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Zanidatamab: Pivotal Phase 3 HERIZON-GEA-01 Trial Results in Gastroesophageal Adenocarcinoma (GEA) Innovating to Transform the Lives of Patients and Their Families January 9, 2026 Intended for U.S. investor audiences only.
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January 9, 2026 Transforming Lives. Redefining Possibilities. Caution Concerning Forward-Looking Statements Intended for U.S. investor audiences only. This presentation contains forward-looking statements and financial targets, including, but not limited to, statements related t o: the Company’s development, regulatory and commercialization strategy; the advancement of pipeline programs and the timing of development activities, regulatory activit ies and submissions related thereto; the Company’s expectations with respect to its products and product candidates and the potential of the Company’s products and product cand idates, including the potential therapeutic benefits of zanidatamab and of combination therapies with zanidatamab, zanidatamab's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers, the potential of zanidatamab to be more than a two billion dollar peak potential and to become the therapy of choice for multiple HER2+ tum ors, expected timing of interim OS data from the pivotal Phase 3 HERIZON-GEA-01 trial, plans to submit an sBLA in first half of 2026; the Company’s ability to realize the commercial potential of its products including the commercial pla ns with respect to zanidatamab in 1L GEA, if approved; potential regulatory approvals; and other statements that are not historical f acts. These forward-looking statements are based on the Company’s current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and unce rtainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the successful completion of development and regulatory activities with respect to the Company’s product candidates including zanidatamab in multiple HER2+ tumors; obtaining and maintaining adequate coverage and reimbursement for the Company’s product s; the time-consuming and uncertain regulatory approval process, including the risk that the Company’s current and/or planned regulatory submissions may not be submitted, a ccepted or approved by applicable regulatory authorities in a timely manner or at all, including the risk that the Company's supplemental biologics license application for zanidatamab’s use in combination with chemotherapy, with or without the PD-1 inhibitor tislelizumab, as first-line treatment for HER2-positive (HER2+) locally advanced or metastatic GEA may not be approved in a timely manner or at all, the costly and time-consuming pharmaceutical product development and the uncertainty of clinical success, including risks related to failure or delays in s uccessfully initiating or completing clinical trials and assessing patients; global economic, financial, and healthcare system disruptions and the current and potential future negative impacts to the Company’s business operations and financial results; protecting and enhancing the Company’s intellectual property rights and the Company’s commercial success being dependent upon the Company obtaining, maintaining and defending intellectual property protection and exclusivity for its products and product candidates; delays or problems in the supply or manufacture of the Company’s products and product candidates; complying with applicable U.S. and non-U.S. regulatory requirements, including those governing the research, development, manufa cturing and distribution; government investigations, legal proceedings and other actions; the sufficiency of the Company’s cash flows and capital resources; and other risks and uncerta inties affecting the Company, including those described from time to time under the caption “Risk Factors” and elsewhere in the Company’s Securities and Exchange Commission filings and r eports, including the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, as supplemented by the Company’s Quarterly Report on Form 10 -Q for the quarter ended September 30, 2025, and future filings and reports by the Company. Other risks and uncertainties of which the Company is not currently aware may also affect the Company’s forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. 2 January 9, 2026
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January 9, 2026 Agenda Introduction and Overview Renee Gala President and Chief Executive Officer Results from the Phase 3 HERIZON-GEA-01 Trial and Clinical Perspective Geoffrey Ku, M.D. Associate Attending Physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center Zanidatamab: Shifting Treatment Paradigm Rob Iannone, M.D., M.S.C.E. Executive Vice President, Global Head of Research and Development and Chief Medical Officer Zanidatamab: Commercial Perspective Sam Pearce Executive Vice President, Chief Commercial Officer 3 Intended for U.S. investor audiences only.
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Introduction and Overview Renee Gala President and Chief Executive Officer Intended for U.S. investor audiences only.
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January 9, 2026 Phase 3 HERIZON-GEA-01 Data Presented at ASCO GI Zanidatamab + chemotherapy ± tislelizumab for first-line HER2-positive locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma: Primary analysis from HERIZON-GEA-01 Intended for U.S. investor audiences only. 5 January 9, 2026
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Geoffrey Ku, MD is a Medical Oncologist who specializes in the treatment of malignancies of the gastrointestinal tract at Memorial Sloan Kettering Cancer Center in New York, New York. He is an Associate Attending physician and Head of the Esophagogastric Section on the Gastrointestinal Oncology Service and a Member of the Cellular Therapy Service, both in the Department of Medicine. His research focuses on the evaluation of novel therapies, including cellular therapies, and combined modality treatments for esophagogastric cancer. He is a member of the Esophagogastric Task Force of the National Cancer Institute and of the Gastrointestinal (non-Colorectal Cancer) Committee of the NRG Cooperative Group. He graduated from the University of Pennsylvania School of Medicine and completed his Internal Medicine Residency in New York Presbyterian Hospital, Weill Cornell Campus, prior to his Medical Oncology Fellowship at MSKCC. Post-fellowship, he spent one year at the Immune Monitoring Facility at MSKCC, which is part of the Ludwig Center for Cancer Immunotherapy. Geoffrey Y. Ku, M.D. Associate Attending Physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center Intended for U.S. investor audiences only.
