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 pipelines in the industry, spanning Immuno-Oncology, DNA Damage Response and targeted therapies.

Respiratory, Inflammation Respiratory, Inflammation and Autoimmunity & Autoimmunity iMed

AstraZeneca holds a unique position in respiratory disease, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with a range of differentiated, potential medicines in development by leveraging novel combinations, biologics and devices. The pipeline also has a number of promising assets in inflammatory and autoimmune diseases within areas such as psoriasis, psoriatic arthritis, gout, systemic lupus and rheumatoid arthritis.

We also pursue opportunity- Neuroscience iMed driven projects in Neuroscience. Neuroscience The Neuroscience iMed model is unique in that it is dynamic, small and predominantly externalised, forming partnerships with leading-edge academic researchers, foundations and companies to create a portfolio of discovery and early development projects in neurological and psychiatric disease.

8 9 Developing science talent

Our Graduate Programme is designed for those Graduate Post doctoral Chief Scientist with a passion for science, and a desire to make programme programme programme a genuine difference to the lives of patients – A two year programme, graduates The Post-Doc Programme brings As part of our drive for the best science today and in the future. complete three placements across together motivated and innovative post- we are committed to working with the Innovative Medicines and Early doctoral scientists who have a passion best scientists, both inside and Development with a focus on breadth for great ideas and a desire to make outside the pharmaceutical industry. of experience. In addition to three a difference through an academic- To ensure that we are able to attract top placement line managers, graduates are style post-doctoral position in a global science talent from academia, we have supported by a mentor for the duration pharmaceutical setting. developed our flexible Chief Scientist of the programme to offer career programme. By tailoring individual counselling and guidance. The two year programme funds post- arrangements to enable scientists to doctoral projects originating from work with AstraZeneca IMED full time, In addition to developing your technical internal scientists/clinicians across part time, or on assignment from a skills working with world-class scientists the research areas and scientific university, we encourage a permeable with state-of-the-art facilities, all disciplines within AstraZeneca. research environment meeting the needs graduates are enrolled onto the Global These projects address fundamental of both the institution and individual. Graduate Development Programme scientific challenges that underpin drug where we focus on the softer skills that discovery and development. In addition, Being flexible in our approach enables are required to make the successful each post-doctoral scientist receives scientists of the highest calibre to transition into industry. a tailored training and development stay connected to their research, their programme encompassing key skills universities and to work flexibly between such as presentation delivery and their commitments, while allowing us to publication writing. connect with the best scientific minds to discover and develop new medicines.

“Throughout AstraZeneca, there is true intent to follow the science. Combining my academic and clinical work with my AstraZeneca role puts me at the hard face of drug development. I see my primary job as being part of the IMED and driving our portfolio, but I have a live interface with patients and academia which keeps me awake and sharp, and which gives me many ideas.At AstraZeneca you can do world-class science but you can explore your scientific talents as well as your leadership talents. It’s a friendly, collaborative company and there is such a wide spread of people, skills and experiences. AstraZeneca offers an opportunity for curious people to explore.” Prof. Dr Maarten Kraan MD PhD VP, RIA iMed, Adjunct Professor of Rheumatology at Gothenburg University

11 Open for collaboration Working more openly with leading scientists around the world

Our teams are leading the way in creating an open Our dedicated open innovation portal makes it easier research environment that goes beyond the usual for external researchers to access the full range of open collaboration models. innovation programmes and identify ways to collaborate with our teams.

We continue to find new and Through this website, external scientists can access: innovative ways of collaborating with academic institutions, A clinical compound bank of ‘patient-ready’ active and discontinued compounds. In previous trials, biotechs and pharmaceutical these compounds have shown evidence of human companies. In many cases, our target coverage and tolerability. They are being scientists work side-by-side with offered for novel clinical and translational research partner scientists, advancing the science together as one team. A pharmacology toolbox, which comprises compounds with strong pharmacological properties. These compounds are being made available for We are open to exploring new and preclinical research to explore novel disease biology different kinds of collaborations. and advance scientific knowledge Current partnership models include in-licensing of new Collaborative efforts to validate new targets, which chemical modalities and platforms; could include the availability of high throughput screening capabilities to investigators partnerships to leverage our compound collection to uncover Advanced cheminformatic capabilities to explore the novel target opportunities and properties and therapeutic innovation potential of collaborations designed to new molecules build our understanding of the Researchers can also suggest solutions to R&D challenges, mechanisms of disease. or suggest fantastic ideas above and beyond ideas related to compounds and screening. AstraZeneca is seeking to During the last two years alone, collaborate with and reward those who bring innovative our teams have established more solutions to ongoing challenges. than 130 new collaborations and partnership agreements. http://openinnovation.astrazeneca.com/

