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Investigator-Initiated Research Investigator Guide

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Contents

• General Principles • Therapeutic Areas of Interest • Submission Eligibility • Proposal Types

• Brief Proposal • Full Proposal

• Information and Documents Needed For Proposal Submission • Brief Proposal • Full Proposal

• Shire’s Review and Approval Process

• Documents Required Prior to Study Start

• Study Drug • Resupply • Quarantine/Destruction

• Study Updates • Amendments • Payments and Invoicing • Study Close-Out • Contact Information

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General Principles

• In an effort to advance research and enhance understanding of disease, Shire supports independent research relating to disease areas of interest to Shire or relating to Shire's products

• Shire responds to unsolicited requests for support of investigator-initiated research through its Investigator-Initiated Research ('IIR') program, in which IIR investigators and/or their affiliated institutions assume responsibility for all aspects of the study, including design, regulatory approval, initiation, conduct and monitoring as well as analysis and publication of study results

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Areas of Interest

• Shire’s current areas of research interest can be found at www.ShireSupport.com, Shire’s Investigator-Initiated Research portal

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Submission Eligibility

• Shire will review requests from independent researchers who have the necessary scientific background and experience to conduct an independent scientific investigation for a specific research project. This includes: • Physicians and other Health Care Providers • Researchers • Institutions interested in conducting their own research

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Proposals

• IIR proposals submitted to Shire are reviewed by its scientific and medical committees for scientific merit, safety, legal, ethical, and budgetary considerations.

• Support for approved proposals is provided in the form of financial support, study drug supply, or both as requested in the study design.

• Requests for both clinical and pre-clinical studies are considered.

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Types of Proposals

• You can submit either a brief (concept) proposal or a fully detailed proposal

• Brief proposals require less information than full proposals, and can be used to gauge Shire’s interest in your research prior to submitting a full proposal • If there is interest in your brief proposal, you will be asked to

submit a full proposal.

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Brief Proposal – Information needed at submission

• Basic Study Information • Title, Hypothesis, Overall Project Cost

• Study Details • Brief Inclusion and Exclusion Criteria, and Primary Objective

• Study Design • Number of Sites, Experimental Design

• Additional Study Information and Justification for sample size

• Primary Investigator CV • Additional documents can be uploaded as needed

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Full Proposal – Information needed at submission

• Basic Study Information • Title, Background/Rationale, Hypothesis

• Study Details • Brief Inclusion/Exclusion Criteria, Primary Objective

• Study Design • Number of Sites, Experimental Design

• Additional study detail, including estimated recruitment period and study timelines

• Study Event Information • treatment information, drug supply requirements (if applicable),

statistical analysis plan, etc. • Itemized, Detailed Budget • Medical License Number and Primary Investigator CV • Additional documents can be uploaded as needed

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Review and Approval Process

• Brief proposals are reviewed as they are received. If a brief proposal is of interest, a full proposal will be requested. Interest in a brief proposal does not guarantee approval of the full proposal.

• Meetings to review full proposals are held on a bi-monthly basis. Investigators are notified when a decision has been made.

• If Shire reviewers have questions about your proposal, you may receive a request for additional information through the ShireSupport portal.

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Documents Required Prior to Study Start

• US • Signed contract between Shire and the Institution and

Investigator • Investigational New Drug (IND) Approval or IND Exemption • Ethics Committee (Internal Review Board) Approval

documentation • DEA Certificate of Registration (DEA223) if appropriate

• Outside US • Signed Contract between Shire and the Institution and

Investigator • Clinical Trial Authorization (CTA, or local equivalent) Approval or

CTA Exemption • Ethics Committee Approval documentation

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Study Drug (if applicable)

• An IIR Manager will contact the investigator prior to study start to verify drug supply needs

• Study drug cannot be ordered until the contract is signed, and EC/IRB and IND or CTA approval/exemption documentation has been received by Shire

• Drug supply timelines should be kept in mind when determining a potential start date for the trial • It takes up to 12 – 16 weeks after contract signature to receive

drug supply for blinded/placebo-controlled studies

• Investigators are responsible for the control of, access to, and administration of all study drugs, and must provide drug accountability data at the end of the study

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Study Updates

• Study updates are required monthly at www.shiresupport.com. Required information includes:

• Study information, if subjects are being enrolled • # of subjects screened • # of subjects enrolled • # of subjects completed • # of subjects terminated

• Milestone Information • Adjust projected milestone dates if needed • Has the next milestone been met? • Study registry and identifying number

• Drug Supply Information, if applicable • Is additional drug supply needed?

• If so, type and quantity

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Amendments

• Once a study has begun, any changes or study amendment requests must be submitted via the ShireSupport portal at www.ShireSupport.com

• Amendments may include changes to the protocol and/or requests for additional funding. Amendments will be reviewed and either approved or declined.

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Payments and Invoicing

• A purchase order and account will be generated for each study and will be sent to the site along with invoicing instructions

• It is the responsibility of the site to invoice Shire for all payments based on milestones in the executed agreement

• Payments other than those in the approved agreement cannot be made without an amendment

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Study Close-Out

• Once a study has been completed, a final study report must be submitted to Shire

• All publications based on the study must be sent to Shire for review before publication

• Any remaining study drug must be destroyed and documentation sent to Shire

• All study funds must be reconciled and accounted for • When the final study report has been reviewed and

approved, a final invoice can be sent and the study closed

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Contact Information

Shire Office of Investigator-Initiated Research • E-mail: ShireSupportIST@shire.com • Phone: 484-595-2330