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Zanidatamab + chemotherapy ± tislelizumab for first-line HER2-positive locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma: Primary analysis from HERIZON-GEA-01 Elena Elimova1, Sun Young Rha2, Kohei Shitara3, Tianshu Liu4, Josep Tabernero5, Keun-Wook Lee6, Michael Schenker7, Niall Tebbutt8, Jaffer Ajani9, Norhidayu Bt Salimin10, Geoffrey Ku11, Jong Gwang Kim12, Inmaculada Ales Diaz13, Jingdong Zhang14, Filippo Pietrantonio15, Li- Yuan Bai16, Samuel Le Sourd17, Ye Chen18, Jonathan Grim19, Lin Shen20 1Princess Margaret Cancer Centre, ON, Canada; 2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; 3National Cancer Center Hospital East, Kashiwa, Japan; 4Zhongshan Hospital, Fudan University, Shanghai, China; 5Vall d’Hebron Hospital Campus & Institute of Oncology (VHIO), IR-HUVH, UVic-UCC, Barcelona, Spain; 6Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; 7Sfantul Nectarie Oncology Center and University of Medicine and Pharmacy of Craiova, Craiova, Romania; 8Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, VIC, Australia; 9The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 10National Cancer Institute, Putrajaya, Malaysia; 11Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Kyungpook National University, Daegu, Republic of Korea; 13Hospital Regional Universitario de Malaga, Malaga, Spain; 14Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China; 15Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 16China Medical University Hospital, Taichung, Taiwan; 17Centre Eugène-Marquis, Rennes, France; 18BeOne Medicines, Ltd., Beijing, China; 19Jazz Pharmaceuticals, Palo Alto, CA, USA; 20State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumor, Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China Intended for U.S. investor audiences only. 7 January 9, 2026
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Key Takeaway Points HERIZON-GEA-01 supports zanidatamab as a new standard in HER2-targeting agents, potentially replacing trastuzumab, as well as the use of tislelizumab in 1L HER2+ mGEA Progression-Free Survival and Overall Survival • Statistically significant ~35% reduction in the risk of disease progression or death for both zanidatamab + CT and zanidatamab + tislelizumab + CT vs trastuzumab + CT (>4-month improvement in median PFS) • There was a strong trend toward statistical significance for OS favoring zanidatamab + CT vs trastuzumab + CT (5-month improvement in median OS) • Statistically significant 28% reduction in the risk of death for zanidatamab + tislelizumab + CT vs trastuzumab + CT (>7-month improvement in median OS) • The PFS and OS benefits were generally observed across key prespecified subgroups, including in patients with PD-L1 TAP scores <1% and ≥1% Safety Profile • The safety profile was consistent with the known profiles of each individual treatment 8 January 9, 2026Intended for U.S. investor audiences only.
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Background • Outcomes with current SoC for 1L HER2+ mGEA remain modest, with an mPFS of <1 year and mOS of <2 years1-7 • Zanidatamab is a dual HER2-targeted bispecific IgG1-like antibody that binds to extracellular domains 2 and 4 on HER2 in a trans configuration8 ▪ This biparatopic binding enables zanidatamab to crosslink neighboring HER2 proteins, leading to receptor clustering ▪ In preclinical studies, zanidatamab enhanced HER2 internalization, reduced downstream signaling, and promoted immune-mediated cytotoxicity (CDC, ADCC, ADCP) • Tislelizumab is a high-affinity immune checkpoint inhibitor targeting PD-1 and is specifically engineered to minimize Fcγ receptor binding on macrophages9,10 • Promising efficacy and a tolerable safety profile were observed with zanidatamab + chemotherapy ± tislelizumab across independent phase 2 trials in 1L HER2+ mGEA11,12 1. Bartley AN, et al. J Clin Oncol. 2017;35(4):446-64. 2. Lordick F, et al. Ann Oncol. 2022;33(10):1005-20. 3. US Food and Drug Administration. FDA approved pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). Accessed October 14, 2025. http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma. 4. Bang YJ, et al. Lancet. 2010;376(9742):687-97. 5. Janjigian YY, et al. N Engl J Med. 2024;391(14):1360-2. 6. Janjigian YY, et al. Lancet. 2023;402(10418):2197-208. 7. Meric-Bernstam F, et al. Nat Commun. 2025;16(1):4293. 8. Weisser NE, et al. Nat Commun. 2023;14(1):1394. 9. Hong Y, et al. FEBS Open Bio. 2021;11(3):782-92. 10. Zhang T, et al. Cancer Immunol Immunother. 2018;67(7):1079-90. 11. Elimova E, et al. Lancet Oncol. 2025;26(7):847- 59. 12. Lee KW, et al. Clin Cancer Res. 2025. http://doi.org/10.1158/1078-0432.CCR-24-4295. Fc region Biparatopic antibody binding in trans HER2 HER2 IV II IV II Intended for U.S. investor audiences only. 9 January 9, 2026