Harnessing our footprint Partnering with the best “This is a unique collaboration, With research facilities in a number of UK Sweden Our agreements with the UK Medical Research Council, the world’s established and emerging which is helping to maximise the the National Institutes of Health in the US, and the National scientific centres, we recognise the 300 collaborations 100 collaborations potential of many compounds, any Research Program for Biopharmaceuticals in Taiwan, have importance of leveraging our footprint to one of which could prove a scientific enabled academic researchers to start unlocking the full connect with the best external science, potential of some of our discontinued compounds to develop accelerating our scientific partnerships breakthrough. Our partnership new medicines for diseases such as Alzheimer’s and cancer. and alliances with leading academic with AstraZeneca is a perfect and biotech partners around our sites. In addition, collaborations with renowned academic Europe combination because it enables organisations such as Karolinska Institutet in Sweden and with 160 collaborations academia to benefit from the work leading charities and governmental organisations, including of a leading pharmaceutical Cancer Research UK, the National Cancer Institute and the National Institute of Mental Health in the US, are enabling our company in a way that could teams to work side by side with like-minded scientists who advance scientific understanding share our passion for transforming the lives of patients. of a wide range of diseases.” Chris Watkins, Director of Translational Research, UK Medical Research Council US Asia

340 collaborations 80 collaborations

12 13 Challenging convention

We believe in combining scientific rigour with a Preparing for the future desire to always ask the “what if” question. It’s how with our ‘IMED Futures’ we continue to push the boundaries of science. teams

Delivering the next wave of life-changing medicines requires a new way of thinking. To ensure the IMED Biotech Unit remains at the cutting-edge of scientific innovation, we established our IMED Futures programme. Delivering the next generation of It needs people who continue to Within the IMED Biotech Unit we life changing medicines requires push themselves to be the best are creating a dynamic culture a new way of thinking that at what they do. And it needs where anything is possible; where embraces alternative ideas and people who will rigorously our people are encouraged to new methods. It needs people interrogate what they know, challenge the status quo and are who can pioneer new practices relentlessly searching for new rewarded for following the science Advanced Drug Delivery Preclinical Biosensors and work across fields of opportunities to bring benefit and seeking the truth. Improved understanding of the physiological barriers to To enhance the impact of current online data monitoring, our scientific discovery. to patients. efficient drug delivery has resulted in significant advances teams have been exploring the possibilities within the rich data in delivery systems. This, coupled with novel analytical and source provided by sensor technology and wearable devices. imaging techniques allow for even more sophisticated delivery Incorporating biosensor technology into our pre-clinical studies systems opening up new target space. Our team is looking to will allow us to change current practice, improve translation and improve target efficacy by enhancing our targeting capabilities safety read-outs, while reducing the number of animal studies. to allow delivery of both small molecules and oligonucleotide therapeutics – miRNA, mRNA and antisense. To do this our team Current technology allows measuring the body’s vital signs is focused on three key areas: 1) cellular targeting, 2) improving using health patches but our team recognises the true value for cellular uptake and 3) enhancing drug delivery. In the latter case, pre-clinical monitoring lies with invasive biosensor technology. Entrepreneurial thinking we have already initiated collaborations with BIND Therapeutics In the future, developing pre-clinical sensors that monitor for its ACCURINS® polymeric nanoparticle technology and drug exposure and biomarkers of safety and efficacy will have drives new research with Starpharma exploring their dendrimer technology platform. the potential for clinical use – providing online biosensors for Both these technologies improve therapeutic index and ability to patients, and hence changing the status quo for patient care. approaches formulate challenging molecules. The IMED Biotech Unit forged a unique iDecide new model to drive neuroscience iLead in Lead Generation iDecide’ is a clinical informatics research and development innovation – the Neuroscience How can IMED deliver a therapeutic agent for any portfolio framework enabling early and better decision-making in clinical virtual iMed. This bold approach to target? The team is developing strategies that explore next- studies. In collaboration with the Manchester Cancer Research neuroscience drug discovery research generation approaches to small molecule hit identification Centre (MCRC), iDecide is designed to integrate, maintain and and development was designed to and the application of peptides and cyclic peptides as novel assess data during an ongoing study utlising real time feedback address the significant challenges the therapeutic modalities. from patients. Leveraging this patient-centric information in a pharmaceutical industry faces in bringing timely manner enables appropriate adjustment to clinical trial new neuroscience medicines to market. Organs on a Chip design, saving resources and time while helping us administer As we advance our understanding of biology and integrate the right dose, of the right drug to the right patient. our knowledge of cellular behaviour and tissue function, it is apparent that the current pre-clinical in vitro models have Digital IMED limitations when predicting organ functionality. Complex The wealth of ‘big data’ in healthcare is revolutionising In 2015, we established Entasis cellular microphysiological systems (MPS), consisting of our approach to R&D. We are already seeing how the next Therapeutics, an independent interacting organs-on-chips or tissue-engineered, 3D organ generation of medicines are being shaped by our ability to company focused on the discovery and constructs, present an opportunity to bring new tools to capture, interpret and apply data. Combining insight from development of novel antibacterials biology, medicine, pharmacology, physiology, and toxicology. clinical health records with large-scale genomics data is to address the serious medical need By placing human or animal cells in a more ‘natural’ enabling scientists to better predict disease outcomes in the posed by multidrug-resistant bacterial environment, we can start to recapitulate the dynamics of clinic. Our team has been investigating connecting multiple data infections. The team enjoys the culture drug-organ, drug-drug, and drug-organ-organ interactions stacks from anywhere and of any type, from proprietary data and energy of a small biotech, combined to allow better predictivity of clinical translation. Our team is to real world evidence, even social media platforms. This data with the expertise and portfolio of a collaborating with some of the leading experts in the world at stack would truly allow us to map 360 degree views of patient global pharmaceutical company. In TissUse, Harvard and Vanderbilt Universities. journeys and gain understanding of the interplay between addition to driving internal research ‘nature’ (from genetic information) and ‘nurture’ (environmental programmes, the team also seeks to data e.g. smartphone/ sensor data) to make breakthroughs in engage with external partners. science and ultimately patient care.

