GDSRM Value Story

SAFEGUARDING THROUGH SCIENCE global drug safety & risk management





THE LEGACY OF THALIDOMIDE NEW BEGINNINGS INNOVATION IS ROOTED IN OUR ORIGINS Thalidomide was developed In 1964, a leprosy patient in Jerusalem was LQ WKH ¶V E\\ &KHPLH given thalidomide as a sleep aid and the Grünenthal GmbH and licensed lesions associated with the leprosy reduced. in July 1956 for prescription-free )XUWKHU VWXG\\ ZLWK $,'6 DQG RWKHU FDQFHUV revealed that thalidomide had positive “We are consoled to over-the-counter sale in Germany and most H̆HFWV EXW LW WRRN PDQ\\ \\HDUV EHIRUH WKLV know that Celgene of Europe as a sleep aid and to reduce controversial drug would be brought back to Corporation has instituted morning sickness. This made it very popular market. a comprehensive program with pregnant women. By 1959 reports of to help physicians and birth defects in babies led to further study THE EMERGENCE OF PHARMACOVIGILANCE pharmacists inform patients and thalidomide was withdrawn from the about side effects and risks market in 1961, when these birth defects )URPWKHWKDOLGRPLGHWUDJHG\\WZRPDQGDWHV and ensure that they are were linked to women taking thalidomide were introduced. The regulation that all aware of precautions they GXULQJ SUHJQDQF\\ $SSUR[LPDWHO\\  products undergo developmental toxicology must take before, during, infants were born with thalidomide birth tests in two species, one of which is not a and after therapy.” defects and worldwide drug development rodent. Pharmacovigilance – the science and and drug perception changed forever. activities relating to the ongoing detection, - Thalidomide Survivor 1950's 1964 1959 1968 Thalidomide Reports 1961 Thalidomide is widely used of unusual shown to reduce as a sedative increase in birth Thalidomide lesions in leprosy (Rx and OTC) and defects (phocomelia) withdrawn from the is considered began to be seen patients safe even in in Germany market WHO Program pregnancy for International Drug Monitoring 4 established

assessment, and understanding of adverse believing that there was medical value in thalidomide were important stakeholders HYHQWV $(V RU DGYHUVH GUXJ UHDFWLRQV this compound and its analogues, changed and were vocal about never accepting a world $'5V WR DVVHVV D SURGXFW¶V ULVN SUR¿OH the course of human health and the lives of with thalidomide in it. In 1998, Warren 7KH :+2 3URJUDP IRU ,QWHUQDWLRQDO 'UXJ many patients everywhere. Rudolph, a thalidomide survivor, spoke 0RQLWRULQJ 3,'0 ZDV HVWDEOLVKHG DQG DW WKH ¿QDO )'$ PHHWLQJ DERXW WKLV PRUDO SURYLGHVDIRUXPIRU:+2PHPEHUVWDWHVWR A BOLD PURSUIT quandary of the century. His words are collaborate in the monitoring of drug safety, SURPLQHQWO\\ GLVSOD\\HG LQ WKH 7+$/20,'® DQG QRWDEO\\ WKH LGHQWL¿FDWLRQ DQG DQDO\\VLV 2XU PLWLJDWLRQ VWUDWHJ\\ VWDUWHG ZLWK Patient Guide. of new adverse reaction signals. S.T.E.P.S.® IRU 7+$/20,'® and FRQWLQXHG ZLWK 5HY$VVLVW ZLWK WKH ODXQFK 2005 CELGENE'S EARLY DAYS RI 5(9/,0,'® (lenalidomide). With the ODXQFK RI 320$/<67® (pomalidomide) in The founders of Celgene were a small team  ZH KDUPRQL]HG WR 5(06 IRU DOO WKUHH of highly capable, committed people who products. We are the only company that went in search of solutions to issues where KDQGOHV5(06LQWHUQDOO\\ the standard course of action had proven LQH̆HFWLYH WE LEAD WITH PATIENT SAFETY &HOJHQH WRRN RQ WKH ZRUOG¶V PRVW controversial drug (thalidomide) and Celgene embraced the fact that survivors OLYLQJ ZLWK WKH WHUDWRJHQLF H̆HFWV RI 1992 1986 Celgene 1998 Revlimid® licenses (lenalidomide) is Celgene patent for uses of Thalomid® approved by the FDA VSLQVRɞ thalidomide from approved by FDA from Celanese Rockefeller and FDA works with 5 and becomes an University Celgene to develop the independent ɟUVW5(06WRDYRLG biotechnology company fetal exposure

