THIS DOCUMENT IS IMPORTANT AND REQUIRES YOUR IMMEDIATE ATTENTION. PART II OF THISDOCUMENT COMPRISES AN EXPLANATORY STATEMENT IN COMPLIANCE WITH ARTICLE 126 OF THEJERSEY COMPANIES LAW.

This document contains a proposal which, if implemented, will result in the cancellation of the listing ofShire Shares on the Official List and of trading of Shire Shares on the London Stock Exchange and oftrading of Shire ADSs on NASDAQ. If you are in any doubt as to what action you should take, you arerecommended to seek your own personal financial advice immediately from your stockbroker, bankmanager, solicitor, accountant or other independent financial adviser authorised under the FinancialServices and Markets Act 2000 if you are in the United Kingdom, or from another appropriately authorisedindependent financial adviser if you are taking advice in a territory outside the United Kingdom.

If you sell, have sold or otherwise have transferred all of your Shire Shares or Shire ADSs, please send this

document and the accompanying documents (other than documents or forms personal to you) at once to the

purchaser or transferee, or to the bank, stockbroker or other agent through whom the sale or transfer was effected,

for transmission to the purchaser or transferee. These documents must not, however, be forwarded, distributed or

transmitted in, or into, any jurisdiction in which such act would constitute a violation of the relevant laws of such

jurisdiction. If you sell, have sold, or otherwise have transferred only part of your holding of Shire Shares or Shire

ADSs, you should retain these documents and contact the bank, stockbroker or other agent through whom the sale

or transfer was effected.

The release, publication or distribution of this document and any accompanying documents (in whole orin part) in or into or from jurisdictions other than Jersey and the United Kingdom may be restricted by thelaws of those jurisdictions and therefore persons into whose possession this document and/or anyaccompanying document comes should inform themselves about, and observe, any such restrictions.Failure to comply with any such restrictions may constitute a violation of the securities laws of any suchjurisdiction.

Recommended cash and share offer

for

Shire plcby

Takeda Pharmaceutical Company Limitedto be effected by means of a Scheme of Arrangement underArticle 125 of the Companies (Jersey) Law 1991, as amended

Neither this document nor any of the accompanying documents do, nor are intended to, constitute or form part of

any offer or invitation to purchase, otherwise acquire, subscribe for, sell or otherwise dispose of, any securities or

the solicitation of any vote or approval pursuant to the Scheme or otherwise, in any jurisdiction in which such offer,

invitation or solicitation is unlawful. This document is not a prospectus.

This document (including all information incorporated into this document by reference to another source) should be

read as a whole and in conjunction with the Forms of Proxy (or, if applicable, the ADS Voting Card), Form of

Election and its accompanying notes and any document incorporated by reference. Your attention is drawn to the

letter from the Chairman of Shire in Part I of this document, which contains the unanimous recommendation of the

Shire Directors that you vote in favour of the Scheme at the Court Meeting and the Special Resolution to be

proposed at the Shire General Meeting. A letter from Citigroup Global Markets Limited, Goldman Sachs

International and Morgan Stanley & Co. International plc explaining the Scheme appears in Part II of this document.

Notices of the Court Meeting and the Shire General Meeting, both of which will be held at Block 3, Miesian Plaza,

50-58 Baggot Street Lower, Dublin 2, Ireland on December 5, 2018, are set out in Parts XII (Notice of Court

Meeting) and XIII (Notice of Shire General Meeting) of this document, respectively. The Court Meeting will start at

11.15 a.m. (London time) and the Shire General Meeting at 11.30 a.m. (London time) (or as soon thereafter as the

Court Meeting shall have been concluded or adjourned).

Action to be taken by Shire Shareholders and Shire ADS Holders is set out on pages 5 to 18 of thisdocument. Whether or not they intend to attend the Court Meeting or the Shire General Meeting in person,Shire Shareholders are asked to complete and return the accompanying BLUE and YELLOW Forms ofProxy (or appoint a proxy, electronically, as referred to in this document) in accordance with theinstructions printed thereon as soon as possible, but in any event so as to be received by Equiniti not laterthan 11.15 a.m. (London time) on December 3, 2018 in the case of the Court Meeting and 11.30 a.m.

(London time) on December 3, 2018 in the case of the Shire General Meeting (or, if the Court Meeting or theShire General Meeting is adjourned, not later than 48 hours before the time appointed for the adjournedmeeting). Shire Shareholders who hold Shire Shares in CREST may also appoint a proxy through theCREST electronic proxy appointment service by following the instructions set out on page 6 of thisdocument. If the BLUE Form of Proxy for the Court Meeting is not lodged by the relevant time, it may behanded to Equiniti on behalf of the Chairman of the Court Meeting, or to the Chairman of the CourtMeeting, before the start of the Court Meeting. However, in the case of the Shire General Meeting, if theYELLOW Form of Proxy is not lodged by the relevant time, it will be invalid. The return of a completed Formof Proxy or the appointment of a proxy electronically or through CREST will not prevent a ShireShareholder from attending the Court Meeting or the Shire General Meeting and speaking and voting at therelevant Shire Meeting in person if they are entitled and wish to do so. Registered Shire ADS Holders areasked to complete and return their ADS Voting Cards in accordance with the instructions on the ADSVoting Card as soon as possible. If you hold such Shire ADSs indirectly, you must rely on the proceduresof the custodian, broker or other agent through which you hold your Shire ADSs if you wish to providevoting instructions.

Shire Shareholders (other than Restricted Shire Shareholders) may make certain Elections in relation to the non-

cash portion of the Consideration and the currency of the cash portion of the Consideration payable to them under

the Scheme by completing and returning a Form of Election or (where applicable) by making a TTE Instruction.

Shire Shareholders should refer to pages 5 to 18 of this document for instructions on how to complete a Form of

Election or (where applicable) make a TTE Instruction.

Certain terms used in this document are defined in Part XI (Definitions).

If you have any questions about this document, the Court Meeting or the Shire General Meeting, or are in any doubt

as to how to complete the Forms of Proxy, lodge a Form of Election or make a TTE Instruction, please call Equiniti

between 8.30 a.m. and 5.30 p.m. (London time) Monday to Friday (except public holidays in England and Wales)

on 0330 123 5506 (if calling from within the UK) or +44 (0)121 415 0856 (if calling from outside the UK). Calls are

charged at the standard geographic rate and will vary by provider. Calls outside the United Kingdom will be charged

at the applicable international rate. Different charges may apply to calls from mobile telephones. Please note that

calls may be monitored or recorded and Equiniti cannot provide legal, tax or financial advice or advice on the merits

of the Scheme.

Shire ADS Holders should refer to Part X (Further information for Shire ADS Holders) of this document, which

contains important information relevant to such holders. The helpline for Shire ADS Holders is provided by the Shire

Depositary and is available between 8.30 a.m. and 6.00 p.m. (New York time) Monday to Friday (except public

holidays in the US) toll free from within the US on +1 866 395 6421 or +1 781 575 4555 if calling from outside the

US. Calls are charged at the standard geographic rate and will vary by provider. Calls outside the US will be

charged at the applicable international rate.