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aPhysician’s choice of capecitabine plus oxaliplatin or 5-fluorouracil plus cisplatin. Chemotherapy was administered for at least 6 cycles or until disease progression, unacceptable toxicity, or another criterion for treatment discontinuation was met. bTislelizumab 200 mg was administered IV Q3W. cCT/MRI scans were performed every 6 weeks for the first 54 weeks, then every 9 weeks. HERIZON-GEA-01 Study Design Arm C: Zanidatamab 1800 mg (<70 kg)/2400 mg (≥70 kg) IV Q3W + tislelizumabb + chemotherapya Arm B: Zanidatamab 1800 mg (<70 kg)/2400 mg (≥70 kg) IV Q3W + chemotherapya Arm A: Trastuzumab + chemotherapya CT/MRIc Q6W Dual Primary Endpoints • PFS (per BICR) • OS Select Secondary Endpoints • cORR (per BICR) • Frequency and severity of AEs Prophylaxis to prevent IRR and diarrhea was mandatory in the zanidatamab-containing arms Treatment until disease progression/death/unacceptable toxicity Chemotherapy could be discontinued after 6 cycles R 1:1:1 ClinicalTrials.gov: NCT05152147 Stratification Factors • Geographic region • HER2 status • ECOG PS Global phase 3 trial of zanidatamab + chemotherapy ± tislelizumab vs trastuzumab + chemotherapy in previously untreated patients with HER2+ mGEA Key Eligibility Criteria • Age ≥18 years • Unresectable, locally advanced, recurrent or metastatic GEA • HER2 IHC 3+ or IHC 2+/ISH+ per central testing • ECOG PS 0 or 1 • No prior treatment for locally advanced or metastatic disease • No prior HER2-targeted agents or immunotherapy in any setting N = 914 Intended for U.S. investor audiences only. 10 January 9, 2026
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aFor the primary analysis of PFS, the 2-sided alpha was 0.05. bFor the first interim analysis of OS, the 2-sided alpha was 0.020. Statistical Design • Dual primary endpoints (PFS and OS): Analyzed in the intent-to-treat population using log-rank tests with a 2-sided α = 0.05 • Primary PFS analysis: After target event count was reached and patients had ≥7 months of follow-up • First interim OS analysis: Performed at the time of data cutoff for the primary PFS analysis Fixed-Sequence Testing Procedure OSbPFSaPFSa OSb OS Zani + TIS + CT vs Tras + CT Zani + CT vs Tras + CT Zani + TIS + CT vs Tras + CT Zani + CT vs Tras + CT Zani + TIS + CT vs Zani + CT Intended for U.S. investor audiences only. 11 January 9, 2026
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Ongoing treatment, n = 69 (23%) Discontinued treatment, n = 231 (76%) • Progressive disease, n = 132 • Adverse event, n = 25 • Death, n = 27 • Withdrawal by patient, n = 23 • Physician decision, n = 19 • Other, n = 5b Survival follow-up, n = 69 (23%) Zanidatamab + CT n = 304; 300 patients treateda Median (range) follow-up 26.0 (7.6–46.0) months Patient Disposition Randomized N = 914 Ongoing treatment, n = 88 (29%) Discontinued treatment, n = 211 (70%) • Progressive disease, n = 117 • Adverse event, n = 27 • Death, n = 26 • Withdrawal by patient, n = 26 • Physician decision, n = 13 • Other, n = 2b Survival follow-up, n = 58 (19%) Zanidatamab + tislelizumab + CT n = 302; 299 patients treateda Median (range) follow-up 25.9 (7.9–45.5) months Ongoing treatment, n = 37 (12%) Discontinued treatment, n = 265 (86%) • Progressive disease, n = 200 • Adverse event, n = 10 • Death, n = 17 • Withdrawal by patient, n = 20 • Physician decision, n = 13 • Other, n = 5b Survival follow-up, n = 81 (26%) Trastuzumab + CT n = 308; 302 patients treated Median (range) follow-up 25.8 (7.5–45.6) months A total of 914 patients were randomized, and median follow-up was >2 years aTreated includes all randomized patients who received any amount of any study treatment and does not necessarily reflect the safety analysis set. Five patients assigned to the zanidatamab-tislelizumab-chemotherapy arm did not receive tislelizumab and are included in the safety analysis set for the zanidatamab- chemotherapy arm. bIncludes protocol violations and “other” reasons. Intended for U.S. investor audiences only. 12 January 9, 2026