Since 2005, we have human health, while always putting patients ¿UVW Establishing our global footprint strategically developed and to put patients first continuously evolved our Our Journey safety and risk management capabilities around the world, 2XU H[SDQVLRQ DQG JURZWK KDYH EHHQ guided by a keen focus on current and amidst the continuous growth emerging business needs, as well as integrity, and passion for the patient. We and geographic expansion of the company. have proactively created new roles, new capabilities and new initiatives to account :HQRZ¿QGRXUVHOYHVSURYLGLQJSRVWPDUNHW for the ever-changing external environment which has seen new regulations emerge, an safety support in over 70 markets, enabling explosion in the volume of the Company to develop and deliver data, rapid evolution innovative medicines while staying true to 2006 its promise to change 2009 the course of 2008 2012 Celgene Int'l 2007 Introduction 2013 HQ established, of Global Risk *'650)XQFWLRQDO Management Good Redesign, Company Pharmacovigilance 6DIHW\\&RPPLWWHH Oversight Committee Practices established (GRMOC) Preparedness *OREDO6DIHW\\ )RUPDWLRQRI6DIHW\\ Formation of Network Management Teams DVLQJOHXQLɟHG Aggregate Reporting (VWDEOLVKHG Group 6

of technology, medical innovation, and a level of compliance and quality. for one process, one assessment, and one heightened emphasis on the management position on all safety issues. RI EHQH¿WULVN DVVHVVPHQWV DQG ULVN THE Global Safety Network minimization of our products, all for the Company Safety Committee (CSC) EHQH¿W RI RXU SDWLHQWV 7KH SXUSRVHIXO $VSDUWRIRXUJRYHUQDQFHPRGHOZHVWDUWHG UHGHVLJQ RI WKH *OREDO 'UXJ 6DIHW\\  5LVN with the establishment of the Global Safety $WWKHWRSRIWKLVJRYHUQDQFHPRGHOVWRRGWKH 0DQDJHPHQW IXQFWLRQ WRRN SODFH LQ  1HWZRUN DQG RXU µGRFWULQH RI VLQJXODULW\\¶ Company Safety Committee, an executive This saw us establishing a set of guiding a series of guiding principles that level group of stakeholders responsible for principles and a corresponding governance outlined how we intended to work across making critical decisions and ensuring model to enable us to stay ahead of the organizational and geographic boundaries implementation of actions regarding safety landscape, while maintaining the highest to ensure harmonization of our safety issues; this enables us to make the right SHUVSHFWLYH RQ RXU SURGXFWV 7KH /HDG decisions in the interest of our patients 3URGXFW 6DIHW\\ 3K\\VLFLDQ /363 UROH around the world. was created, allowing us to aim 2014 2018 2015 2016 6WUDWHJLF5HYLHZ /RFDO6DIHW\\ OUTCOMES of Organization 2ɡFHV5HSRUW ACTION Directly into Global ASSESSMENT Model ANALYSIS Introduction DATA ACQUISITION Formal establishment RI3DWLHQW6DIHW\\ of PV Innovation Oversight Board Function 7

“One process, Safety Management Teams 3UHVLGHQW RI :RUOGZLGH 0DUNHWV 7KH one assessment, ,0L' SURGXFWV DUH QRZ DYDLODEOH LQ RYHU one position on The Global Safety Network took shape with 80 markets worldwide with the Risk all safety issues.” the establishment of global, regional and 0DQDJHPHQW 3ODQV VXFFHVVIXOO\\ PLWLJDWLQJ local capabilities, and soon after Safety risk for our patients, based on aligned 8 0DQDJHPHQW 7HDPV ZHUH HVWDEOLVKHG standards. to serve as the company guardian for individual product safety. With dedicated PATIENT Safety Oversight Board /HDG 3URGXFW 6DIHW\\ 3K\\VLFLDQV /363V (PSOB) and Safety Scientists ensuring independent risk-focused analysis, the Safety $V WKH FRPSOH[LW\\ RI RXU EXVLQHVV HYROYHG 0DQDJHPHQW 7HDPV VHUYH WR DXJPHQW and the portfolio of developmental the clinical development process and compounds and approved products stakeholders to enrich the knowledge on the increased, we established the Patient Safety VDIHW\\SUR¿OHRIRXUSURGXFWV 2YHUVLJKW%RDUGLQWRSURYLGHYLVLELOLW\\ to our cross-functional stakeholders on Global Risk Management Oversight key safety activities, issues, metrics and Committee (GRMOC) LQVLJKWV 'LVWLQFW IURP WKH &6& WKLV IRUXP VRXJKW WR HQJDJH )UDQFKLVH /HDGV 6DIHW\\ $V WKH JOREDO UHDFK RI WKH ,0L' SURGXFWV began to expand, we established a Global OUTCOMES DRIVE 5LVN 0DQDJHPHQW 2YHUVLJKW &RPPLWWHH to ensure that local risk management ACTION SODQV IRU WKH ,0L' SURGXFWV ZHUH DOLJQHG to a set of globally determined core ASSESSMENT principles for pregnancy prevention, SULRU WR FRPPHUFLDOL]DWLRQ 7KH *502& ANALYSIS membership comprises key executive VWDNHKROGHUV LQFOXGLQJ WKH &KLHI 0HGLFDO 2̇FHU *OREDO +HDG RI *'650 DQG DATA ACQUISITION