Learn more: www.entasistx.com

14 15 Our people, skills and values Key skills and capabilities in the IMED Biotech Unit

In pushing the boundaries of science, we continue Translational science Medicinal Chemistry Drug safety and to harness our unique mix of scientific skills and & biology metabolism capabilities, by providing our people with the Our medicinal chemistry capabilities Our bioscience groups are accountable enable us to integrate structural, We apply our drug metabolism and tools they need to deliver industry-leading R&D for testing biological hypotheses pharmacological, pharmacokinetic and pharmacokinetics (DMPK) expertise to performance. by using in vitro and in vivo assays toxicological information to support deliver in vitro and in vivo data, mass and innovative disease models. Our the innovative design of novel chemical spectrometry imaging data, expertise teams excel in the analysis of disease compounds. Pushing the boundaries of and isotopically labelled compounds to tissue and the application of bio- medicinal chemistry enables the delivery our project teams. By following the informatic approaches to support the of new candidate drugs into our pipeline science and combining our expertise But we also know that by itself, capacity to transform the lives of Our people are passionate identification and validation of targets and is the foundation of small molecule with that of our external partners, our this will not be enough. We need patients. You will notice the pride about their work. They are also regulating biological processes. We drug discovery across the company. We teams accelerate the discovery and people with a burning passion our people have in what we’ve creative and entrepreneurial with run an active post doc programme, also work on next-generation devices development of safe, new medicines for what science can do. achieved; the breakthroughs a relentless drive to translate the pursuing blue skies research to help and delivery through our pharmaceutical across our focus areas. We also apply we’ve made, the medicines great science happening in our improve our understanding of disease. development group. our discovery safety expertise to deliver When you visit an IMED site, we’ve developed and the lives labs into the next generation of Our translational expertise enables in silico, in vitro and in vivo data for target you will meet people who are we’ve helped to transform. medicines to transform disease. us to accelerate the development and chemical risk assessments and inspired by science and its of new druggable targets in human Clinical development deliver quantitative translational safety disease and select the right patients models for functional and pathological in early clinical trials. Our Early Clinical safety signals. Development team specialises in Our Early Clinical Development team Interested in joining our IMED Biotech Unit? interpreted quantitative data analysis designs and delivers early phase www.astrazenecacareers.com/career-areas/research-and-development/IMED developed using the latest, model- development strategies and exploratory Pharmaceutical Sciences based drug development techniques studies that build the credentials of and technologies. novel targets. Clinical Operations delivers global clinical trials for late Pharmaceutical Sciences ensures we stage projects across our pipeline, using implement intelligent design of medicines Our people make us stand out and our both internal and external programme and delivery systems. By focusing on Personalised healthcare and study management expertise. Our three priority areas – Early Chemical values define us leading expertise in large outcomes Development, Early Product Development, and Advanced Drug As a leader in personalised healthcare, trials enables us to deliver multi-country, Across AstraZeneca, our values define how we work. Delivery, the team supports formulation we are committed to matching new multi-site studies with thousands of Science and patients come first. Entrepreneurial thinking is and delivery for IMED’s portfolio across medicines to the patients most in patients, many of which include a encouraged – as is speaking up. the main therapy areas, from early need. We combine industry-leading personalised approach. discovery to Phase IIb clinical trials. The We want people to be candid and do the right thing – not just expertise in companion diagnostics group is closely involved with project the easy thing. These values help us drive scientific leadership with laboratory science in molecular teams to influence the design of new and make a meaningful difference to patients. diagnostics, tissue diagnostics, imaging Discovery sciences molecules and early clinical trials, and and protein biomarkers, working specialise in cutting-edge drug delivery collaboratively with our external partners system technology to support our ever to harness break-through technologies Our leading High Throughput Screening expanding drug platforms and modalities. Our AstraZeneca values across the life-cycle of our medicines. capabilities ensure we can develop and deliver novel reagents and high quality assays to support efficient and We follow the science effective pre-clinical drug discovery and biomarker development in later We put patients first clinical phases. In parallel to this, we use our screening capabilities to provide We play to win project teams with mechanism of action, biology, safety and drug metabolism and pharmacokinetics (DMPK) insights We do the right thing across lead generation and lead optimisation projects, while our structure We are entrepreneurial and biophysics group use protein structure and biophysics to understand the relationships between target protein and chemical space.

