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ALX Oncology SABCS Evorpacept + Zanidatamab Breast Cancer Presentation December 17, 2024
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2 | © ALX Oncology. Confidential. 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-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. This data involves 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.
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3 | © ALX Oncology. Confidential. ALX Oncology SABCS Breast Cancer Data Review Closing remarks and Q&A ALX Oncology Introduction SABCS ‘24 Clinical Data Review Fireside Chat on SABCS ‘24 Clinical Data 4 3 2 1 AGENDA Jason Lettmann CEO, ALX Oncology Jason Lettmann CEO, ALX Oncology Dr. Alberto Montero, MD Professor, UH Seidman Cancer Center & Case Western Reserve University Medical School Dr. Alan Sandler, MD CMO, ALX Oncology
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4 | © ALX Oncology. Confidential. ALX Oncology is transforming cancer treatment for patients by developing evorpacept as a first- in-class foundational checkpoint immunotherapy ALX Oncology is advancing a highly differentiated immuno-oncology pipeline led by evorpacept, a potential best and first-in-class CD47 innate immune system checkpoint inhibitor that has been studied in >700 patients treated to date Differentiated mechanism of action as evorpacept is the only CD47 in development with a dead Fc with a clear biomarker to target patients (eg, HER2 expression) Multiple positive clinical studies across bladder, NHL, gastric, and head and neck (HNSCC) and currently pursuing additional studies in combination with 3 therapeutic classes: anti-cancer antibodies, checkpoint inhibitors & ADCs Expanding evorpacept to new indications supported by multiple pharma partnerships, building a strong pipeline beyond evorpacept, and a strong balance sheet with cash runway through Q1 2026. Evorpacept is the first and only CD47 agent to demonstrate both durable improvement in overall response rate and a well-tolerated safety profile in a prospective randomized study New Data at SABCS ‘24 Demonstrated Evorpacept in Combination with Zanidatamab Generated Promising Antitumor Activity in Advanced Breast Cancer
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5 | © ALX Oncology. Confidential. A differentiated CD47 blocker High affinity CD47 binding domains of SIRPα Inactive Fc domain Target cells overexpress CD47 to evade destruction by macrophages Evorpacept: A first-in-class approach to targeting CD47 Evorpacept Fc receptor Fc receptor Don't eat meMacrophage Cancer cell CD47SIRPα Dendritic cell Don't eat me CD47SIRPα Red blood cell Macrophage
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6 | © ALX Oncology. Confidential. Evorpacept has demonstrated robust enhancement of combinations and consistent tolerability 1. AUGME NT study 3. Burtness, Lancet, 2019; 4. Cohen, Lancet, 2018.; 5 EV-301 study ASPEN-06 Randomized Ph2 (HER2+ gastric, ORR) 40% 26% Evo + controlControl: vs ASPEN-01 Ph1b (1L HNSCC, OS @ 12 months) ASPEN-01 Ph1b (≥2L HNSCC OS, @ 12 months) 88% 80% 53% 37% Keytruda + chemo benchmark3 Keytruda benchmark4Evo + Keytruda + chemo Evo + Keytruda ASPEN-01 Ph1b (R/R indolent NHL, CR) 54% 18% Evo + rituximabRituximab benchmark1 NHL IST (R/R indolent NHL, CR) 34% Evo + R2R2 benchmark1 83% • Strong activity observed across 5 different clinical trials to date • Evorpacept is the only CD47 blocker to demonstrate activity across both heme and solid cancers • Further, evo is the only CD47 to demonstrate positive data in a large randomized trial
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7 | © ALX Oncology. Confidential. Evorpacept Evorpacept’s differentiated design results in differentiated safety profile and robust clinical activity Higher affinity CD47 binding More potently blocks CD47 signal on cancer cells Robust clinical activity Inactive Fc domain Less ”sink effect” = more targeted No known dose dependent cytopenia = higher dosing Best-in-class safety profile Lower molecular weight Increased solid tumor penetration and higher effective dosing Strong solid tumor activity Antibody-like pharmacokinetics Long half life = less frequent dosing and matching regimen with combinations Broad combination potential
