AstraZeneca highlights continued progress of oncology pipeline at the 2016 ASCO Annual Meeting

LEADERSHIP IN DNA DAMAGE RESPONSE THERAPIES

73 abstracts presented at the 2016 ASCO Annual Meeting with 19 related to Lynparza and new potential medicines targeting DNA damage response in multiple tumour types

Continued momentum of immuno-oncology medicines including new data on durvalumab in bladder cancer, underpinning the Breakthrough Therapy Designation, and new data in first-line NSCLC

Further insights on Tagrisso’s ability to penetrate the blood-brain barrier in patients with metastatic lung cancer, and acalabrutinib in chronic lymphocytic leukaemia

19 May 2016

AstraZeneca and its global biologics research and development arm, MedImmune, will provide an update on their extensive oncology pipeline at the annual meeting of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA, on 3-7 June 2016.

Highlights will include new data demonstrating the strength and versatility of AstraZeneca’s industry-leading line of DNA damage response (DDR) medicines in multiple types of cancer. New data will highlight the continued momentum behind AstraZeneca’s numerous immuno-oncology (IO) programmes, and showcase small-molecule developments including Tagrisso (osimertinib) in leptomeningeal (brain) disease and the highly-selective Bruton’s tyrosine kinase (BTK) inhibitor, acalabrutinib, in chronic lymphocytic leukaemia (CLL).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Oncology is a strategic priority for AstraZeneca because of the potential of our broad pipeline to offer transformational therapies in cancer care. At the 2016 ASCO Annual Meeting, we will update on our next-generation portfolio focusing on DNA damage response as a breakthrough paradigm in cancer treatment, including new long-term overall survival data for Lynparza. Our increased commitment to DDR therapies complements developments in our exciting immuno-oncology pipeline, from which we are expecting clinical results over the coming year.”

DDR: A promising scientific platform, a leading position for AstraZeneca

DDR is a term describing the network of cellular pathways that minimise the daily impact of DNA damage. Currently, many cancers are known to have defects in DDR pathways, which makes them dependent on and therefore, highly sensitive to inhibition of the remaining DDR pathways. Targeting DDR deficiencies to preferentially kill cancer cells, while minimising the impact on normal cells, has potential for more selective, better tolerated therapies to improve survival in multiple cancers.

AstraZeneca is developing a comprehensive pipeline of compounds that target molecular pathways across the DDR system. These include the PARP inhibitor Lynparza (olaparib); Wee1 inhibitor AZD1775, ATM inhibitor AZD0156; ATR inhibitor AZD6738, and Aurora B Kinase inhibitor AZD2811. These compounds act on different cell-cycle points to prevent tumour cells from reproducing.

At the 2016 ASCO Annual Meeting congress, DDR presentations will highlight:

• The potential for maintenance of DDR therapies as shown by Lynparza overall survival data from Study 19 in ovarian cancer (Abstract # 5501). This abstract has been selected as a “Best of the 2016 ASCO Annual Meeting” abstract.
• Opportunities for combination approaches with DDR and immuno-oncology therapies as shown in a Phase I study of the PD-L1 inhibitor, durvalumab, in combination with Lynparza or a VEGFR inhibitor, cediranib, in women's cancers (Abstract # 3015)
• The importance of selecting patients with a DDR pathway defect using the right diagnostic tool (abstract #4041)
• The potential of DDR therapies against multiple biological DDR targets in different tumour types, with studies of the highly-selective WEE1 inhibitor, AZD1775, in advanced high-grade serous ovarian cancer (Abstract # TPS5610), squamous cell carcinoma of the head and neck (SCCHN) (Abstract # TPS6106), advanced solid tumours (Abstract # TPS2608) and glioblastoma (GBM) (Abstract # 2008)

Immuno-Oncology: Robust development momentum on track for read-outs in H1 2017

AstraZeneca is leading in a number of first-line studies with its IO strategy, where combined PD-L1 and CTLA-4 blockade - through the combination of durvalumab and tremelimumab - may address a significant unmet medical need for cancer patients who may not benefit from PD-1 pathway drugs in monotherapy.

Key updates include presentations covering pre-clinical data, late-stage trials and biomarker research:

• Early study results of durvalumab monotherapy in urothelial bladder cancer from Phase Ib Study 1108 (Abstract # 4502)
• Final results from a Phase III study of tremelimumab in mesothelioma (Abstract # 8502)
• New study results on safety and clinical activity of durvalumab as first-line treatment in non-small cell lung cancer (NSCLC) (Abstract # 9029)
• Ongoing investigation of the potential synergistic effects of durvalumab and the CTLA-4 inhibitor, tremelimumab, in bladder cancer (DANUBE trial - Abstract # TPS4574) and SCCHN (KESTREL trial - Abstract # TPS6101)
• Enhanced understanding of PD-L1 biomarker expression in relation to primary versus metastatic tumours and sample age (Abstract # 3025)

Tagrisso in brain metastasis; acalabrutinib in CLL

AstraZeneca’s strong heritage in developing innovative targeted small molecules was underscored by the recent approval of Tagrisso as the first indicated treatment for EGFR T790M mutation-positive metastatic NSCLC in the US, EU and Japan. At the 2016 ASCO Annual Meeting, new data will highlight the importance of Tagrisso activity in leptomeningeal disease through its ability to penetrate the blood-brain barrier. Further presentations will show the growing role of circulating tumour DNA (ctDNA) testing for diagnosis and treatment monitoring.

Key updates will also include presentation on the potential of our potent, highly-selective BTK inhibitor, acalabrutinib, in chronic lymphocytic leukaemia (CLL):

• Data from the BLOOM study of Tagrisso in patients with leptomeningeal disease as a complication of EGFRm-metastatic NSCLC (Abstract # 9002)
• Intensive plasma ctDNA profiling in experimental trials to identify markers of acquired drug resistance (Abstract # 11530)
• Acalabrutinib – preliminary results from a first-line study as first-line therapy in CLL (Abstract # 7521) and in a Phase II study in combination with pembrolizumab in metastatic pancreatic cancer (Abstract # 4130)

NOTES TO EDITORS

Support materials

To download additional supporting material including abstract chart, animations, video and infographics please visit AstraZeneca
2016 ASCO Annual Meeting

Supporting material covers:

DDR • IO • Ovarian • Lung

Media Briefing

A Media Briefing on Saturday, 4 June 2016, 18:00-19:00 CDT, at the Hyatt Regency (room Columbus I-J) will update journalists on latest advances in AstraZeneca’s oncology portfolio being reported at the 2016 ASCO Annual Meeting. In addition, the briefing will focus on the potential of DDR therapies as a breakthrough paradigm in cancer treatment.

If you are interested to attend, please contact:

• Neil Burrows (neil.burrows@astrazeneca.com; +44 7842 350541)
• Karen Birmingham (Karen.birmingham@astrazeneca.com; +44 7818 524012)

An Investor science event on Monday, 6 June 2016, 19:00-20:30 CDT will highlight the continuing momentum behind new developments in AstraZeneca’s Oncology therapy area.

Investors and analysts wishing to attend are invited to register here or contact the Investor Relations Team (details below).

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least 6 new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms -- immuno-oncology, the genetic drivers of cancer and resistance, DNA damage response and antibody drug conjugates -- and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as in infection and neuroscience. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.

CONTACTS

Key: RIA - Respiratory, Inflammation and Autoimmunity, CVMD - Cardiovascular and Metabolic Disease,

ING - Infection, Neuroscience and Gastrointestinal