What science can do April 2015 Circulating tumour DNA AstraZeneca 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. At AstraZeneca, our purpose is to push the boundaries of science A message 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 from is this commitment that drives our ability to discover, develop and Pascal Soriot 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. Minute pieces Every day and everywhere AstraZeneca employees work, we of tumour DNA endeavour to transform people’s lives through science. I hope you circulating in the see in all your interactions with us this commitment to unlocking the bloodstream. power of what science can do. Pascal Soriot Chief Executive Officer What science can do Oncology combination therapies AstraZeneca 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. Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti-tumour immunity. Helping more people survive cancer Our ambition is to transform the lives of people with cancer and, through our research and scientific partnerships, we seek to eliminate cancer as a cause of death. AstraZeneca has a deep-rooted heritage in oncology. AstraZeneca and the future of cancer care 1 Our vision is to help patients by redefining the way Tumour drivers and resistance mechanisms in which cancer is diagnosed and treated, through The inhibition of genetic disease drivers is a powerful way scientific innovation, accelerated clinical programmes to shrink tumours and improve progression-free survival and collaboration. Our broad pipeline of medicines is in many types of cancer. Tumours, however, eventually focused on four main disease areas: breast, ovarian, develop resistance to therapy. Our research in this area lung and haematological cancers. seeks to develop novel therapies that target both the mutations that cause cancer cells to proliferate and the We believe that the challenge of beating cancer can mechanisms of resistance. be met through the development of novel targeted monotherapies (both small molecules and biologics) DNA damage repair and combinations that specifically address the Our research programmes focus on identifying and underlying mechanism of the disease or how it evades exploiting vulnerabilities that are unique to cancer effective immune response. Our goal is to understand cells, so that new therapies can be developed that these mechanisms and develop treatment options that selectively damage tumour cell DNA. We are exploring significantly improve patient survival rates and quality tumour cell deficiencies such as enhanced sensitivity of life through a more complete tumour response, to DNA damage or the potential to initiate programmed suppression of tumour growth and delayed or reduced cell death, to kill cancer cells while at the same time tumour recurrence. Our industry-leading oncology minimising toxicity to the patient. pipeline is broad and exciting, addressing multiple disease pathways and allowing for combination Antibody-drug conjugates therapies to increase the benefit to patients. Antibody-drug conjugates offer a highly potent approach that selectively targets cancer cells. We are seeking to 1 AstraZeneca press release. Demonstrating our combine innovative antibody engineering capabilities oncology science at ASCO 2014, 30 May 2014. with cytotoxic drug ‘warheads’ to selectively attack and http://www.astrazeneca.com/About-Us/Features/ kill the tumour while again keeping the toxic effects on Article/20140530--demonstrating-AstraZeneca-oncology- the patient to a minimum. science-ASCO-2014. Last accessed 23 February 2015. 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. Making hearts healthier We push the boundaries of science to create innovative medicines that address multiple cardiovascular risk factors and diseases, offer individualised approaches for diabetes patients, treat chronic kidney disease, and ultimately save lives. AstraZeneca is prioritising the treatment of cardiovascular and The future of Cardiovascular and Metabolic diseases metabolic diseases, focusing on bringing life-changing medicines Cardiovascular disease to patients with thrombosis, atherosclerosis, dyslipidaemia, Our scientific area of focus is cardiac regeneration, where we hypertension, heart failure and metabolic diseases, including are investigating potential therapies by activating endogenous diabetes and related complications. stem cells in the heart to regenerate the lost muscle tissue in patients with heart failure and cardiac dysfunction post-myocardial We invest both in the development of new treatments and in better infarction. If successful, such therapies could offer a potential scientific understanding of our many existing medicines, in order cure for heart disease. to increase our understanding of them and explore possible new indications in areas of unmet medical need. We are also expanding Diabetes our capabilities and research programmes into new modalities and We are investigating the underlying mechanisms of diabetes, regenerative medicine to provide new treatment paradigms for heart specifically looking beyond glucose control to studies that include failure, diabetes and chronic kidney disease. measurements of microvascular benefit and disease progression, such as β-cell mass. Our researchers are also exploring avenues 2 Jha et al. Chronic kidney disease: global dimension and perspectives. with the potential to stop and reverse diabetes-related kidney The Lancet 2013; 382:260-272. damage, as well as ways to address co-morbidities such as obesity 3 https://www.clinicaltrials.gov/ct2/show/NCT02104817. by targeting appetite control in the brain. In our early programmes Last accessed February 2015. we are aiming to find routes that could stop, reverse or even cure Messenger RNA diabetes through innovative breakthrough science that targets insulin being read by a resistance and increases the functional β-cell mass. ribosome to produce Chronic kidney disease (CKD) signalling proteins. 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 lowering AstraZeneca 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 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 Understanding eosinophils respiratory disease with several projects Our bold ambition is to transform the way in late stage clinical development or in which we treat asthma. registration. Across both asthma and COPD, AstraZeneca is progressing late- Eosinophils (a type of white blood cell) stage clinical development of targeted have been shown to play a significant role biological agents including highly selective in the cause and severity of asthma, and to monoclonal antibodies that have