NEW DATA PRESENTED AT EHA 2024 SHOW THE POTENTIAL OF CALQUENCE (ACALABRUTINIB) COMBINATION THERAPY TO PROVIDE DURABLE AND PROLONGED PROGRESSION-FREE SURVIVAL IN PATIENTS WITH MANTLE CELL LYMPHOMA

UK medical and industry media only Press Release GB-56433 Date of preparation: June 2024 STRICTLY EMBARGOED UNTIL SUNDAY 16 JUNE 08:45 BST NEW DATA PRESENTED AT EHA 2024 SHOW THE POTENTIAL OF CALQUENCE (ACALABRUTINIB) COMBINATION THERAPY TO PROVIDE DURABLE AND PROLONGED PROGRESSION-FREE SURVIVAL IN PATIENTS WITH MANTLE CELL LYMPHOMA • Results from the ECHO Phase III trial demonstrated that Calquence (acalabrutinib) in combination with bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy in previously untreated adult patients with mantle cell lymphoma (MCL).1 • Calquence is the first Bruton’s tyrosine kinase (BTK) inhibitor to show a favourable trend in overall survival compared to standard-of-care chemoimmunotherapy in this setting. 1 • Around 600 people are diagnosed with MCL each year in the UK as it is often diagnosed at a late-stage and has historically been associated with poor-long term survival.2,3,4 London, UK, Monday 17 June 2024 – Today, AstraZeneca presented results from the ECHO Phase III trial at the European Haematology Association (EHA) Congress 2024 which showed that acalabrutinib in combination with bendamustine and rituximab demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and showed a favourable trend in overall survival (OS) compared to standard-of-care chemoimmunotherapy in elderly patients (>65 years old) with previously untreated mantle cell lymphoma (MCL). 1 MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a late-stage disease, resulting when B-lymphocytes mutate into malignant cells within the region of the lymph node known as the mantle zone.4,5 Around 600 people are diagnosed with MCL each year in the UK, and it is historically associated with poor long-term survival compared with other B-cell malignancies.2,3 Dr Toby Eyre, Consultant Haematologist at Oxford University NHS Foundation Trust, said: “These positive data from the ECHO Phase III trial highlight that acalabrutinib delivered alongside bendamustine-rituximab has the potential to significantly delay disease progression and extend overall progression-free survival when compared to bendamustine-rituximab for patients living with mantle cell lymphoma (MCL). Delivery of efficacious treatment of MCL can be challenging in older patients and survival can be limited as a result. This is a potentially significant milestone in the treatment of MCL, particularly for older patients, who find it more challenging to tolerate the more intensive chemotherapy often delivered to younger patients as a first-line treatment.” David Harland, Head of Oncology Medical Affairs, AstraZeneca UK, said: “Results presented at EHA today highlight acalabrutinib’s potential to provide prolonged progression free-survival and change the standard-of-care for patients with previously untreated mantle cell lymphoma, further strengthening acalabrutinib’s clinical profile, which is already established in chronic lymphocytic leukaemia. AstraZeneca continues to push the boundaries of science to redefine cancer care and these positive results take us one step closer to eliminating cancer as a cause of death in the UK.” Results from the randomised, double-blind, placebo-controlled ECHO Phase III trial showed that acalabrutinib in combination bendamustine and rituximab reduced the risk of disease progression or death by 27% (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.57-0.94, p=0.016) UK medical and industry media only Press Release GB-56433 Date of preparation: June 2024 compared to standard-of-care chemoimmunotherapy in previously untreated adult patients with mantle cell lymphoma (MCL).1 Results also demonstrated a median progression-free survival (PFS) of 66.4 months for the acalabrutinib combination compared to 49.6 months for standardof-care (hazard ratio [HR] 0.73; 95% CI 0.57, 0.94; p=0.016).1 For the secondary endpoint of overall survival (OS), a trend in favour of acalabrutinib plus bendamustine and rituximab was observed, despite 51 patients crossing over from the placebo arm to the acalabrutinib arm, however, there was no statistical significance (HR 0.86; 95% CI 0.65, 1.13; p=0.27). 1 The OS data were not mature at the time of this analysis and the trial will continue to assess OS as a key secondary endpoint. 1 The ECHO trial enrolled during the pandemic period, and a pre-specified analysis censoring for COVID-19-related deaths was conducted to assess the impact. PFS was further improved in both arms, with the Calquence combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI; 0.48-0.84; p=0.0017).1 Median PFS was not reached among patients treated with the Calquence combination versus 61.6 months for standard-of-care chemoimmunotherapy (HR 0.64, 95% CI, 0.48-0.84; p=0.0017).1 A favourable trend was seen for OS in this analysis for the Calquence combination (HR 0.75; 95% CI 0.53-1.04; p=0.0797). 