17 Our thriving science centres Creating vibrant Biohubs

Stimulating ‘cross-fertilisation’, both between the hub companies and with AstraZeneca, is key to the success of the biohub approach in our evolving sites.

A bold, new R&D initiative to foster life sciences discovery and the exchange of ideas between scientists, our “AstraZeneca has been on a transformative journey Gatehouse Park BioHub, along with over the past few years, placing great science at the BioVentureHub at the Gothenburg the heart of everything we do in the delivery of UK – Cambridge Sweden – Gothenburg site in Sweden, and the BioHub at breakthrough medicines to patients. Our ambition our Alderley Park site in the UK, all is to improve the lives of 200 million people by In 2013, AstraZeneca announced plans to move Our strategic R&D centre in Gothenburg is the have vibrant but distinctive features 2025. Such an ambition would not be possible our UK research activities to a new $500m facility centre of our research for two of our therapy offering an energising environment, all about sharing ideas and tapping without establishing collaborations of all types in the centre of Cambridge. Our new facility at the areas of cardiovascular & metabolic diseases and with academia and industry. Our biohubs provide Cambridge Biomedical Campus will become the respiratory & inflammation. It is also home to a into great science. company’s largest centre for oncology research large number of our scientists from our early phase a fantastic opportunity to explore collaboration and a centre of excellence for pre-clinical research, Discovery Sciences unit and our Drug Safety and even further.” medicinal chemistry and high-throughput screening. Metabolism team. Our vibrant Gothenburg facility Kumar Srinivasan, Head of AstraZeneca R&D Boston and As we expand our presence in the city, our transition has seen their BioVentureHub go from strength VP Scientific Partnering and Alliances from the North West means a small number of IMED to strength since its inception in 2014, with both colleagues will remain at our Macclesfield campus, industry and academic groups now working in this and at Alderley Park until our R&D exit of the site innovative ecosystem. is completed. The growing Alderley Park BioHub is successfully creating an optimum environment for emerging businesses to thrive.

US – Boston China – Shanghai

Boston is home to AstraZeneca’s small-molecule Our small molecule research facility in China is research in North America, with state-of-the-art located at the Zhangjiang High Tech Park in the laboratories in Waltham, just west of the city centre. Pudong area of Shanghai. Our research teams Our Boston-based scientists focus on the discovery here focus on discovering potential new medicines and development of new medicines for the treatment that meet the unique needs of patients in Asia and of cancers and neurological disorders. The site also driving forward translational science across our core houses the Gatehouse Park BioHub, which is thriving therapy areas. with a number of research companies already in place since launch towards the end of 2015.

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