1. CONFIDENTIAL Accelerating Drug Development through Drug & Companion Diagnostic Co-Development Mark Roberts PhD Director, Diagnostics Development Covance Central Laboratory Services

2. CONFIDENTIAL 22 Our Environment Today Pressured Cycle of Dependencies The pressures are the same across the marketplace… why are some companies succeeding while others continue to struggle? Patients Pharma SitesCMOs, etc CROs R&D Cost Pressures Funding Needed For Innovation Target Scarcity Consumer Price Pressure Regulations Patent Cliffs Healthcare Models Partnerships Emerging Markets Price Pressures Market Realities +

3. CONFIDENTIAL 3 Drugs Don’t Work for all Patients Antidepressants Cancer Drugs Diabetes Drugs Arthritis Drugs Asthma Drugs Source : Personalized Medicine Coalition Estimated $350 billion wasted in 2011

4. CONFIDENTIAL 44 The Future Is ……… Personalized Medicine Providing  the right treatment  for the right person  at the right time  in the right dose

5. CONFIDENTIAL The New Drug Development Paradigm Personalized Medicine Companion Diagnostics are integral to the new Personalized Medicine paradigm Personalized Medicine Targeted Therapeutic Biomarker An “in vitro” device that provides information that is essential for the safe and effective use of a corresponding therapeutic product” Source : US Food & Drug Administration

6. CONFIDENTIAL 6 Many ‘Companion’ Diagnostics developed after a drug is on market Retrospective validation using banked samples: potential IRB / informed consent issues / new trial Drug manufacturer unlikely to change labeling unless required to do so by FDA : may consider extra testing / expense to be a detriment to clinical use 6 CDx: Historical Perspective

7. CONFIDENTIAL 7 Better understanding of the genetic and polypharmacy causes of adverse reaction Increasing utility of pre-dosing patient stratification through understanding of ‘pathway’ targets Targeted therapy improves clinical outcome –Enhanced safety profile : and reduced liability claims? –Enhanced therapeutic efficacy Enhanced healthcare economics 7 CDx: A New Perspective

8. CONFIDENTIAL 8 FDA :Drug & CDx Co-Development “In most circumstances, if use of an in vitro companion diagnostic device is essential for the safe and effective use of a therapeutic product, the IVD companion diagnostic device and therapeutic product should be approved or cleared contemporaneously by FDA for the use indicated in the therapeutic product labeling,”

9. CONFIDENTIAL Drug / CDx co-development successes Targets ALK mutation in NSCLC Occurs in 4% - 5% of patients Tumor shrinkage in 83% of ALK +ve patients (4-5% of NSCLC) Drug and CDx (Abbott) launched in 2011 Targets V600E mutated BRAF in advanced melanoma Occurs is ca. 60% of mm patients Drug and device approved together in 2011

10. CONFIDENTIAL 10 QUESTION: What role do you see CROs playing in the development of companion diagnostics over the coming years? Voice of the Client Survey : 2011

11. CONFIDENTIAL 11 Clients had not considered CROs role – Dx focused Clients continue to define their needs (lack clarity) Clients voiced the need for : –Capabilities: Fill the gap where clients lack ability or expertise –Flexibility: Resource flexibility under an outsource model –Integration: Providers able to integrate services are valuable –CDx vision & direction: Clients are struggling and need a partner with vision AND capabilities to guide their path forward Summary of VOC Feedback

12. CONFIDENTIAL TodayYesterday 12 Charting a New Model Diagnostic Devices CONFIDENTIAL Drugs & Biologics Diagnostic Devices The future of Healthcare will require a new mindset: Products and industries once considered separate and distinct move to integration Drugs & Biologics Integrated with Diagnostics

13. CONFIDENTIAL 13 Why Rx / CDx Co-Development? Potential to: enhance therapeutic efficacy increase safety & reduce risk Speed-up development process improve trial design increase commercial success improve trial design enhance safety profile enhance therapeutic efficacy accelerate trial outcome Increase commercial success

14. CONFIDENTIAL 14 Hurdles Under the New Model 14 Success Begins with the Right Partners

15. CONFIDENTIAL Global Diagnostics Market $ 44 billion in 2011 > 5% CAGR to $62 billion in 2016 Largest Players –Roche$ 7.4 billion –Siemens $ 5.2 billion –Danaher$ 4.4 billion –Abbott $ 4.3 billion

