1. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 1 ​ The Implementation Toolkit is: – High level roadmap of activities designed to support implementation of the Common Protocol Template (CPT) across project management, people, process & technology – Templates and materials to communicate the initiative to various audiences – Available to any Company or Sponsor who chooses to implement ​.. but is not: – A detailed step-by-step workplan – Activities that must be followed exactly, including Company or Sponsor-specific documentation Objectives and Guiding Principles for the Implementation Leader ​ Guiding Principles – Each TransCelerate member company or non-member Sponsor is free to decide and must decide for itself whether and in what manner to adopt any or all of the CPT components. – This toolkit is intended to help those Companies or Sponsors who decide to adopt any CPT component to do so in the most efficient way possible. – Implementation components are generic and may need to be tailored to a sponsor prior to use – While TransCelerate member companies or non-member Sponsors have absolute discretion to implement TransCelerate solutions as they see fit, changing certain CPT tools will likely reduce some of the efficiencies for sites, investigators, and sponsors. – It is up to each TransCelerate member company or non-member Sponsor to define further the detailed steps for each implementation component within their respective organization. The toolkit can be used in a highly flexible manner, as reflected in the guiding principles below. i

2. ​ Common Protocol Template (CPT) Implementation Toolkit

3. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 3 TABLE OF CONTENTS ​ Introduction to TransCelerate ​ Common Protocol Template (CPT) ​ Background ​ Model for the CPT ​ CPT Implementation Plan: Stakeholders, Advisors, and Company Plans ​ CPT Tools and Training for implementation ​ Other Tools to Support Implementation

4. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 4 What is TransCelerate? Our vision ​ To improve the health of people around the world by accelerating and simplifying the research and development of innovative new therapies. Our mission ​ To collaborate across the global research and development community to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient, effective and high-quality delivery of new medicines. TransCelerate is a not-for-profit entity created to drive collaboration across the pharmaceutical industry as a means to developing solutions for overcoming inefficiencies Our core values  Quality  Transparency & Openness to new ideas  Trust & Integrity  Collaboration  Courage

5. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 5 Engagement With the Wider Clinical Ecosystem Globally Research and CRO Community Investigative sites Strategically focusing engagement efforts with selected key stakeholder groups – the intent is not to recreate, but partner whenever feasible Regulatory Bodies Industry Initiatives

6. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 6 How Does TransCelerate Work? Member Companies WORKSTREAM Define problem scope Share best practices Discuss challenges Co-create solutions Support & Resources (subject matter experts, time, overhead) Industry Solutions

7. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 7 CPT Connectivity to Other Workstreams TransCelerate’s Portfolio of Initiatives focus on Patient Safety, and Accelerated Development Timelines. Clinical Trial Diversification Pediatric Trial Efficiencies Active Design, Develop, & Deploy Phase Realization Phase Clinical Trial Diversification Pediatric Trial Efficiencies Site Qualification and Training Shared Investigator Platform Risk Based Monitoring Quality Management System Patient Awareness & Access Investigator Registry eLabels Comparator Drugs Clinical Data Standards Clinical Data Transparency Common Protocol Template eConsent eSource Placebo / Standard of Care Data Sharing

8. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 8 TransCelerate and CPT Workstream Membership 8 19 member companies in TransCelerate 17 member companies participate in the Common Protocol Template workstream

9. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 9 Why a Common Protocol Template? ​ Heard at a June 2015 DIA meeting… “Patient recruitment is challenged by the complexity of protocols. Sponsors do the same things too many different ways. Just make it the same!” “If you have standards without traceability, then you aren't really CDISC compliant.” Investigator FDA “Just because ‘subject’ is in the regs, doesn’t mean you have to use it. Patients think of ‘subject’ as a verb, and who wants to be subjected to something? Please use ‘trial participant’ instead.” Patient Advocate

10. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 10 ​ Problem Statement – Format and core content of study protocols vary from sponsor to sponsor making interpretation difficult for study sites, IRBs, and regulators. – Study protocols have become increasingly complex and lengthy driving up cost and time. – Manual set-up of clinical systems based on non-standard “manual” protocols is time consuming, costly, and prone to error. ​ Solutions – Develop a streamlined model clinical trial protocol, including format and core content, to ease interpretation and enable down-stream automation of many clinical processes. – Develop model protocol endpoint definitions, incorporate into piloting of the template. Background: Why a Common Protocol Template? ​ Guiding Principles – “Common” in a CPT: information always in the same place, means the same thing. – Is it better? Move beyond incremental improvements and current limitations. – It has to be better for everyone, but Investigators/Sites are the first priority. – A human readable template that paves the way for an automated solution and facilitates the use of data standards.

11. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 11 End-User Stakeholders and Key “Must Haves” Define Scope and Solutions Objectives Endpoints Methods Time & Events Supplies Objectives Endpoints Methods Time & Events Supplies Protocol Representation Models (CDISC) Data Flows Data Standards Protocol Elements Concepts Protocol Representation Models (CDISC) Data Flows Data Standards Protocol Elements Concepts Investigators / Sites IRBs Metadata Traceability Reuse Automation

12. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 12 Near Term Benefits to Sites Protocols streamlined and organized with an investigator focus Reduced burden on sites working on multiple studies The Common Protocol Template Potentially Benefits Many Stakeholders Sponsor Sites IRB Patient Regulator Near Term Benefits to Sponsors Reduction in redundant protocol content Enabling of therapeutic area standards Improved conduct of the study and quality of data collected Potential Future Benefits to Sponsors Automation of downstream processes and reuse of content Enabling of therapeutic area standards in additional TAs Enabling collaborative clinical trials Potential Future Benefits to Sites Opportunity to harmonize additional documentation Enable consistency of some case report forms Near Term Benefits to IRBs Increased consistency between sponsor protocols: easier review and faster approval Potential Future Benefits to IRBs Enabler for automation of IRBs submissions Near Term Benefits to Patients Increased efficiency / quality in clinical development for participants & future patients Potential Future Benefits to Patients Improved access to protocol information Getting medicines faster, for participants & future patients Near Term Benefits to Regulators Protocols streamlined, increased consistency between sponsor protocols to ease review Potential Future Benefits to Regulators Increased ease of data interpretation and ability to compare protocols (improves input on protocol design), Increased use of data standards enabling end-to-end use of metadata and traceability Near Term Potential Future State

13. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 13 A common protocol template structure with harmonized language Streamlined content enables identification of critical information for end users Begin working towards model endpoint definitions to align with Clinical Data Interchange Standards Consortium (CDISC) Therapeutic Area (TA) data standards. Asthma and Diabetes available in the first release. Reconnect processes (protocol, eCRF, development) Transformation of the design process o Analytics-driven trial design, modelling, scenario planning Role-based access to protocol information (Principal Investigator [PI], Ethics, Participants) Connection to other systems Common Protocol Template is Intended to Prepare for the Future State Human- Readable Protocol IRB/IECs Sites Regulators Foundation Machine- Readable Protocol Metadata driven processes Content Reuse Disclosure SAP CSR eCRF Statistical Output Future

14. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 14 Template Development: Structure and Content Structure – Level 1 and 2 Headings Main focus - Streamlined structure for logical flow Review of structure (Table of Contents) of member company templates Input from SCRS (Society for Clinical Research Sites) Site Advocacy Group Section Content Identification of common wording in Core Backbone Review of GCP, ICH, and EU requirements Review of content from member company templates Final CPT Structure and Content Focus on sites (investigators and study staff) to have access to protocol information 1.CPT Structure and Content will provide value to Investigators, site staff, IRBs, regulators  The same information is located in the same place and means the same thing across Sponsors  Locked text (Level 1 and 2 Headings) is not to be modified or removed. “Not Applicable” is inserted if a section is not applicable. 2.Specific information to evaluate the ability to conduct a protocol, e.g. does the site have the patient population. 3.Refer to primary sources of information (e.g. Investigator Brochure) instead of duplicating information in the protocol 4.Model sections and text located in Appendices to be accessible, but will not impact the flow of the core protocol-specific information

15. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 15 The Model for the Common Protocol Template Libraries Core Protocol Backbone Common Level 1 & 2 Headings Common text Used across all phases Focus on investigators Healthy Volunteer Patient Asthma Diabetes Appendices Non-study specific info, items triggered by event Implementation materials in Toolkit Core is streamlined and focused on site needs Proposed Appendices to apply as applicable Libraries group and store content which is used to populate the template Model Endpoint Definitions developed for asthma and diabetes A sustainable Governance Model is currently in development Common Protocol Template and Guidance Governance Model

16. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 16 The Common Protocol Template is NOT…. A training document for protocol writing teams. A training document for inexperienced sites. A document for internal contracting of downstream actions within the sponsoring organization. An enrollment feasibility document (specifically referring to the Synopsis section). An exposition of the Sponsor’s development program. A substitute for or duplicate of the Investigators’ Brochure or Statistical Analysis Plan (SAP). Intended to meet the needs of any possible reader, but specifically written to meet the needs of investigative sites and regulatory reviewers.

17. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 17 ​ Basic Word Edition Document Based Template to enable harmonization Public Release: December 2015 ​ Technology Enabled Edition An MSWord-based template with automation to leverage “point and click” protocol text, to capture of protocol-level metadata, and to facilitate content reuse. Public Release: June 2016 ​ For Microsoft Windows-based usage, not compatible with Apple iOS. CPT Editions

18. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 18 Tech-Enabled Edition Common Protocol Template: What does it look like? Data Sources Pane A.Filter: select participant and therapeutic area libraries B.Folder: navigate to all libraries C.Instructional Text Box Panel: section-specific guidance D.Library Content Panels: (D1) Navigate to library text. Click once to preview content (D2); click twice to add to protocol. Add-Ins E.Add Variables: Reuse content F.Example Text Tools: Convert example text to protocol text, remove example text G.About: Link to guides for use & implementation, releases H.Instructional Text: Toggle Data Sources Pane I.Manage Variables: Add custom variables J.Data Tools: Export variables and text to XML; import variables J

19. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 19 Advisory Committee eProtocol Advisory Committee “…to inform the development of a common human readable and electronic protocol template and provide a forum for key stakeholders to inform future direction and provide know-how (Committee Charter)” “EMA has not agreed to take up a position on the Advisory Committee…..Happy to provide comments on any draft templates…” Other Advisors or Influencers FDA 18-Mar-2016: “Today we’re announcing a draft clinical trial protocol template developed by the Food and Drug Administration (FDA) and National Institutes of Health (NIH) that should help with that. …..We are aware of other efforts in this area, including one undertaken by TransCelerate Biopharma Inc. (TransCelerate), which has issued a common protocol template intended to be the basis for a forthcoming electronic protocol. Although our initial target audiences differ, we plan to collaborate with groups like TransCelerate to help ensure consistency for the medical product development community.”

20. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 20 Status of Implementation 727 downloads of the CPT from TransCelerate website across 400+ unique organizations (Dec 2015 – Apr 2016) Implementation Plans by 15 Member Companies Responding to an Optional, Anonymous Survey as of May 2016 Implementing the CPT in some form 73% Implementing the Basic Word edition of the CPT 60% Implementing the Tech-Enabled edition of the CPT 33% Drafted any protocols using the CPT 33% Finalized, sent to sites, but not yet submitted to HA/IRB/ERC, any protocols using the CPT 13% Finalized, and submitted to HA/IRB/ERC, any protocols using the CPT 7% Had any CPT protocols approved by ERCs *One member company reported the CPT Level 1-2 heading structure was used in approximately 100 trials with no rejections. 7%

21. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 21 Ongoing CPT Maintenance/Governance: Business Continuity Plans Ongoing Maintenance & Governance of Template* Collect and report metrics and feedback Updates to the templates and libraries  Governance Model being refined  Posted Template & Implementation Toolkit Metrics to monitor extent of adoption, regulator feedback Metrics to assess efficiencies gained Feedback collected via the TransCelerate website Update of the template and libraries as needed based on stakeholder feedback, regulatory guidance etc. Additional TA libraries

22. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 22 How will we go about adopting the CPT? ​ Options for Adoption of Common Protocol Template TransCelerate  Sponsor ​ Mapping Table Exercise for assessing the impact of CPT ​ Plan for Implementation at _Sponsor_ Each Sponsor to tailor this slide. !

23. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 23 Options for Adoption of the Common Protocol Template Companies and Sponsors choose their own path to adoption By phases By use of libraries By use of Word or technology-enabled template By use of organization/structure and content only (i.e., existing sponsor technology used, but headings/content adapted to mirror CPT) Companies and Sponsors set their roll- out timeline Slowly introduce through pilots Hard cut over date Somewhere in between Harmonization Value

24. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 24 Mapping Table Exercise to Assess Impact of CPT Completing the Mapping Table Exercise will highlight the impacts and risks of adopting the CPT. Consider: -Impact to sites/regulators -Sponsor responsibility for regulatory compliance -Impact to internal sponsor processes and documents downstream from protocol Identify content used in a company/sponsor template that is not included in the CPT -Consider: Is this information found elsewhere (e.g., CTA, Monitoring Guidelines, Standard Operating Procedures, policy documents)? Identify content in the CPT that is not currently in a company/sponsor template. -Consider: Impact to adding this content? Identify differences in wording of same topics in company/sponsor template vs CPT. -Consider: Can company decide to accept CPT wording? EXAMPLE

25. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 25 Mapping Tool: Results of Initial Impact Assessment ​ *Insert Company or Sponsor Specific Details* ​ Share results of Mapping Tool Exercise ​ Propose mitigation for content removed from template ​ Downstream impacts of content changes – distinguish between what needs to be mitigated for initial implementation vs longer term updates to SOPs Documents (SOPs, monitoring plans, agreements, etc.) Processes Technology Each Company or Sponsor to tailor this slide. !

26. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 26 Proposed Implementation at ____Sponsor ___ ​ *Insert Company or Sponsor Specific Details* ​ Pilot with X trials Trials X, Y, Z Use template on desktop, not installed in authoring tool for initial implementation Training/Orientation to template details Timing Assessment of results Each Company or Sponsor to tailor this slide. !

27. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 27 Technology Enabled Edition  CPT Core Backbone and Libraries in MSWord (.dotx)  CPT Add-Ins (MSWord buttons)  Installation Kit: Installation files; Installation instructions  User Documentation: Step by step instructions; “How to” videos; Modules targeted to technical staff and users of the template Basic Word Edition  CPT Core Backbone and Libraries in MSWord (.docx)  Instructional text provided as red hidden text available by toggling paragraph marks  Word doc, no installation needed (Open file and “Save As”) Install on workstation to author a protocol leveraging technology enhancements ​ NOTE: For Microsoft Windows-based usage, not compatible with Apple operating systems. Open on a workstation to author a protocol or Use for mapping exercise to compare CPT to company template – no need to install How to Use the Common Protocol Template

28. Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 28 What will be provided to support Implementation? ToolsWhat is it? Executive Summary – Slide deck Used for communication to company or sponsor senior leadership audiences. Provides a very brief summary of the rationale for development of the CPT, and a value proposition for adoption by companies or sponsors. Summary of CPT Releases – Slide A table summarizing all CPT releases including release date, intended audience, and template version(s). CPT Implementation Toolkit – Slide deck This deck. Used for communication to various company or sponsor audiences – e.g. senior leadership, group of stakeholders for doing impact assessment, participants authoring “pilot” trials, team members who will review and approve the protocol for “pilot” trials, broad audiences for awareness. Guidance for Use (Tech- Enabled Edition) Guide for using the Tech-Enabled Edition of the CPT, including videos demonstrating selected steps. Release 3.0 Highlights Slide deck; Track-Change versions A slide deck summarizing the changes to template function and content that are included in Release 3.0 of the CPT, and a Word Track-Change versions documenting the specific changes made to CPT content files. Frequently Asked Questions (FAQs) A summary of questions, and responses from the team, that various stakeholders may have about how the CPT was developed, how it will be implemented, and how it will be maintained. Mapping Table Exercise; Mapping Table Instructions A tool to compare the CPT to a company or sponsor protocol template. Allows identification, section by section, of differences in headings and content, and prompts team members to assess impact of implementation and possible mitigations needed. Stakeholder MapA tool to assess the impact that implementing the CPT will have on each stakeholder group. Allows the Implementation Lead to plan for appropriate training and mitigation of concerns. Text color guideColor coding used within the Common Protocol Template to distinguish common, suggested, example and instructional text. CPT FeedbackFeedback can be submitted via the TransCelerate website http://www.transceleratebiopharmainc.com/ http://www.transceleratebiopharmainc.com/

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