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8 | © ALX Oncology. Confidential. Pursuing a robust development plan Indication Evorpacept Combination Agent Discovery IND Enabling Phase 1 Phase 2 Phase 3 Fast Track Supplier/ Collaborator Evorpacept Combination Studies ANTI-CANCER ANTIBODIES AND ADCS GC Gastric/Gastroesophageal Junction Cancer Herceptin + Cyramza + Paclitaxel (ASPEN-06) Urothelial Cancer Padcev (ASPEN-07) Breast Cancer Zanidatamab Enhertu (I-SPY) MM Multiple Myeloma Sarclisa + Dexamethasone CHECKPOINT INHIBITORS HNSCC Head And Neck Squamous Cell Carcinoma Keytruda (ASPEN-03) Keytruda + 5FU + Platinum (ASPEN-04) 1 ALX Oncology c onducts and sponsors AS PEN-06, Lilly supplies Cyramza. 2 Jazz Pharmac euticals conducts and sponsors c linical trial, ALX Oncology supplies evorpacept 3 Quantum Leap Healthcare Collaborative conducts and sponsors c linical trial, ALX Oncology supplies evorpacept. 4 Sanofi c onducts and sponsors clinical trial, ALX Oncology supplies evorpacept. 5 ALX Oncology c onducts and sponsors AS PEN-03 and ASPEN-04, Merck supplies Keytruda 1 2 3 4 5 5 Jazz Pharmaceuticals conducted and sponsored clinical trial and ALX Oncology supplied evorpacept
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9 | © ALX Oncology. Confidential. Dr. Alan Sandler Chief Medical Officer Acquired by BMS Chief Medical Officer Head of Global Development Oncology Global Head of Product Development, Oncology
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10 | © ALX Oncology. Confidential. Evorpacept HER2 thesis is validated by new data in combination with zanidatamab in breast cancer • Zanidatamab (ZW25) is a Zymeworks-created bispecific that binds the HER2 extracellular domains targeted by trastuzumab (ECD4) and pertuzumab (ECD2) • Zanidatamab is a IgG1 antibody that when combined with evorpacept, will drive additional ADCP • As MOA of evorpacept + zanidatamab is fundamentally different than any HER2-targeted antibody alone, combo may drive responses where patients have progressed following HER— targeted therapy • Limited single agent activity is expected from either agent in R/R population heavily pretreated with HER2-targeted agents Evorpacept Zanidatamab Evo + Zani is a chemo-free regimen targeting the unmet need in breast cancer of patients who have progressed on multiple HER2-targeted agents including Enhertu
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11 | © ALX Oncology. Confidential. Evorpacept + Zanidatamab Mechanism of Action Evorpacept Fc receptor SIRPα Macrophage Cancer cell CD47 Zanidatamab HER2 Evorpacept may drive antitumor activity of zanidatamab by targeting HER2 - expressing cells for phagocytosis
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12 | © ALX Oncology. Confidential. Dr. Alberto Montero Research interests Improvement of clinical outcomes in patients with breast cancer through the development of novel targeted therapies, with a particular interest in immune-based therapies and the mechanism by which tumors evade the immune system. Clinical Director Breast Cancer Medical Oncology Program Medical Director Oncology Clinical Trials Unit University Hospitals Seidman Cancer Center Member of several educational and scientific committees and others Professor of Medicine Case Western Reserve University School of Medicine Prior reviewer and study chair for the Department of Defense Breast Cancer Research Program
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13 | © ALX Oncology. Confidential. Research Funding: Scorpion Therapeutics, Jazz, Iambic, NIH Consulting: Paragon Healthcare, Astra Zeneca, Welwaze Medical, Gilead, Scorpion Therapeutics, ALX Oncology Stock/Equity Ownership: Celcuity and CareVive (stock options) Financial Relationships/Disclosures
