evo60 mg/kg (Q4W)L+R+Phase 2 (1L)RecruitingEvo60 mg/kg (Q4W)L+R+N=17 N=24 Enrolled: n=18 patients with indolent lymphomas (n=15 with follicular and n=3 with marginal zone), all of whom had prior anti-CD20 targeted therapy
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Placebo+ RituximabN=180R2AUGMENTN=178Evo+ R2Ph1/2 MDACC ISTN=1855%78%94%83%34%18%0%20%40%60%80%100%Evorpacept-Based Regimen Compares Favorably to Benchmark Trial R2 = Lenalidomide + Rituximab; N = Response Evaluable Patients; Indolent = Follicular Lymphoma and Marginal Zone Lymphoma; CRR = Complete response rate; ORR = Objective response rate; IST = Investigator Sponsored TrialALX Oncology R&D Day66 R2 in iNHL MD Anderson SponsoredP. Strati. AACR 2024, OralPresentation. Abstr #CT037Data Cutoff as of December 2023Volume 37, Number 14March 2019AUGMENT: A Phase III Study of Lenalidomide Plus RituximabVersus Placebo Plus Rituximab in Relapsed or Refractory Indolent LymphomaCRRORR CRRORR Data coming 2Q 2025 at major medical meetingMarch 5, 2025
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Ongoing Trial of Evorpacept + the CD38-Targeted Antibody SARCLISA (Isatuximab) Sponsored by Sanofi Multiple myeloma trial sponsored by Sanofi with ALX collaboration Phase 1/2 Multiple Myeloma Study (UMBRELLA Trial)ExperimentalEvorpacept+SARCLISA (isatuximab)+pomalidomide+dexamethasoneALX Oncology R&D Day67 First patients dosed September 2024,currently enrollingActive ComparatorSARCLISA (isatuximab)+pomalidomide+dexamethasoneKey eligibility criteria•Relapsed or refractory multiple myeloma, two or more prior therapies•Prior therapy with proteasome inhibitor (PI) and immunomodulatory drug (IMiD)•Anti-CD38 therapy naïve or at least 12 months after last dose•No prior anti-CD47•ECOG 0 or 1March 5, 2025
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BUILDING THE EVORPACEPT FRANCHISECommercial Opportunity Allison Dillon, PhDCBO, ALX Oncology
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Lead indications with potentialfor acceleratedapproval Lead indications with potentialfor acceleratedapprovalALX Oncology R&D Day69 Building the Evorpacept Franchise *7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and JapanSource: Clarivate Market Forecast, gastroesophageal cancer, December 2024HER2+ gastric cancer~12,000*2L+ HER2+ patients•Biomarker-driven patient population identified•Pending FDA feedback on AA path•Addresses 1L patients with HNSCC irrespective of PD-L1 expression•Expansion opportunity into other pembrolizumab-based standards of careHNSCC~57,000*1L patientsMarch 5, 2025
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Current wave of development Current wave of development Lead indication with potentialfor acceleratedapproval Lead indication with potentialfor acceleratedapprovalALX Oncology R&D Day70 Building the Evorpacept Franchise *7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and JapanSource: Clarivate Market Forecast, gastroesophageal cancer, December 2024Metastatic Breast Cancer~48,000*2L+ HER2+ patients2L CRC~60,000*2L RAS/BRAF wildtype patients~69,000*2L+ HER2+ gastric cancer•Potential to be first new treatment for second-line wild-type CRC patients •Potential expansion of evorpacept + EGFR into patients with right-sided tumors•Derisked by multiple evorpacept clinical trials•Urgent area of unmet need for HER2+ breast cancer patients •Expansion opportunities in multiple lines of therapy, (neo)adjuvant setting, and with additional HER2-targeted1L HNSCCMarch 5, 2025
