Urothelial Carcinoma of the Urinary Bladder

Advanced oncology pipeline including more than 20 active Phase 2 and Phase 3 clinical trials with a strategic focus on two priority pan-tumor programs: next-generation immunomodulator candidate BNT327 and mRNA cancer immunotherapies Multiple data readouts expected in 2025 and 2026 aimed at providing clinical proof of BioNTech’s pipeline strategy and advancing the Company towards becoming a diversified multi-product oncology portfolio company by 2030 Completed acquisition of Biotheus securing full control of next-generation immunomodulator candidate BNT327, a bispecific antibody targeting PD-L1 and VEGF-A1 Successfully launched JN.1- and KP.2-adapted COVID-19 vaccines across different countries and regions and maintained global market leadership Fourth quarter and full year 2024 revenues of €1.2 billion and €2.8 billion**, respectively Full year 2024 net loss of €0.7 billion and diluted loss per share of €2.77 ($3.00)1 Cash and cash equivalents plus security investments of €17.4 billion as of December 31, 20242 Expects 2025 total revenues between €1.7 billion and €2.2 billion Conference call and webcast scheduled for March 10, 2025, at 8:00 a.m. EDT (1:00 p.m. CET) MAINZ, Germany, March 10, 2025 (GLOBE NEWSWIRE) -- BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today reported financial results for the three months and full year ended December 31, 2024, and provided an update on its corporate progress. “From the very beginning, BioNTech’s vision has been to translate our science into survival and become an immunotherapy powerhouse. In 2024, we made significant progress towards our vision through important oncology pipeline advancements, including the initiation of global Phase 3 clinical trials for our anti-PD-L1/VEGF-A bispecific antibody candidate BNT327 and key data updates from our mRNA cancer immunotherapy programs,” said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. “We expect 2025 to be a data-rich year with multiple important updates from our priority programs, which we believe have disruptive potential and could improve the standard of care, if successfully developed and approved.” Financial Review for Fourth Quarter and Full Year 2024 Financial Results Total revenues reported were €1,190.0 million for the three months ended December 31, 2024, compared to €1,479.0 million for the comparative prior year period. For the year ended December 31, 2024, revenues were €2,751.1 million, compared to €3,819.0 million for the comparative prior year period. The decrease in revenues was primarily driven by lower sales of the Company’s COVID-19 vaccines due to reduced market demand. In addition, write-downs by BioNTech’s collaboration partner Pfizer Inc. (“Pfizer”) significantly reduced the Company’s gross profit share which negatively influenced its revenues. Cost of sales were €243.5 million for the three months ended December 31, 2024, compared to €179.1 million for the comparative prior year period. For the year ended December 31, 2024, cost of sales were €541.3 million, compared to €599.8 million for the comparative prior year period. Cost of sales were influenced by COVID-19 vaccine sales and inventory write-downs and scrapping. Research and development (“R&D”) expenses were €611.8 million for the three months ended December 31, 2024, compared to €577.8 million for the comparative prior year period. For the year ended December 31, 2024, R&D expenses were €2,254.2 million, compared to €1,783.1 million for the comparative prior year period. R&D expenses were mainly influenced by advancing clinical studies for the Company’s late-stage oncology product candidates. Further contributions to the increase came from higher personnel expenses resulting from an increase in headcount. Sales, general and administrative (“SG&A”)3 expenses, in total, amounted to €132.1 million for the three months ended December 31, 2024, compared to €142.3 million for the comparative prior year period. For the year ended December 31, 2024, SG&A expenses were €599.0 million, compared to €557.7 million for the comparative prior year period. SG&A expenses were mainly influenced by the setup and enhancement of commercial IT platforms and personnel expenses resulting from an increase in headcount. Other operating results amounted to negative €54.0 million during the three months ended December 31, 2024, compared to negative €53.6 million for the comparative prior year period. For the year ended December 31, 2024, other operating result amounted to negative €670.9 million compared to negative €188.0 million for the prior year period. The decrease was mainly due to the settlement of contractual disputes and related expenses to such disputes and other litigations. The amounts for contractual disputes are net of the related reimbursements expected to be received. Income taxes were accrued with an amount of €41.7 million in tax expenses for the three months ended December 31, 2024, compared to €205.3 million in accrued tax expenses for the comparative prior year period. For the year ended December 31, 2024, income taxes were realized with an amount of €12.4 million in tax income for the year ended December 31, 2024, compared to €255.8 million of accrued tax expenses for the comparative prior year period. Net profit was €259.5 million for the three months ended December 31, 2024, compared to €457.9 million net profit for the comparative prior year period. For the year ended December 31, 2024, net loss was €665.3 