Building the future Annual report and accounts 2018 Oxford Biomedica in brief The arrival of gene and cell therapy is clear. 1 Oxford Biomedica is a pioneer of gene and cell therapy with a leading Landmark regulatory approvals of these position in lentiviral vector research, development and bioprocessing. Gene and cell therapy is the treatment of disease by the delivery of life-changing treatments are now happening, therapeutic DNA into a patient’s cells. This can be achieved either in vivo and include the very first commercial use of (referred to as gene therapy) or ex vivo (referred to as cell therapy), Oxford Biomedica’s LentiVector® technology. the latter being where the patient’s cells are genetically modified outside the body before being re-infused. Our science is now a therapeutic reality for Oxford Biomedica is focused on developing life changing treatments patients suffering from some of the most serious for serious diseases. Oxford Biomedica and its subsidiaries (the “Group“) diseases. What we are witnessing is just the Introducing Oxford Biomedica have built a sector leading lentiviral vector delivery platform, LentiVector, which the Group leverages to develop in vivo and ex vivo products beginning... both in-house and with partners. The Group has created a valuable ——— proprietary portfolio of gene and cell therapy product candidates in the areas of oncology, ophthalmology and CNS disorders. The Group has also entered into a number of partnerships, including with Novartis, Sanofi, Axovant Gene Therapies, Orchard Therapeutics, Boehringer Ingelheim, the UK Cystic Fibrosis Gene Therapy Consortium and Imperial Innovations, through which it has long-term economic interests in other potential gene and cell therapy products. Oxford Biomedica is based across several locations in Oxfordshire, UK and employs more than 430 people. 1 Introducing Oxford Biomedica 11 Sector and technology overview 12 Gene and cell therapy sector 13 LentiVector delivery platform 16 Products 19 Strategic report 20 Our business model 22 Operational highlights 23 Financial highlights 24 Chairman’s statement 26 Chief Executive Officer's review 30 Management team 32 2018 performance review 36 Delivery of our 2018 objectives 37 Objectives for 2019 38 Financial review 44 Corporate responsibility 51 Corporate governance 52 Principal risks, uncertainties and risk management 59 The Board of Directors 62 Corporate governance report 69 Directors’ remuneration report 90 Directors’ report We are delivering 96 Independent auditors’ report 103 Group financial statements 104 Consolidated statement of comprehensive income 105 Balance sheets 106 Statements of cash flows 107 Statements of changes in equity attributable to owners of the parent 108 Notes to the consolidated financial statements 145 Other matters 145 Glossary 148 Advisers and contact details Oxford Biomedica plc | Annual report and accounts 2018 3 2 Personalised gene-based medicine is entering the mainstream. It is an area of healthcare bursting with new ideas around many unmet needs. We have always seen its potential and are playing a crucial role in making new curative treatments. Introducing Oxford Biomedica ——— Oxford Biomedica is one of the original pioneers of gene and cell therapy. We continue to lead the way, setting new standards and benchmarks for everyone’s benefit. Innovating Oxford Biomedica plc | Annual report and accounts 2018 Oxford Biomedica plc | Annual report and accounts 2018 5 4 Innovating Turning ideas into therapeutic reality Introducing Oxford Biomedica Our LentiVector technology is Lentiviral AAV Introducing the next gene and cell becoming increasingly attractive Vectors Vectors therapy industry standards Efficientin vivo gene The most commonly used vectors delivery • • • • • • As we continue to trail blaze this Safe and well tolerated • • • • • • for gene and cell therapy are based burgeoning sector, we are constantly on lentiviruses and adeno-associated Large therapeutic payload • • • innovating and finding ways to make No pre-existing immunity • • • viruses (AAV). Lentiviral vectors offer Permanent modification gene and cell therapy work better, be clear advantages over AAV such as of dividing cells • • • safer and more cost effective. better payload capacity and permanent IP protection • • • We have developed the TRiP System™ to modification of dividing cells such as Ease of manufacture • • • • maximise vector yields and particle purity T cells and stem cells, and there is no Lentiviral Vectors vs AAV Vector and standardise downstream processes. pre existing immunity unlike with AAV. This new development substantially limits With several several years of clinical potential detrimental effects on vector data now available, our LentiVector function and purification. It can be used to platform has more compelling results benefit all delivery systems including AAV. than any other. Read more about our LentiVector platform on page 13. Read more about the TRiP System and other LentiVector platform $8bn developments on page 