If you have recently purchased or been transferred Shire ADSs and you are a registered holder of Shire ADSs, you

should contact the helpline for Shire ADS Holders on the number indicated above to obtain an ADS Voting Card.

If you hold such Shire ADSs indirectly, you should contact the custodian, broker or other agent through which you

hold such Shire ADSs for details on how to provide voting instructions. Please note that only Shire ADS Holders

as of the ADS Voting Record Time are entitled to instruct the Shire Depositary on how to vote the Shire Shares

represented by their Shire ADSs.

Citigroup Global Markets Limited, which is authorised by the Prudential Regulation Authority and regulated by the

Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting exclusively as

financial adviser to Shire and no one else in connection with the Acquisition, the contents of this document and the

matters described herein, and shall not be responsible to anyone other than Shire for providing the protections

afforded to clients of Citi or for providing advice in connection with the Acquisition, the contents of this document

or any matter referred to herein. Neither Citi nor any of its subsidiaries, branches or affiliates owes or accepts any

duty, liability or responsibility whatsoever (whether direct or indirect, whether in contract, in tort, under statute or

otherwise) to any person who is not a client of Citi in connection with the Acquisition, the contents of this document

or any matter referred to herein.

Goldman Sachs International, which is authorised by the Prudential Regulation Authority and regulated by the

Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting exclusively as

financial adviser to Shire and no one else in connection with the Acquisition, the contents of this document and the

matters described herein, and shall not be responsible to anyone other than Shire for providing the protections

afforded to clients of Goldman Sachs or for providing advice in connection with the Acquisition, the contents of this

document or any matter referred to herein. Neither Goldman Sachs nor any of its subsidiaries, branches or affiliates

owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, in contract, in tort, under

statute or otherwise) to any person who is not a client of Goldman Sachs in connection with the Acquisition, the

contents of this document or any matter referred to herein.

Morgan Stanley & Co. International plc, which is authorised by the Prudential Regulation Authority and regulated

by the Financial Conduct Authority and the Prudential Regulation Authority in the United Kingdom, is acting

ii

exclusively as financial adviser to Shire and no one else in connection with the Acquisition, the contents of this

document and the matters described herein, and shall not be responsible to anyone other than Shire for providing

the protections afforded to clients of Morgan Stanley or for providing advice in connection with the Acquisition, the

contents of this document or any matter referred to herein. Neither Morgan Stanley nor any of its subsidiaries,

branches or affiliates owes or accepts any duty, liability or responsibility whatsoever (whether direct or indirect, in

contract, in tort, under statute or otherwise) to any person who is not a client of Morgan Stanley in connection with

the Acquisition, the contents of this document or any matter referred to herein.

Evercore Partners International LLP, which is authorised and regulated in the United Kingdom by the Financial

Conduct Authority, is acting as financial adviser exclusively to Takeda and no one else in connection with the

Acquisition and this document and will not regard any other person as its client in relation to the Acquisition or this

document and shall not be responsible to anyone other than Takeda for providing the protections afforded to clients

of Evercore, or for providing advice in connection with the Acquisition, this document or any matter referred to

herein. Neither Evercore nor any of its subsidiaries, branches or affiliates owes or accepts any duty, liability or

responsibility whatsoever (whether direct or indirect, in contract, in tort, under statute or otherwise) to any person

who is not a client of Evercore in connection with the Acquisition, this document or any matter referred to herein.

JPMorgan Securities Japan Co., Ltd., together with its affiliate J.P. Morgan Securities plc (which conducts its UK

investment banking business as J.P. Morgan Cazenove and which is authorised in the United Kingdom by the

Prudential Regulation Authority and regulated in the United Kingdom by the Prudential Regulation Authority and

the Financial Conduct Authority), is acting as financial adviser exclusively to Takeda and no one else in connection

with the Acquisition and will not regard any other person as its client in relation to the Acquisition and shall not be

responsible to anyone other than Takeda for providing the protections afforded to clients of J.P. Morgan, or for

providing advice in connection with the Acquisition or any matter referred to herein.

Nomura International plc, which is authorised by the Prudential Regulation Authority and regulated by the

Prudential Regulation Authority and the Financial Conduct Authority in the United Kingdom, is acting as financial

adviser exclusively to Takeda and no one else in connection with the Acquisition and this document and Nomura,

its affiliates and its respective officers, employees, agents, representatives and/or associates will not regard any

other person as their client, nor will they be responsible to anyone other than Takeda for providing the protections

afforded to clients of Nomura or for giving advice in relation to the Acquisition, this document or any matter referred

to herein. Neither Nomura nor any of its subsidiaries, branches or affiliates owes or accepts any duty, liability or

responsibility whatsoever (whether direct or indirect, in contract, in tort, under statute or otherwise) to any person

who is not a client of Nomura in connection with the Acquisition, this document or any matter referred to herein.

No person has been authorised to give any information or make any representations other than those contained in

this document and, if given or made, such information or representations must not be relied upon as having been

authorised by Shire, the Shire Directors, Takeda, the Takeda Directors or by Citi, Goldman Sachs, Morgan Stanley,

Evercore, J.P. Morgan, Nomura or any other person involved in the Acquisition. Neither the delivery of this

document nor holding the Shire Meetings, the Court Sanction Hearing, or filing the Court Order shall, under any

circumstances, create any implication that there has been no change in the affairs of the Shire Group or the Takeda

Group since the date of this document or that the information in, or incorporated into, this document is correct as

at any time subsequent to its date.

iii

IMPORTANT NOTICES

This document does not constitute, and may not be used for the purposes of, an offer to sell or an

invitation or the solicitation of an offer to subscribe for or buy any securities by any person in any

jurisdiction: (i) in which such offer or invitation is not authorised; (ii) in which the person making such

offer or invitation is not qualified to do so; and/or (iii) in which, or to any person to whom, it is unlawful

to make such offer, solicitation or invitation or where the making of such offer, solicitation or invitation

would impose any unfulfilled registration, qualification, publication or approval requirements on Shire,

Takeda or any of their respective directors, officers, agents, affiliates and advisers. No action has been

taken nor will be taken in any jurisdiction by any such person that would permit a public offering of any

securities in any jurisdiction where action for that purpose is required, nor has any such action been

taken with respect to the possession or distribution of this document other than in any jurisdiction where

action for that purpose is required. Neither Shire nor Takeda, nor their respective directors, officers,

agents, affiliates or advisers accepts any responsibility for any violation of any of these restrictions by

any other person.

Notice to Overseas Shareholders

The release, publication or distribution of this document and/or any accompanying documents (in whole

or in part) in, or into, or from jurisdictions other than Jersey and the United Kingdom may be restricted

by the laws of those jurisdictions and therefore persons into whose possession this document and/or

any accompanying document comes should inform themselves about, and observe, any such

restrictions or other applicable requirements. In particular, the ability of persons who are not resident in

Jersey or the United Kingdom to vote their Shire Shares with respect to the Scheme at the Court

Meeting, to execute and deliver Forms of Proxy appointing another to vote at the Court Meeting on their

behalf, or to hold or vote Takeda Shares may be affected by the laws of the relevant jurisdiction in which

they are located. Any failure to comply with any such restrictions may constitute a violation of the

securities laws of any such jurisdiction. To the fullest extent permitted by applicable law, the companies

and persons involved in the Acquisition disclaim any responsibility or liability for the violation of such

restrictions by any person.