million, compared to a net profit of €930.3 million for the comparative prior year period. Cash and cash equivalents plus security investments2 as of December 31, 2024, reached €17,359.2 million, comprising of €9,761.9 million in cash and cash equivalents, €6,536.2 million in current security investments and €1,061.1 million in non-current security investments. Diluted earnings per share was €1.08 for the three months ended December 31, 2024, compared to €1.88 for the comparative prior year period. For the year ended December 31, 2024, diluted loss per share was €2.77, compared to diluted earnings per share of €3.83 for the comparative prior year period.Shares outstanding as of December 31, 2024, were 239,970,804, excluding 8,581,396 shares held in treasury. “Through strategic investments in our priority programs like our next-generation immunomodulator candidate BNT327, we strive to meaningfully improve treatments for patients,” said Jens Holstein, CFO of BioNTech. “Our strong financial position enables us to fuel our R&D activities and to prepare for multiple product launches in the coming years. With our targeted investments we aim to create long-term value for the benefit of BioNTech’s stakeholders.” 2025 Financial Year Guidance4 BioNTech expects its revenues for the full 2025 financial year to be in the range of €1,700 - €2,200 million and revenue phasing similar to 2024, primarily concentrated in the last three to four months, driving the full year revenue figure. The revenue guidance assumes: relatively stable vaccination rates, pricing levels and market share compared to 2024; estimated inventory write-downs and other charges by BioNTech’s collaboration partner Pfizer that negatively influence BioNTech’s revenues; anticipated revenues from a pandemic preparedness contract with the German government; and anticipated revenues from the BioNTech Group service businesses. Planned 2025 Financial Year Expenses and Capex BioNTech expects to continue to focus investments on R&D and scaling the business for late-stage development and commercial readiness in oncology, while continuing to be cost disciplined. Strategic capital allocation will remain a key driver of the Company’s trajectory. As part of BioNTech’s strategy, the Company may continue to evaluate appropriate corporate development opportunities with the aim of driving sustainable long-term growth and create future value. The full audited consolidated financial statements as of and for the year ended December 31, 2024, can be found in BioNTech’s Annual Report on Form 20-F filed today with the United States Securities and Exchange Commission (“SEC”) and available at www.sec.gov. Endnotes1 Calculated applying the average foreign exchange rate for the year ended December 31, 2024, as published by the German Central Bank (Deutsche Bundesbank). 2 Payments associated with the closing of the Biotheus acquisition and with the resolved settlement of a contractual dispute with the National Institutes of Health (“NIH”) are expected to result in a cash outflow of approximately $1.6 billion to be reflected in cash & cash equivalents in the Company’s first quarter 2025 financial results. The settlement payment of $467 million related to a contractual dispute with the University of Pennsylvania is expected to be reflected in the Company’s second quarter 2025 financial results. In connection with these settlements, BioNTech expects to be reimbursed approximately $535 million by its partner during 2025 and 2026. 3 Sales, general and administrative expenses (“SG&A”) include sales and marketing expenses as well as general and administrative expenses. 4 Excludes external risks that are not yet known and/or quantifiable, including, but not limited to the effects of ongoing and/or future legal disputes and related activities, certain potential one-time effects and charges related to portfolio prioritization, as well as potential changes to the law or governmental policy, including public health policy, at the state or national level, and evolving public sentiment around vaccines and mRNA technology, in the United States and/or elsewhere. It includes effects identified from licensing arrangements, collaborations or potential M&A transactions to the extent disclosed and may be subject to update. The Company does not expect to report a positive net income figure for the 2025 financial year. Operational Review for the Fourth Quarter 2024, Key Post Period-End Events and 2025 Outlook Selected Oncology Pipeline UpdatesIn 2024, the Company’s pipeline continued to mature towards later stages of clinical development with a focus on two priority programs: our investigational next-generation immunomodulator candidate BNT327 and mRNA cancer immunotherapies. BioNTech’s oncology pipeline currently contains over 20 ongoing Phase 2 and 3 clinical trials. In 2025, the Company plans to continue progressing its pipeline towards commercialization, with its first oncology launch expected in 2026. Next-Generation Immunomodulators BNT327 is a bispecific antibody candidate combining PD-L1 checkpoint inhibition with VEGF-A neutralization. In December 2024, BioNTech initiated a global randomized Phase 3 clinical trial (NCT06712355) evaluating BNT327 plus chemotherapy compared to atezolizumab plus chemotherapy in first-line extensive-stage small cell lung cancer (“ES-SCLC”). In December 2024, BioNTech initiated a global randomized Phase 2/3 clinical trial (NCT06712316) evaluating BNT327 plus chemotherapy compared to pembrolizumab