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All data are shown as n (%) unless otherwise indicated. aOne patient in the zanidatamab-tislelizumab-chemotherapy arm had an ECOG PS score of 2 at baseline. bPD-L1 status was missing for 7.1% (n = 65) of patients across arms. Baseline Demographics and Disease Characteristics Demographics and clinical characteristics were balanced across all 3 treatment arms Zanidatamab + CT (n = 304) Zanidatamab + tislelizumab + CT (n = 302) Trastuzumab + CT (n = 308) Age, median (range), years 62.5 (25–87) 63.0 (22–81) 64.0 (21–84) Male sex 244 (80.3) 244 (80.8) 238 (77.3) Geographic region Asia 163 (53.6) 159 (52.6) 165 (53.6) EU/North America 91 (29.9) 95 (31.5) 93 (30.2) Rest of the world 50 (16.4) 48 (15.9) 50 (16.2) ECOG PSa 0 134 (44.1) 121 (40.1) 120 (39.0) 1 170 (55.9) 180 (59.6) 188 (61.0) Disease status Metastatic 295 (97.0) 284 (94.0) 299 (97.1) Unresectable locally advanced 9 (3.0) 18 (6.0) 9 (2.9) Zanidatamab + CT (n = 304) Zanidatamab + tislelizumab + CT (n = 302) Trastuzumab + CT (n = 308) Anatomical subtype Gastric 204 (67.1) 208 (68.9) 226 (73.4) GEJ 61 (20.1) 74 (24.5) 60 (19.5) Esophageal 39 (12.8) 20 (6.6) 22 (7.1) HER2 IHC 3+ 251 (82.6) 251 (83.1) 255 (82.8) PD-L1 statusb TAP score <1% 108 (35.5) 90 (29.8) 98 (31.8) TAP score ≥1% 178 (58.6) 187 (61.9) 188 (61.0) Choice of chemotherapy backbone CAPOX 276 (90.8) 273 (90.4) 282 (91.6) FP 28 (9.2) 29 (9.6) 26 (8.4) Intended for U.S. investor audiences only. 13 January 9, 2026
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Patients at risk Zani + CT 304 231 175 137 105 70 53 37 34 26 14 12 8 1 0 Tras + CT 308 247 168 97 63 37 23 16 13 10 6 4 3 2 0 Primary Endpoint: PFS per BICR Statistically significant and clinically meaningful improvement in PFS with zanidatamab + CT vs trastuzumab + CT (>4-month prolongation in median PFS) Zanidatamab + CT Trastuzumab + CT 12.4 (9.8–14.5) 8.1 (7.0–8.9) 0.65 (0.52–0.81) P <0.0001 Median PFS (95% CI), mo HR (95% CI) Progression-free survival (%) 59.4% (95% CI: 53.1–65.2) 38.0% (95% CI: 31.5–44.4) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Censored Zanidatamab + CT 43.7% (95% CI: 37.5–49.7) 20.9% (95% CI: 15.3–27.2) Trastuzumab + CT 0 25 50 75 100 Months from randomization 15.6% (95% CI: 10.1–22.1) 31.5% (95% CI: 24.9–38.3) Intended for U.S. investor audiences only. 14 January 9, 2026
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Patients at risk Zani + TIS + CT 302 240 183 147 113 90 65 46 42 30 27 20 13 6 2 0 Tras + CT 308 247 168 97 63 37 23 16 13 10 6 4 3 2 0 Primary Endpoint: PFS per BICR Statistically significant and clinically meaningful improvement in PFS with zanidatamab + tislelizumab + CT vs trastuzumab + CT (>4-month prolongation in median PFS) Median PFS (95% CI), mo HR (95% CI) Progression-free survival (%) 59.7% (95% CI: 53.6–65.4) 43.9% (95% CI: 37.4–50.1) Censored Zanidatamab + tislelizumab + CT 43.7% (95% CI: 37.5–49.7) 20.9% (95% CI: 15.3–27.2) Trastuzumab + CT 0 25 50 75 100 Months from randomization 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 15.6% (95% CI: 10.1–22.1) 38.2% (95% CI: 31.4–45.0) Zanidatamab + tislelizumab + CT Trastuzumab + CT 12.4 (9.8–18.5) 8.1 (7.0–8.9) 0.63 (0.51–0.78) P <0.0001 Intended for U.S. investor audiences only. 15 January 9, 2026
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PFS in Key Prespecified Subgroups Subgroup Category Zanidatamab + tislelizumab + CT Zanidatamab + CT Trastuzumab + CT All patients 154/302 160/304 196/308 0.63 (0.51–0.78) 0.65 (0.52–0.81) Age, years <65 79/163 94/174 105/162 0.55 (0.41–0.74) 0.63 (0.47–0.83) ≥65 75/139 66/130 91/146 0.71 (0.52–0.96) 0.72 (0.53–1.00) Geographic region Asia 78/159 81/163 106/165 0.56 (0.42–0.75) 0.64 (0.48–0.86) EU/NA 47/95 49/91 55/93 0.65 (0.44–0.97) 0.73 (0.49–1.08) ROW 29/48 30/50 35/50 0.74 (0.45–1.23) 0.63 (0.39–1.04) ECOG PS 0 51/121 63/134 74/120 0.51 (0.35–0.73) 0.63 (0.45–0.89) 1 103/180 97/170 122/188 0.69 (0.53–0.90) 0.70 (0.53–0.91) Anatomical subtype Gastric 105/208 112/204 140/226 0.61 (0.47–0.79) 0.74 (0.57–0.95) GEJ 43/74 29/61 44/60 0.70 (0.46–1.08) 0.52 (0.32–0.83) Esophageal 6/20 19/39 12/22 0.32 (0.12–0.85) 0.60 (0.29–1.25) HER2 status IHC 3+ 121/251 125/251 167/255 0.54 (0.43–0.69) 0.55 (0.43–0.69) IHC 2+/ISH+ 33/51 35/51 29/52 1.08 (0.65–1.78) 1.73 (1.06–2.83) PD-L1 status TAP <1% 47/90 61/108 71/98 0.47 (0.32–0.69) 0.62 (0.44–0.87) TAP ≥1% 91/187 94/178 114/188 0.65 (0.49–0.86) 0.74 (0.56–0.98) Favors Zani + TIS + CT Favors Tras + CT Events/patients Improvements in PFS were generally consistent across major prespecified subgroups aThe widths of the confidence intervals were not adjusted for multiplicity and cannot be used to infer treatment effects. Favors Zani + CT Favors Tras + CT Intended for U.S. investor audiences only. 16 January 9, 2026
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Patients at risk Zani + CT 304 277 257 222 187 156 121 98 78 56 41 28 21 6 3 1 0 Tras + CT 308 284 261 219 178 140 106 77 61 50 33 22 17 8 2 2 0 Primary Endpoint: Overall Survival At this interim analysis, there was a strong trend toward significance for OS favoring zanidatamab + CT vs trastuzumab + CT (5-month improvement in median OS) Zanidatamab + CT Trastuzumab + CT 24.4 (20.4–30.0) 19.2 (16.8–21.8) 0.80 (0.64–1.01) P = 0.0564 Median OS (95% CI), mo HR (95% CI) Months from randomization 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 50.3% (95% CI: 43.6–56.6) 42.2% (95% CI: 35.1–49.2) Zanidatamab + CT 38.8% (95% CI: 32.2–45.4) 30.0% (95% CI: 23.4–36.8) Trastuzumab + CT 0 25 50 75 100 Overall survival (%) Censored Intended for U.S. investor audiences only. 17 January 9, 2026