/HDGV5HJXODWRU\\$̆DLUV*HQHUDO&RXQVHO ONE &KDLUPDQ DQG &KLHI ([HFXWLYH 2̇FHU &KLHI 0HGLFDO 2̇FHU &KLHI &RPSOLDQFH unified voice 2̇FHU DQG 5 ' RQ D TXDUWHUO\\ EDVLV The commitment of these stakeholders to 9 proactively engage in this capacity displays &HOJHQH¶V XQLTXH FRPPLWPHQW WR PDNLQJ patient safety a priority. GLOBAL regional LOCAL N BY GOVERNANCE COMPANY SAFETY COMMITTEE GLOBAL RISK MANAGEMENT OVERSIGHT COMMITTEE SAFETY MANAGEMENT TEAMS GLOBAL SAFETY NETWORK

Our Activities Span the Entire PHASE I PHASE II Product Lifecycle STUDIES STUDIES “Celgene is Urgent Safety Measures a pioneering early entrant Developmental Core Safety Information (DCSI) in establishing Developmental Risk Management Plans (D-RMP) pre-approval Investigator Brochures & Informed Consent safety.” Clinical Study Reports OUTCOMES Developmental Safety Update Reports (DSUR) ACTION Product Safety Monitoring ASSESSMENT Clinical Trials Statistical Analysis Plans ANALYSIS Serious Adverse Event (SAE) Reporting 10 DATA ACQUISITION Study Protocol Design Every Market | Every Country Every Physician | Every Patient)URP WKH DFTXLVLWLRQ RI GDWD WKH DQDO\\VLV assessment and subsequent actions taken, Timely Collection of Relevant Safety Informationour outcomes are driven by a series of key Robust Hypothesis Regarding Potential Safety Risksoutputs. This starts with data acquisition from every market and comes together to Synthesis of Relevant Information & Assessment of Overall RiskIRUP D XQL¿HG VDIHW\\ SHUVSHFWLYH ZKLFK Determination & Implementation of Critical Decisions Regarding Safetyinforms key actions at an enterprise wide Safeguarding Patientslevel. OUR OUTPUTS2XU RXWSXWV VDWLVI\\ ERWK FRPSOLDQFH DQG regulatory requirements as well as enable and support stakeholders and processes across the business; this includes clinical GHYHORSPHQW UHJXODWRU\\ ¿OLQJV DQG VFLHQWL¿FFRPPXQLFDWLRQV

PHASE III PRODUCT LICENSE PHASE IIIB/IV MARKETING STUDIES APPLICATION STUDIES Company Core Data Sheet (CCDS) Changes in Product Use Risk Management Plans Labeling Development Epidemiology CCDS Updates Integrated Summary of Safety (ISS) RMP Implementation Labeling Updates Targeted Pharmacovigilance 3HULRGLF%HQHɟW5LVN(YDOXDWLRQ5HSRUWV3%5(5 Integrated Summary of Safety (ISS) Analysis Plan Regulatory Inquiries Disease Epidemiology Studies Post-Market Adverse Event Reporting Post Authorization Safety Studies & Registries COMPLIANCE BASED 2XU SURDFWLYH GDWD JHQHUDWLRQ DQG - Expedited Safety Reports communication activities go above - Pharmacovigilance Agreements and beyond those required for ongoing - Periodic Safety Update Reports post-marketing surveillance. - Development Safety Update Reports This includes disease epidemiology studies VALUE BASED which improve our understanding of - Publications background disease factors before the - Signal Detection Reporting introduction of treatment into the market, - Safety Monitoring Team Analyses IDFLOLWDWLQJ D PRUH UREXVW EHQH¿WULVN - Clinical Study Reports evaluation in the post-marketing setting. - Pregnancy Prevention Programs - DMC Safety Data Analyses These Safety-led studies are represented in - Integrated Summaries of Safety medical congresses and journals, ultimately %HQHɟW5LVN$VVHVVPHQWV supporting our healthcare decision makers. 5LVN0DQDJHPHQW3ODQV - Regulatory Query Responses 11 - Company Safety Committee Recommendations