plus chemotherapy in first-line non-small cell lung cancer (“NSCLC”). In December 2024, at the San Antonio Breast Cancer Symposium (“SABCS”), interim data were presented from the Phase 1/2 clinical trial (NCT05918133) evaluating BNT327 in combination with chemotherapy in a cohort of patients with locally advanced, previously untreated triple-negative breast cancer (“TNBC”). In 42 patients, first-line treatment with BNT327 combined with nab-paclitaxel chemotherapy showed encouraging antitumor activity and survival outcomes regardless of PD-L1 status, together with a manageable safety profile. A global randomized Phase 3 clinical trial evaluating BNT327 in first-line TNBC is on track to start in 2025. Data from the ongoing global Phase 2 dose optimization clinical trials evaluating BNT327 in combination with chemotherapy in first-line small cell lung cancer (“SCLC”) (BNT327-01, NCT06449209) and TNBC (BNT327-02, NCT06449222) are planned to be published in 2025. Data from two Phase 2 clinical trials conducted in China in first- and second-line SCLC (NCT05844150, NCT05879068, respectively) are expected to be presented at the European Lung Cancer Congress (“ELCC”) taking place March 26-29, 2025 in Paris, France. Title: Phase 2 study of the efficacy and safety of BNT327 plus systemic chemotherapy as first-line therapy for ES-SCLCPresentation Date: March 28, 2025Poster Number: 302PAuthor: Y. Cheng Title: Updated Phase 2 efficacy and safety results of BNT327 combined with paclitaxel as second-line therapy in SCLCPresentation Date: March 28, 2025Poster Number: 332PAuthor: Y. Cheng First clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating the combination of BNT327 and BNT325/DB-1305, a TROP2-targeted antibody-drug conjugate (“ADC”) candidate, are planned to be published in 2025. Additional clinical trials exploring novel combinations of BNT327 with the ADC candidates BNT323/DB-1303 (trastuzumab pamirtecan) targeting HER2, BNT324/DB-1311 targeting B7-H3 or BNT326/YL202 targeting HER3 are planned to start in 2025. BNT316/ONC-392 (gotistobart) is an anti-CTLA-4 monoclonal antibody candidate being developed in collaboration with OncoC4, Inc. (“OncoC4”). In December 2024, the U.S. Food and Drug Administration (“FDA”) lifted the partial clinical hold on the OncoC4-sponsored Phase 3 clinical trial (PRESERVE-003; NCT05671510) evaluating the efficacy and safety of BNT316/ONC-392 as monotherapy in patients with metastatic NSCLC that progressed under previous PD-(L)1-inhibitor treatment. Based on the available clinical trial data and upon alignment with the FDA, the companies will solely continue enrollment of patients with squamous NSCLC. mRNA Cancer Immunotherapies Autogene cevumeran (BNT122/RO7198457) and BNT111 are investigational immunotherapies for the treatment of cancer based on BioNTech’s systemically administered uridine mRNA-lipoplex technology. Autogene cevumeran is an individualized neoantigen-specific mRNA cancer immunotherapy candidate being developed in collaboration with Genentech, Inc. (“Genentech”), a member of the Roche Group (“Roche”). In December 2024, the first patient was treated in a global randomized Phase 2 clinical trial (IMCODE004; NCT06534983) evaluating autogene cevumeran in combination with nivolumab compared to nivolumab alone as an adjuvant treatment in high-risk muscle-invasive urothelial carcinoma (“MIUC”). In January 2025, a manuscript summarizing the results of a Phase 1 clinical trial (NCT03289962) evaluating autogene cevumeran in combination with atezolizumab in patients with advanced solid tumors was published in Nature Medicine (Lopez et al., 2025). In February 2025, a manuscript denoting follow up data from an investigator-initiated Phase 1 clinical trial (NCT04161755, Rojas et al., 2023) evaluating autogene cevumeran in combination with atezolizumab in patients with pancreatic ductal adenocarcinoma (“PDAC”) in an adjuvant treatment setting was published in Nature (Sethna et al., 2025). First data from the ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran as an adjuvant treatment compared to watchful waiting after standard of care chemotherapy in resected circulating tumor DNA+ (“ctDNA”) stage II (high-risk) and III colorectal cancer (“CRC”) are anticipated in late 2025 or early 2026. BNT111 is based on BioNTech’s fully owned, off-the-shelf FixVac platform, and encodes four melanoma-associated antigens. BioNTech plans to present data from the ongoing Phase 2 clinical trial (BNT111-01; NCT04526899) at a medical conference in 2025. In 2024, an initial topline readout was provided noting that the clinical trial had met its primary efficacy outcome measure, demonstrating a statistically significant improvement in overall response rate (“ORR”) in patients with anti-PD-(L)1 refractory/relapsed, unresectable stage III or IV melanoma treated with BNT111 in combination with cemiplimab as compared to historical control in this treatment setting. Antibody-Drug Conjugates BNT323/DB-1303 (trastuzumab pamirtecan) is an ADC candidate targeting HER2 that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”). BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. Data from patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced endometrial carcinoma are expected in 2025. A confirmatory Phase 3 clinical trial (NCT06340568) is planned to start in 2025. Preparation of a potential Biologics License Application (“BLA”) submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer in 2025. BNT324/DB-1311 is