This document and the accompanying documents have been prepared for the purposes of complying

with Jersey law, the Takeover Code and the Listing Rules and the information disclosed may not be the

same as that which would have been disclosed if this document had been prepared in accordance with

the laws of any other jurisdiction. Nothing in this document or the accompanying documents should be

relied upon for any other reason. This document is not a prospectus for the purposes of the Companies

(General Provisions) (Jersey) Order 2002.

Unless otherwise determined by Takeda or required by the Takeover Code, and permitted by applicable

law and regulation, the Acquisition will not be made available, directly or indirectly, in, into or from a

Restricted Jurisdiction where to do so would violate the laws in that jurisdiction. No person may vote in

favour of the Acquisition by any use, means, instrumentality or form, and the Acquisition will not be

capable of acceptance, from or within a Restricted Jurisdiction, if to do so would constitute a violation

of the laws of that jurisdiction. Accordingly, copies of this document and any accompanying documents

are not being, and must not be, directly or indirectly, mailed, transmitted or otherwise forwarded,

distributed or sent in, into or from a Restricted Jurisdiction, where to do so would violate the laws in that

jurisdiction, and persons receiving this document and/or accompanying documents (including

custodians, nominees and trustees) must not mail or otherwise distribute or send them in, into or from

Restricted Jurisdictions, where to do so would violate the laws in that jurisdiction. Any person (including,

without limitation, any custodian, nominee and trustee) who would, or otherwise intends to, or who may

have a contractual or legal obligation to, forward this document and/or any other related document to

any jurisdiction outside Jersey or the United Kingdom should inform themselves of, and observe, any

applicable legal or regulatory requirements of such jurisdiction.

If the Acquisition is implemented by way of a Takeover Offer, then, unless, otherwise permitted by

applicable law and regulation, the Takeover Offer may not be made, directly or indirectly, in or into, or

iv

by the use of mails or any means or instrumentality (including, but not limited to, facsimile, e-mail or

other electronic transmission, telex or telephone) of interstate or foreign commerce of, or of any facility

of a national, state or other securities exchange of, any Restricted Jurisdiction and the Takeover Offer

may not be capable of acceptance by any such use, means, instrumentality or facilities.

The availability of the New Takeda Securities under the Acquisition to Shire Shareholders who are on

the register of members of Shire at the Scheme Record Time and who are not resident in Jersey or the

United Kingdom, or the ability of those persons to continue to hold such securities, may be affected by

the laws or regulatory requirements of the relevant jurisdiction in which they are resident. Persons into

whose possession this document and/or any accompanying document comes who are not resident in

Jersey or the United Kingdom should inform themselves of, and observe, any applicable requirements.

Shire Shareholders who are in any doubt regarding such matters should consult an appropriate

independent financial adviser in their relevant jurisdiction without delay. Any failure to comply with such

restrictions may constitute a violation of the securities laws of any such jurisdiction.

The New Takeda Securities may not be offered, sold or delivered, directly or indirectly, in, into or from

any Restricted Jurisdiction or to, or for the account or benefit of, any Restricted Shire Shareholder

except pursuant to an applicable exemption from, or in a transaction not subject to, applicable securities

laws of those jurisdictions, or otherwise permitted under applicable securities laws of those jurisdictions.

Additional information for US Shareholders and US ADS Holders

None of the SEC, any state securities commission in the United States or any other USregulatory authority has passed upon or determined the adequacy or accuracy of thisdocument. Any representation to the contrary is a criminal offence in the United States.

The Acquisition relates to the shares of a Jersey company and is being made by means of a scheme

of arrangement provided for under the Jersey Companies Law and, accordingly, is not subject to the

tender offer rules or the proxy solicitation rules under the US Exchange Act. The New Takeda Securities

to be issued under the Scheme have not been registered under the US Securities Act, or applicable

state securities laws, and are being issued in reliance on the exemption from registration set forth in

Section 3(a)(10) of the US Securities Act on the basis of the approval of the Court.

For the purpose of qualifying for the exemption provided by Section 3(a)(10) of the US Securities Act,

Shire will advise the Court that its sanctioning of the Scheme will be relied on by Takeda as an approval

of the Scheme following a hearing on its fairness to Shire Shareholders, at which Court hearing all Shire

Shareholders on the register of members at the Voting Record Time are entitled to attend in person or

through counsel to support or oppose the sanctioning of the Scheme and with respect to which

notification will be given to all such holders.

Under US securities laws, persons who are or will be deemed to be affiliates (as defined under the US

Securities Act) of Takeda within 90 calendar days of the Effective Date may not resell the New Takeda

Securities received under the Scheme without registration under the US Securities Act, except pursuant

to an applicable exemption from, or in a transaction not subject to, the registration requirements of the

US Securities Act. Whether a person is an affiliate of a company for such purposes depends upon the

circumstances, but affiliates of a company can include certain officers and directors and significant

shareholders. Shire Shareholders and Shire ADS Holders who believe they may be or become (within

10 calendar days of the Effective Date) affiliates for the purposes of the US Securities Act should

consult their own legal advisers before any resale of New Takeda Securities received under the

Scheme.

The New Takeda Securities generally should not be treated as “restricted securities” within the meaning

of Rule 144(a)(3) under the US Securities Act and persons who receive securities under the Scheme

(other than “affiliates” as described in the paragraph above) may resell them without restriction under

the US Securities Act.

US Shareholders and US ADS Holders should be aware that the exchange of their Shire Shares or

Shire ADSs for New Takeda Securities and/or cash as described herein is expected to be a taxable

v

exchange for US federal income tax purposes. For a general summary of certain material US federal

income tax considerations of exchanging Shire Shares or Shire ADSs for New Takeda Securities and/or

cash pursuant to the Scheme for US Shareholders and US ADS Holders, see Part VII (Taxation) of this

document.

US Shareholders and US ADS Holders are advised to consult their own tax advisers to determine the

particular United States tax consequences to them of the Scheme in light of their particular situation, as

well as any tax consequences that may arise under the laws of any other relevant foreign, state, local

or other taxing jurisdiction.

The Acquisition is subject to the disclosure requirements and practices applicable in the United

Kingdom and Jersey to schemes of arrangement which differ from the disclosure requirements of

United States tender offer and proxy solicitation rules and the US Securities Act.

Financial information of Shire included in this document has been prepared in accordance with US

GAAP. Financial information of Takeda included in this document has been prepared in accordance with

IFRS, which may not be comparable to financial information of US companies or companies whose

financial statements are prepared in accordance with US GAAP.

It may be difficult for US Shareholders to enforce their rights and any claim arising out of the US

securities laws against Takeda and Shire, since Takeda and Shire are located primarily in a non-US

jurisdiction, and some or all of their officers and directors may be residents of a non-US jurisdiction. US

Shareholders may not be able to sue a non-US company or its officers or directors in a non-US court

for violations of the US securities laws. Further, it may be difficult to compel a non-US company and its

affiliates to subject themselves to the jurisdiction and judgment of a US court.

If, in the future, Takeda exercises the right to implement the Acquisition by way of a Takeover Offer, the

Acquisition will be made in compliance with applicable United States laws and regulations, including

any applicable exemptions under the US Exchange Act.

