Capabilities and Services for Clinical Research December 2008

1. Capabilities and Services for Clinical Research December 2008

2. Presentation Outline • Company History and Overview • Capabilities and Services • Systems and Tools • Processes and Procedures • Experience and Expertise

3. Company History and Overview • Previously, a well-established and high performing unit of Pharmacia Corporation, with 12 years experience in providing statistical and data management services. • Became an independent Contract Research Organization (CRO) in January 2004 after the Pfizer acquisition of Pharmacia. • Have been successful for 5 years operating as an independent CRO. Built partnership or preferred vendor relationship with a number of major pharmaceutical companies and other smaller pharmaceutical and biotech companies. • Have a resource level of 55 full-time employees (FTEs) and approximately 15 part-time consultants including freelance medical writers. • Offices located in Toronto, Ontario, Canada and in Little Falls, New Jersey, USA. • Promotes High Quality Standards, Customer Focused, Can-Do Spirit, Advanced Technologies, Continuous Improvement, and high level Ethical and Professional Standards.

4. Legacy Pharmacia Statistical Operations Unit • High Quality Standards • Customer Focused • Can-Do-Spirit • Advanced Technology • Continuous Improvement • Ethical and Professional We Continue The 12-Year Legacy Built Under Pharmacia We Strive To Become A Center of Excellence For What We Do

5. Capabilities and Services • Biostatistics and Statistical Programming • Clinical Data Management, Medical Coding • Trial Subject Randomization using IWRS (Interactive Web-based Response System) • Trial Drug Dispensing and Inventory Management using IWRS • Development and Maintenance of Web Portals and Study Websites • Medical Writing for Clinical Study Reports, Abstracts, Manuscripts, Posters, etc. • Regulatory Submission Support Using eCTD • Administration of Clinical Trial Data and Safety Monitoring Boards • Trial Management and Site Monitoring Using Partnering Clinical Management Firms

6. Functions and Structure Finance/Accounting and Legal Services President/CEO Scientific and Operational Advisory HR, Training, Corporate Affairs Strategic Planning & Business Development, Contract Negotiation Clinical Data Management Biostatistical Sciences Medical Coding, Safety Monitoring, Medical Writing Network & Security, System Administration, Web Technologies Statistical Programming & Database Administration Regulatory Submission Support (eCTD) Project Management & Quality Delivery Quality Assurance and Compliance

7. Biostatistics and Programming Services • Trial design, sample size calculation, subject randomization, data analysis and reporting (covers phase I – IV trials) • Exploratory data analysis for completed trials – for publications, signal detection, and new trial development • Statistical consultation to clinical research and market support professionals • Using Study Websites within secure web portals to disseminate study results to authorized personnel • Well-designed workflow processes and procedures (SOPs in all areas of statistical operations), including templates for Statistical Analysis Plan, Statistical Analysis and Programming QC/QA Plan, Statistical Report, etc. • Following ICH, GCP, and FDA guidelines for trial design, data analysis and reporting • Using CDICS standards in preparation for statistical analyses and drug submissions to regulatory agencies • Major contributor to the writing of Clinical Study Reports, abstracts, manuscripts, and development of presentations and posters

8. Clinical Data Management Services • CRF design using FrameMaker • Data capture and management using both Electronic Data Capture Systems and Paper-based System (refer to next slide) • Database integrity checks and trial monitoring reports within data management systems, and outside data management systems using SAS • Using Study Websites within secure web portals to disseminate database information, subject progress and trial monitoring reports • Medical terminology coding using MedDRA, medication coding using WHODRUG • Well-designed workflow processes and procedures (SOPs in all areas of data management operations), including templates for Data Management Plan, Database Quality Acceptance Sampling Report, Database Lock Checklist, etc. • Following ICH, GCP, and Good Clinical Data Management Practices • All data management systems are 21 CFR Part 11 compliant • All systems were validated according to Everest’s System Validation Policies and SOPs wherever applicable

9. Main Data Management Systems Currently we use 4 Web-based Electronic Data Capture applications: • InForm (Phase Forward) • iDataFax • Express (PDS) • Clinical Analytics (TrialStat) • (We will use the EDC system requested by the sponsor, however our standard EDC systems are InForm and iDataFax) • We also perform data management for paper flow studies using the paper/fax/imaging based system DataFax. • (This system can handle both EDC and paper CRFs within the same database. A trial can be completely paper based, or can use both paper/fax CRFs and EDC eCRFs. In this case some sites using web-based EDC data entry and other sites sending in paper CRFs to the data center for centralized data processing).