an ADC candidate targeting B7-H3 that is being developed in collaboration with DualityBio. The program has received Fast Track designation from the FDA for the treatment of patients with advanced castration-resistant prostate cancer (“CRPC”) who have progressed on or after standard systemic regimens and Orphan Drug designation for the treatment of patients with advanced esophageal squamous cell carcinoma. In December 2024, preliminary data from the first-in-human, open-label Phase 1/2 clinical trial (NCT05914116) were presented at the 2024 European Society for Medical Oncology (“ESMO”) Asia Congress, demonstrating encouraging efficacy and a manageable safety profile across a range of advanced solid tumors. Cell Therapies BNT211 consists of a CAR-T cell product candidate targeting CLDN6-positive solid tumors in combination with a CAR-T cell-amplifying RNA cancer immunotherapy encoding CLDN6. In January 2025, the FDA granted Regenerative Medicine Advanced Therapy (“RMAT”) designation for BNT211. The RMAT designation is designed to expedite the development and review process for promising pipeline products, including cell therapies. A pivotal Phase 2 clinical trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging clinical activity observed in this patient population in the ongoing Phase 1 clinical trial (NCT04503278). The Phase 1 clinical trial is ongoing to evaluate BNT211 in other CLDN6+ cancer types, including NSCLC and gynecologic cancers. Selected Infectious Diseases Pipeline Updates BioNTech and Pfizer developed, manufactured and delivered JN.1- and KP.2-adapted COVID-19 vaccines which received multiple regulatory approvals and marketing authorizations in more than 40 countries and regions. In 2024, BioNTech and Pfizer delivered approximately 180 million variant-adapted COVID-19 vaccine doses worldwide. BioNTech and Pfizer continue to invest in the research and development of next-generation and combination COVID-19 vaccine candidates. Corporate Update for the Fourth Quarter 2024 and Key Post Period-End Events In November 2024, BioNTech signed an agreement to acquire Biotheus and obtain full global rights to BNT327 and to all other candidates from Biotheus’ pipeline, as well as to its in-house antibody generation platform and bispecific ADC capability. The transaction amounted to an upfront consideration of $800 million, plus additional performance-based payments of up to $150 million. The acquisition was completed in February 2025. Upcoming Investor and Analyst Events Sustainability Report 2024 Publication: March 24, 2025 Annual General Meeting: May 16, 2025 Innovation Series AI Day: October 1, 2025 Innovation Series R&D Day: November 18, 2025 Conference Call and Webcast InformationBioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, March 10, 2025, at 8:00 a.m. EDT (1:00 p.m. CET) to report its financial results and provide a corporate update for the fourth quarter and full year 2024. To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a PIN number will be provided. The slide presentation and audio of the webcast will be available via this link. Participants may also access the slides and the webcast of the conference call via the “Events & Presentations” page of the Investor section of the Company’s website at www.BioNTech.com. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call. About BioNTechBiopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel investigative therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic modalities with the intent of rapid development of novel biopharmaceuticals. Its diversified portfolio of oncology product candidates aiming to address the full continuum of cancer includes mRNA cancer immunotherapies, next-generation immunomodulators and targeted therapies such as antibody-drug conjugates (ADCs) and innovative chimeric antigen receptor (CAR) T cell therapies. Based on its deep expertise in mRNA development and in-house manufacturing capabilities, BioNTech and its collaborators are researching and developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. For more information, please visit www.BioNTech.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: BioNTech’s expected revenues and net profit/(loss) related to sales of BioNTech’s COVID-19 vaccine, referred to as COMIRNATY where approved for use under full or conditional marketing authorization, in territories controlled by BioNTech’s collaboration partners, particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand, including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the expected timing of initiation, enrollment, and completion of studies or clinical trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational clinical trials, and the registrational potential of any clinical trial BioNTech may initiate; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; the impact of BioNTech’s collaboration and licensing agreements; the development, nature and feasibility of sustainable vaccine production and supply solutions; the deployment of AI across BioNTech’s preclinical and clinical operations; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses and capital expenditures for operating activities; BioNTech’s expectations regarding upcoming payments relating to litigation settlements; BioNTech’s expectations for upcoming scientific and investor presentations; and BioNTech’s expectations of net profit/(loss). In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, projected data release