Our Commitment to “We have a notorious drug, and we have been OUR TALENT IS THE CORNERSTONE OF Patients Unites Us allowed to reintroduce it. We take a rigorous view of OUR SUCCESS 2XUXQL¿HGFRPPLWPHQWFRPHV not only from our Company this responsibility.” YDOXHV EXW LQ *'650 RXU (DFK ORFDO 'UXJ 6DIHW\\ DQG 5LVN 0DQDJHPHQW 5HSUHVHQWDWLYH QXUWXUHV doctrine of singularity. Through this we relationships with key stakeholders at the local level and ensures that each Risk “I joined GDSRM two have a series of guiding principles which 0DQDJHPHQW3ODQ503PHHWVRXUJOREDOO\\ GH¿QH RXU DFWLYLWLHV UHVSRQVLELOLWLHV DQG DOLJQHG VWDQGDUGV ZKLOH ¿WWLQJ ORFDO expectations. This includes considerations months after college collective outputs. This has cultivated a for local execution, the legal framework, graduation, in case sense of belonging to a single corporate supply chain and infrastructure. management. I never function, alignment at the global, regional and local levels, and importantly, a singular We Listen to Our Customers imagined I would voice to lead the patient safety mission. 2XU FROOHDJXHV KDYH WDNHQ RZQHUVKLS RI the risk management process and are become a published exceedingly committed to maintaining quality, being customer-focused, and author, whose subject keeping patients safe. matter expertise $PRQJWKH865(06SURJUDPVDFURVV the industry, we are the only company now includes topics WKDW UHWDLQV RXU 5(06 DFWLYLWLHV LQ house. By listening to our customers and ɀɖƬǝƏɀƏȸɎǣ˾ƬǣƏǼ exercising empathy, we fuel opportunities to lessen the burden on them. This includes intelligence Ownership of Responsibility and change management.” 2XUSURGXFWSUR¿OHVDUHXVHGLQWKHJUDYHVW of illnesses to address unmet need, and as such, we have made a commitment to have a 'UXJ6DIHW\\5HSUHVHQWDWLYHDWHYHU\\&HOJHQH ṘFHDURXQGWKHZRUOG 12

improving their experience through a range preceptorships we continue to educate and STATISTICAL ANALYSIS of initiatives including new technology empower people to develop new skills applications. We successfully maintain and experiences across functions customer satisfaction scores over 90%, and geographies. The power superior to that of the industry benchmark of 70%. Continuous Development and INNOVATION LIFECYCLE MANAGEMENT Empowerment ,Q *'650 ZH KDYH D VWURQJ PUBLIC SPEAKING culture of talent development and PROCESS DESIGN professional growth. Through a dedicated learning and development in this is capability, global training UHÀHFWHG LQ RXU Cumulatively our very low rate of VWDɞKDV programs, career ladders, and global turnover. 2500+ years of drug safety experience SIGNAL DETECTION Our people have 'HYHORSLQJ RXU VWD̆ UHPDLQV D SULRULW\\ LITERATURE REVIEW a wide range as we adapt to the changing environment MEDICAL WRITING of capabilities which demands greater emphasis on data OPERATIONAL INTELLIGENCE science, insight generation, and stakeholder that continue to HQJDJHPHQW %HFDXVH RI WKHVH H̆RUWV ZH evolve and grow ensure our people, the backbone of this as we adapt to organization, are equipped as leaders to our ever changing H̆HFWLYHO\\FRPPXQLFDWHVDIHW\\LQIRUPDWLRQ and outcomes. surroundings LEAD SAFETY PUBLICATION STRATEGY RISK MANAGEMENT PLAN DEVELOPMENT & EXECUTION MONITOR & MANAGE PRODUCTS' BENEFIT/RISK PROFILES DEVELOP SAFETY SECTIONS FOR THE NDA/MAA, INVESTIGATORS 13 BROCHURES, COMPANY CORE DATA SHEETS, DSURS, & PSURS

GDSRM A DECADE IN DATA Provides Lifecycle Safety Expertise on across over >50 ~90 175 Products Indications Clinical Trials 400 27Through offices employees across OUR COMMITMENT >1,000,000Patients have received an IMiD 80across over Markets 0with Children born with congenital anomalies 186through PPPs

OUR PERFORMANCE >50 ~140 >100 Publications SDEAs across Filings supported by >100 partners the Safety Management Teams OUR EXCELLENCE 1 successfully managed Article 20 procedure involving Revlimid® (lenalidomide) 95% of Celgene US REMS Customer Care Center calls are answered in 20 seconds 99% of GDSRM related inspections had no critical findings >1.2 millionEvaluated ICSRs with 99% Regulatory Compliance PPP=Pregnancy Prevention Program; SDEA=Safety Data Exchange Agreement; ICSR=Individual Case Safety Report

