Jazz Pharmaceuticals plc Proxy Statement 2016 Annual Report June 20, 2017 DEAR SHAREHOLDERS, 2016 was a busy and productive year for Jazz Pharmaceuticals. We remained focused on improving patients’ lives by identifying, developing and commercializing clinically meaningful and differentiated products while delivering strong, double-digit top-line growth. We made meaningful investments in R&D and corporate development through the disciplined allocation of resources with a focus on generating shareholder value. We received marketing authorization for and successfully launched Defitelio® (defibrotide sodium) in the U.S., the first and only FDA-approved treatment MEET SAM for adults and children who develop a rare, but often fatal, complication following hematopoietic stem cell Our cover highlights Sam. Sam was transplantation (HSCT) known as hepatic veno-occlusive diagnosed with narcolepsy in 2013. As a disease (VOD). We continued adding potentially teenager, Sam struggled with undiagnosed innovative products and product candidates to our narcolepsy. He was incredibly tired all the portfolio by executing on several corporate development time, and he had difficulty functioning. In transactions, including the acquisition of Celator college, his symptoms got progressively Pharmaceuticals, Inc., through which we acquired worse, he struggled to attend classes and worldwide development and commercialization rights he often needed to sleep all day. Despite to Vyxeos™ (cytarabine and daunorubicin) liposome spending so many hours sleeping, Sam for injection, or CPX-351, an investigational product continued to have trouble staying awake. candidate for the treatment of acute myeloid leukemia. Sam sought help from multiple physicians We also progressed and expanded our R&D pipeline, before finally being diagnosed with with several significant advancements, including: narcolepsy, more than ten years after his • Completed patient enrollment in three Phase 3 studies initial narcolepsy symptoms appeared. Sam’s of our product candidate, JZP-110, a differentiated story is not uncommon. It is estimated that wake-promoting agent for the treatment of excessive more than half of patients with narcolepsy sleepiness (ES) associated with obstructive sleep have not been diagnosed.1 Patients like Sam apnea (OSA) and with narcolepsy have inspired us to focus on increasing the • Initiated a rolling new drug application (NDA) awareness of narcolepsy. Through our More submission for Vyxeos in the U.S. Than Tired campaign, we are committed • Announced the development of two late-stage oxybate to working with the narcolepsy community product candidates, JZP-507 and JZP-258, which to reduce the time to diagnosis for patients have the potential to offer improved treatment options struggling with undiagnosed narcolepsy. for narcolepsy patients Sam is equally passionate about this cause • Initiated a Phase 3 study of defibrotide for the prevention and shares his story through the campaign of VOD in high risk patients following HSCT to help others who may not realize they have • Completed patient enrollment in a Phase 3 study of the condition. Xyrem® (sodium oxybate) oral solution in pediatric narcolepsy patients with cataplexy. 1 Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371–381. 2016 FINANCIAL AND OTHER HIGHLIGHTS This is an unprecedented time on the regulatory front for Jazz, with five planned submissions in 2017 and early • Total revenues of $1.5 billion, an increase of 12% over 2018, including: 2015, driven primarily by an increase in sales of two of • Completion of our rolling NDA submission for Vyxeos our key marketed products, Xyrem and Defitelio. (which we accomplished in March 2017) • GAAP net income of $396.8 million and GAAP • NDA submission for JZP-110 for narcolepsy and OSA net income per diluted share of $6.41, representing by late 2017 increases of 20% and 23%, respectively, over 2015. • Supplemental NDA submission for Xyrem for pediatric • Adjusted net income of $627.2 million and adjusted narcolepsy with cataplexy in the fourth quarter of 2017 net income per diluted share of $10.14, representing • Marketing Authorization Application submission for increases of 5% and 7%, respectively, over 2015. Vyxeos in the second half of 2017 • In 2016, we spent a total of $278.3 million to • NDA submission for JZP-507 for narcolepsy by the repurchase 2.2 million of our ordinary shares under first quarter of 2018 share repurchase programs authorized by our board of directors. In addition to the planned regulatory submission for Vyxeos • We began shipping Xyrem from our manufacturing in the EU, our global expansion efforts include potential and development facility in Athlone, Ireland. regulatory approval for Defitelio in