Delivering our pipeline through scientific leadership Innovative Medicines & Early Development Biotech Unit 2016 – A year in review Delivering our pipeline through scientific leadership 1 Introduction Contents Introduction 02 The next wave of scientific innovation: An introduction from Mene Pangalos 04 IMED Biotech Unit 2016 in numbers Therapy area progress Therapy area progress 06 Oncology 16 Respiratory, Inflammation and Autoimmunity 26 Cardiovascular and Metabolic Diseases 36 Neuroscience IMED functions functions IMED 44 IMED Asia 54 Case Study: NiCoLA-B 56 Discovery Sciences 62 Case Study: Single Molecule Detection 64 Drug Safety and Metabolism 72 Early Clinical Development 82 Pharmaceutical Sciences 90 Case Study: Nucleotide platforms 92 Personalised Healthcare and Biomarkers 102 Case Study: Harnessing the code of life to develop new treatments science innovation Collaborating for Collaborating for science innovation 106 Case Study: Max Planck Institute and AstraZeneca 108 Enterprise leadership through collaboration 112 Collaborating and sharing data to redefine the future of drug discovery 116 Open Innovation 118 Innovation without boundaries 120 Case Study: Foundation Medicine and AstraZeneca where science thrives An environment An environment where science thrives 122 Inspiring great scientists 126 Our strategic science centres 128 Building our future 132 Our reputation for scientific leadership 136 High impact publications in 2016 140 Preparing for the future with our IMED Futures teams 2 IMED Annual Review 2016 Delivering our pipeline through scientific leadership 01 Introduction Introduction The next wave of scientific innovation An introduction from Mene Pangalos Therapy area progress Mene Pangalos Executive Vice President IMED Biotech Unit and Global Business Development In 2016 we set ourselves As I reflect on the past six years leading The breadth and depth of pipeline AZD1419, our inhaled TLR9 agonist, the I am also immensely proud of our ambitious targets to ensure Innovative Medicines & Early Development progress made by the IMED Biotech first ever study designed to investigate scientific leadership and our ability to (IMED), I am immensely proud of our Unit in 2016 can be highlighted by whether asthma patients can be kept follow the science. At the beginning of 2016 was an important year we remain fully on-track to transformational achievements. Every year examples from across all therapy areas. in remission rather than simply treating the year, we knew it would be tough for AstraZeneca in which deliver our company’s bold since 2010, we have met or exceeded our In Oncology we supported the transition their symptoms. to outperform our number of high pipeline goals across all of our therapy of five molecules into pre-clinical impact and high quality publications we made further significant ambition – to improve the In cardiovascular disease, AZD8601 - the areas - testament to the calibre of our development, of which three – inhibitors from 2015. We didn’t just beat the progress on the delivery of functions IMED world’s first modified RNA for VEGF-A lives of 200 million patients scientists, their dedication and passion of MCL1, Bcl2/xL and CDK9- are all target from last year - we smashed it. from our Moderna partnership - received our science-led strategy. for science and our culture to challenge targeting pro-survival proteins in support In 2016, we delivered 40 high impact and be a $45 billion company positive regulatory approvals to enter Some of the most innovative conventional thinking. of our goal to build an industry-leading and 311 high quality publications, and Phase I clinical development. VEGF-A is a by 2023. It is clear from our ‘tumour cell death’ portfolio. Resistance a total of 552 publications overalll. This research and development Taking a view of our pipeline delivery key protein in new blood vessel formation flourishing pipeline that a new to cell death is one of the hallmarks of is truly phenomenal progress that not against industry benchmarks, we continue and cardiomyocyte proliferation. AZD8601 being undertaken at the cancer. These programmes drive cancer only reflects the quality of the research AstraZeneca is emerging. to make remarkable improvements in is being investigated as a regenerative moment is taking place in our cells to apoptosis and look particularly conducted in our laboratories and with cycle times and success rates. When we treatment option for patients with heart exciting for research in haematological our partners, but also the strength and IMED Biotech Unit, including compare our productivity from 2005-2010 failure, in diabetic wound healing and malignancies, including in combination depth of our science across the IMED transformative new platforms, to