2XU FURVVIXQFWLRQDO UDWHGDERYH6DIHW\\SUR¿OHSHUVSHFWLYH safety data acquisition, contribution to We are a Trusted and Valued partnerships include Clinical product development, marketed product Partner Across the Corporation 5HVHDUFK  'HYHORSPHQW support, risk management and compliance. 5HJXODWRU\\ $̆DLUV 7R[LFRORJ\\ Clinical Pharmacology, Project The Lead Product Safety Physician /HDGHUVKLS %LRVWDWLVWLFV 7KH /HDG 3URGXFW 6DIHW\\ 3K\\VLFLDQ  &OLQLFDO7KHUDSHXWLF$UHD3K\\VLFLDQSDUWQHU 0HGLFDO $̆DLUV +HDOWK (FRQRPLFV throughout the development phases with FOHDUO\\GH¿QHGDFFRXQWDELOLWLHV DQG 2XWFRPHV 5HVHDUFK 6FLHQWL¿F $V DQ LQWHJUDO PHPEHU RI WKH SURGXFW DQG &RPPXQLFDWLRQV /HJDO&RPSOLDQFH FOLQLFDO GHYHORSPHQW WHDPV WKH /363V provide strategic safety advice as well as DQG %XVLQHVV 'HYHORSPHQW$OOLDQFH leadership in the analysis, interpretation, and reporting of safety signals in addition to 0DQDJHPHQWDPRQJRWKHUV acting as the primary link to the Company In a survey of internal business partners RQ WKH ZRUN DQG FRQWULEXWLRQ RI *'650 colleagues globally, 95% of nearly 1000 respondents felt the overall value of the *'650 IXQFWLRQ ZDV IDYRUDEOH 7KH following core services and deliverables were *'650SOD\\VDNH\\UROHLQSURYLGLQJVWUDWHJLFVXSSRUW WRUHJXODWRU\\ɟOLQJVZLWKRYHUɟOLQJVVXSSRUWHG As an example of our expertise and value add contribution to regulatory applications, RXU/363SURYLGHGDGLɞHUHQWVWDWLVWLFDODSSURDFKDVDVROXWLRQWRDGGUHVV challenging safety questions posed by the regulatory authorities. This enabled the FURVVIXQFWLRQDOWHDPWRHYDOXDWHDQGDSSURSULDWHO\\FKDUDFWHUL]HWKHEHQHɟWULVN of Revlimid®(lenalidomide) in a new patient population. There were ultimately no VLJQLɟFDQWUHJXODWRU\\TXHVWLRQVUHODWLQJWRVDIHW\\DQDO\\VHVDQGWKH&RPSDQ\\ZDV successful in securing approval for a new indication by both the EMA and FDA. 16

THE LEAD PRODUCT SAFETY PHYSICIAN & CLINICAL THERAPEUTIC AREA PHYSICIAN 6DIHW\\ &RPPLWWHH 7KHUDSHXWLF $UHD PARTNER THROUGHOUT THE DEVELOPMENT PHASES WITH CLEARLY DEFINED Clinicians provide consideration which informs trial safety, however this does not Clinical Physician ACCOUNTABILITIES Safety Physician compromise our principles and standards for safety. STUDY PLANNING 6 A Informed consent R R 6 A &OLQLFDOSURWRFRODQGVDIHW\\HQGSRLQWVGHɟQLWLRQ 6 6 2XU JXLGDQFH WR WKH 'HYHORSPHQW 7HDP LV 6 A 6 the result of an independent and focused Core data sheet creation 6 6 DVVHVVPHQW RI WKH SURGXFW¶V VDIHW\\ SUR¿OH R A Target package insert/label draft A R and target population epidemiology. 6 R R This complements rather than duplicates 6 A Signal detection plan R 6 H[SHUWLVHSURYLGHGE\\WKH7KHUDSHXWLF$UHD 6 A Data standards creation A Clinicians, and safeguards our patients. 6 R 6 R Trial coding review 6 6 $V D NH\\ H[DPSOH *'650 LV DFFRXQWDEOH 6R A Safety statistical analysis plan R R for the development and approval of the 6R A Clinical data management plan R 6 Integrated Safety Summary (ISS) for the A Case report form development A 6 )'$DQG(0$UHJXODWRU\\¿OLQJV 6 A Coding conventions creation and review R 6 R STUDY CONDUCT 6 A Protocol review R 6 6 A Signal detection execution R 6 .(< Accountable STUDY REVIEW A R 6 A Responsible 6 A Investigator brochure A 6 R 6XSSRUWV 6 Informed consent updates R 6 17 6 A FAQ and standard letters R 6 6 6 Core data sheet updates R 6 R A 6 R A Regulatory inquiries A 6 Preparation for regulatory inspection A 6 6 A A 6 6 A IRB updates responses A 6 R Dr. Doctor letter A R6 6 R A R Package Insert/labeling updates A S 6 6 SAE reconciliation R R R R R 6 Clinical line listing analysis and reporting A R 6 R Risk management plan updates R R A R 6 Scheduled safety reviews/periodic review 6 S A Crisis management reporting A S 6R A R 6 Development Safety Update Report A R Business partner contracts 6 R Signal detection and analysis 6 Clinical study report IND annual review A 6 Integrated Summary of Safety (ISS) 120 day update A R Regulatory inquiries and submission 5LVNEHQHɟWDQDO\\VLVIRUPDUNHWLQJDSSOLFDWLRQV Periodic Safety Update Reports Quality safety recall Execution of Risk Management Plan