33. Haemophilia A and B market Projected to increase to $8 billion by 2026. Sanofi, We are the only people in the world with whom we have two partnered pipeline products, is expected to become the second biggest player Developing our own new products who can do this right now with global sales of $1.4 billion by 20251. in key areas of unmet need Hospitals are offering CAR-T therapy Kymriah 1. Source: GlobalData, July 2017 The NHS agreed a commercial deal with Novartis The delivery of gene and cell therapies to offer ground-breaking CAR-T therapy Kymriah, We have already experienced success with which uses our LentiVector technology, to children into patients is a complex and highly our partners’ products, but we also have with advanced leukaemia. It took the NHS less than specialised process, and one that has 10 days after Kymriah won marketing authorisation, our own products under development. making it one of the fastest funding approvals in its taken us many years to perfect. 63% 70-year history. Global CAR-T cell therapy market As we uncover greater potential from Forecast to grow at a CAGR of over 63% from 2018 our LentiVector platform we are pushing Oxford Biomedica is the only group in to 20222. The majority of therapies in the global the world with a GMP-approved facility CAR-T cell therapy market are still in the early stages forward with our efforts to discover new of clinical trials, many of which could potentially for commercial scale lentiviral vector use our LentiVector technology. treatments for diseases with serious manufacturing. When we say we have 2. Source: Technavio, October 2018 unmet need, such as rare retinal and know-how and experience we really motor neurone diseases, to add to our mean it. development pipeline. Read more about the opportunities within the sector on page 12. See our product development pipeline on page 16. Oxford Biomedica plc | Annual report and accounts 2018 Oxford Biomedica plc | Annual report and accounts 2018 7 6 The gene and cell therapy industry is growing rapidly and we are expanding to meet the demand. To exploit our leading position we are investing in our future so that we continue to be a partner of choice for lentiviral vector manufacture. Introducing Oxford Biomedica ——— We have seen rapidly growing revenues from process development, bioprocessing and royalty generating partnerships over the past few years. Our economic interest in a diverse range of products is also growing and we continue to invest in technology and proprietary gene and cell therapy concepts. Expanding Oxford Biomedica plc | Annual report and accounts 2018 Oxford Biomedica plc | Annual report and accounts 2018 9 8 Expanding Gene and cell therapy is growing fast Introducing Oxford Biomedica A highly valuable market Doubling our capacity 12,000 The gene and cell therapy sector is 40% Oxford Biomedica is already working with 11,000 developing into a multi-billion $ market. Increase in workforce some of the biggest names in pharma, 10,000 We are planning to create over 160 new highly 9,000 skilled positions at our facilities in Oxford in 2019 We estimate that the lentiviral vector helping them to progress and deliver gene 8,000 to meet the expected growth in demand for gene manufacturing market alone will grow and cell therapies. and cell therapies. We are experiencing 7,000 to be worth $800 million by 2026. 1 huge demand for our LentiVector 6,000 technology, process development and 5,000 Upsurge in gene and cell therapies manufacturing services. This important 4,000 £20m 3,000 The potential gene and cell therapy holds Investment in new facility revenue stream is running at full, or close 2,000 for curative treatments for a broad range Our new full-service site was funded through our to full capacity. 1,000 successful Placing in March 2018. This investment 0 of diseases with inadequate options will allow us to exploit the immediate market opportunity and meet expected long-term demand. We already have two independent 2013 2014 2015 2016 2017 2018 2019 2020 makes it an incredibly exciting, and urgent GMP approved manufacturing area of healthcare. Bioprocessing capacity through to 2020 facilities, together with state-of-the-art We are planning to more than double our current capacity for bioprocessing and GMP manufacturing The US Food and Drug Administration laboratories with process development over the next 18 months. (FDA) currently has around 800 and analytical cababilities. Our new active gene and cell therapy-based manufacturing facility, due to begin investigational new drugs on file and has operations in 2020, will more than double 25–30% forecast another 200 applications each our capacity enabling us to meet existing 25–30% year from 2020. It is a booming sector contracts and take on new ones. In bursting with potential. addition, we have taken a lease on another $200m $800m 2017 2026 1. Company estimates building which will become our discovery Manufacturing facility and innovation facility. Read more in the sector and technology overview on page 12.