Jazz Pharmaceuticals plc Jazz Pharmaceuticals plc Proxy Statement 2018 Annual Report Proxy Statement — 2018 Annual Report Proxy June 14, 2019 DEAR SHAREHOLDERS, Over the last year, Jazz Pharmaceuticals has continued to deliver life-changing medicines to patients across the world. With four globally marketed products, more than 20 active or planned research and development programs across two key therapeutic areas and access to three innovative platform technologies, the company is well positioned for sustainable long-term growth. In the past five years, we generated approximately $3 billion in cash from operations, allowing us to invest significantly in R&D and corporate development transactions to diversify and expand our commercial and development portfolios with differentiated products and product candidates. In our sleep therapeutic area, we remain dedicated to MEET JACKIE expanding available options for patients suffering from chronic and debilitating sleep disorders. In 2018 and early 2019, our Our patient story highlights Jackie. significant accomplishments included: In 2002, Jackie was diagnosed with obstructive • U.S. Food and Drug Administration (FDA) approval of sleep apnea (OSA), a highly prevalent disease in which Xyrem® (sodium oxybate) oral solution for the treatment of excessive daytime sleepiness (EDS) is a major presenting cataplexy or excessive daytime sleepiness (EDS) in children complaint. EDS can negatively impact the lives of people and adolescents with narcolepsy. Narcolepsy is often living with OSA at work, at home or in daily activities. underdiagnosed, especially in children, and we are pleased Xyrem is now available for narcolepsy patients seven years Prior to her diagnosis, Jackie was working full-time as a nurse practitioner while raising four children with her of age and older. husband. During this time in her life, Jackie struggled with EDS and would fall asleep during daily activities and even • Announcement of positive top-line results from our Phase while driving, regardless of how much sleep she obtained. 3 study evaluating the efficacy and safety of JZP-258 for After her diagnosis, Jackie received Continuous Positive the treatment of EDS and cataplexy in adult patients with Airway Pressure (CPAP) therapy to manage her OSA. narcolepsy. JZP-258 is a novel oxybate product candidate Despite CPAP therapy, Jackie’s EDS persisted and she with a 92% reduction in sodium content compared to struggled to stay awake during the day. Jackie’s doctor Xyrem. Given the extensive body of evidence linking advised her of a clinical trial for Sunosi (known then as excessive consumption of sodium to increased risk of stroke, JZP-110) which, at that time, was an investigational medicine cardiovascular disease and other adverse outcomes, we under evaluation for patients with excessive sleepiness associated with OSA or with narcolepsy. Jackie had a believe this reduction in sodium represents a significant positive clinical trial experience with Sunosi which she benefit for patients on chronic therapy. We are focused on credits for allowing her to stay alert throughout the day. submitting a New Drug Application package for JZP-258 to the FDA and look forward to bringing this new therapeutic In March 2019, the U.S. Food and Drug Administration option to narcolepsy patients. (FDA) approved Sunosi™ (solriamfetol) to improve wakefulness in adults living with EDS associated with • Initiation of a Phase 3 study of JZP-258 in idiopathic 1 narcolepsy or OSA. hypersomnia, a sleep disorder characterized by chronic and disabling EDS for which there are no approved therapies. The patient story shared in this communication depicts an individual patient’s response to our medicine and is not representative of all patient responses. • FDA approval of Sunosi™ (solriamfetol) in March 2019. Sunosi is the first dual-acting dopamine and norepinephrine 1 Jazz expects Sunosi will be commercially available in the reuptake inhibitor approved to treat EDS in adults living with U.S. in July 2019. narcolepsy or OSA. • Submission of a marketing authorization application to 2018 FINANCIAL HIGHLIGHTS the European Medicines Agency for solriamfetol as a treatment to improve wakefulness in adult patients with EDS In 2018, we delivered strong top- and bottom-line growth associated with narcolepsy or OSA. with total revenues increasing 17% to $1.9 billion and adjusted earnings per share of $13.708, a 24% increase compared In our hematology/oncology therapeutic area, we are to 2017. In 2018, we invested $197 million in non-GAAP committed to growing and advancing our R&D pipeline, R&D9 and returned $524 million of capital to shareholders including leveraging multiple technologies and approaches to through share repurchases. At the end of 2018, we