LEAD PRODUCT SAFETY PHYSICIANS ARE CENTRAL TO THE GDSRM MANDATE “We aspire LPSPs and Safety Scientists link EXECUTIVE COMMITTEE to bring an between product development CLINICAL DEVELOPMENT COMMITTEE independent and teams PRODUCT DEVELOPMENT COMMITTEE objective view to PROJECT DEVELOPMENT COMMITTEE the safety of our (QVXUHPDLQWHQDQFHRISURGXFWVDIHW\\ products.” - Inject strategic safety advice COMPANY SAFETY COMMITTEE 9(QVXUHDGHTXDWHVDIHW\\GDWDUHYLHZ SAFETY MANAGEMENT TEAM 18 - Recommend potential responses to emerging issues COMPANY SAFETY COMMITTEE STRUCTURED BENEFIT/RISK AT CELGENE $V WKH HPSKDVLV RQ SDWLHQW VDIHW\\ DQG $W &HOJHQH ZH WDNH D VWUXFWXUHG proactive safety management continue DSSURDFK WR EHQH¿WULVN DVVHVVPHQW WR PRXQW 0HGLFDO *RYHUQDQFH LV FULWLFDO throughout the product development and WR HQVXULQJ H̆HFWLYH RXWFRPHV IURP WKH commercialization lifecycle. This involves pharmacovigilance system. The Company clear accountabilities across the clinical and Safety Committee provides a disciplined safety physicians which complement each structure for the company to control and other and safeguard the company from a proactively manage medical issues to ensure safety and risk management perspective. that both the patient and the brand are To that end, we can ensure a targeted, protected. independent and transparent assessment. Examples of key outputs include support of Since 2006, over 50 CSC meetings have WKH SLSHOLQH FRPPLWWHH GHFLVLRQV EHQH¿W deliberated on important safety related ULVN ZLWKLQ 1'$0$$ DSSOLFDWLRQV DQG actions. Examples of recommendations aiding in annual program reviews. LQFOXGH &RPSDQ\\ &RUH 'DWD 6KHHW XSGDWHV SURWRFRO DPHQGPHQWV 5LVN 0DQDJHPHQW Plan updates, etc.

Clinical Physicians BENEFIT Safety Physicians are accountable for B/R are accountable for DVVHVVPHQWRIEHQHɟW assessment of risk RISK GDSRM has experience with responding to the most complex regulatory authority procedures ,QZHIDFHGDQ$UWLFOHSURFHGXUHTXHVWLRQLQJWKHRYHUDOOEHQHɟWULVN SURɟOHRIRQHRIRXUɠDJVKLSSURGXFWV$Q$UWLFOHSURFHGXUHLQ(XURSHUHVXOWV from a regulatory evaluation of pharmacovigilance data, and could potentially lead to suspension or revocation of marketing authorization. 7KURXJKWKHKLJKO\\FURVVIXQFWLRQDODQGYLVLEOHHɞRUWVOHGE\\WKH*'650 organization, we successfully completed this procedure in which EU regulatory DXWKRULWLHVFRQFOXGHGWKDWWKHEHQHɟWRIWKLVSURGXFWFRQWLQXHVWRRXWZHLJKWKH risk, a critical outcome for our Company and for the patients we serve. 19