16. CONFIDENTIAL 16 Companion Diagnostics Market World Companion Diagnostics Market 2010-2021 ($Billions) (incl. the sales of testing kits and testing service revenues). “Companion Diagnostics World Market 2011-2021”, VisionGain (2011) CAGR 21.6%

17. CONFIDENTIAL Nature of Diagnostic Target (biomarker) Required Turn around Time of Result Channel to Market Economics 17 Considerations in Choice of Commercial Partner

18. CONFIDENTIAL Rx / CDx Co-Development Value for Stakeholders 18 Stake HolderBenefit BioPharma Companies Reduced Drug Development Costs Improved safety-efficacy profile of drug Increased cost effectiveness of drug Accelerated regulatory approval Competitive advantage (differentiated therapeutic) Rescued drugs Premium pricing for “targeted” drug Dx Companies New market opportunities Develop new partnership with Pharma companies Premium pricing for CDx Increase distribution of their product

19. CONFIDENTIAL 19 Hurdles Under the New Model 19 Success Begins with the Right Partners

20. CONFIDENTIAL 20 Leveraging Complementary Competencies CRODx Partner Sole focus of supporting Clinical Development Focus on delivering innovative Dx products Experienced collaborator for novel assays, technologies and Dx devices Experienced in assay development & technology Complementing competencies Technical agility Global reach Commitment to quality Experience in Project Management Complementing competencies Deep technical proficiency Limited reach Experience in product development Experience in Regulatory Submission

21. CONFIDENTIAL 21 CDx Rx / CDx Co-Development Strategic Agility Medical Device Partner Technology/Platform Global Reach Intellectual Property Regulatory Path 21 IVDPharma Partnership Unbiased approach enables a straightforward path to commercialization CRO

22. CONFIDENTIAL 22 Technology leadership Global Execution Sample Handling / Storage Expertise Regulatory Experience Strong Commercial Partnerships CRO Partner Expertise Required

23. CONFIDENTIAL (4) Needs a partner for IVD manufacturing and global commercialization (1) Biomarker identification & CDx development (3) Already has an assay development/ commercialization partner (2) Assay development and validation (5) Requires single strategic partner with broad capabilities/expertise Drug Development Biomarker/CDx Development DiscoveryPre-ClinicalPhase IPhase IIPhase III NDA Submission Biomarker Discovery & Development CDx Assay Feasibility CDx Development & Validation Regulatory Submission & CDx Launch Flexibility and access along the continuum is critical Your Partnership Needs CDx Development Stages 23

24. CONFIDENTIAL Examples of CDx Validation and Rx / CDx Co-Development Mark Roberts PhD Director, Diagnostics Development Covance Central Laboratory Services

25. CONFIDENTIAL 25 Collaboration on a CDx Clinical Validation Clinical Candidate Proprietary CDx Commercial Platform USA Europe Asia-Pac China Platform expanded for global clinical studies Collaborative assay evaluation & troubleshooting CDx validation 25 Dx Partner Pharma Client

26. CONFIDENTIAL 26 Global Reach & Data Combinability Global Consistency 1 instrument1 technologist1 point in timeSame reagents globally Fewer Laboratories = Higher Quality Data

27. CONFIDENTIAL 27 Points to consider in Rx / CDx Co-Development CDx manufacturer distinct from Rx client Parties may have different priorities All parties need to be at the table Not all assays are created equal : ● Assay must be very robust in order to be ‘plug and play’ ● Development assays require more attention Rx / CDx : A different business model

28. CONFIDENTIAL 28 CDx Rx / CDx Co-Development Strategic Agility Medical Device Partner Technology/Platform Global Reach Intellectual Property Regulatory Path 28 IVDPharma Partnership Unbiased approach enables a straightforward path to commercialization CRO

29. CONFIDENTIAL 29 CONFIDENTIAL - FOR INTERNAL OR CLIENT USE ONLY “Delivering on the promise of Personalized Medicine requires Precision Co-Development”

30. CONFIDENTIAL Thank You 30