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14 | © ALX Oncology. Confidential. Breast Cancer Epidemiology HER2 Expression in Patients with Breast Cancer 31.9% 0% 25% 50% 75% 100% Localized Regional Distant Unknown 5-Year Relative Survival in Breast Cancer SEE R cancer stat facts access December 2024 Top 10 Types of Cancer by Incidence (thousands) (298) (288) (238) (153) (98) (82) (82) (81) (66) (64) 43 35 127 53 8 17 15 20 13 51 400 300 200 100 0 100 200 Breast Prostate Lung and bronchus CRC Melanoma Bladder Kidney NHL Uterine Pancreatic DeathsIncidence 55% (37,000) 30% (20,000) 15% (10,000) HER2-Positive (Amplified/Overexpressed) HER2-Ultra Low & Negative HER2-Low HER2-positive: IHC3+ or IHC2+/ISH+ HER2-low: IHC2+/ISH- or IHC1+ HER2-ultralow: IHC with faint or incomplete membrane staining in ≤ 10% of tumor cells Adopted from Krop, ASCO 2024 LBA1000 discussion; Tarantino, JCO 2020; AztraZeneca Epidemiology Data May 2024 1L addressable patients
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15 | © ALX Oncology. Confidential. Metastatic HER-2+ BC patients are in need of novel, chemo -free therapeutics that are efficacious particularly after progressing on several prior lines of HER2 -targeted therapy Trastuzumab + pertuzumab + taxane (known as THP or Cleopatra regimen)* T-DXd (Enhertu) * T-DM1Tucatinib + trastuzumab + capecitabine* Margetuximab + chemo Trastuzumab + chemo Neratinib + chemo Trastuzumab + lapatinib 1L 2L 3L 4L+ *NCCN Category 1 preferred regimen for this line of therapy Adapted from NCCN guidelines v6.2024 • Ongoing DESTINY-Breast09 Phase 3 trial of 1L T-DXd +/- pertuzumab could change paradigm • Very few chemo-free options in later line setting • As Enhertu likely moves to earlier in line, options for patients that progress on Enhertu are increasingly important
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16 Zanidatamab in Combination With Evorpacept in HER2-Positive and HER2-Low Metastatic Breast Cancer: Results From a Phase 1b/2 Study Alberto J. Montero1*, Kari B. Wisinski2, Bruno Fang3, Kelly E. McCann4, Sara Hurvitz5, Kay T. Yeung6, Ritesh Parajuli7, Jorge Chaves8, Adam Brufsky9, Peter A. Kaufman10, Manish R. Patel11, Timothy Pluard12, Bob Salim13, Kavita V. Shah13, Shanhong Guan14, Athanasios C. Tsiatis14, Sophia Randolph14, Funda Meric-Bernstam15 Abstract #SESS-2007 at SABCS 2024 1UH Cleveland Medical Center/Seidman Cancer Center Case W estern Reserve University, Cleveland, OH, USA; 2University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA; 3Astera Cancer Care, East Brunswick, NJ, USA; 4David Geffen School of Medicine, University of California at Los Angeles, CA, USA; 5Fred Hutchinson Cancer Center, University of Washington School of Medicine, Seattle, WA, USA; 6University of California San Diego Health Moores Cancer Center, La Jolla, CA, USA; 7University of California, Irvine, Orange, CA, USA; 8Nort hwest Medical Specialties, Tacoma, WA, USA; 9University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 10Larner College of Medicine at t he University of Vermont, Burlington, VT, USA; 11Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL, USA; 12Saint Luke’s Cancer Inst itute, Kansas Cit y, MO, USA; 13Jazz Pharmaceuticals, Palo Alt o, CA, USA; 14ALX O ncology Inc., Sout h San Francisco, CA, USA; 15The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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17 | © ALX Oncology. Confidential. Phase 1b/ 2 Study Design: Evorpacept plus zanidatamab in HER2+ and HER2-low in patients who have progressed on prior HER2-directed therapy Study conducted by Jazz Pharmaceuticals Key eligibility criteria: Unresectable, locally advanced and/or metastatic HER2- expressing cancer Cohort 1 (Parts 1 & 2): ▪ 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 Cohort 2 (Parts 1 & 2): ▪ HER2-low breast cancer (IHC 1+ or IHC 2+/FISH-negative); and never been HER2-positive ▪ ≥2 prior regimens (T-DXd allowed)1 Cohort 3 (Part 2 only): ▪ HER2-positive GEA or other HER2-overexpressing non- breast cancer Cohort 1 and 2 only: evorpacept 20 mg/kg (1A) OR 30 mg/kg (1B) + Zanidatamab 1200 mg (<70 kg) or 1600 mg (≥ 70kg) IV Q2W every 28 days Up to 4 safety cohorts Part 1: Safety This study provides clinical data supporting further development of evorpacept with HER2- targeted agents in patients with breast cancer Primary Endpoints ▪ Part 1: Safety ▪ Part 2: Confirmed ORR Secondary Endpoints Part 2 ▪ DCR ▪ CBR ▪ DOR ▪ PFS ▪ OS ▪ Safety ▪ PK ▪ Immunogenicity assessments Exploratory Biomarker Endpoints (Part 2) Part 2: Expansion cohorts2,3 (1) Prior HER2-targeted therapies were initially excluded; the protocol was amended to allow prior treatment with T -DXd following its approval in this patient population. (2) RP2D Zanidatamab 1200 mg (<70 kg) or 1600 mg (≥ 70kg) and evorpacept 30 mg/kg IV Q2W on days 1 and 15 of each 28-day cycle. (3) Mandatory IRR prophylactic treatment included corticosteroids, antihistamines, and acetaminophen. Cohort 1: HER2-positive mBC (n=21) Cohort 2: HER2-low mBC (n=15) Cohort 3: HER2-positive GEA or other HER2-overexpressing non-breast cancer (n=8)
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18 | © ALX Oncology. Confidential. b. Includes patients with gastroesophageal adenocarcinoma (n=4), colorectal cancer (n=3), and salivary gland cancer (n=1). Patient Demographics and Baseline Disease Characteristics Data cut off date 1 August 2024 Characteristic Cohort 1 HER2-Positive (n=21) Cohort 2 HER2-Low (n=15) Cohort 3 Other HER2- Overexpressing Cancers (n=8)b Age, median, years (range) 58.0(34.0 -81.0) 63.0 (42.0-74.0) 48.5 (36.0-74.0) Female, n (%) 21 (100) 15 (100) 4 (50.0) Race, n (%) White 14 (66.7) 9 (60.0) 6 (75.0) Asian 0 (0) 2 (13.3) 0 (0) Black or African American 4 (19.0) 3 (20.0) 0 (0) Multiple/Other 1 (4.8) 0 (0) 2 (25.0) Unknown/Not reported 2 (9.5) 1 (6.7) 0 (0) Baseline ECOG PS, n (%) 0 1 9 (42.9) 12 (57.1) 8 (53.3) 7 (46.7) 4 (50.0) 4 (50.0) HER2 status per central assessment, n (%) IHC 0 2 (9.5) 0 (0) 1 (12.5) IHC 1+ or IHC 2+/FISH – 10 (47.6) 14 (93.3) 3 (37.5) IHC 2+/FISH+ or IHC 3+ 9 (42.9) 0 (0) 4 (50.0) Unknown 0 (0) 1 (6.7) 0 (0) Median number of prior systemic cancer therapy regimens in the metastatic setting (range) 6 (2.0-10.0) 5 (2.0-9.0) 3.5 (2.0-11.0) Prior HER2 -targeted therapies, n (%) T-DXd 21 (100) 5 (33.3) 5 (62.5) Trastuzumab 21 (100) 0 (0) 8 (100) Pertuzumab 20 (95.2) 0 (0) 3 (37.5) T-DM1 14 (66.7) 0 (0) 1 (12.5) Tucatinib 12 (57.1) 0 (0) 0 (0) Neratinib 5 (23.8) 0 (0) 0 (0) Margetuximab 4 (19.0) 0 (0) 0 (0) Lapatinib 3 (14.3) 0 (0) 0 (0) Prior brain metastases, n (%) 9 (42.9) 4 (26.7) 1 (12.5) De novo metastatic disease, n (%) 7 (33.3) 4 (26.7) 3 (37.5) Montero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007 • Population represented heavily pretreated R/R population – Median of 6 prior therapies in Cohort 1 and 5 prior therapies in Cohort 2, including multiple HER2-targeted therapies • Notably, 100% of patients in cohort 1 and 33% of patients in cohort 2 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 in cohort 1, 8 (40%) were confirmed HER2-positive by central assessment (1 centrally HER2-positive patient did not have local assessment). – For cohort 2, 14/15 (93%) patients were confirmed HER2-low by central assessment
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19 | © ALX Oncology. Confidential. All Patients (N=52) Any TRAE, n (%) 45 (86.5) Grade 1-2 38 (73.1) Grade 3 7 (13.5) Grade 4-5 0 (0) Serious TRAEs, n (%) 3 (5.8)b TRAEs leading to treatment discontinuation, n (%) 2 (3.8)c TRAEs leading to dose reductions, n (%) 0 (0) Treatment-related AESI, n (%) Left ventricular dysfunctional 1 (1.9) IRR 12 (23.1) Non-infectious pulmonary toxicities 0 (0) Most common TRAEs* n (%) Grade 1 Grade 2 Grade 3 Diarrhea 20 (38.5) 9 (17.3) 3 (5.8) Fatigue 9 (17.3) 7 (13.5) 1 (1.9) Nausea 11 (21.2) 3 (5.8) 0 (0) IRR 3 (5.8) 7 (13.5) 2 (3.8) The combination of evorpacept and zanidatamab was well -tolerated with a