What science can do

Circulating tumour DNAAstraZeneca has pioneered the use of circulating tumour DNA (ctDNA) in the diagnosis of cancer. Pieces of DNA break off from a tumour and circulate in the bloodstream where they can be analysed to give genetic information about a patient’s tumour. This allows healthcare professionals to determine the right treatment for the patient using a non-invasive blood test.

April 2015

A message from Pascal Soriot

At AstraZeneca, our purpose is to push the boundaries of science to deliver life-changing medicines. We believe the best way we can achieve this is to put science at the centre of everything we do. It is this commitment that drives our ability to discover, develop and deliver the advancements the world needs in complex and difficult diseases like cancer, heart disease, diabetes, COPD and asthma.

For us, the discovery of medicines starts with our rare combination of scientific capabilities in small molecules and biologics, immunotherapies, protein engineering technologies, oligonucleotides and devices. When combined with our strong focus on translational science and personalised healthcare, we believe that we have a unique and strong foundation for speeding novel, targeted therapies from biologic concept to care.

We know that the best science doesn’t happen in isolation - it happens through collaboration. That is why we seek to work so extensively with scientific, academic and healthcare organisations around the world - from the earliest discovery work in our research labs, to our clinical trial programmes and to joint working with health care providers to achieve optimal treatment outcomes.

We also take smart risks in developing and applying new technologies which help us to explore new mechanisms of action and create new types of treatments. It is when our scientists are empowered to follow these transformative areas of science that we see the most significant breakthroughs.

Every day and everywhere AstraZeneca employees work, we endeavour to transform people’s lives through science. I hope you see in all your interactions with us this commitment to unlocking the power of what science can do.

Pascal SoriotChief Executive Officer

Minute pieces of tumour DNA circulating in the bloodstream.

What science can do

Oncology combination therapiesAstraZeneca is investigating combinations of biologic and small molecule therapies for the treatment of cancer. These combinations target the tumour directly and some help boost the body’s own immune system to induce tumour cell death.

Helping more people survive cancer Our ambition is to transform the lives of people with cancer and, through our researchandscientificpartnerships, we seek to eliminate cancer as a cause of death.

AstraZeneca has a deep-rooted heritage in oncology. Our vision is to help patients by redefining the way in which cancer is diagnosed and treated, through scientific innovation, accelerated clinical programmes and collaboration. Our broad pipeline of medicines is focused on four main disease areas: breast, ovarian, lung and haematological cancers.

We believe that the challenge of beating cancer can be met through the development of novel targeted monotherapies (both small molecules and biologics) and combinations that specifically address the underlying mechanism of the disease or how it evades effective immune response. Our goal is to understand these mechanisms and develop treatment options that significantly improve patient survival rates and quality of life through a more complete tumour response, suppression of tumour growth and delayed or reduced tumour recurrence. Our industry-leading oncology pipeline is broad and exciting, addressing multiple disease pathways and allowing for combination therapies to increase the benefit to patients.

AstraZeneca and the future of cancer care 1

Tumour drivers and resistance mechanisms The inhibition of genetic disease drivers is a powerful way to shrink tumours and improve progression-free survival in many types of cancer. Tumours, however, eventually develop resistance to therapy. Our research in this area seeks to develop novel therapies that target both the mutations that cause cancer cells to proliferate and the mechanisms of resistance.

DNA damage repair Our research programmes focus on identifying and exploiting vulnerabilities that are unique to cancer cells, so that new therapies can be developed that selectively damage tumour cell DNA. We are exploring tumour cell deficiencies such as enhanced sensitivity to DNA damage or the potential to initiate programmed cell death, to kill cancer cells while at the same time minimising toxicity to the patient.

Antibody-drug conjugates Antibody-drug conjugates offer a highly potent approach that selectively targets cancer cells. We are seeking to combine innovative antibody engineering capabilities with cytotoxic drug ‘warheads’ to selectively attack and kill the tumour while again keeping the toxic effects on the patient to a minimum.

Immunotherapy Our ambition is to be a scientific leader in immunotherapy, a promising therapeutic approach that harnesses the patient’s own immune system to help fight cancer. We are working to understand how cancer evades the immune system and to identify approaches that enhance the immune system’s ability to fight cancer.

1 AstraZeneca press release. Demonstrating our oncology science at ASCO 2014, 30 May 2014. http://www.astrazeneca.com/About-Us/Features/Article/20140530--demonstrating-AstraZeneca-oncology-science-ASCO-2014. Last accessed 23 February 2015.

Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti-tumour immunity.