timelines, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; BioNTech’s pricing and coverage negotiations regarding its COVID-19 vaccine with governmental authorities, private health insurers and other third-party payors; the future commercial demand and medical need for initial or booster doses of a COVID-19 vaccine; competition from other COVID-19 vaccines or related to BioNTech’s other product candidates, including those with different mechanisms of action and different manufacturing and distribution constraints, on the basis of, among other things, efficacy, cost, convenience of storage and distribution, breadth of approved use, side-effect profile and durability of immune response; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; the ability of BioNTech’s COVID-19 vaccines to prevent COVID-19 caused by emerging virus variants; BioNTech’s and its counterparties’ ability to manage and source necessary energy resources; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech's development candidates and investigational medicines; the impact of COVID-19 on BioNTech’s development programs, supply chain, collaborators and financial performance; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market BioNTech’s COVID-19 vaccine and, if approved, its product candidates; BioNTech’s ability to manage its development and related expenses; regulatory and political developments in the United States and other countries; BioNTech’s ability to effectively scale its production capabilities and manufacture its products and product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time. You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Report on Form 20-F for the period ended December 31, 2024 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at www.sec.gov. These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. CONTACTS Investor RelationsMichael HorowiczInvestors@biontech.de Media Relations Jasmina Alatovic Media@biontech.de Target abbreviation directory Consolidated Statements of Profit or Loss Consolidated Statements of Financial Position Consolidated Statements of Cash Flows 1 All target abbreviations are compiled in an abbreviation directory at the end of this press release.** All numbers in this press release have been rounded.

WILMINGTON, Del.--( BUSINESS WIRE )--Results from a post-hoc exploratory subgroup analysis from the NIAGARA Phase III trial showed AstraZeneca’s IMFINZI ® (durvalumab), administered perioperatively in combination with neoadjuvant chemotherapy, demonstrated improvements in event-free survival (EFS) and overall survival (OS) versus neoadjuvant chemotherapy with radical cystectomy alone in patients with or without a pathologic complete response (pCR) in muscle-invasive bladder cancer (MIBC). Patients were treated with four cycles of IMFINZI in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by eight cycles of IMFINZI monotherapy. These new data were presented today at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California (abstract #659). In NIAGARA, treatment with the IMFINZI perioperative regimen improved EFS and OS versus the comparator arm both in patients who achieved pCR and those who did not. This regimen reduced the risk of disease progression, recurrence, not undergoing surgery, or death by 42% in patients who achieved pCR and by 23% in those who did not; and reduced the risk of death by 28% in patients who achieved pCR and by 16% in those who did not (see data table below for details). The IMFINZI perioperative regimen also improved metastasis-free survival (MFS) and disease-specific survival (DSS), two secondary endpoints, versus the comparator arm in the intent-to-treat (ITT) population. This regimen reduced the risk of developing distant metastases or death by 33% and the risk of death specifically due to bladder cancer by 31% versus the comparator arm (see data table below for details). Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA Investigator and Steering Committee member, said: “ These NIAGARA data confirm the compelling efficacy of the durvalumab perioperative regimen in muscle-invasive bladder cancer, and importantly, show this regimen improved outcomes regardless of whether patients achieved a pathologic complete response. This insight, together with the data showing the durvalumab perioperative regimen extended the time patients live before distant metastases develop, is favorable news for patients with muscle-invasive bladder cancer who are in need of better treatment options.” Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “ NIAGARA was the first Phase III trial of a perioperative immunotherapy regimen in muscle-invasive bladder cancer to show statistically significant and clinically meaningful improvements in event-free and overall survival. The 33 percent reduction in the risk of distant metastases, which are associated with a poorer prognosis, further reinforces the potential of perioperative IMFINZI to become a new standard of care in this setting.” These new data build on findings presented at the European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine which showed NIAGARA met the primary endpoint of EFS and the key secondary endpoint of OS. In the ITT population, patients treated with the IMFINZI perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm, as well as a 25% reduction in the risk of death. There was also a 10% improvement in the pCR rate versus the comparator arm. Summary of exploratory post-hoc analysis: NIAGARA Patients with