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Primary Endpoint: Overall Survival Zanidatamab + tislelizumab + CT demonstrated a statistically significant and clinically meaningful OS benefit with a >7-month improvement in median OS vs trastuzumab + CT Patients at risk Zani + TIS + CT 302 267 246 222 190 157 125 96 82 64 49 36 27 10 4 2 0 Tras + CT 308 284 261 219 178 140 106 77 61 50 33 22 17 8 2 2 0 Zanidatamab + tislelizumab + CT Trastuzumab + CT 26.4 (21.5–30.3) 19.2 (16.8–21.8) 0.72 (0.57–0.90) P = 0.0043 Median OS (95% CI), mo HR (95% CI) 0 25 50 75 100 Overall survival (%) 54.3% (95% CI: 47.6–60.5) 30.0% (95% CI: 23.4–36.8) 43.8% (95% CI: 36.5–50.9) Censored Zanidatamab + tislelizumab + CT Trastuzumab + CT 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Months from randomization 38.8% (95% CI: 32.2–45.4) Intended for U.S. investor audiences only. 18 January 9, 2026
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aThe widths of the confidence intervals were not adjusted for multiplicity and cannot be used to infer treatment effects. OS in Key Prespecified Subgroups Subgroup Category Zanidatamab + tislelizumab + CT Trastuzumab + CT All patients 134/302 170/308 0.72 (0.57–0.90) Age, years <65 68/163 99/162 0.60 (0.44–0.82) ≥65 66/139 71/146 0.91 (0.65–1.28) Geographic region Asia 63/159 89/165 0.64 (0.46–0.88) EU/NA 46/95 52/93 0.84 (0.57–1.25) ROW 25/48 29/50 0.80 (0.47–1.36) ECOG PS 0 41/121 52/120 0.72 (0.48–1.09) 1 92/180 118/188 0.72 (0.55–0.95) Anatomical subtype Gastric 87/208 127/226 0.63 (0.48–0.83) GEJ 42/74 33/60 1.14 (0.72–1.80) Esophageal 5/20 10/22 0.51 (0.17–1.52) HER2 status IHC 3+ 106/251 138/255 0.70 (0.55, 0.91) IHC 2+/ISH+ 28/51 31/52 0.83 (0.50, 1.39) PD-L1 status TAP <1% 38/90 65/98 0.49 (0.33–0.74) TAP ≥1% 79/187 92/188 0.82 (0.60–1.10) Favors Zani + TIS + CT Favors Tras + CT Events/patients Improvements in OS occurred across major prespecified subgroups, including regions and PD-L1 TAP scores Intended for U.S. investor audiences only. 19 January 9, 2026
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0 20 40 60 80 100 cORR (%) Zanidatamab + CT Trastuzumab + CTZanidatamab + tislelizumab + CT 70.7% 95% CI (65.0–76.0) 65.7% 95% CI (59.9–71.2) PR 51.1% PR 54.8% PR 52.5% 69.6% 95% CI (63.9–75.0) Key Secondary Endpoint: Antitumor Activity Confirmed ORR in patients with measurable disease Responses were deeper and more durable in the zanidatamab-containing arms vs the trastuzumab + CT arm Median DOR (95% CI), moCR 19.6% CR 11.0% cORR was defined as the proportion of patients achieving a best overall response of CR or PR, as determined by BICR using RECIST v1.1, with the response confirmed at a subsequent visit ≥28 days after the initial assessment. DOR was assessed among patients with measurable disease at baseline who achieved a confirmed objective response by BICR per RECIST v1.1. The widths of the confidence intervals were not adjusted for multiplicity and cannot be used to infer treatment effects. Zanidatamab + CT (n = 186) Zanidatamab + tislelizumab + CT (n = 195) Trastuzumab + CT (n = 198) 14.3 (11.5–21.9) 20.7 (12.6–37.7) 8.3 (6.7–9.8) Intended for U.S. investor audiences only. 20 January 9, 2026 CR 17.1%
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aFive patients who were assigned to the zanidatamab-tislelizumab-chemotherapy arm did not receive tislelizumab. Data from these patients are summarized in the zanidatamab-chemotherapy arm. bAESIs for zanidatamab were IRRs, noninfectious pulmonary toxicities, and left ventricular dysfunction; AESIs for tislelizumab were IRRs and immune-mediated AEs. AESIs for zanidatamab and tislelizumab were reported in all treatment groups, even if the study agent was not administered in that group. Safety Summary The safety profile was generally manageable, and no unexpected safety signals were identified Zanidatamab + CT (n = 305)a Zanidatamab + tislelizumab + CT (n = 294)a Trastuzumab + CT (n = 302) Duration of treatment, median (IQR), weeks 31.0 (53.8) 43.1 (56.7) 30.0 (32.2) Any-grade TEAE, n (%) 301 (98.7) 293 (99.7) 297 (98.3) TRAE, n (%) 296 (97.0) 289 (98.3) 291 (96.4) Grade ≥3 180 (59.0) 211 (71.8) 180 (59.6) Serious TEAEs, n (%) 150 (49.2) 172 (58.5) 128 (42.4) Treatment-related 86 (28.2) 121 (41.2) 61 (20.2) TEAEs leading to death, n (%) 25 (8.2) 28 (9.5) 22 (7.3) Treatment-related 1 (0.3) 7 (2.4) 4 (1.3) Discontinuation due to TRAEs, n (%) Any component 105 (34.4) 125 (42.5) 88 (29.1) Zanidatamab or trastuzumab 26 (8.5) 35 (11.9) 7 (2.3) Tislelizumab — 42 (14.3) — AESIsb, n (%) 93 (30.5) 102 (34.7) 56 (18.5) IRRs 77 (25.2) 74 (25.2) 40 (13.2) Noninfectious pulmonary toxicities 4 (1.3) 20 (6.8) 3 (1.0) Left ventricular dysfunction 19 (6.2) 26 (8.8) 13 (4.3) Immune-mediated AEsb, n (%) 38 (12.5) 111 (37.8) 31 (10.3) Intended for U.S. investor audiences only. 21 January 9, 2026