manageable safety profile that is consistent with prior experience with each agent a. TRAEs defined as events with an onset during or after receipt of the first dose of study treatment within 30 days af ter the last dose and were determined as related to zanidat amab and/or evorpacept by t he investigators. b. Two addit ional event s (diarrhea and LVEF decreased) occurred outside the 30-day w indow f or TRAEs. c. Both events were grade 3 IRRs that resolved follow ing treatment discontinuation. dDefined as LVEF <50% with absolut e decrease of ⩾10 percentage point s below pretreat ment baseline and/or grade ⩾2 heart failure. eGrades 1-3 occurring in ⩾20% of patient s or ⩾2 patient s. AESI , adverse event of special interest; I RR, infusion-related reaction; LVEF, left ventricular ejection fraction; TR AE, treatment-related adverse event. Data cut off date 1 August 2024 • Most treatment-related adverse events were grade 1 or 2 (related to zanidatamab and/or evorpacept) – The most common grade 3 TRAEs were diarrhea (5.8%) and IRRs (3.8%); there were no grade 4 TRAEs – Serious TRAEs included dyspnea, gamma-glutamyltransferase increased, and IRR (occurring in 1 patient each) – TRAEs of special interest included: 1 (1.9%) patient with grade 3 ejection fraction decreased and 12 (23.1%) patients with IRRs – All IRRs resolved; 1 (%) 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 deaths Montero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007
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20 | © ALX Oncology. Confidential. Breast cancer patients with confirmed HER2 -positivity by central assessment had the greatest benefit from evorpacept + zanidatamab 1) JAMA Oncol. 2021;7(4):573-584. doi:10.1001/jamaoncol.2020.7932 • Chemo-free regimen of evo+ zani post-Enhertu compares favorably with chemo regimen with no prior Enhertu – SOPHIA study (n=536) of margetuximab + chemo vs. trastuzumab + chemo 22% vs. 16% cORR1 • Highest responses observed in patients with confirmed HER2- postivity Encouraging activity of a chemo free regimen in an R/R and T-DXd (Enhertu) experienced population Cohort 1 Cohort 2 HER2-Positive by Central (n=9) HER2- Low/Ultralow* by Central (n=12) HER2-Low mBC (n=15) cORR, n (%) [95% CI] CR, n (%)a PR, n (%) SD, n (%) PD, n (%) NE, n (%) 5 (55.6) [21.2, 86.3] 0 (0) 5 (55.6) 2 (22.2) 1 (11.1) 1 (11.1) 2 (16.7) [2.1, 48.4] 0 (0) 2 (16.7) 6 (50.0) 4 (33.3) 0 (0) 3 (20.0) [4.3, 48.1] 0 (0) 3 (20.0) 3 (20.0) 7 (46.7) 2 (13.3) DCR, n (%) [95% CI] 7 (77.8) [40.0, 97.2] 8 (66.7) [34.9, 90.1] 6 (40.0) [16.3, 67.7] Median DOR, months (range)c NE (5.6-25.9) NE (3.6-15.0) 5.5 (3.6-11.0) Median PFS, months (95% CI) 7.4 (0.6, NE) 3.5 (1.6, 14.6) 1.9 (1.6, 3.9) aThere was one HER2-positive mBC patient treated at the lower dose of evorpacept in Part 1 that achieved a complete response (med ian DOR: 20.2 months) cORR, confirmed objective response rate; CR, complete response; DCR, disease control rate; DOR, duration of response; HER2, h uman epidermal growth factor receptor 2; mBC, metastatic breast cancer; NE, not evaluable; PD, progressive disease; PFS, median progression-free survival; PR, partial response; SD, stable disease. Data cutoff August 1, 2024. *HER2-Low/Ultralow = IHC1+, IHC2+ / ISH-, IHC 0 Median follow-up (range) was 9.6 (0.6, 29.7) months, with 6 patients on treatment at data cutoff as of August 1, 2024
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21 | © ALX Oncology. Confidential. 71% of patients (15/21) in cohort 1 (HER2+ BC) had a reduction in target lesion size from baseline Data cut off date 1 August 2024 Montero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007
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22 | © ALX Oncology. Confidential. Encouraging durability with evorpacept and zanidatamab in breast cancer patients Data cut off date 1 August 2024 • Eight patients in cohort 1 were on treatment for 6+ months and 4 for 12+ months • Two patients in cohort 2 were on treatment for 6+ months Montero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007