Further information

This document, including, in particular, the letter from the Chairman of Shire in Part I (Letter from the

Chairman of Shire plc) and the Explanatory Statement in Part II (Explanatory Statement), has been

prepared solely to assist Shire Shareholders and Shire ADS Holders in deciding how to vote on the

Scheme. The summary of the principal provisions of the Scheme contained in this document is qualified

in its entirety by reference to the Scheme itself, the full text of which is set out in Part III (The Scheme

of Arrangement) of this document. Shire Shareholders and Shire ADS Holders are urged to read and

consider carefully the text of the Scheme itself.

Shire Shareholders and Shire ADS Holders are urged to read in particular the risk factors set outin Appendix I (Risk Factors) to this document and the other information relating to the NewTakeda Securities set out in Part V (Takeda Securities) of this document.

Shire Shareholders and Shire ADS Holders should not construe anything contained in this document

as legal, financial or tax advice and should consult their own professional advisers for any such advice.

Medical information

This document contains information about products that may not be available in all countries, or may

be available under different trademarks, for different indications, in different dosages, or in different

strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for

any prescription drugs, including the ones under development.

Forward-looking statements

This document contains certain statements about the Shire Group, Takeda Group and the Combined

Group that are, or may be, “forward-looking statements”, which are prospective in nature. All statements

other than statements of historical or current fact included in this document and any accompanying

vi

documents are forward-looking statements. Without limitation, forward-looking statements often include

words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “will”,

“may”, “should”, “would”, “could”, “anticipates”, “estimates”, “projects” or words or terms of similar

substance or the negative thereof. By their nature, forward-looking statements involve risk and

uncertainty, because they relate to events and depend on circumstances that will occur in the future and

the factors described in the context of such forward-looking statements in this document and any

accompanying documents could cause actual results and developments to differ materially from those

expressed in or implied by such forward-looking statements. Such risks and uncertainties include, but

are not limited to, the possibility that the Acquisition will not be pursued or consummated, failure to

obtain necessary regulatory approvals or to satisfy any of the other Conditions to the Acquisition if it is

pursued, adverse effects on the market price of Takeda Shares, Shire Shares, Takeda ADSs or Shire

ADSs and on Takeda’s or Shire’s operating results because of a failure to complete the Acquisition,

failure to realise the expected benefits of the Acquisition, negative effects relating to any further

announcements relating to the Acquisition or the consummation of the Acquisition on the market price

of Takeda Shares, Shire Shares, Takeda ADSs or Shire ADSs, significant transaction costs and/or

unknown liabilities, general economic and business conditions that affect the Combined Group following

the consummation of the Acquisition, changes in global, political, economic, business, competitive,

market and regulatory forces, future exchange and interest rates, changes in tax laws, regulations,

rates and policies, future business combinations or disposals and competitive developments. Although

it is believed that the expectations reflected in such forward-looking statements are reasonable, no

assurance can be given that such expectations will prove to have been correct and Shire Shareholders

and Shire ADS Holders are therefore cautioned not to place undue reliance on these forward-looking

statements, which speak only as at the date of this document.

Additional information about economic, competitive, governmental, technological and other factors that

may affect future results are contained in: (i) Appendix I (Risk Factors) to this document; and (ii) Shire’s

most recent annual report on Form 10-K and in Shire’s subsequent quarterly reports on Form 10-Q, in

each case including those risks outlined in ‘ITEM1A: Risk Factors’ (available at www.shire.com and

www.sec.gov), the contents of which are not incorporated by reference into, nor do they form part of,

this document. These risk factors expressly qualify all forward-looking statements contained in this

document and should also be considered by the reader.

All forward-looking statements attributable to Takeda or Shire or any person acting on either company’s

behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not

to place undue reliance on these forward-looking statements that speak only as of the date hereof.

Except to the extent otherwise required by applicable law, neither Takeda nor Shire undertakes any

obligation to update or revise forward-looking statements, whether as a result of new information, future

events or otherwise.

No profit forecasts or estimates or quantified financial benefits statements

Unless expressly stated otherwise, no statement in this document is intended as a profit forecast, profit

estimate or quantified financial benefits statement and no statement in this document should be

interpreted to mean that earnings per Shire Share or Takeda Share for the current or future financial

years would necessarily match or exceed the respective historical published earnings per Shire Share

or Takeda Share or to mean that the Combined Group’s earnings in the first 12 months following

completion of the Acquisition, or in any subsequent period, would necessarily match or be greater than

those of the Shire Group or the Takeda Group for the relevant preceding financial period or any other

period.

Rounding

Certain figures included in this document have been subjected to rounding adjustments. Accordingly,

figures shown for the same category presented in different tables may vary slightly and figures shown

as totals in certain tables may not be an arithmetic aggregation of the figures that precede them.

vii

Provision of information

Please be aware that addresses, electronic addresses and certain other information provided by Shire

Shareholders, Shire ADS Holders, persons with information rights and other relevant persons for the

receipt of communications from Shire may be provided to Takeda during the Offer Period as required

under Section 4 of Appendix 4 to the Takeover Code.

Publication on website and availability of hard copies

A copy of this document, together with all information incorporated into this document by reference, will

be made available, subject to certain restrictions relating to persons resident, located or with a

registered address in a jurisdiction where the availability of the Acquisition would breach any applicable

law, on Shire’s and Takeda’s websites at www.shire.com and www.takeda.com, respectively, by no later

than 12 noon (London time) on the Business Day following the date of publication of this document.

Except as expressly referred to in this document, the contents of the websites referred to in thisdocument are not incorporated into, and do not form part of, this document.

You may request a hard copy of this document and all information incorporated into this document by

reference by writing to Equiniti, Corporate Actions, Aspect House, Spencer Road, Lancing, West

Sussex BN99 6DA, United Kingdom or by calling them on 0330 123 5506 if calling from within the UK

or +44 (0)121 415 0856 if calling from outside the UK. Calls are charged at the standard geographic

rate and will vary by provider. Calls outside the United Kingdom will be charged at the applicable

international rate. Different charges may apply to calls from mobile telephones. The helpline is open

between 8.30 a.m. and 5.30 p.m. (London time) Monday to Friday, excluding public holidays in England

and Wales. Please note that Equiniti cannot provide any financial, legal or tax advice and calls may be

recorded and monitored for security and training purposes.

If you hold Shire ADSs, you should instead make the request by writing to the Shire Depositary, c/o

Citibank Shareholder Services, PO Box 43099, Providence, RI 02940-5000, USA. The Shire Depositary

can also be reached by calling them between 8.30 a.m. and 6.00 p.m. (New York time) on +1 866 395

6421 toll free from within the US or +1 781 575 4555 if calling from outside the US. Calls are charged

at the standard geographic rate and will vary by provider. Calls outside the US will be charged at the

applicable international rate.

You may also request that all future documents, announcements and information to be sent to you in

relation to the Acquisition should be in hard copy form.