Making hearts healthier We push the boundaries of science to create innovative medicines that address multiple cardiovascular risk factors and diseases, offerindividualisedapproachesfordiabetes patients, treat chronic kidney disease, and ultimately save lives.

AstraZeneca is prioritising the treatment of cardiovascular and metabolic diseases, focusing on bringing life-changing medicines to patients with thrombosis, atherosclerosis, dyslipidaemia, hypertension, heart failure and metabolic diseases, including diabetes and related complications.

We invest both in the development of new treatments and in better scientific understanding of our many existing medicines, in order to increase our understanding of them and explore possible new indications in areas of unmet medical need. We are also expanding our capabilities and research programmes into new modalities and regenerative medicine to provide new treatment paradigms for heart failure, diabetes and chronic kidney disease.

2 Jha et al. Chronic kidney disease: global dimension and perspectives. The Lancet 2013; 382:260-272. 3 https://www.clinicaltrials.gov/ct2/show/NCT02104817. Last accessed February 2015.

The future of Cardiovascular and Metabolic diseasesCardiovascular diseaseOur scientific area of focus is cardiac regeneration, where we are investigating potential therapies by activating endogenous stem cells in the heart to regenerate the lost muscle tissue in patients with heart failure and cardiac dysfunction post-myocardial infarction. If successful, such therapies could offer a potential cure for heart disease.

Diabetes We are investigating the underlying mechanisms of diabetes, specifically looking beyond glucose control to studies that include measurements of microvascular benefit and disease progression, such as β-cell mass. Our researchers are also exploring avenues with the potential to stop and reverse diabetes-related kidney damage, as well as ways to address co-morbidities such as obesity by targeting appetite control in the brain. In our early programmes we are aiming to find routes that could stop, reverse or even cure diabetes through innovative breakthrough science that targets insulin resistance and increases the functional β-cell mass.

Chronic kidney disease (CKD) CKD is a critical healthcare problem that affects several millions of people worldwide.2 New treatments are required to help patients manage their condition and AstraZeneca is accelerating potential new therapies using a variety of approaches, including small molecules, antibodies, peptides and proteins.

Lipid loweringAstraZeneca is currently running the largest cardiovascular outcomes trial of any prescription omega-3, STRENGTH, (STatin Residual risk reduction with EpaNova in hiGh cardiovascular risk paTients with Hypertriglycerideamia). STRENGTH will provide important insight into the impact of lowering triglycerides with EPANOVA (omega-3-carboxylic acids, the only free-fatty acid prescription omega-3) in combination with statin therapy, in patients with mixed dyslipidaemia who are at increased risk of cardiovascular disease.3

Messenger RNA being read by a ribosome to produce signalling proteins.

Helping people breathe more easily Through the introduction of new biologics and more targeted therapies, we can help to transform the way we treat asthma.

We are making significant progress in respiratory disease with several projects in late stage clinical development or registration. Across both asthma and COPD, AstraZeneca is progressing late-stage clinical development of targeted biological agents including highly selective monoclonal antibodies that have the potential to transform disease management. In addition to asthma and COPD, our research could lead to the availability of the first biological treatment for idiopathic pulmonary fibrosis, another disease with a high unmet medical need.

Understanding eosinophilsOur bold ambition is to transform the way in which we treat asthma.

Eosinophils (a type of white blood cell) have been shown to play a significant role in the cause and severity of asthma, and to be elevated during COPD exacerbations, thus eosinophil depletion suggests the potential for significant clinical benefit.

AstraZeneca is working on a unique monoclonal antibody directed at the interleukin-5 alpha (IL-5Rα) that depletes eosinophils and basophils. This research has the potential to bring a new therapeutic option to patients with a clear unmet medical need - the severe eosinophilic asthma and COPD patients not benefiting from current treatments.

Natural killer cell recruited by biologic.

Eosinophil just before apoptosis.

We are developing several promising investigational agents for the treatment of inflammation and autoimmune diseases, including psoriasis, gout, systemic lupus and rheumatoid arthritis. Our development programmes are focused on understanding the shared biological pathways of these diseases and how their related pathophysiology differs in target populations.

We are building a pipeline across the inflammation and autoimmune spectrum, with the potential to launch numerous novel first and best-in-class products in the next decade.

Transforming inflammation and autoimmune disease

AstraZeneca at a glance

CRISPR: Technology for genome editing

Pioneering the next generation of drug discovery technology In order to harness the latest technology and most advanced scientific knowledge, one approach we are taking is to use what is effectively a pair of molecular scissors to cut and edit the genome at specific points. This technique, called CRISPR allows scientists to make changes in individual genes far faster and in a much more precise way than ever before. CRISPR will allow us to identify new genes that are implicated in disease and test whether these genes and their products could be targets for new medicines in models that more closely resemble human disease.