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Hematologic malignancies Hematologic malignancies Current wave of development Current wave of development Lead indication with potentialfor acceleratedapproval Lead indication with potentialfor acceleratedapprovalALX Oncology R&D Day71 Building the Evorpacept Franchise *7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and JapanSource: Clarivate Market Forecast, gastroesophageal cancer, December 20241L follicularlymphoma~36,000* 1L follicular lymphoma patientsMultiple myeloma~50,000* 3L+ multiple myeloma patients2L+ HER2+ breast cancer2L CRC~108,000* •Building on potentially best-in-class activity from Ph1b trials•Significant opportunity for expansion with rituximab-based standards of care in B-cell lymphomas•Ongoing Sanofi-sponsored trialin combination with isatuximab~69,000*2L+ HER2+ gastric cancer1L HNSCCMarch 5, 2025
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ALX Oncology R&D Day72 Building the Evorpacept Franchise Continued broadeningof evorpaceptindications Continued broadeningof evorpaceptindications Hematologic malignancies Hematologic malignancies Current wave of development Current wave of development Lead indication with potentialfor acceleratedapproval Lead indication with potentialfor acceleratedapproval*7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and JapanSource: Clarivate Market Forecast, gastroesophageal cancer, December 20242L+ HER2+ breast cancer2L CRC1L follicular lymphoma3L+ multiple myeloma~108,000*~86,000*Neoadjuvant HER2+ breast cancer1L HER2+ breast cancer1L CRCDiffuse large B-cell lymphoma (DLBCL)~279,000*~69,000*2L+ HER2+ gastric cancer1L HNSCCMarch 5, 2025
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ALX Oncology R&D Day73 Building the Evorpacept Franchise *7 major markets: US, EU5 (UK, Spain, Italy, Germany, France) and JapanSource: Clarivate Market Forecast, gastroesophageal cancer, December 2024 Continued broadeningof evorpaceptindications Continued broadeningof evorpaceptindications Hematologic malignancies Hematologic malignancies Current wave of development Current wave of development Lead indication with potentialfor acceleratedapproval Lead indication with potentialfor acceleratedapproval~69,000*2L+ HER2+ gastriccancer2L+ HER2+ breast cancer2L CRC1L follicular lymphoma3L+ multiple myeloma~108,000*~86,000*Neoadjuvant HER2+ breast cancer1L HER2+ breast cancer1L CRCDLBCL~279,000*1L HNSCC Ongoing studies for evorpacept target over 250,000patients in the US, EU5, and JapanMarch 5, 2025
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ALX2004New Antibody-Drug Conjugate Clinical Candidate Jaume Pons, PhDCSO, ALX Oncology
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EGFR-binding epitope distinct from cetuximab and panitumumabAffinity tuned to maximize therapeutic windowEnhanced bystander effect compared to DXdLinker with improved ADC stability compared to DXdUniform drug loading DAR 8 and well-behaved physico-chemical propertiesIP: patent applications covering multiple classes of payloads,payload linkers, and ADCs75 ALX2004: First Drug Candidate That Was Internally Developed Using ALX’s Linker-Payload Platform ALX2004EGFR-targeted ADC with proprietary topoisomerase I inhibitor payloadIND filing Q1 2025ALX Oncology R&D DayMarch 5, 2025