pCR Patients without pCR ITT population IMFINZI- based regimen (n=199) Neoadjuvant chemotherapy (n=146) IMFINZI- based regimen (n=334) Neoadjuvant chemotherapy (n=384) IMFINZI- based regimen (n=533) Neoadjuvant chemotherapy (n=530) pCR i pCR rate (%) - - - - 37.3 27.5 p-value ii - - 0.0005 EFS i EFS rate, 24 months 92.1 85.8 53.3 49.5 67.8 59.8 (%) HR (95% 0.58 0.77 0.68 CI) (0.33-1.00) (0.63-0.95) (0.56-0.82) OS i OS rate, 24 months (%) 95.5 91.1 74.1 68.9 82.2 75.2 HR (95% 0.72 0.84 0.75 CI) (0.37-1.43) (0.66-1.07) (0.59-0.93) i Data cut-off: April 29, 2024 ii Nominal p-value Summary of additional secondary endpoint outcomes (ITT): NIAGARA IMFINZI-based regimen (n=533) Neoadjuvant chemotherapy (n=530) MFS i MFS rate, 24 months (%) 75.1 65.1 Number of MFS events 152 201 (%) (28.5) (37.9) Median MFS (95% CI) (in NR ii NR ii months) (NR ii -NR ii ) (48.0-NR ii ) HR (95% CI) 0.67 (0.54-0.83) DSS i DSS rate, 24 months (%) 89.2 82.2 Number of deaths due to 85 114 bladder cancer (%) (15.9) (21.5) Median DSS (95% CI) (in NR ii NR ii months) (NR ii -NR ii ) (NR ii -NR ii ) HR (95% CI) 0.69 (0.52-0.91) i Data cut-off: April 29, 2024 ii NR, not reached IMFINZI was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding IMFINZI to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of IMFINZI, manageable and mostly low-grade. Perioperative IMFINZI in combination with neoadjuvant chemotherapy was granted Priority Review in the US in December 2024 for the treatment of patients with MIBC. Regulatory applications are also currently under review in the European Union (EU), Japan and several other countries based on the NIAGARA trial. IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI ® (durvalumab) or IMJUDO ® (tremelimumab-actl). Severe and Fatal Immune-Mediated Adverse Reactions Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Immune-Mediated Pneumonitis IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. IMFINZI as a Single Agent In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy. IMFINZI with IMJUDO Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Immune-Mediated Colitis IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. IMFINZI as a Single Agent Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. IMFINZI with IMJUDO Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients. Immune-Mediated Hepatitis IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal. IMFINZI as a Single Agent Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. IMFINZI with IMJUDO Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions. Immune-Mediated Endocrinopathies Adrenal Insufficiency : IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions. Hypophysitis : IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. IMFINZI as a Single Agent Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. IMFINZI with IMJUDO Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism) : IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. IMFINZI as a Single Agent Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. IMFINZI with Carboplatin and Paclitaxel Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel. Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis : Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. INFINZI as a Single Agent Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. IMFINZI with IMJUDO Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions. Immune-Mediated Nephritis with Renal Dysfunction IMFINZI and IMJUDO can cause immune-mediated nephritis. IMFINZI as a Single Agent Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-Mediated Dermatology Reactions IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. IMFINZI as a Single Agent Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. IMFINZI with IMJUDO Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Immune-Mediated Pancreatitis IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Other Immune-Mediated Adverse Reactions The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors. Cardiac/vascular : Myocarditis, pericarditis, vasculitis. Nervous system : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy. Ocular : Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Gastrointestinal : Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and connective tissue disorders : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine : Hypoparathyroidism. Other (hematologic/immune) : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection. Infusion-Related Reactions IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMFINZI as a Single Agent Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Complications of Allogeneic HSCT after IMFINZI Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Embryo-Fetal Toxicity Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO. Lactation There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose. Adverse Reactions Unresectable Stage III NSCLC In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%). In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms. Resectable NSCLC In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions. In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. Metastatic NSCLC In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%). In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients. Limited-stage Small Cell Lung Cancer In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia. In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each). Extensive-stage Small Cell Lung Cancer