10. Quality and Timely Data Collection, Cleaning, and Database Lock Using EDC Applications • Data review, querying, and reconciliation are performed promptly as data is entered by the study sites. Outstanding queries are kept to a minimum • Data review, querying, and reconciliation processes for individual studies are outlined in the Data Management Plans (DMP). Cleaning and review of the data is on-going throughout the study lifecycle up to database lock • Database acceptance checks are performed by the internal statistical team during the initial data extraction test run, and the dry runs for interim and final analyses. This process ensures database issues are detected and resolved early • The database can be locked within 5 working days of the last patient’s last visit and receipt of last subject’s data records, including electronic data transfers (central lab data, eDiaries, ECGs, other specialty labs, etc.) • The database lock checklist is followed to ensure all steps including coding, medical review, SAE reconciliation, 3rd party data transfer and cleaning, statistical dry runs, etc. are all completed prior to locking the database

11. Quality and Timely Data Collection, Cleaning, and Database Lock Using Paper/Fax-based System • Electronic CRF images for the completed CRFs are accessible by authorized trial personnel via a secure Web Portal/Study Website • Data review, querying, and reconciliation are performed promptly as CRF pages are received. Outstanding queries are kept to a minimum • Data review, querying, and reconciliation processes for individual studies are outlined in the Data Management Plans (DMP). Cleaning and review of the data is on-going throughout the study lifecycle up to database lock • Database acceptance checks are performed by the internal statistical team during the initial data extraction test run, and the dry runs for interim and final analyses. This process ensures database issues are detected and resolved early • The database can be locked within 5-10 working days of the last patient’s last visit and receipt of last subject’s CRFs, including electronic data transfers (central lab data, eDiaries, ECGs, other specialty labs, etc.) • The database lock checklist is followed to ensure all steps including coding, medical review, SAE reconciliation, 3rd party data transfer and cleaning, statistical dry runs, etc. are all completed prior to locking the database

12. Trial Subject Randomization using IWRS • Statistical consultation on trial design, sample size estimation and justification, and subject randomization requirements and procedures • Development of IWRS specifications, facilitating sponsor review and confirmation, and obtaining authorization of the specifications • Design and development of IWRS database and web interface, implement functionalities as specified in the IWRS specifications • Design and development of IWRS application test plan with test scripts. Execution of the test plan and reporting test findings • Facilitating sponsor user acceptance testing and incorporating sponsor comments • Deployment of IWRS application and conducting user training using a parallel and independent training IWRS website, which has the same functionalities as implemented in the production IWRS for the trial • Performing IWRS application monitoring and user support • Ongoing data transfer to sponsor special randomization unit via a secure file transfer protocol

13. Study Drug Dispensing and Management using IWRS • Consultation and discussion with sponsor trial team and drug supply personnel on drug supply and management requirements (e.g. subject visit and dosing requirements, drug supply flow, central and local depots, shipment methods, amounts on initial release and re-supply, handling of damaged drugs, low inventory alerts, drug supply and inventory monitoring reports, etc.) • Development of IWRS specifications, facilitating sponsor review and confirmation, and obtaining authorization of the specifications • Design and development of IWRS database and web interface for the drug supply and management components, in conjunction with the subject randomization components • Following the same processes and procedures as for the subject randomization components for application testing, user acceptance testing, user training, application monitoring and support • Ongoing data transfer to sponsor special randomization unit via a secure file transfer protocol

14. Advantages of IWRS Over IVRS • IWRS is more cost-effective than IVRS (eliminates the need for voice recording, editing, and programming) • Set up time for IWRS is much shorter than that for IVRS. The same is applicable to changes or modifications to the system • Visual display instructions (IWRS) has been proven to be easier to follow than audio instructions (IVRS) in an international clinical trial setting • IWRS uses simple instructions on data entry screens, which minimizes the need for multiple languages for IWRS applications in international clinical trials • Fewer key entry errors may occur using IWRS than using IVRS (computer keyboard vs. phone keypad) • IWRS login can be integrated within EDC systems or Study Web Portals/Websites

