Introducing the IMED Biotech Unit What science can do 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. 1 What science can do At AstraZeneca, our purpose is to push the boundaries of science to deliver life-changing medicines. We will achieve this by placing science at the centre of everything we do. The future of treatment for many of today’s diseases lies in uncovering mechanisms that are newly emerging or still to be discovered. We believe the best way to help patients is to focus on breakthrough science to identify these mechanisms and then use our distinctive capabilities to develop novel, targeted therapies. Our approach to Research & Development It’s science that Distinctive science starts in our two biotech units, which conduct innovative discovery research and early-stage development from compels us to push the initial target selection to Phase II trial completion before transitioning to Global Medicines Development. boundaries of what is possible. We trust in the IMED Biotech Unit MedImmune Global Medicines potential of ideas and Focuses on using state-of-the Focuses on biologics across our Development art discovery platforms and core areas and pioneers innovative pursue them, alone and translational science in small research using unparalleled expertise The science engine room that drives with others, until we molecules, oligonucleotides and in protein engineering, translational late-stage development of our other emerging technologies. sciences and immunology. innovative pipeline, transforming have transformed the exciting science into valued new medicines and ensuring patients treatment of disease. around the world can access them. 2 3 Our IMED Biotech Unit “Now is a great time to be a scientist in AstraZeneca. Working across a range of therapy areas, our IMED teams are focused on translating the really cool science that is happening in our labs into the next generation of medicines We are committed to driving scientific advances that patients need. To make this happen, we need great partners who share in small molecules, oligonucleotides and other our passion for science and who have the drive and determination to meet the emerging technology platforms to push the unmet needs of patients around the world.” boundaries of medical science. Mene Pangalos, EVP, IMED Biotech Unit Each year we invest in excess Partnering and collaboration creating a permeable research of $1bn on discovering and is a way of life for our teams. environment where scientists developing the next generation We work alongside scientists can more freely share their ideas of life changing medicines, from at many of the world’s leading and collaborate on projects with initial target selection through academic institutions to increase the best external scientists. We to the end of Phase 2 trials. our understanding of disease remain committed to openness We employ over 2,000 physiology and help identify and accessibility, and will continue scientists and undertake potential new drugs. to identify new and innovative research on a truly global scale, ways to connect the great science operating vibrant science We are pioneering new happening in our labs with the centres across three continents. approaches to open innovation, best external science around. We believe in the potential of ground-breaking science to transform the lives of patients. We do this by focusing on three key priorities. Fostering a culture where Creating an environment open Challenging conventional science thrives – one for innovation - where our thinking - we encourage our that is dynamic, agile and teams work side by side with our people to apply scientific rigour in entrepreneurial. academic and industry partners to challenging the way we do things. make the next breakthrough. 4 5 Where science thrives We are achieving scientific leadership through a Focusing on quality dynamic, agile and entrepreneurial culture that not quantity feels like a biotech but has the resources of a major A comprehensive review of our IMED small-molecule drug global pharmaceutical company. projects took place from between 2005 and 2010. This helped us identify the most important factors for project success and pipeline quality. We call this our 5R framework. The 5R framework emphasises quality rather than quantity Inspiring great scientists in our research and development. That’s why a sixth critical factor is having the right culture. IMED has established a culture where our teams are ‘truth seeking’ in their behaviour Our plan to achieve scientific leadership rests on our ability to and rigorous in their approach to asking the critical ‘killer’ attract and retain the best scientists. We continue to attract ~2,500 questions. Rather than being rewarded for hitting the next senior scientists from academia and industry. Why? Because milestone, our scientists are rewarded for thinking about the quality of our science and the potential of our pipeline make people with a what it would take to deliver a viable, differentiated medicine. passion for science the IMED Biotech unit a great place to work. Both our IMED teams and our Early Stage Portfolio At the same time, we are committed to inspiring the next Committee (ESPC) use this framework to ensure we are generation of scientists by giving them opportunities to develop progressing the right projects, asking the right questions their skills and follow the science they are passionate about. and making the right decisions at key review points Almost throughout the drug development process. This approach is now embedded into the way our teams work and is used by the ESPC to review and approve pipeline progressions. 1,000 Building our scientific reputation papers published Our scientists and teams are encouraged to publish their Our 5R framework over 2014 and 2015 work in peer reviewed journals. Demonstrating the quality of the research conducted in our labs, particularly in high Right target quality and high impact journals, is an essential element in • Strong link between target and disease building our scientific reputation and our plans to achieve • Differentiated efficacy scientific leadership for AstraZeneca. It is also a critical • Available and predictive biomarker Over consideration for recruiting and retaining the best scientists from around the world. Right tissue • Adequate bioavailability and tissue exposure • Definition of PD biomarkers 45 • Clear understanding of preclinical and clinical PK/PD High Impact publications Delivering a step change in R&D • Understanding of drug-drug interactions in past two years productivity and output Right safety Since it was formed in 2010, the IMED Biotech Unit has helped • Differentiated and clear safety margins deliver sustainable improvements in R&D productivity across • Understanding of secondary pharmacology risk AstraZeneca. In recent years, we have created a leaner, simpler • Understanding of reactive metabolites, Over organisation, focused on driving distinctive science across our genotoxicity, drug-drug interactions key therapy areas. • Understanding of target liability Through a rigorous focus on great science, we have developed Right patients $1bn a robust clinical pipeline across our core therapy areas of • Identification of the most responsive patient oncology, respiratory and inflammation and cardiovascular population invested in scientific disease. We also continue to progress the most promising • Definition of risk-benefit for given population research each year projects in neuroscience in collaboration with partners and in small molecule anti-infectives through our standalone company, Entasis Therapeutics. Right commercial opportunity • Differentiated value proposition versus future standard of care • Focus on market access, payer and provider Lessons learned from the fate of AstraZeneca’s drug • Personalised healthcare strategy, including pipeline: a five-dimensional framework Cook et al diagnostic and biomarkers Nature Reviews Drug Discovery 13, 419–431 (2014) 6 Our therapeutic focus The future of treatment for many of today’s diseases Cardiovascular & Metabolic lies in uncovering mechanisms that are newly Diseases iMed emerging or are still to be discovered. Our strategy in CVMD focuses on ways to reduce morbidity, mortality and organ damage by addressing multiple risk factors across cardiovascular (CV) disease, diabetes and chronic kidney disease indications. The patient-centric approach is reinforced by science-led lifecycle management programmes and technologies, including early research into regenerative methods. We believe the best way to help patients is to focus on Cardiovascular and breakthrough science to discover Metabolic diseases these mechanisms and develop novel, targeted therapies that interact with them. Our focus in IMED is on the following three Oncology iMed main therapy areas: Our vision is clear. To help patients by redefining the cancer- treatment paradigm, with the aim of bringing six new cancer medicines to patients between 2013 and 2020. A broad pipeline of next-generation medicines is focused principally on four disease areas – breast, ovarian, lung and Oncology haematological cancers. We have one of the broadest and deepest