Disclosure requirements of the Takeover Code

Under Rule 8.3(a) of the Takeover Code, any person who is interested in one per cent. or more of any

class of relevant securities of an offeree company or of any securities exchange offeror (being any

offeror other than an offeror in respect of which it has been announced that its offer is, or is likely to be,

solely in cash) must make an Opening Position Disclosure following the commencement of the Offer

Period and, if later, following the announcement in which any securities exchange offeror is first

identified. An Opening Position Disclosure must contain details of the person’s interests and short

positions in, and rights to subscribe for, any relevant securities of each of: (i) the offeree company; and

(ii) any securities exchange offeror(s). An Opening Position Disclosure by a person to whom Rule 8.3(a)

applies must be made by no later than 3.30 p.m. (London time) on the 10th business day following the

commencement of the Offer Period and, if appropriate, by no later than 3.30 p.m. (London time) on the

10th business day following the announcement in which any securities exchange offeror is first

identified. Relevant persons who deal in the relevant securities of the offeree company or of a securities

exchange offeror before the deadline for making an Opening Position Disclosure must instead make a

Dealing Disclosure.

Under Rule 8.3(b) of the Takeover Code, any person who is, or becomes, interested in one per cent. or

more of any class of relevant securities of the offeree company or of any securities exchange offeror

must make a Dealing Disclosure if the person deals in any relevant securities of the offeree company

or of any securities exchange offeror. A Dealing Disclosure must contain details of the dealing

viii

concerned and of the person’s interests and short positions in, and rights to subscribe for, any relevant

securities of each of: (i) the offeree company; and (ii) any securities exchange offeror, save to the extent

that these details have previously been disclosed under Rule 8. A Dealing Disclosure by a person to

whom Rule 8.3(b) applies must be made by no later than 3.30 pm (London time) on the business day

following the date of the relevant dealing.

If two or more persons act together pursuant to an agreement or understanding, whether formal or

informal, to acquire or control an interest in relevant securities of an offeree company or a securities

exchange offeror, they will be deemed to be a single person for the purpose of Rule 8.3.

Opening Position Disclosures must also be made by the offeree company and by any offeror and

Dealing Disclosures must also be made by the offeree company, by any offeror and by any persons

acting in concert with any of them (see Rules 8.1, 8.2 and 8.4).

Details of the offeree and offeror companies in respect of whose relevant securities Opening Position

Disclosures and Dealing Disclosures must be made can be found in the Disclosure Table on the Panel’s

website at www.thetakeoverpanel.org.uk, including details of the number of relevant securities in issue,

when the Offer Period commenced and when any offeror was first identified. If you are in any doubt as

to whether you are required to make an Opening Position Disclosure or a Dealing Disclosure, you

should contact the Panel’s Market Surveillance Unit on +44 (0)20 7638 0129.

Date of publication

This document is published on November 12, 2018.

ix

Table of Contents

Page

EXPECTED TIMETABLE OF PRINCIPAL EVENTS 1

ACTION TO BE TAKEN: DOCUMENTS AVAILABLE TO SHIRE SHAREHOLDERS 4

ACTION TO BE TAKEN: VOTING AT THE SHIRE MEETINGS 5

ACTION TO BE TAKEN: MAKING AN ELECTION IN RESPECT OF THE CONSIDERATION 10

PART I LETTER FROM THE CHAIRMAN OF SHIRE PLC 19

PART II EXPLANATORY STATEMENT 32

PART III THE SCHEME OF ARRANGEMENT 93

PART IV CONDITIONS TO, AND FURTHER TERMS OF, THE IMPLEMENTATION

OF THE SCHEME AND THE ACQUISITION 114

PART V TAKEDA SECURITIES 125

PART VI FINANCIAL AND RATINGS INFORMATION 147

PART VII TAXATION 149

PART VIII ADDITIONAL INFORMATION 163

PART IX NOTES FOR MAKING ELECTIONS 210

PART X FURTHER INFORMATION FOR SHIRE ADS HOLDERS 222

PART XI DEFINITIONS 226

PART XII NOTICE OF COURT MEETING 240

PART XIII NOTICE OF SHIRE GENERAL MEETING 243

APPENDIX I RISK FACTORS 248

APPENDIX II CORPORATE NOMINEE FACILITY TERMS AND CONDITIONS 272

APPENDIX III STATEMENT ON QUANTIFIED FINANCIAL BENEFITS 282

APPENDIX IV NOTES TO THE UNAUDITED PRO FORMA CONDENSED

COMBINED FINANCIAL DATA 285

APPENDIX V PROPOSED MEMBERS OF THE FUTURE TAKEDA

EXECUTIVE TEAM (POST-EFFECTIVE DATE) 296

APPENDIX VI NON-GAAP RECONCILIATIONS 297

x

EXPECTED TIMETABLE OF PRINCIPAL EVENTS

All times shown are London times unless otherwise stated. All dates and times are indicative only, arebased on Shire’s and Takeda’s current expectations and are subject to change (including as a result ofchanges to Court times). If any of the dates and/or times in this expected timetable change, the reviseddates and/or times will be notified to Shire Shareholders and Shire ADS Holders by announcementthrough a Regulatory Information Service, which Shire will furnish to the SEC on Form 8-K.

Event Expected time/date

ADS Voting Record Time 5.00 p.m. (New York time)

on November 7, 2018

Latest time for receipt of ADS Voting Cards

(or valid telephone or internet voting instructions) 10.00 a.m. (New York time)

for the Court Meeting and the Shire General Meeting on November 29, 2018(1)

Latest time for receipt of Forms of Proxy for:

• Court Meeting (BLUE form) 11.15 a.m. on December 3, 2018(2)

• Shire General Meeting (YELLOW form) 11.30 a.m. on December 3, 2018(3)

Voting Record Time 6.30 p.m. on December 3, 2018(4)

Takeda Extraordinary General Meeting 10.00 a.m. (Tokyo time) on December 5, 2018

Court Meeting 11.15 a.m. on December 5, 2018(5)

Shire General Meeting 11.30 a.m. on December 5, 2018(5)(6)

The following dates are indicative only and subject to change; please see note (7) below:

Last time for Shire ADS Holders to present their

Shire ADSs for cancellation and take delivery of

Shire Shares to become Shire Shareholders 5.00 p.m. (New York time)

before the Scheme Record Time on December 26, 2018

Latest time for receipt of Forms of Election 6.00 p.m. on January 2, 2019

Court Sanction Hearing 10.00 a.m. on January 3, 2019

Last time for dealings in Shire Shares on

the London Stock Exchange 4.30 p.m. on January 4, 2019

Latest time for receipt of TTE Instructions and

disablement of Shire Shares in CREST 6.00 p.m. on January 4, 2019

Scheme Record Time 6.00 p.m. on January 4, 2019

Last time for dealings in Shire ADSs on NASDAQ close of business (New York time)

on January 4, 2019

Suspension of dealings in Shire Shares on

the London Stock Exchange before open of business on January 7, 2019

Halt of dealings in Shire ADSs on NASDAQ before open of business (New York time)

on January 7, 2019

Commencement of “when issued” dealings in 9.30 a.m. (New York time)

the New Takeda ADSs on the New York Stock Exchange on January 7, 2019

Effective Date of the Scheme January 8, 2019

1

Event Expected time/date

Effective date of the issue of the New Takeda Shares January 8, 2019

Cancellation of listing of Shire Shares on the premium

listing segment of the Official List and the main market

of the London Stock Exchange 8.00 a.m. on January 9, 2019

Delisting of Shire ADSs by 9.30 a.m. (New York time)

on January 9, 2019

Settlement Account credited with New Takeda Shares by 00.01 a.m. (9.01 a.m.