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Common TRAEs (≥20% of Patients in Any Arm) Diarrhea was the most common TRAE in all treatment arms aFive patients who were assigned to the zanidatamab-tislelizumab-chemotherapy arm did not receive tislelizumab. Data from these patients are summarized in the zanidatamab-chemotherapy arm. . Diarrhea Nausea Vomiting Decreased appetite Anemia PSN Weight decreased IRR Neutrophil count decreased Hypokalemia Platelet count decreased PPES 48% 42% 28% 28% 37% 32% 12% 13% 29% 14% 30% 82% 51% 38% 40% 38% 27% 22% 25% 25% 21% 22% 18% 21% Patients (%) 0 10 20 30 40 50 60 70 80 90 100 76% 50% 39% 36% 35% 31% 26% 25% 22% 21% 20% 16% Zani + CT (n = 305)a Zani + TIS + CT (n = 294)a Tras + CT (n = 302) Grade 1–2 Grade ≥3 Intended for U.S. investor audiences only. 22 January 9, 2026
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Zanidatamab + CT (n = 305)a Zanidatamab + tislelizumab + CT (n = 294)a Trastuzumab + CT (n = 302) Treatment-related diarrhea, n (%) Any grade 233 (76.4) 240 (81.6) 146 (48.3) Grade ≥3 61 (20.0) 72 (24.5) 39 (12.9) Treatment-related diarrhea leading to discontinuation, n (%) Any component 15 (4.9) 22 (7.5) 5 (1.7) Zanidatamab or trastuzumab 4 (1.3) 12 (4.1) 0 Tislelizumab — 6 (2.0) — Time to first onset of diarrhea, median (IQR), days Any grade 6.0 (12.0) 7.0 (14.5) 10.0 (30.0) Grade 3/4 11.0 (23.0) 16.0 (43.0) 37.0 (56.0) Duration of first diarrhea event, median (95% CI), days Any grade 17.0 (13.0–20.0) 14.0 (11.0–18.0) 10.0 (7.0–15.0) Grade 3/4 9.0 (6.0–11.0) 8.0 (7.0–9.0) 9.0 (6.0–12.0) aFive patients who were assigned to the zanidatamab-tislelizumab-chemotherapy arm did not receive tislelizumab. Data from these patients are summarized in the zanidatamab-chemotherapy arm. Treatment-Emergent Diarrhea Mandatory diarrhea prophylaxis for patients in the zanidatamab-containing arms Loperamide (4 mg BID) for the first 7 days of cycle 1 only Treatment-emergent diarrhea generally occurred early in treatment and resolved within 3 weeks, and few patients discontinued zanidatamab due to diarrhea Intended for U.S. investor audiences only. 23 January 9, 2026
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Discussion • Treatment with zanidatamab-containing regimens led to a clinically meaningful prolongation of PFS that was statistically superior to trastuzumab + CT (>4-month prolongation of median PFS) • At this interim analysis, there was a strong trend toward statistical significance for OS favoring zanidatamab + CT vs trastuzumab + CT (5-month improvement in median OS) • The trial is ongoing with additional OS analyses planned for zanidatamab + CT • Zanidatamab + tislelizumab + CT demonstrated a clinically meaningful and statistically superior prolongation of OS vs trastuzumab + CT (>7-month prolongation of median OS) • The OS and PFS benefits were generally observed across key prespecified subgroups, including in patients with PD-L1 TAP scores <1% and ≥1% • The safety profile was consistent with the known profiles of each individual treatment • For patients who experienced diarrhea, events generally occurred early in treatment and resolved within 3 weeks • These findings support zanidatamab as a promising new standard in HER2-targeting agents, with potential to replace trastuzumab in first-line treatments for HER2+ mGEA • The clinically meaningful survival benefit further supports zanidatamab plus tislelizumab and CT as an important new treatment option for this patient population • HERIZON-GEA-01 is the first phase 3 study in mGEA to demonstrate a median PFS >1 year and a median OS >2 years Intended for U.S. investor audiences only. 24 January 9, 2026
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Acknowledgments • Clinical research was funded by Jazz Pharmaceuticals in collaboration with BeOne Medicines and Zymeworks • Under the direction of the authors, Charlotte Pettigrew, PhD, CMPP, of Red Nucleus, Yardley, PA, USA, provided medical writing support, which was funded by Jazz Pharmaceuticals in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022) The authors would like to thank all the patients and their families as well as all the investigators, clinical trial researchers, personnel, and staff who contributed to or participated in the trial Intended for U.S. investor audiences only. 25 January 9, 2026
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Zanidatamab: Shifting Treatment Paradigm Rob Iannone, M.D., M.S.C.E. Executive Vice President, Global Head of Research & Development, Chief Medical Officer Intended for U.S. investor audiences only.