Our Safety Commitment Our Operations are Best in Class Celgene is committed to While the industry is facing the challenge of changing the course of human unsustainable individual case safety report (ICSR) volumes, Celgene has experienced health through bold pursuits a steeper increase year-over-year. Since  &HOJHQH¶V DYHUDJH \\HDURYHU\\HDU in science, life-enhancing ICSR growth has been about 16%. In 2017, &HOJHQH¶V,&65YROXPHVURVHFRPSDUHG therapies and a promise to to just 6% for other industry members1. In &HOJHQH*'650LVH[SHFWHGWRKDQGOH DOZD\\VSXWSDWLHQWV¿UVW well over 200,000 ICSRs; and while most companies have increased their external :H¶UH D FRPSDQ\\ EXLOW RQ WDNLQJ FKDQFHV H̆RUW IRU ,&65 SURFHVVLQJ WR  &HOJHQH – beginning with bringing thalidomide to has been able to operate leveraging only market to treat patients with serious rare 10%1. diseases who had limited treatment options. We have products that require rigorous To execute its bold vision to meet unmet oversight, and we believe it is imperative to QHHGV &HOJHQH 'UXJ 6DIHW\\ DQG 5LVN maintain all high-value Pharmacovigilance 0DQDJHPHQW KDG WR GHPRQVWUDWH RXU DQG5LVN0DQDJHPHQWIXQFWLRQVLQKRXVH unwavering expertise in ensuring patient wellbeing. Through our unique ability to 2XULQWHUQDOSURGXFWLYLW\\LVDOVRDPRQJWKH proactively address the balance between highest in the industry, with a below average WKHEHQH¿WDQGULVNRIRXUSURGXFWVZHKDYH cost per case relative to other members established a premier drug safety and risk within PVnet1. management function. Our Focus on Excellence 2XUSDVVLRQIRUWKHSDWLHQWDQGXQZDYHULQJ A Mindset of Inspection-Readiness dedication to excellence is evident in our track record of regulatory compliance and Since 2006, Celgene has undergone 49 case quality which is unprecedented when LQVSHFWLRQVE\\GL̆HUHQWKHDOWKDXWKRULWLHV benchmarked against our industry peers. DURXQGWKHZRUOG$JDLQVWDEDFNJURXQGRI We pride ourselves on sustaining this, high compliance scrutiny, only 1 inspection despite rapidly increasing case volumes. observation has been critical. Notably, we 20 1Navitas Life Sciences. 2018 Member Exchange Meeting. 5 September 2018.

KDYHKDGLQVSHFWLRQVZLWK]HUR¿QGLQJV We have made it our mission to embed in the number of reports generated. With increasing volume and advancements 2XUSKLORVRSK\\DQGDSSURDFKWRPDQDJLQJ inspection-readiness and continuous LQ WHFKQRORJ\\ RXU $JJUHJDWH 5HSRUWLQJ DQG $QDO\\WLFV WHDPV KDYH FUHDWHG D these types of challenges is proactive and LPSURYHPHQW LQWR RXU FXOWXUH 2XU self-service model for data generation ZKLFK VLJQL¿FDQWO\\ UHGXFHV WKH H̆RUW DQG collaborative, where global colleagues colleagues proactively and regularly seek time required to submit these reports to regulatory authorities. implement a highly cross-functional opportunities to improve our approach, US REMS Portal Enhancements task force to provide support for elevate our outputs, and grow as an Tremendous oversight is required for our products and Celgene has designed and built local issues. The outcome organization, even if the current WKHPRVWUREXVWDQGFRPSOH[5(06IXQFWLRQ LQWKHLQGXVWU\\2IWKH5(06SURJUDPV is not only correction, but Celgene has maintained system is satisfactory. LQWKH8QLWHG6WDWHVZHDUHWKHRQO\\FRPSDQ\\ an opportunity to exceed 99% ICSR submission to require patient surveys monthly. The expectations and compliance to regulatory Continuous Improvement number of transactions occurring on the ensure transparency. authorities over the last Lessens the Burden for 5(06 SRUWDOV KDYH GRXEOHG VLQFH  ,Q our Stakeholders the spirit of continuous improvement and 10 years innovation, we have turned to technology and digitization to support the growing Self-Service transactions. In 2017, the average cost of ICSR Data Generation 6LQFHWKHLPSOHPHQWDWLRQRIWKHFXUUHQW86 processing was $78 per case, and for Aggregate 5(06V\\VWHPLQRXUDLPKDVEHHQWR Celgene's cost was $71 per case1 Reporting lessen the burden faced by our prescribers, SKDUPDFLVWV DQG SDWLHQWV 5HY$VVLVW RQOLQH Given our expanding ZDVRXU¿UVWVWHSLQWRZHEEDVHGVROXWLRQV ZH H[SDQGHG WR &HOJHQH5LVN0DQDJHPHQW Pharmacy Compliance has increased 47% product portfolio, FRP WKH &HOJHQH 5(06 3KDUPDF\\ 3RUWDO since REMS initiated an audit program &HOJHQH¶V $JJUHJDWH DQG LQ  LPSOHPHQWHG WKH ¿UVW &HOJHQH Reporting team is expected 0RELOH$SSIRUL3DGV including individualized pharmacy feedback to complete about 70 reports As a respected and credible leader in REMS, this year, comprised of both we have a history of engaging with the FDA '685V DQG 3685V ,Q MXVW ¿YH \\HDUV this team has seen a three-fold increase to shape REMS practices and standards Celgene Signal Detection has elected to continually mine signals for over a decade. Despite the amount of work required, our safety scientists maintain strict oversight of these products. As a result of their PRQLWRULQJRIDOOVLJQDOVPLQHGKDYHDɞHFWHGRXUSURGXFWODEHOV 21