Canada andd a recentlyt announced partnership for the planned developmentl t andd PREPARING FOR FUTURE GROWTH commercialization of Defitelio and VyxeosV in Japan.J THROUGH DISCIPLINED INVESTMENTS Our recent settlement agreementt resolvingl our XyremX Our investments in our R&D portfolio in recent years patent litigation with Hikma, ththe firstfi generic filfiler ffor have laid a strong foundation for our future growth. For Xyrem, allows us to better planl andd executet on our 2017, we are focused on continuing to deliver on our strategic initiatives to drivei futureft growth.th AsA partt of R&D goals of growing and diversifying our development our overall strategy,y identificationidentification and developmentde l pmen of pipeline, preparing for multiplepg regulatory submissions promising new assets,assets, expansionexpansion into newn meaningfuleanin ful and product launches over the coming yearsy and diseases and opportunitiespportunities for comcommercializationmerc lization ooff ouourr expandingpanding our commercialcommercial portfolio with the potentialpotentia products in multiplemultiple geographiesgeographies are key toto our ongoingongoing FDADA approvalapproval and commercialcommercial launchlaunc of VyxeosVyxeos in theth success and long-terml t growth.th U.S.S. thisthis yearyear. Ourur strong cashcash generationgeneration continuescontinues toto provideprovide usus withwith Our R&DR&D goals includeinclude multiplemultiple clinicalclin cal developmentdevelopment thee financial flexibilityflexibility to ssupportupport oourur ccapitalapital deplodeploymentyment milestones,ilestones, some of whichwhich we achievedachiev d in the first halfhalf strategyrategy withwith an emphasisemphasis on reireinvestingnvesting iinn our R&R&D&D off 20172017 withwith the release ofof positiveositive top-linetoop-line results fromfro pipeline.peline. IdentifyingIdentifying and pursuingpursuing opopportunitiesportunnities to furfurtherther ourur threethree Phase 3 studiesstudies of JZP-1JZP-1100 in papatientstients witwithh EES diversifyversify ouourr cocommercialmmercial and RR&D&D pportfolioortfollioo throuthroughggh associatedssociated with OSA andand in patientspatients with ES associassociatedated corporateorporate developmentdevelopment transactionstransactions remainsremainnss a high priority.priority. with narcolepsynarcolepsy and popositivesitive top-lintop-linee results from oourur Phase 2/32/3 study of XyremXyrem in pediatricpediatrric narcolepsynarcolepsy Inn closing, I want to thankthank our employeesemployees acrossaaccross thethee globe,globe, patientspatients withwith cataplexy. We seek to ooptimizeptimize the vavaluelue whose dedicateddedicated workwork aandnd ppassionassion hhaveave lleleded to iimportantmpportant of our existingexisting products andand productproductt candidatescandidates by new therapiestherapies for patients.patients. AndAnd mostmost importantly,impoortantly, I am exploringexploring new indicationsindications such as ourouur Phase 2 studystudy deeply gratefulgrateful to the manymany patientspatients aandnd theirthheeir familfamiliesies who of JZP-110JZP-110 for ES associatedassociated with Parkinson’sParrkinson’s diseasedisease put their trusttrust in our productsproducts andand continuecontinuee toto inspireinspirre us,us, as and ourour Phase 3 study of JZP-258JZP-258 inin narcolepsy,narcolepsy, bobothth we fulfill ourour missionmission of improvingimproving patients’patients’’ lives.lives. of which we initiated earlierearlier this year. In additionaddition to our ongoingongoing Phase 3 study of defibrotiddefibrotidee for the prevenpreventiontion SincerelySincerely, of VOD, we also plan toto initiateinitiate a PhasePhaase 2 studystudy of ddefibro fib tidtide ffor ththe prevent tiion of f acu tte graft ft versus hhost t didisease ffo llllowing i HSCT. Bruce C. Cozadd Chairman aandnd Chief ExeExecutivecutive OffiOfficer R&D PIPELINE Gif[lZk :Xe[`[Xk\ ;`j\Xj\ 8i\X&=fZlj Gi\$:c`e`ZXc G_Xj\ ( G_Xj\ ) G_Xj\ * I\^lcXkfip Mpo\fj :GO$*,( ?`^_$i`jb 8DC AQG$((' <J `e FJ8 Xe[ `e eXiZfc\gjp E;8 jlYd`jj`fe \og\Zk\[ cXk\ )'(. Opi\d :XkXgc\op `e g\[`Xki`Z eXiZfc\gjp jE;8 jlYd`jj`fe \og\Zk\[ +H(. ;\]`Yifk`[\ Gi\m\ek`fe f] MF; AQG$),/ <;J&&ZXkXgc\op `e eXiZfc\gjp =G@ (H(. AQG$((' <J `e GXib`ejfeËj [`j\Xj\ =G@ (H(. ;\]`Yifk`[\ Gi\m\ek`fe f] XZlk\ >m?; AQG$,'. <;J&&ZXkXgc\op `e eXiZfc\gjp E;8jlYd`jj`fegi\gXiXk`fe FopYXk\ FeZ\$e`^_kcp [fj`e^ `e eXiZfc\gjp( 8jgXiX^`eXj\) 8CC Xe[ fk_\i _\dXkfcf^`ZXc [`jfi[\ij ?\dXkfcf^pp&FeZfcf^p 1 Evaluation of deuterated oxybate continues as part of the once-nightly development process; JZP-386 formulation work ongoing. 2 Evaluating early stage product candidates, including recombinant pegaspargase. AML = Acute Myeloid Leukemia, NDA = New Drug Application,