In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%). In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. Locally Advanced or Metastatic Biliary Tract Cancers In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%). In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients). Unresectable Hepatocellular Carcinoma In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%). In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients. Primary advanced or Recurrent dMMR Endometrial Cancer In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%). In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%). The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. Indications: IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO . You may report side effects related to AstraZeneca products . Notes Muscle-invasive bladder cancer Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year. 1 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract. 2 Approximately one in four patients with bladder cancer has evidence of the tumor invading the muscle wall of the bladder (without distant metastases), known as MIBC. 3-4 In MIBC, a curative-intent setting, approximately 117,000 patients are treated with the current standard of care, which includes neoadjuvant chemotherapy and radical cystectomy. 5-6 However, even after cystectomy, approximately 50% of patients experience disease recurrence and have a poor prognosis. 6 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting. NIAGARA NIAGARA is a randomized, open-label, multi-center, global Phase III trial evaluating perioperative IMFINZI as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomized to receive IMFINZI plus neoadjuvant chemotherapy prior to cystectomy followed by IMFINZI , or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting. The trial is being conducted at 192 centers across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pCR, the latter defined as the proportion of patients with no detectable cancer cells (T0N0M0) at the time of cystectomy. Key secondary endpoints are OS and safety. IMFINZI IMFINZI ® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses. IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO ® (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC. In addition to its indications in lung cancers, IMFINZI is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU. IMFINZI is also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by IMFINZI monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, IMFINZI plus chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer, and IMFINZI plus chemotherapy followed by IMFINZI alone is approved for patients with dMMR disease. In Japan, IMFINZI plus chemotherapy followed by IMFINZI monotherapy has also been approved as 1st-line treatment in primary advanced or recurrent endometrial cancer, and IMFINZI plus chemotherapy followed by IMFINZI and olaparib has been approved for patients with pMMR disease. Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumors. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on socia media @AstraZeneca . References World Health Organization. International Agency for Research on Cancer. Bladder Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf . Accessed February 2025. American Cancer Society. What Is Bladder Cancer? Available at: https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html . Accessed February 2025. Burger M, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol . 2013;63(2):234-241. National Collaborating Centre for Cancer. Bladder Cancer: Diagnosis and Management. London: National Institute for Health and Care Excellence (NICE). Available at: https://www.ncbi.nlm.nih.gov/books/NBK356289 . Accessed February 2025. Cerner CancerMPact database. Accessed February 2024. Reflects epidemiology estimates across G8 countries (US, EU, Japan, China). Witjes JA, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol . 2021;1-94. US-98018 Last Updated 2/25

NEW YORK--( BUSINESS WIRE )--Pfizer Inc. (NYSE: PFE) today announced positive topline results from its pivotal Phase 3 CREST trial evaluating sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with Bacillus Calmette-Guérin (BCG) as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). The study met its primary endpoint of event-free survival (EFS) by investigator assessment, demonstrating a clinically meaningful and statistically significant improvement with sasanlimab in combination with BCG (induction and maintenance) as compared to BCG alone (induction and maintenance). “ Patients with BCG-naïve high-risk non-muscle invasive bladder cancer have high rates of recurrence and progression,” said Neal Shore, M.D., FACS, Medical Director for the Carolina Urologic Research Center, and lead investigator for the CREST trial. “ These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naïve, high-risk non-muscle invasive bladder cancer, including patients with carcinoma in-situ (CIS), providing prolonged event-free survival which may delay or reduce the need for more aggressive treatment options. Administered subcutaneously every four weeks, sasanlimab, if approved, could also help lower the treatment burden on both patients and healthcare systems.” Each year, approximately 100,000 people globally are diagnosed with high-risk NMIBC. 3 Induction therapy with BCG followed by maintenance has been the standard of care for patients with high-risk NMIBC for decades. 