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23 | © ALX Oncology. Confidential. SABCS Conclusions • This is the first study reporting data on the safety and efficacy of evorpacept, a CD47 blocker in combination with zanidatamab, a dual HER2 -targeted bispecific antibody,, in previously treated patients with HER2 -expressing cancers • Evorpacept + zanidatamab showed promising antitumor activity in patients with heavily pretreated HER2-positive mBC including after progression on prior T -DXd (cORR: 55.6%; mPFS: 7.4 months in patients with centrally confirmed HER2 -positive mBC) • Antitumor activity was also observed in patients with heavily pretreated HER2 -low mBC (cORR: 20.0%) • Among all patients, the combination therapy was well tolerated with a manageable safety profile that is consistent with prior experience with each agent • Based on the results presented here, further development of this novel chemotherapy -free regimen is warranted Montero. et. Al. SABCS 2024, Poster Spotlight Presentation. Abstr #SESS-2007 Data cut off date 1 August 2024
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24 | © ALX Oncology. Confidential. Fireside Chat Dr. Alberto Montero, MD Professor Case Western Reserve University School of Medicine Dr. Alan Sandler, MD Chief Medical Officer ALX Oncology
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25 | © ALX Oncology. Confidential. This study again demonstrates the power of evorpacept engaging the innate immune response and further validates its mechanism with anti -cancer antibodies particularly in HER2+ tumors • In ASPEN-06, evorpacept + TRP demonstrated an ORR of 40.3% compared to the TRP control ORR of 26.6% and 15.7 months compared to 7.6 months mDOR • Evo+ zani had an ORR of 33% in heavily pre-treated HER2+ BC in the ITT population • Evorpacept + TRP was well- tolerated with a safety profile consistent with that of the backbone TRP therapy • Evorpacept + zanidatamab was well-tolerated with a manageable safety profile consistent with zanidatamab alone • Efficacy demonstrated in patients that had all progressed on prior trastuzumab • Efficacy demonstrated in patients who had all progressed on several HER2-targeted agents and Enhertu • In ASPEN-06, evorpacept + TRP demonstrated an ORR of 59.1% in patients with fresh HER2+ biopsies vs. 23.1% in control • Evo+ zani had an ORR of 55% in heavily pre-treated HER2+ BC patients confirmed via central lab Evorpacept has now delivered consistent data in two different HER2+ tumor types with two different Fc-active antibodies de-risking the program significantly Robust and Durable Clinical Activity in HER2+ Cancers Validated Mechanism of Action with a Clear Biomarker Consistently Well-Tolerated with HER2-targeted agents Active in patients that have progressed on conventional HER2-directed therapy HER2+ Gastric/ GEJ Cancer HER2+ Breast Cancer
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26 | © ALX Oncology. Confidential. ALX Conclusions and Next Steps • This study adds to the growing body of evidence suggesting that evorpacept can combine with various therapies to treat HER2-positive cancers in patients that have already received multiple HER2-targeted agents • This data demonstrates that patients with heavily pre-treated HER2-positive breast cancer , who have seen a median of 5 to 6 prior lines of treatment, including multiple HER2-targeted agents and Enhertu had benefit from the combination of evorpacept and zanidatamab, a novel, chemo-free regimen • Validation of biomarker strategy as patients with confirmed HER2-positivity had the greatest benefit, across both studies • These findings provide us with the POC necessary to accelerate clinical development plans in HER2+ BC 1. HER2+ by central assess ment Next Data Update: ASPEN-06 HER2+ Gastric Cancer Study Update: Medical Meeting in Q1 ‘25
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27 Q&A
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Thank you!