(Tokyo time)) on January 10, 2019

New Takeda Shares transferred from the Settlement from January 10, 2019, but in any

Account to JASDEC Accounts of former Shire event not later than 14 calendar days

Shareholders after the Effective Date(8)

Listing of, and commencement of dealings in,

the New Takeda Shares on the Tokyo Stock Exchange

and the Local Japanese Stock Exchanges January 10, 2019

New Takeda Shares transferred from the Settlement

Account to the Takeda Depositary’s JASDEC Account January 10, 2019

New Takeda ADSs and CDIs representing New Takeda from January 10, 2019, but in

ADSs delivered to former Shire Shareholders any event not later than 14 calendar

days after the Effective Date(9)

New Takeda ADSs delivered to former Shire ADS Holders from January 10, 2019(10)

Listing of, and commencement of regular-way dealings in, by 9.30 a.m. (New York time)

New Takeda ADSs on the New York Stock Exchange on January 11, 2019(11)

CREST accounts of former Shire Shareholders

credited with cash due under the Scheme and in within 14 calendar days of the

relation to fractional entitlements Effective Date(12)

Processing of electronic BACs transfers to former

Shire Shareholders in respect of cash due under the within 14 calendar days of the

Scheme and in relation to fractional entitlements Effective Date

Despatch of cheques to former Shire Shareholders for

the cash due under the Scheme and in relation to within 14 calendar days of the

fractional entitlements Effective Date

Despatch of cheques to former Shire Shareholders in

relation to the New Takeda Shares sold under within 14 calendar days of the

the Dealing Facility Effective Date

Payment of the cash due to former Shire ADS following receipt of funds by

Holders by the Shire Depositary the Shire Depositary(13)

Latest date by which Scheme may become Effective May 8, 2019(14)

Notes:

(1) In order to validly instruct the Shire Depositary as to voting at the Shire Meetings, the ADS Voting Card must be

received by the Shire Depositary by 10.00 a.m. (New York time) on November 29, 2018 for each Shire Meeting or, if

either Shire Meeting is adjourned, such later date as may be notified by the Shire Depositary, having consulted with

Shire. Please see “Action to be taken” on pages 5 to 18.

(2) The BLUE Form of Proxy for the Court Meeting, if not received by Equiniti by the time stated above, may be handed

to a representative of Equiniti, on behalf of the Chairman of the Court Meeting, or to the Chairman of the Court

Meeting, before the start of the Court Meeting.

2

(3) In order to be valid, the YELLOW Form of Proxy must be received by Equiniti not later than 11.30 a.m. on December

3, 2018 (or, if the Shire General Meeting is adjourned, not later than 48 hours before the time appointed for the

adjourned Shire General Meeting).

(4) If either the Court Meeting or the Shire General Meeting is adjourned, the Voting Record Time for the relevant

adjourned Shire Meeting will be 6.30 p.m. (London time) on the date falling two calendar days before the date

appointed for such adjourned Shire Meeting and the ADS Voting Record Time for the relevant adjourned Shire

Meeting will be such later date as may be notified by the Shire Depositary, having consulted with Shire.

(5) In the event that the Takeda Extraordinary General Meeting is postponed or adjourned, the Court Meeting and Shire

General Meeting will be adjourned so that they will take place on the same date as the Takeda Extraordinary General

Meeting.

(6) To commence at 11.30 a.m. (London time) or as soon thereafter as the Court Meeting shall have concluded or been

adjourned.

(7) These times and dates are indicative only and represent the earliest possible dates for the relevant principal events.

These dates will depend, among other things, on the dates upon which: (i) the Conditions are satisfied or (where

applicable) waived; (ii) the European Commission gives its approval to proceed to completion of the Acquisition (see

paragraph 7 of Part I (Letter from the Chairman of Shire PLC) of this document for further details); (iii) the Court sanctions

the Scheme; and (iv) the Court Order is delivered to the Registrar of Companies. If it becomes necessary to change

any of the dates and/or times in the expected timetable, including as a result of the timing of receipt of approval from

the European Commission to proceed to completion of the Acquisition, it is intended that the Effective Date will be as

soon as practicable after January 8, 2019. Shire will give adequate notice of any changes by issuing an announcement

through a Regulatory Information Service and will furnish such announcement to the SEC on Form 8-K.

(8) In order to avoid a delay in the completion of any such transfer, Shire Shareholders who make a valid JASDEC

Election to deliver their New Takeda Shares into an account with an AMI should contact their AMI to confirm any

necessary steps in order for the AMI to record the delivery of the New Takeda Shares from the Settlement Account.

(9) The date on which New Takeda ADSs will be delivered to Shire Shareholders will depend on the type of ADS Election

made. In order to avoid a delay in receiving their New Takeda ADSs, Shire Shareholders who make a valid ADS

Election to deliver their New Takeda ADSs to their broker or other securities intermediary in DTC should contact their

broker or other securities intermediary to request that it, or the DTC participant through which it clears, inputs valid

instructions to receive delivery of the New Takeda ADSs free of payment from the Takeda Depositary’s DTC

participant account (account number 2504).

(10) New Takeda ADSs will be delivered to the Shire Depositary from January 10, 2019 (and in any event not later than

14 calendar days after the Effective Date).

The date on which New Takeda ADSs will be delivered to Shire ADS Holders will depend on the way in which such

Shire ADS Holders held their Shire ADSs. It is expected that Shire ADS Holders holding through participants in DTC

will receive delivery shortly after the receipt by the Shire Depositary of the New Takeda ADSs and that registered

Shire ADS Holders holding uncertificated Shire ADSs (that is, Shire ADSs held outside of DTC for which no

certificates have been issued) will be issued New Takeda ADSs in uncertificated form beginning approximately one

week thereafter (and will receive a statement by post reflecting the issuance of New Takeda ADSs in their name).

Registered Shire ADS Holders holding certificates for their Shire ADSs will only receive delivery of their New Takeda

ADSs after they return their signed letter of transmittal and Shire ADS certificate to the Shire Depositary.

(11) The listing of, and commencement of regular-way dealings in, New Takeda ADSs on January 11, 2019 is subject to

DTC having completed its allocation of New Takeda ADSs to former Shire ADS Holders and the Shire Depositary

having made the relevant notification to the New York Stock Exchange in time for the New York Stock Exchange to

make the relevant announcement prior to close of business (New York time) on January 10, 2019.

(12) Shire Shareholders who hold Shire Shares in uncertificated form and receive the cash portion of the Consideration

in US Dollars must ensure that an active US Dollar Cash Memorandum Account is in place in CREST by no later than

the Scheme Record Time. In the absence of a US Dollar Cash Memorandum Account, the payment of the cash

portion of the Consideration will not settle, resulting in a delay and the settlement of the cash portion of the

Consideration outside of CREST.

(13) In the case of Shire ADS Holders who hold Shire ADSs in certificated form, subject to presentation by such holders

of their signed letters of transmittal and Shire ADS certificates to the Shire Depositary.