Celgene has built and We are Pioneering Innovation in maintained a strong foundation The COMPANION APP VXSSRUWV WKH  RIRSHUDWLRQDOH[FHOOHQFHLQ'UXJ patients per month who are transferred from their pharmacy to our Customer Care Center Patient Safety 6DIHW\\ DQG 5LVN 0DQDJHPHQW to complete their patient survey necessary for Building on Celgene's legacy of product dispenses. By alerting patients when they need to complete their survey, we avoid innovation, we are committed delays in dispensing and reduce the pharmacy’s HɞRUWLQFRQWDFWLQJSDWLHQWVHDFKPRQWK to exploring and implementing technology The COMMERCIAL EXPOSURE APP was developed innovation and digitization to transform E\\ *'650 DQG ZDV WKH ɟUVW YDOLGDWHG ELJ GDWD application for Celgene. The app integrates the practice of pharmacovigilance and risk disparate sources of data, including real-world claims databases, supply chain data, commercial management across the industry. GDWD DQG 86 5(06 GDWD DQG HQDEOHV UREXVW calculation of estimated patient exposure, across This is our imperative given the the Celgene product portfolio. unsustainable volume of incoming Individual Case Safety Reports (ICSRs) and SMARTR is an end-to-end solution that covers 5(06 SDWLHQW WUDQVDFWLRQV WKH HPHUJLQJ signal detection, signal management, signal advances in healthcare and medical validation, risk monitoring, risk management innovation, and our commitment to our and reporting. This solution is a validated patients. system that is end-user driven and supports the WUDFHDELOLW\\RIRXUVFLHQWLɟFHYDOXDWLRQV Learn more about our research We are pioneering the application of and experience through our open $UWL¿FLDO ,QWHOOLJHQFH $, DQG 1DWXUDO The ANNOTATED TRAINING CORPUS was /DQJXDJH 3URFHVVLQJ 1/3 LQ WKH GHYHORSHG E\\ *'650 DQG FRQVLVWV RI  access publications SKDUPDFRYLJLODQFH VSDFH 2XU WKRXJKW LQGLYLGXDOFDVHVDIHW\\UHSRUWV,&65VDQGLVXVHG leadership has been recognized among to support the training of cognitive models. We 22 industry peers and regulators as we are KDYH GHYHORSHG DQG YDOLGDWHG RYHU  XQLTXH often sought out to share our learnings machine-learning algorithms for data extraction DQG EHVW SUDFWLFHV LQ YDULRXV IRUXPV 2XU DQG FODVVLɟFDWLRQ 7KLV LV LQWHQGHG WR PLQLPL]H research comprised nearly half of all those the burden on our safety professionals. RQ $, DW WKH  ,QWHUQDWLRQDO 6RFLHW\\ RI 3KDUPDFRYLJLODQFH ,623 PHHWLQJ DQG RXUSXEOLFDWLRQLQ3KDUPDFHXWLFDO0HGLFLQH was among the top 5 articles downloaded in 2018.

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Our Future is Bright Celgene is a world leader in &HOJHQH¶V FRPPLWPHQW WR SDWLHQW VDIHW\\ KLJKO\\ H̆HFWLYH GUXJ VDIHW \\ DQG is embedded within the fabric of this risk management – it is central organization. We seek to continue to lead WR WKH FRPSDQ\\¶V SKLORVRSK\\ ZLWKSDWLHQWVDIHW\\WRDFFHOHUDWHRXUH̆RUWV DQG EXVLQHVV PRGHO &HOJHQH¶V to develop and deliver innovative medicines commitment to patient safety to help patients prevail over serious diseases. has led us to develop unique industry-leading Pregnancy Prevention Programs (PPP), which have enabled hundreds of thousands of patients worldwide to access the clinical EHQH¿WVRIRXUWKHUDSLHV 2XUIXWXUHLVEULJKWEXWLW VDOVRLQFUHDVLQJO\\ complex. Regulations are constantly evolving, the data and technology landscape LV H[SORGLQJ DQG ZH H[SHFW VLJQL¿FDQW advances in medical innovation including personalized medicine. Traditional approaches to pharmacovigilance are not sustainable and are ripe for transformation. We have already progressed on our journey to transform the practice of pharmacovigilance to address the safety and risk management needs for novel therapies. 24

The future of pharmacovigilance is Infinite





3.1.2019