4 40-50% of patients experience recurrent disease, often requiring radical cystectomy, 5,6,7 which is associated with significant risks 8,9,10 and bladder-sparing treatment options are still limited. 11,12 “ The initial therapy of high-risk, non-muscle invasive bladder cancer with BCG has not advanced in decades. Today’s pivotal Phase 3 CREST results are potentially practice-changing, representing the first advance in therapy for BCG-naïve, high-risk, non-muscle invasive cancer in over 30 years,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “ These results reinforce Pfizer’s leadership in genitourinary cancer research and development, demonstrating our ongoing commitment to deliver new treatment options for patients with bladder cancer.” The overall safety profile of sasanlimab in combination with BCG was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab. The profile of sasanlimab was also generally consistent with the reported safety profile of PD-1 inhibitors. Results will be submitted for presentation at an upcoming medical congress. Pfizer plans to discuss these data with global health authorities to support potential regulatory filings. Sasanlimab also continues to be investigated in combination with Pfizer’s antibody drug conjugate (ADC) portfolio in advanced solid tumors. About CREST The CREST trial is a Phase 3, multinational, randomized, open-label, three parallel-arm study of sasanlimab, an anti-PD-1 mAb, in combination with BCG (BCG induction with or without BCG maintenance) versus BCG (induction and maintenance) in participants with BCG-naïve, high-risk NMIBC. Patients were randomized to receive sasanlimab 300 mg by subcutaneous (SC) injection every four weeks up to cycle 25 (cycle = four weeks), in combination with BCG once weekly for six consecutive weeks (induction period) followed (Arm A) or not (Arm B) by maintenance with BCG, or BCG induction and maintenance up to cycle 25 (Arm C). The primary endpoint is EFS as assessed by the investigator, between Arm A and C, defined as the time from randomization to the earliest of recurrence of high-grade disease, progression of disease, persistence of CIS, or death. Key secondary endpoints include EFS as assessed by the investigator between Arm B and Arm C. About Sasanlimab Sasanlimab is a humanized immunoglobulin G4 mAb that binds to human programmed death-1 (PD-1) to block its interaction with PD-1 and PD-L1/PD-L2. PD-1 is a protein expressed on T cells, dendritic cells, natural killer cells, macrophages, and B cells, that functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands and may play an important role in tumor evasion from host immunity. It can be administered through a once every four weeks subcutaneous injection by prefilled syringe (2mL). In early-stage clinical studies, sasanlimab administered at 300 mg SC every four weeks showed clinical efficacy in advanced solid tumors and advanced urothelial cancer. In addition to NMIBC, sasanlimab is being evaluated in several ongoing clinical trials with other novel combinations. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . Disclosure Notice The information contained in this release is as of January 10, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology, sasanlimab, an investigational anti-PD-1 monoclonal antibody, in combination with Bacillus Calmette-Gurin (BCG), as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer, including their potential benefits, the CREST results and plans to share the results with global health authorities to support potential regulatory filings, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when applications for sasanlimab in combination with BCG may be filed in any jurisdictions for any potential indications; whether and when any such applications for sasanlimab in combination with BCG that may be filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether sasanlimab in combination with BCG will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of sasanlimab in combination with BCG; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “ Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com . References Bladder cancer statistics. World Cancer Research Fund International. Accessed November 26, 2024. https://www.wcrf.org/cancer-trends/bladder-cancer-statistics/ Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin . 2024;74(3):229–263. Data on File. Babjuk M, Bohle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71(3):447–61. Babjuk M, Burger M, Compérat EM, Gontero P, Mostafid AH, Palou J, et al. European association of urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ): 2019 update. Eur Urol . 2019;76(5):639–657. Gaul Frau J, Palou J, Rodriguez O, et al. Failure of Bacillus Calmette-Guerin therapy in non-muscle-invasive bladder cancer: definition and treatment options. Arch Esp Urol. 2016;69(7):423–33. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol . 2016;196(4):1021–1029. Liedberg F. Early Complications and Morbidity of Radical Cystectomy. Eur Urol. Supplements, 2010;9(1)25–30. Shabsigh A, Korets R, Vora KC, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol . 2009;55(1):164–76. Tan WS, Lamb BW, Kelly JD. Complications of radical cystectomy and orthotopic reconstruction. Adv Urol . 2015:323157. Dinney CP, Greenberg RE, Steinberg GD. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guérin. Urol Oncol . 2013;31(8):1635–1642. Steinberg, GD, Bahnson R, Brosman S, et al. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol . 2000;163(3):761–7. Category: Research