We are collaborating with some of the world’s best CRISPR scientists in line with our porous approach, including those at the Wellcome Trust Sanger Institute (UK), The Innovative Genomics Initiative (US), Thermo Fisher Scientific (US) and Whitehead Institute (US). We will share cell lines and compounds with our partners and work with them to publish findings of the application of CRISPR technology, contributing to broader scientific progress in the field.

Source: AstraZeneca PLC. Fourth quarter and full year results 2014, 5 February 2015. http://www.astrazeneca.com/Research/Our-pipeline-summary. Last accessed 23 February 2015.

CRISPR geneediting tool.

We operate in more than

100countries worldwide

More than

850current collaborations and partnerships globally

$26.1 billionin worldwide sales in 2014

118projects were in clinical development in 2014

Our three strategic R&D centres:• Cambridge, UK - Planned global R&D centre and Corporate HQ• Gaithersburg, Maryland US• Mölndal, Sweden

We invested over

$4.9 billionin the discovery and development of life- changing medicines

Thirteen new molecular entities (NMEs) in late stage clinical development or under regulatory review in 2014

Our three main therapy areas:• Cardiovascular and Metabolic diseases (CVMD)• Oncology• Respiratory, Inflammation and Autoimmunity (RIA)

57,500employees worldwide

Third fastest-growing top 10 multinational pharmaceutical company in Emerging Markets in 2014

Our Products

Trade mark Generic name Therapy area

Atacand/Atacand HCT/Atacand Plus candesartan cilexetil Hypertension/heart failure

Brilinta/Brilique ticagrelor Acute coronary syndromes

Crestor rosuvastatin calcium Dyslipidaemia, hypercholesterolemia

Plendil felodipine Hypertension, angina

Seloken/Toprol-XL metoprolol succinate Hypertension, heart failure, angina

Tenormin atenolol Hypertension, angina pectoris

Zestril lisinopril dihydrate Hypertension

Byetta exenatide injection Type 2 diabetes mellitus

Bydureon exenatide extended-release for injectable suspension

Type 2 diabetes mellitus

Bydureon Pen exenatide extended-release for injectable suspension

Type 2 diabetes mellitus

Forxiga/Farxiga dapagliflozin Type 2 diabetes mellitus

Kombiglyze XR saxagliptin and metformin XR Type 2 diabetes mellitus

Komboglyze saxagliptin and metformin HCl Type 2 diabetes mellitus

Myalept metreleptin for injection Congenital/acquired generalised lipodystrophy

Onglyza saxagliptin Type 2 diabetes mellitus

Symlin pramlintide acetate Type 1/Type 2 diabetes mellitus

Xigduo dapagliflozin and metformin hydrochloride

Type 2 diabetes mellitus

Xigduo XR dapagliflozin and metformin hydrochloride extended-release

Type 2 diabetes mellitus

Trade mark Generic name Therapy area

Accolate zafirlukast Asthma

Bricanyl Turbuhaler terbutaline in a dry powder inhaler Asthma and COPD

Duaklir Genuair (licensed to AZ by Almirall S.A.)

aclidinium/formoterol COPD

Eklira Genuair/Tudorza/Bretaris (licensed to AZ by Almirall S.A.)

aclidinium COPD

Oxis Turbuhaler formoterol in a dry powder inhaler Asthma and COPD

Pulmicort Turbuhaler/Pulmicort Flexhaler budesonide in a dry powder inhaler Asthma

Pulmicort Respules budesonide inhalation suspension Asthma

Rhinocort budesonide Allergic rhinitis (hay fever), perennial rhinitis and nasal polyps

Symbicort pMDI budesonide/formoterol in a pressurised metered-dose inhaler

Asthma and COPD

Symbicort Turbuhaler budesonide/formoterol in a dry powder inhaler

Asthma and COPD

Trade mark Generic name Therapy area

Arimidex anastrozole Breast cancer

Caprelsa vandetanib Medullary thyroid cancer

Casodex bicalutamide Prostate cancer

Faslodex fulvestrant Breast cancer

Iressa gefitinib Non-small cell lung cancer (NSCLC)

Nolvadex tamoxifen citrate Breast cancer

Lynparza olaparib Ovarian cancer

Zoladex goserelin acetate implant Prostate cancer, breast cancer gynaecological disorders

Cardiovascular and Metabolic diseases Respiratory, Inflammation and Autoimmunity

Oncology

Atlas Approval ID: 687,023.011 Date of preparation February 2015Date of expiry February 2016

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