that of today, we can see that we have other vascular diseases. with acalabrutinib, our best-in-class Biotech Unit. improved our success rates from first such as oligonucleotides, BTK inhibitor. Finally, AZD3293, our BACE1 inhibitor in time in man and successful completion Whilst it is impossible to capture all of co-development with Lilly for Alzheimer’s nanoparticles and modified of Phase III from three and a half per cent In Respiratory, Inflammation and the achievements from across our teams disease transitioned into Phase III. We RNA and new technologies to over 15 per cent - a clear improvement Autoimmunity we refocused our efforts in the past year, I hope the IMED Annual now have two late stage trials running over the current industry average of on lung epithelium, lung immunity and Review 2016 gives you a feel for the to advance our work in science innovation Collaborating for simultaneously and are poised to be one four per cent. Even more importantly, lung regeneration to allow us to better outstanding calibre of our science and personalised healthcare, of the first to launch a disease-modifying this is translating into the delivery of define novel disease drivers and treatment our scientists and how we strive to push treatment for Alzheimer’s. genomics and genome editing. new medicines, with drugs like olaparib, options for patients with respiratory the boundaries of science to deliver life- This work is being propelled osimertinib and CAZ AVI having graduated diseases. Within lung immunity, we One of my personal highlights of 2016 was changing medicines for patients around to a successful launch. initiated a landmark Phase II trial with the announcement of our new genomics the world. by the entrepreneurial culture initiative and I was particularly delighted that IMED has fostered, Professor David Goldstein joined our collaborations that have team in September. Professor Goldstein will play a key role in ensuring we have been established with world- the right skills and people to launch our leading partners and by the dedicated Centre for Genomics Research, Mene Pangalos outstanding people who work as well as providing strategic guidance Executive Vice President here at AstraZeneca, whose to integrate our genomics initiative into IMED Biotech Unit and Global our research and development pipeline Business Development passion for science is helping where science thrives An environment and into work with our partners. I would us to discover and deliver the also like to call out the outstanding next generation of medicines to achievements our entrepreneurial Scientific Partnering and Alliances transform the lives of patients (SP&A) team made in 2016, creating over around the world.” $150 million in value for AstraZeneca in externalisation revenue. Working closely Pascal Soriot, Executive Director with groups across IMED, the SP&A team and Chief Executive Officer strengthened our global partnerships with leading scientists from academia, biotech and pharma. Pancreatic beta cells at different stages of regeneration 02 IMED Annual Review 2016 Delivering our pipeline through scientific leadership 03 Introduction Introduction IMED Biotech Unit 2016 in numbers >95% Therapy area progress 115 of IMED projects with post docs a personalised ~2,300 healthcare approach people in IMED 23 functions IMED Phase I and II starts (New 69 $13.5M Molecular generated clinical project Entities) from Open 6 combinations Innovation diagnostics in oncology launched science innovation Collaborating for 552 peer reviewed publications ~1,000 31 40 current clinical projects high impact 3 collaborations (New Molecular publications Phase III Entities) investment where science thrives An environment 125 decisions new hires 04 IMED Annual Review 2016 Delivering our pipeline through scientific leadership 05 “2016 has been an impressive year for IMED Oncology with Introduction Therapy area progress significant developments in all areas - from Phase III progression of savolitinib to the multitude of Phase II trials, the nomination of five Oncology candidate drugs and a strong discovery portfolio. We have increased the number of external collaborations supporting the portfolio and have driven expansion of our key areas: DNA damage response, tumour drivers and resistance and small molecule immuno- oncology. Overall, we are in a great position to continue the delivery of new medicines to patients through 2017 and beyond.” Oncology tumour drivers – cell surface Susan Galbraith, VP IMED Oncology and lipid bilayer with receptor Therapy area progress IMED functions IMED science innovation Collaborating for where science thrives An environment 06 IMED Annual Review Review 2016 2016 Delivering our pipeline through scientific leadership 0707 Introduction