Ziihera® (zanidatamab-hrii) Combinations Achieve Unprecedented Results in First-Line HER2+ Locally Advanced or Metastatic GEA Including More Than Two Years Median Overall Survival Benefit

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Positive Phase 3 HERIZON-GEA-01 results support Ziihera as the HER2-targeted agent-of-choice in HER2+ first-line metastatic GEA and Ziihera plus chemotherapy to replace trastuzumab as the new standard of care, with or without tislelizumab regardless of PD-L1 status Late-breaking results to be presented at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI) on January 8, 2026 For U.S. media and investors only DUBLIN , Jan. 6, 2026 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced positive efficacy and safety results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera® (zanidatamab-hrii) in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra® (tislelizumab), as first-line treatment for adults with HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (GEA), including cancers of the stomach, gastroesophageal junction and esophagus. The data will be presented as a late-breaking oral presentation at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco on January 8, 2026 from 8:57- 9:07 a.m. PST (abstract number: LBA285). The study found: Both investigational arms, Ziihera plus tislelizumab and chemotherapy, and Ziihera plus chemotherapy, led to a statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with approximately 35% reduction in the risk of disease progression or death versus trastuzumab plus chemotherapy. This resulted in a median PFS of more than one year, representing a greater than four-month improvement compared to the control arm. Ziihera plus tislelizumab and chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit with a median OS of more than two years (26.4 months), the longest reported in a Phase 3 trial in GEA, representing a greater than seven-month improvement in median OS and a 28% reduction in the risk of death versus trastuzumab plus chemotherapy. At this first interim analysis, Ziihera plus chemotherapy showed a median OS of more than two years, with a strong trend toward statistical significance, favoring Ziihera plus chemotherapy versus trastuzumab plus chemotherapy. An additional planned OS interim analysis for Ziihera plus chemotherapy is currently expected in mid-2026. The OS and PFS benefits were generally consistent across major prespecified subgroups including geographic region and PD-L1 status for both investigational arms. "Reaching more than two years of median overall survival in a global Phase 3 trial for HER2+ metastatic GEA is truly unprecedented," said Elena Elimova, M.D., Princess Margaret Cancer Centre , the presenting author of the late-breaking data. "The HERIZON-GEA-01 results represent the longest survival outcomes in a Phase 3 trial ever reported in this setting, with the zanidatamab plus tislelizumab and chemotherapy regimen improving median overall survival by more than seven months versus the control arm. The fact that both zanidatamab plus chemotherapy and zanidatamab plus tislelizumab and chemotherapy achieved median progression-free survival beyond one year further reinforces the depth and durability of benefit. These findings signal a meaningful step forward for patients who have historically faced very limited long-term outcomes." "The results of the HERIZON-GEA-01 study are practice-changing," said Geoffrey Ku , M.D., associate attending physician on the Gastrointestinal Oncology Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center and study co-author. "In addition to the progression-free survival and overall survival benefits, the remarkably long duration of response and consistent benefit across relevant subgroups, including PD-L1 positive and negative tumors, strongly suggest that zanidatamab plus chemotherapy, with or without tislelizumab, should become the new standard of care for patients with HER2+ first-line locally advanced unresectable or metastatic GEA." Efficacy Summary from HERIZON-GEA-01 Primary Endpoints Endpoint Trastuzumab plus chemotherapy(control arm) Ziihera plus chemotherapy Ziihera plus tislelizumab and chemotherapy Median PFS (95% confidence interval[CI]) 8.1 months (7.0–8.9) 12.4 months (9.8–14.5) 12.4 months (9.8–18.5) PFS Hazard Ratio(HR) (95% CI) — 0.65 (0.52–0.81) P10% and decreased to 2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA. The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%). USE IN SPECIFIC POPULATIONS Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients. Geriatric Use Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older. No overall differences in safety or efficacy were observed between these patients and younger adult patients. The full U.S. Prescribing Information for ZIIHERA, including BOXED Warning, is available at: https://pp.jazzpharma.com/pi/ziihera.en.USPI.pdf ® TEVIMBRA (tislelizumab) is a registered trademark of BeOne Medicines. Dr. Ku has financial interests related to Jazz Pharmaceuticals. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases — often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information. Cautionary Note Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to the potential therapeutic benefits of Ziihera and of combination therapies with Ziihera, Ziihera's potential as a new standard of care in HER2+ first-line GEA and other HER2-expressing cancers, expected timing of OS data from the pivotal Phase 3 HERIZON-GEA-01 and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. 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 regulatory activities and uncertain regulatory approval, risks related to failure or delays in successfully initiating or completing clinical trials and assessing patients and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals Securities and Exchange Commission filings and reports, including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2024, as supplemented by Jazz Pharmaceuticals' Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Contacts: Media Contact: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc [email protected] Ireland +353 1 637 2141U.S. +1 215 867 4948 Jazz Investor Contact: Jack Spinks Executive Director, Investor Relations Jazz Pharmaceuticals plc [email protected] Ireland +353 1 634 3211U.S. +1 650 496 2717 ___________________________1 Abrahao-Machado I.F ., et al. HER2 testing in gastric cancer: An update WorldJGastroenterol. 2016;22(19):4619-4625.2 Van Custem E., et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.3 Stroes, C.I., et al. A systematic review of HER2 blockade for the curative treatment of gastroesophageal adenocarcinoma: Successes achieved and opportunities ahead. CancerTreatRev. 2021;99:102249.4 Battaglin F, et al. Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions. Cancer Cell International . 2018;18(99).5 ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA : Jazz Pharmaceuticals, Inc. ) View original content to download multimedia: https://www.prnewswire.com/news-releases/ziihera-zanidatamab-hrii-combinations-achieve-unprecedented-results-in-first-line-her2-locally-advanced-or-metastatic-gea-including-more-than-two-years-median-overall-survival-benefit-302654193.html SOURCE Jazz Pharmaceuticals plc

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