(14) The latest date by which the Scheme may become Effective may be extended by agreement in writing between Shire

and Takeda with the prior consent of the Panel and (if required) the approval of the Court.

3

ACTION TO BE TAKEN:

DOCUMENTS AVAILABLE TO SHIRE SHAREHOLDERS

All Shire Shareholders (other than Restricted Shire Shareholders)

Please check that you have received the following hard copy Forms of Proxy with this document:

• a BLUE Form of Proxy for use in respect of the Court Meeting on December 5, 2018; and

• a YELLOW Form of Proxy for use in respect of the Shire General Meeting on December 5, 2018.

Shire Shareholders (other than Restricted Shire Shareholders) who hold Shire Shares incertificated form

Please check that you have received (in addition to the Forms of Proxy listed above):

• a hard copy WHITE Certificated Form of Election (and its accompanying notes on how to

complete the Certificated Form of Election) for use in connection with the making of a Currency

Election and a Securities Election;

• an envelope, for use in the United Kingdom only, for returning the WHITE Certificated Form of

Election; and

• if you are considered likely to be eligible to make an election for the Dealing Facility, a hard copy

of the Dealing Facility Terms and Conditions.

Shire Shareholders (other than Restricted Shire Shareholders) who hold Shire Shares inuncertificated form (that is, in CREST)

Please check that you have received (in addition to the Forms of Proxy listed above):

• a hard copy GREEN CREST Form of Election (and its accompanying notes on how to complete

the CREST Form of Election) for use in connection with the making of a JASDEC Election,

Corporate Nominee Election or ADS Election (other than an ADS Election to receive CDIs

representing New Takeda ADSs or a Currency Election, which should be made by TTE

Instruction – see paragraph 2.1(c) of Part IX (Notes for making Elections) of this document); and

• an envelope, for use in the United Kingdom only, for returning the GREEN CREST Form of

Election.

Shire ADS Holders

Please check that you have received a copy of the following:

• an ADS Voting Card in respect of Shire ADSs; and

• the Notice of Court Meeting and Extraordinary General Meeting document issued by the Shire

Depositary.

If you have not received all applicable documents, please contact the relevant helpline on the number

indicated below or your financial intermediary.

Helplines

The helpline for Shire Shareholders is available between 8.30 a.m. and 5.30 p.m. (London time)

Monday to Friday (except public holidays in England and Wales) on 0330 123 5506 if calling from within

the UK or +44 (0)121 415 0856 if calling from outside the UK. Calls are charged at the standard

geographic rate and will vary by provider. Calls outside the United Kingdom will be charged at the

applicable international rate. Different charges may apply to calls from mobile telephones. Please note

that calls may be recorded or monitored.

The helpline for Shire ADS Holders is provided by the Shire Depositary and is available between

8.30 a.m. and 6.00 p.m. (New York time) Monday to Friday (except public holidays in the US) on +1 866

395 6421 from within the US or +1 781 575 4555 if calling from outside the US. Calls are charged at

the standard geographic rate and will vary by provider. Calls outside the US will be charged at the

applicable international rate.

Neither the Shire Shareholder Helpline nor the Shire ADS Holder Helpline can provide advice on the

merits of the Acquisition or give any financial, legal or tax advice.

4

ACTION TO BE TAKEN:

VOTING AT THE SHIRE MEETINGS

This section should be read in conjunction with the rest of this document, the accompanying Forms of

Proxy and Form of Election (including the accompanying notes on how to complete the relevant Form

of Election) and any document incorporated by reference.

The Shire Board considers the Acquisition to be in the best interests of the Shire Shareholderstaken as a whole. For the reasons set out in this document, the Shire Board unanimouslyrecommends that you vote in favour of the Scheme at the Court Meeting and the SpecialResolution relating to the Acquisition to be proposed at the Shire General Meeting, as the ShireDirectors who hold Shire Shares and/or Shire ADSs (as applicable) have irrevocably undertakento do in respect of their own beneficial holdings of Shire Shares (including such Shire Sharesunderlying Shire ADSs). The Shire Board therefore unanimously recommends that you take theaction described below.

IT IS IMPORTANT THAT, FOR THE COURT MEETING, AS MANY VOTES AS POSSIBLE ARE CASTSO THAT THE COURT MAY BE SATISFIED THAT THERE IS A FAIR AND REASONABLEREPRESENTATION OF SHIRE SHAREHOLDER OPINION. YOU ARE THEREFORE STRONGLYURGED TO COMPLETE, SIGN AND RETURN YOUR FORMS OF PROXY (OR APPOINT A PROXYONLINE OR THROUGH THE CREST ELECTRONIC PROXY APPOINTMENT SERVICE) OR ADSVOTING CARD AS SOON AS POSSIBLE.

The Scheme will require approval at a meeting of Shire Shareholders entitled to vote which is being

convened with the permission of the Court and is to be held at Block 3, Miesian Plaza, 50-58 Baggot

Street Lower, Dublin 2, Ireland at 11.15 a.m. (London time) on December 5, 2018. Implementation of

the Scheme will also require approval by Shire Shareholders of the Special Resolution relating to the

Acquisition to be proposed at the Shire General Meeting. The Shire General Meeting will be held at the

same place as the Court Meeting on December 5, 2018 at 11.30 a.m. (London time) (or as soon

thereafter as the Court Meeting shall have concluded or been adjourned).

Proxy appointment

Shire Shareholders entitled to attend and vote at the Shire Meetings are entitled to appoint a proxy to

exercise all or any of their rights to attend, speak and vote at the Court Meeting and/or Shire General

Meeting. A proxy need not be a Shire Shareholder. The completion and return of a Form of Proxy or the

appointment of a proxy or proxies through CREST or www.sharevote.co.uk shall not prevent a Shire

Shareholder from attending and voting in person at either Shire Meeting or any adjournment thereof, if

a Shire Shareholder so wishes and is so entitled. In the event of a poll on which a Shire Shareholder

votes in person, their proxy votes previously lodged with Equiniti, Shire or www.sharevote.co.uk will be

excluded.

Please note that the appointment of a proxy or proxies is separate for each of the Court Meeting and

the Shire General Meeting.

A person who has been nominated under article 59 of the Shire Articles to enjoy information rights (a

“Nominated Person”) may have a right under an agreement between him/her and the member bywhom he/she was nominated to be appointed, or to have someone else appointed, as a proxy for each

of the Court Meeting and the Shire General Meeting. If a Nominated Person has no such proxy

appointment right or does not wish to exercise it, he/she may have a right under such an agreement to

give instructions to the member as to the exercise of voting rights. The statement of the rights of

members to appoint proxies above does not apply to a Nominated Person. The rights described above

can only be exercised by Shire Shareholders. Nominated Persons are reminded that they should

contact the registered shareholder (and not Shire) on matters relating to the Shire Shares.