18. Development and Maintenance of Trial Web Portal/Study Websites • Each trial sponsor may have a secure trial web portal where Study Websites may be built • Authorized trial personnel will have access to the Study Website for trial related information (sponsor will decide what will be made available in the Study Website: trial documents, trial team and site contact information, trial benchmarking or monitoring reports, etc.) • Perform access control, monitoring, and user support

21. Medical Writing of Clinical Study Reports and Publications • Write Clinical Study Reports (CSR), abstracts, manuscripts, and develop presentations/posters • For each trial, a medical writer with previous experience in the study disease area will be identified and teamed with a biostatistician, a QC peer reviewer, a graphic designer if necessary, and document publishing support personnel • Sponsor provides CSR template, or Everest CSR template will be used (which was developed based on ICH E3 CSR guidelines) • A CSR Shell will be developed and reviewed by internal peer reviewer. Sponsor comments will be obtained and incorporated before a full CSR will be drafted • Facilitate review cycles of the draft CSR. Finalize CSR when all comments have been properly addressed • CSR publishing procedures and final QC/QA review will be performed before CSR signing off

22. Regulatory Submission Support Using eCTD • To date: 14 eCTD submissions sent directly to Regulatory Agencies on Sponsor’s behalf: 11 to FDA; 3 to EMEA; No agency validation findings/faults • In-house submission build with options for document publishing, CDISC dataset preparation, SPL build, Standard Letter or A4 paper submission printing for Agencies or EU Member States as necessary • Dedicated server able to send and receive documents by secure VPN connecting to sponsor • SOP controlled process from start to finish. Sponsor Audited in 2007; FDA remote audit of documentation in July 2008 (FDA on site at Sponsor) with no findings/faults • Regulatory Support for Agency communications available through partnering regulatory firms

23. Administration of Clinical Trial DSMBs • Write Charters for clinical trial Data and Safety Monitoring Boards (DSMB) • Identify and engage board members • Design and develop trial data review summary tables, subject data listings, and graphs (TLGs) • Generate and validate trial data review TLGs and provide them to the DSMB prior to the DSMB data review meetings • Schedule and facilitate DSMB meetings, take meeting minutes (DSMB Secretary) • Interact and communicate with trial sponsor and with regulatory agencies on behalf of the trial sponsor in accordance with the DSMB Charter

24. Trial Management and Site Monitoring • Everest is continuing to develop its clinical trial management and site monitoring capabilities by working seamlessly with its partnering clinical management firms to provide quality services in clinical operations • Trial sponsors will benefit from the combined powers of two strong functional service providers while administratively dealing with a single point of contact (one primary contact from the combined teams per trial, single contract for each trial, and a single invoice will cover services from both partnering companies) • Through the years conducting clinical trials together, both companies know about each other’s processes and procedures, systems and tools. Function as an unified organization • One set of SOPs will be followed per functional area

25. Trial Sponsors’ Feedback “It has been a great pleasure to work with the Everest teams.” “They are highly motivated and always go above and beyond to provide us with quality and timely services.” “You are really a ‘Can-Do’ team! You always try your hardest and find solutions for problems…. your ‘Can-Do’ attitude results in continuous improvements in all of the things you do….” “We are very impressed by everything your team has done, they have contributed a lot to the success of the projects.”

26. Therapeutic Area Expertise and Experience • Oncology • Hepatology • Immunology/Autoimmune/Rheumatology • Virology • Allergy/Respiratory • Infectious Diseases • Nephrology • Cardiovascular Diseases • Endocrinology • Urology • Ophthalmology • CNS • Women’s Health • Dermatology

27. Benefits of Using Our Services • Due to the low overhead of the organization, quality and timely services can be offered at a competitive rate • Well-defined and streamlined processes and procedures enable efficiency gains and error prevention • Standardization in systems/tools, CRFs/eCRFs, datasets, common data displays, standard SAS programs, standard work templates or checklists, etc., enables resources/cost saving • Everest’s relatively stable workforce enables knowledge and experience retention, minimizes the costs in hiring and initial investment in developing new staff members • Customer-focused is our tradition • Flexibility is our strength

28. Everest Contact Information Irene Zhang Office Phone: 1- 905 – 752 - 5201 Office Phone: 1 - 973 - 774 - 1160 Cell Phone: 1- 416 – 788 - 8678 Everest Corporate Website Address: www.ecrscorp.com Company Locations: 675 Cochrane Drive Suite 408, East Tower Markham, Ontario Canada L3R 0B8 150 Clove Road, Suite 502 Little Falls, New Jersey USA 07424