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January 9, 2026 Zanidatamab: Unique MOA Drives Compelling Clinical Profile and Patient Outcomes 27 Favorable tolerability with manageable AE profile Compelling and durable responses help drive improved patient outcomes in HER2+ patients Unique dual-targeting HER2 bispecific antibody provides differentiated treatment Combination data supports ability to combine with other agents in multiple HER2+ indications Intended for U.S. investor audiences only.
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January 9, 2026 mOS 26.4m 24.4m 20.0m 13.8m mPFS 10.0m 6.7m 12.4m 12.4m January 9, 202628 Primary Endpoints of OS and PFS for Intent-to-Treat Population HR = 0.80 HR = 0.74 HR = 0.71 Immature at this analysis2 HR = 0.72 HR = 0.63 HR = 0.65 HR = 0.73 Zanidatamab + Tislelizumab + Chemo Zanidatamab + Chemo Trastuzumab + Pembrolizumab + Chemo (KN-811) Trastuzumab + Chemo (TOGA) Zanidatamab + Tislelizumab + Chemo Zanidatamab + Chemo Trastuzumab + Pembrolizumab + Chemo (KN-811) Trastuzumab + Chemo (TOGA) 1 1 1 1 3 3 4 4 Zanidatamab + Tislelizumab + Chemo in 1L HER2+ GEA: Clinical Benchmarks Intended for U.S. investor audiences only.
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Zanidatamab + Tislelizumab + Chemo in 1L HER2+ GEA: Clinical Benchmarks Progression-Free Survival Kaplan-Meier Plot 1.00 0.75 0.50 0.25 0.00 Survival Probability 0 63 9 1512 18 2421 27 3330 36 4239 45 5148 HERIZON-GEA-01 trastuzumab + chemo HERIZON-GEA-01 zanidatamab + chemo HERIZON-GEA-01 zanidatamab + tislelizumab + chemo KEYNOTE-811 pembrolizumab + trastuzumab + chemo KEYNOTE-811 trastuzumab + chemo Months Intended for U.S. investor audiences only. Graph to aid investors only. 29 January 9, 2026
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Zanidatamab + Tislelizumab + Chemo in 1L HER2+ GEA: Clinical Benchmarks Overall Survival Kaplan-Meier Plot 1.00 0.75 0.50 0.25 0.00 Survival Probability 0 63 9 1512 18 21 27 3330 36 4239 45 5148 HERIZON-GEA-01 trastuzumab + chemo HERIZON-GEA-01 zanidatamab + chemo HERIZON-GEA-01 zanidatamab + tislelizumab + chemo KEYNOTE-811 pembrolizumab + trastuzumab + chemo KEYNOTE-811 trastuzumab + chemo 24 54 57 60 Months Intended for U.S. investor audiences only. Graph to aid investors only. 30 January 9, 2026
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January 9, 2026 Zanidatamab + Tislelizumab + Chemo in 1L HER2+ GEA: Clinical Benchmarks cORR 70.7% 69.6% 72.6% 47% mDOR January 9, 202631 Secondary Endpoints of cORR and DOR 20.7m 14.3m 11.3m 6.9m Zanidatamab + Tislelizumab + Chemo Zanidatamab + Chemo Trastuzumab + Pembrolizumab + Chemo (KN-811) Trastuzumab + Chemo (TOGA) Zanidatamab + Tislelizumab + Chemo Zanidatamab + Chemo Trastuzumab + Pembrolizumab + Chemo (KN-811) Trastuzumab + Chemo (TOGA) 1,2 1,2 3,4 5 1,2 1,2 3,4 5 Intended for U.S. investor audiences only.
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January 9, 2026 PHASE 1 PHASE 2 PHASE 3 PHASE 4 / REGULATORY Recent / Upcoming Milestones Zanidatamab Plan to submit sBLA in 1H26 Phase 3 confirmatory trial in 1L BTC ongoing Phase 3 EmpowHER-BC-303 trial now enrolling Phase 2 EmpowHER-BC-208 trial now enrolling Novel, collaborative trial for breast cancer Phase 2 DiscovHER-Pan-206 trial now enrolling In collaboration with the MD Anderson Cancer Center In collaboration with the Canadian Cancer Trials Group Novel, collaborative trial for breast cancer Key Ongoing Zanidatamab Clinical Trials Phase 3 1L BTC I-SPY2 Trial: neoadjuvant treatment of locally advanced BC Phase 3 1L GEA (pivotal) Phase 3 BC in patients who have progressed on previous T-DXd treatment Phase 2 pan-tumor trial in HER2+ solid tumors Phase 2 trial in neoadjuvant and adjuvant breast cancer 32 Phase 2 trial + SOC Chemo (1L) in HER2+ solid tumors Phase 1/1b I-SPY in breast cancer Open-label trial in early-stage, low-risk, HER2+ breast cancer Phase 2 trial + paclitaxel and ramucirumab in HER2+ advanced GEA Clinical efficacy and differentiated mechanism of action supports continued advancement of zanidatamab development program focusing on areas where we believe zanidatamab has the potential to be the preferred HER2-targeted therapy Intended for U.S. investor audiences only.
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Zanidatamab: Commercial Perspective Sam Pearce Executive Vice President and Chief Commercial Officer Intended for U.S. investor audiences only.
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January 9, 2026 GEA Represents a Significant Unmet Need 34 U.S. ~8,000 HER2+ GEA patients annually2 GEA opportunity of ~63,000 cases annually2 in U.S., Europe3 and Japan <10% five-year survival rate in mGEA1 Intended for U.S. investor audiences only.