1 The safety and tolerability profile of acalabrutinib in this trial was consistent with the known profile of the medicine and no new safety signals were identified.1 Grade ≥3 adverse events / grade ≥3 serious adverse events were comparable and well balanced between both arms and were reported in 88.9% / 64.3% and 88.2% / 55.9% of patients for acalabrutinib and placebo arms respectively.1 Among grade ≥3 adverse events of clinical interest, atrial fibrillation was reported in 3.7% and 1.7%, hypertension in 5.4% and 8.4%, neutropenia in 35.4% and 37.0%, infections in 41.1% and 34.0%, and pneumonia in 8.8% and 6.4% of patients in the acalabrutinib and placebo arms respectively.1 AEs related to COVID-19 were seen in the trial, including Grade 5 events which occurred in 9.4% (n=28) of patients treated with the Calquence combination and 6.7% (n=20) of patients treated with standard-of-care chemoimmunotherapy. Calquence is currently approved in the UK to treat adults with chronic lymphocytic leukaemia (CLL), a cancer of white blood cells called B-lymphocytes (or B-cells).6,7 These cells are part of the immune system (the body’s defences).7 – ENDS – CONTACTS UK Media Enquiries Emma White, AstraZeneca: 07385 516437 / emma.white1@astrazeneca.com Jack Faulkner, Edelman: 07813 407324 / jack.faulkner@edelman.com NOTES TO EDITORS About mantle cell lymphoma MCL is an uncommon subtype of B-cell non-Hodgkin lymphoma.8 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western UK medical and industry media only Press Release GB-56433 Date of preparation: June 2024 countries; around 600 people are diagnosed with MCL each year in the UK. 2,8 While MCL patients initially respond to treatment, patients do tend to relapse.9 About ECHO ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to standard of care chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=598) with previously untreated MCL.10 In the experimental arms, patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, on 28 day treatment cycles, plus bendamustine on days 1 and 2 and rituximab on day 1.10 After six cycles of Calquence or placebo in combination with bendamustine and rituximab, patients receive Calquence or placebo plus maintenance rituximab for two years and then either Calquence or placebo only until disease progression.10 The primary endpoint is PFS and key secondary endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).10 The trial includes 27 countries across North and South America, Europe, Asia and Oceania.10 The ECHO trial was conducted from 2017 to 2023 continuing through the COVID-19 pandemic.10 Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.11 About Calquence Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK).12 Calquence binds covalently to BTK, thereby inhibiting its activity. In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.12 AstraZeneca in haematology AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease. Following AstraZeneca’s recent acquisition of Gracell Biotechnologies Inc., we have broadened our pipeline of innovative cell therapies with a differentiated manufacturing process to potentially further address haematologic malignancies. By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact. AstraZeneca in oncology UK medical and industry media only Press Release GB-56433 Date of preparation: June 2024 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 catalyse 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 commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide. With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five different locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS. For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK. References 1 Wang M. et al. Acalabrutinib Plus Bendamustine and Rituximab in Untreated Mantle Cell Lymphoma: Results from the Phase 3, Double-Blind, Placebo-Controlled ECHO Trial. Oral Presentation (LB3439) at European Haematology Association (EHA) congress 2024. Available at: https://library.ehaweb.org/eha/2024/eha2024-congress/4136515/. Last accessed: June 2024. 2 Lymphoma Action. Mantle cell lymphoma. Available at: https://lymphoma-action.org.uk/types-lymphoma-nonhodgkin-lymphoma/mantle-cell-lymphoma. Last accessed: June 2024. 3 Schieber M, et al. Current overview and treatment of mantle cell lymphoma. F1000Res. 2018; 25;7:F1000 Faculty Rev-1136. 4 Lymphoma Research Foundation. What is Lymphoma – Mantle Cell Lymphoma Available at: https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/mantle-cell-lymphoma/. Last accessed: June 2024. 5 National Organization for Rare Disorders. Mantle Cell Lymphoma. Available at: https://rarediseases.org/rarediseases/mantle-cell-lymphoma/. Last accessed June 2024. 6 Electronic Medicines Compendium (EMC). Calquence 100 mg film-coated tablets – Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/14853/pil#gref. Last accessed: June 2024. 7 Blood Cancer UK. What is chronic lymphocytic leukaemia? Available at: https://bloodcancer.org.uk/understandingblood-cancer/leukaemia/chronic-lymphocytic-leukaemia-cll/cll-explained/. Last accessed: June 2024. 8 Cheah C, Seymour J, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256-1269. UK medical and industry media only Press Release GB-56433 Date of preparation: June 2024 9 Lymphoma Research Foundation. What is Lymphoma - Mantle Cell Lymphoma: Relapsed/Refractory. Available at: https://www.lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/mantle-cell-lymphoma/relapsedmcl/. Last accessed: June 2024. 10 ClinicalTrials.gov. A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL. Available at: https://clinicaltrials.gov/study/NCT02972840. Last accessed: June 2024. 11 Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation and Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses: Updated 2023 Results from INFORM, a Retrospective Health Database Study in England. Poster P0409 at ECCMID 2024 12 Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).