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76 ALX2004 Shows Potent Anti-Tumor Activity in Multiple Clinically Relevant Xenograft Models NSCLC (HCC827)ALX2004 (1-10 mg/kg)0 10 20 30 400100200300400Days Post DoseMean Tumor Volume (mm3) CRC (COLO205)ALX2004 (1-10 mg/kg)TNBC (MDA-MB-468)ALX2004 (1-10 mg/kg)NPC (FaDu)ALX2004 (1-10 mg/kg)PDAC (CFPAC-1)ALX2004 (1-10 mg/kg) ALX Data on File; TNBC = triple negative breast cancer; NPC = nasopharyngeal carcinoma; PDAC = pancreatic ductal adenocarcinoma; NSCLC = non small cell lung cancer; CRC = colorectal cancer ALX2004 designed to optimize ADC-based mechanisms of anti-tumor activity:•Topoisomerase I inhibition•Increased linker stability to maximize payload delivery to tumor cells•Increased bystander effect •Effector function and signaling inhibition from anti-EGFR antibodyPDAC (CFPAC-1)Cetuximab vs. ALX2004CetuximabALX20041 mg/kg3 mg/kg10 mg/kg1 mg/kg3 mg/kg10 mg/kg1 mg/kg3 mg/kg10 mg/kg1 mg/kg3 mg/kg10 mg/kg1 mg/kg3 mg/kg10 mg/kgPBSPBSPBSPBSPBSPBSALX Oncology R&D DayMarch 5, 2025
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•Need for March 5, 2025 ALX Oncology R&D Day77 ALX2004 Has the Potential To Be a Best- and First-in-Class EGFR ADC… are pursuing targets with limited competition and room to differentiate… leverage validated targets and/or established pathways to mitigate biology risk … utilize clinically validated payloads that are known to be highly efficacious in the clinic… have the potential to be significantly de-risked in early clinical studies Need exists for novel ADCs that:Approved EGFR therapies and most clinical candidates rely on signaling blockadeNo approved EGFR ADCs and only one other EGFR topo-based ADC in the clinicHER2/3 topo-1 ADC clinical success (e.g., ENHERTU) may support EGFR (HER1) ADCs potentialTopo-1 is a highly validated payloadALX2004 addresses EGFR tubulin ADC failures through optimized affinity, payload, stability, and tumor penetrationCombines direct cytotoxicity and bystander effect, signaling blockade, and immune stimulation (ADCC, ADCP , ICD) ALX2004’s Potential ALX will host R&D Call focused on ALX2004 in Q2 2025
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FINANCIAL UPDATES AND MILESTONESUpcoming Catalysts Harish Shantharam, CFA CFO, ALX Oncology
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March 5, 2025 ALX Oncology R&D Day79 Key MilestonesT I M E L I N EU P D A T EI N D I C A T I O NT R I A LP R O G R A M2Q 2025Accelerated Approval pathway – FDA feedbackGastric / GEJASPEN-06Evorpacept(anti-cancer antibody w/ active Fc)2H 2026Interim analysisHER2+ Breast CancerASPEN-Breast1H 2026Safety and early efficacyCRCASPEN-CRC2Q 2025Topline resultsHNSCCASPEN-03Evorpacept(w/checkpoint inhibitors)2Q 2025Topline resultsHNSCCASPEN-042Q 2025Data updateBladder CancerASPEN-07Evorpacept(w/ADC)2H20 25Data updateBreast CancerI-SPY1Q 2025IND submission-Pre-clinicalALX20041H 2026Safety dataMultiplePh1a/1b
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•$131.3M of cash, cash equivalents and investments as of Dec 31, 2024. •Our strategic prioritization and resource optimization efforts enables us to extend cash runway guidance into Q4 2026. •Focused spend on Evorpacept anticancer antibody program (GC/ BC / CRC) and ALX 2004•Gated phase 3 spend while awaiting ASPEN-03/04 results and ASPEN-06 FDA meeting•~30% reduction in force with substantial decrease in preclinical research investments and optimized spend across functionsMarch 5, 2025 ALX Oncology R&D Day80 Financial and Business Update
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Concluding RemarksJason LettmannCEO, ALX Oncology
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Today’s Key Messages 82ALX Oncology R&D DayMarch 5, 2025 3 2 1 4Extended runway into Q4 2026 due to aggressive prioritizationand cost-cuttingPursuing a focused development strategy with several paths to FDA registration across both evorpacept and ALX2004Evorpacept is an active IO agent that has now demonstrated activity in six clinical trials to dateSeveral major catalysts over next 12 to 18 months across active trialsin major oncology indications