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January 9, 2026 Establish Ziihera as the HER2+ Standard of Care Regardless of PDL1 Status 2 3 Utilize Existing Access Infrastructure Leverage Existing Footprint and Infrastructure to Accelerate Launch 1 Establish Belief in Ziihera Based on Unprecedented Clinical Results • Practice-changing results supporting Ziihera as the HER2-targeted agent of choice in HER2+ 1L metastatic GEA, replacing trastuzumab as the new standard of care • The addition of tislelizumab further improved outcomes, regardless of PD-L1 status • Combination regimens including Ziihera were generally well tolerated • High physician awareness of Ziihera due to existing approval in 2L BTC and broad development program • Significant overlap in the customer footprint with GEA and BTC accounts (90+% overlap) • Existing payer access simplifies reimbursement (Example utilize existing J-code) • Robust access and reimbursement support for patients; flexible ordering and fulfillment options 35Intended for U.S. investor audiences only.
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January 9, 2026 Zanidatamab: De-Risked Near-Term Opportunity with $2B+ Peak Potential Ongoing launch in 2L BTC 1L BTC confirmatory trial ongoing Granted conditional marketing authorization by EC in 2L BTC for monotherapy treatment Expanded opportunity across lines of therapy3: • Post T-DXd (Ph 3 EmpowHER-BC-303 trial) • Early lines of therapy (neoadjuvant) • Novel combinations Initiated Phase 2 EmpowHER-208 trial: • Zanidatamab + taxane with or without carboplatin vs TCHP in patients with untreated, histologically confirmed eBC Potential for novel chemo-free regimen for HER2+/HR+ patients3 Ongoing trials in early breast cancer: • I-SPY2 Trial4 • MD Anderson collaboration Goal to be the HER2-targeted agent of choice • Data presented at ASCO GI January 8th • Rapid submission to NCCN Guidelines • Plan to submit sBLA for 1L HER2+ mGEA in 1H26 Biliary Tract Cancer Gastroesophageal Adenocarcinoma Breast Cancer Plan to submit sBLA for 1L GEA in 1H26 Potential to become the new standard of care anti-HER2 therapy for patients with HER2+ first- line metastatic GEA regardless of PD-L1 status3 Opportunity to explore potential in neoadjuvant populations3 36 ~12,000 BTC cases annually1 in U.S., Europe2 and Japan ~150,000 BC cases annually5 in U.S., Europe2 and Japan ~63,000 GEA cases annually1 in U.S., Europe2 and Japan Broad Potential Beyond BTC, GEA, and BC Other HER2-Expressing Cancers Broad potential beyond BTC, GEA and BC in multiple HER2-expressing indications based on compelling clinical activity from early trials6: • Colorectal • NSCLC • Ovarian • Endometrial • Pancreatic • Bladder • Salivary Gland • Ampullary • Other HER2-expressing solid tumors Ongoing Phase 2 DiscovHER-Pan-206 • Zanidatamab monotherapy in previously-treated patients with no available treatment options Intended for U.S. investor audiences only.
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January 9, 2026 … to the numerous patients and their families who participated in our clinical development program. … to the clinical investigators, physicians, nurses, site coordinators, and countless support staff. … to the Jazz team continuously working to deliver this important medicine patients. Intended for U.S. investor audiences only. Thank You
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Q&A Intended for U.S. investor audiences only.
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January 9, 2026 Glossary Acronym Definition 1H First half 1L First-line 2L Second-line ADCC Antibody-dependent cellular cytotoxicity ADCP Antibody-dependent cellular phagocytosis AE Adverse event AESI Adverse event of special interest BC Breast cancer BICR Blinded-independent central review BID Twice daily BTC Biliary tract cancer CAPOX or FP Capecitabine/oxaliplatin or fluoropyrimidine CDC Complement-dependent cytotoxicity cORR Confirmed objective response rate CR Complete response CT Chemotherapy CT Computed tomography DOR Duration of response EC European Commission ECD Extracellular domain ECOG PS Eastern Cooperative Oncology Group performance status EU European Union Fab Fragment antigen binding Fc Fragment crystallizable FP 5-fluorouracil (5-FU) plus cisplatin GEJ Gastroesophageal junction HCP Healthcare provider HER2 Human epidermal growth factor receptor 2 HR Hazard ratio HR+ Hormone receptor-positive Acronym Definition IHC Immunohistochemistry IQR Interquartile range IRR Infusion-related reaction ISH In situ hybridization IV Intravenously M Month mGEA Metastatic gastroesophageal adenocarcinoma MOA Mechanism of action MRI Magnetic resonance imaging NA North America NCCN National Comprehensive Cancer Network NSCLC Non-small cell lung cancer OS Overall survival ORR Objective response rate PD-1 Programmed cell death protein 1 PD-L1 Programmed death-ligand 1 PFS Progression-free survival PPES Palmar-plantar erythrodysesthesia syndrome PR Partial response PSN Peripheral sensory neuropathy Q3W Every 3 weeks Q6W Every 6 weeks R Randomization RECIST v1.1 Response Evaluation Criteria in Solid Tumors version 1.1 ROW Rest of world sBLA Supplemental biologics license application SoC Standard of care scFv Single-chain variable fragment T-DXd Trastuzumab deruxtecan TAP Tumor area positivity Acronym Definition TEAE Treatment-emergent adverse event TCHP Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab TIS Tislelizumab Tras Trastuzumab Zani Zanidatamab 39Intended for U.S. investor audiences only.