had $2.4 develop innovative cancer therapies. In 2018 and early 2019, billion in capital available for deployment to support corporate our key advancements included: development activities and further diversification of our commercial and R&D portfolios. • European Union (EU) approval of Vyxeos® 44 mg/100 mg powder for concentrate for solution for infusion for 2019 AND BEYOND the treatment of adults with newly diagnosed, therapy- related acute myeloid leukemia (t-AML) or AML with In 2019, we anticipate strong top-line growth and a substantial myelodysplasia-related changes and initiation of a rolling increase in our investments to support our R&D efforts and launch of the product in key European countries. key growth initiatives, including the launch of Sunosi in the U.S. this year and its potential launch in the EU next year. • Initiation of multiple clinical studies of Vyxeos alone and in Our R&D investments are critical to advancing multiple early-, combination with other therapeutic agents for AML and mid- and late-stage clinical programs that will support future myelodysplastic syndrome. products or expanded indications for existing products. We continue to explore opportunities offering highly differentiated • Advancement of two ongoing studies of Defitelio® products and product candidates with the potential to provide (defibrotide sodium) in the prevention and treatment new therapeutic options to patients and a meaningful return of life-threatening conditions associated with endothelial to shareholders. cell damage. In closing, I thank you for your continued support as we • Initiation of Investigational New Drug (IND)-enabling focus on transforming biopharmaceutical discoveries into activities for one of our solid tumor opportunities, as well as novel medicines. With over 1,400 employees around the pre-IND exploration of several other hematologic targets, globe, we are committed to conducting our business with the all using our CombiPlex® technology. utmost integrity while making a meaningful contribution to the communities where we operate. Most importantly, I would like • Advancement of our recombinant crisantaspase program to thank the many patients who inspire us each day and are aimed at developing a new asparaginase product with a the driving force behind our dedication and mission to deliver potentially improved target product profile and reliable important, new treatment options. supply chain. Sincerely, • Initiation of a collaboration with Codiak BioSciences, Inc. focused on the research, development and commercialization of exosome therapeutics to treat cancer. This novel therapeutic approach complements our development efforts using our CombiPlex platform as well Bruce C. Cozadd as our ongoing collaboration with ImmunoGen, Inc. using Chairman and Chief Executive Officer its antibody drug conjugate technology. GROWING R&D PIPELINE PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 REGULATORY Oxybate Vyxeos + gemtuzumab4 Defitelio JZP-258 Solriamfetol EU Once Nightly Formulation R/R AML or HMA Prevention of aGvHD Cataplexy & EDS in narcolepsy EDS in OSA and Narcolepsy Failure MDS CombiPlex Vyxeos + venetoclax5 Defitelio5 JZP-258 Solid tumors candidate Low Intensity Dosing for Treatment of TA-TMA Idiopathic hypersomnia unfit AML (Phase 1/2) CombiPlex Vyxeos4,5 Defitelio5 Defitelio Hem/Onc exploratory Low Intensity Dosing for Prevention of CAR-T Prevention of VOD activities higher risk MDS associated neurotoxicity Asparaginase IMGN7792 Vyxeos + venetoclax4 Vyxeos7 ALL/other hematological CD33+ AML de novo or R/R AML AML or HR-MDS (AML19) malignancies Recomb. Pegaspargase2 IMGN6322 Vyxeos5,7 Vyxeos7 Hematological malignancies CD123+ Hematological MDS AML or HR-MDS (AML18) malignancies6 Defitelio Vyxeos7 Exploratory activities R/R AML (COG) Exosome NRAS candidate3 Hematological malignancies Sleep Exosome STAT3 candidate3 Hematology/Oncology Hematological malignancies 2 Opt-in opportunity, 3 Jazz & Codiak collaboration, 4 Jazz & MD Anderson Cancer Center collaboration study, 5 Planned , 6 Including AML and BPDCN, Exosome-based candidates3 7 Cooperative group study Solid tumors/Hematological aGvHD = Acute Graft-vs-Host Disease, ALL = Acute Lymphoblastic Leukemia, BPDCN = Blastic Plasmacytoid Dendritic Cell Neoplasm, CAR-T = Chimeric malignancies Antigen Receptor T-cell Therapy, COG = Children’s Oncology Group, HMA = Hypomethylating Agent, HR-MDS = High-Risk MDS, MDS = Myelodysplastic Syndrome, R/R = Relapsed/Refractory, TA-TMA = Transplant Associated Thrombotic Microangiopathy, VOD = Hepatic Veno-occlusive Disease STRONG FINANCIAL EXECUTION TOTAL REVENUES NON-GAAP ADJUSTED NET TOTAL ADJUSTED SGA and RD9 in millions INCOME PER DILUTED SHARE8 in millions audited unaudited unaudited 13.70 RD SGA $1,891 $11.04