5

(a) Sending Forms of Proxy by post or by hand

Please complete and sign the Forms of Proxy in accordance with the instructions printed on them

and return them (together, if appropriate, with the power of attorney or other written authority

under which the Form of Proxy is signed or a certified copy of such power or authority), either:

(i) by post; or (ii) during normal business hours only, by hand, to Equiniti (Jersey) Limited, c/o

Equiniti Limited at Aspect House, Spencer Road, Lancing, West Sussex, BN99 6DA, United

Kingdom, so as to be received as soon as possible and in any event not later than the relevant

time set out below:

BLUE Forms of Proxy for the Court Meeting 11.15 a.m. (London time) on

December 3, 2018

YELLOW Forms of Proxy for the Shire General Meeting 11.30 a.m. (London time) on

December 3, 2018

or, if in either case the relevant Shire Meeting is adjourned, the relevant Form of Proxy should be

received not later than 48 hours before the time appointed for the adjourned Shire Meeting.

If the BLUE Form of Proxy for the Court Meeting is not returned by such time, it may be handed

to a representative of Equiniti, on behalf of the Chairman of the Court Meeting, or to the Chairman

of the Court Meeting, before the start of the Court Meeting. However, in the case of the Shire

General Meeting, the YELLOW Form of Proxy must be received by Equiniti by the time

mentioned above, or it will be invalid. Such invalidity will not, however, prevent a Shire

Shareholder from attending the Shire General Meeting and speaking and voting at the Shire

General Meeting in person if they are entitled and wish to do so.

Shire Shareholders are entitled to appoint a proxy in respect of some or all of their Shire Shares

and may also appoint more than one proxy, provided that each proxy is appointed to exercise the

rights attached to a different share or shares held by such holder. Shire Shareholders who wish

to appoint more than one proxy in respect of their holding of Shire Shares should contact Equiniti

for further Forms of Proxy or photocopy the Forms of Proxy as required.

(b) Online appointment of proxies

As an alternative to completing and returning the printed Forms of Proxy, proxies may be

appointed electronically by logging on to the following website: www.sharevote.co.uk and

following the instructions there. For an electronic proxy appointment to be valid, the appointment

must be received by Equiniti no later than 11.15 a.m. (London time) on December 3, 2018 for the

Court Meeting and 11.30 a.m. (London time) on December 3, 2018 for the Shire General Meeting

(or, in the case of adjournment(s), not later than 48 hours before the time appointed for the

adjourned Shire Meeting(s)). Full details of the procedure to be followed to appoint a proxy

electronically are given on the website.

In the case of the Court Meeting only, if you have not appointed a proxy electronically by such

time, you may complete the BLUE Form of Proxy and hand it to a representative of Equiniti, or

the Chairman of the Court Meeting, before the start of the Court Meeting.

(c) Electronic appointment of proxies through CREST

If you hold Shire Shares in uncertificated form – that is, in CREST – and wish to appoint a proxy

or proxies for the Shire Meetings (or any adjourned Shire Meeting) by using the CREST

electronic proxy appointment service, you may do so by using the procedures described in the

CREST Manual (please also refer to the accompanying notes to the notices of the Shire Meetings

set out in Part XII (Notice of Court Meeting) and Part XIII (Notice of Shire General Meeting) of

this document). CREST personal members or other CREST sponsored members, and those

CREST members who have appointed any voting service provider(s), should refer to their

CREST sponsor or voting service provider(s), who will be able to take the appropriate action on

their behalf.

6

In order for a proxy appointment or instruction made using the CREST service to be valid, the

appropriate CREST message (a “CREST Proxy Instruction”) must be properly authenticated inaccordance with the specifications of Euroclear and must contain the information required for

such instructions as described in the CREST Manual. The message (regardless of whether it

constitutes the appointment of a proxy or an amendment to the instructions given to a previously

appointed proxy) must, in order to be valid, be transmitted so as to be received by Equiniti

(ID 7RA01) not later than 48 hours before the time appointed for the Court Meeting or Shire

General Meeting (or adjourned Shire Meeting), as applicable. For this purpose, the time of receipt

will be taken to be the time (as determined by the time stamp applied to the message by the

CREST Application Host (as defined in the CREST Manual)) from which Equiniti is able to

retrieve the message by enquiry to CREST in the manner prescribed by CREST. After this time,

any change of instructions to proxies appointed through CREST should be communicated to the

appointee through other means.

CREST members and, where applicable, their CREST sponsors or voting service providers

should note that Euroclear does not make available special procedures in CREST for any

particular messages. Normal system timings and limitations will therefore apply in relation to the

input of CREST Proxy Instructions. It is the responsibility of the CREST member concerned to

take (or, if the CREST member is a CREST personal member or sponsored member or has

appointed any voting service provider(s), to procure that their CREST sponsor or voting service

provider(s) take(s)) such action as shall be necessary to ensure that a message is transmitted by

means of the CREST system by any particular time. In this connection, CREST members and,

where applicable, their CREST sponsors or voting service providers are referred, in particular, to

those sections of the CREST Manual concerning practical limitations of the CREST system and

timings.

Shire may treat as invalid a CREST Proxy Instruction in the circumstances set out in the CREST

Regulations.

Voting on the Acquisition if you are a Shire ADS Holder

A Shire ADS Holder can vote, or direct the voting of, the Shire Shares represented by its Shire ADSs in

a number of ways as further described in Part X (Further information for Shire ADS Holders) of this

document.

(a) Voting via the Shire Depositary

Shire ADS Holders as at the ADS Voting Record Time of 5.00 p.m. (New York time) on

November 7, 2018 should, if they wish to direct the voting of the Shire Shares represented by

their Shire ADSs that are held by the Shire Depositary (or its nominee), sign, complete and return

the ADS Voting Card in accordance with the instructions printed thereon and in the Notice of

Court Meeting and Extraordinary General Meeting received from the Shire Depositary in order to

instruct the Shire Depositary how to vote the Shire Shares represented by their Shire ADSs on

their behalf at the Court Meeting and the Shire General Meeting. The ADS Voting Card should

be returned by mail to Shire plc, c/o Citibank Shareholder Services, PO Box 43099, Providence

RI 02940-5000, USA, as soon as possible and, in any event, so as to be received no later than

10.00 a.m. (New York time) on November 29, 2018 or if either the Court Meeting or the Shire

General Meeting is adjourned, such later date as may be notified by the Shire Depositary, having

consulted with Shire. Alternatively, Shire ADS Holders as at the ADS Voting Record Time of

5.00 p.m. (New York time) on November 7, 2018 may instruct the Shire Depositary with voting

instructions by internet or telephone, as set out in the instructions printed on the ADS Voting Card

and in the Notice of Court Meeting and Extraordinary General Meeting received from the Shire

Depositary.

Shire ADS Holders who hold their Shire ADSs indirectly must follow the instructions from their

custodian, broker or other agent through which they hold their Shire ADSs if they wish to give

voting instructions to the Shire Depositary. Providing voting instructions via a custodian, broker

7

or other agent may require the provision of information by a particular deadline, well in advance

of the deadline to give the Shire Depositary voting instructions, and therefore you are encouraged

to reach out to such custodian, broker or other agent for any such deadline as quickly as

possible.

Following timely receipt of a signed and completed ADS Voting Card (or instructions by internet

or telephone) from a Shire ADS Holder, the Shire Depositary shall endeavour, insofar as

practicable and permitted under the provisions of, or governing, the Shire Shares represented by

Shire ADSs, to vote or cause its nominee to vote (by means of the appointment of a proxy or

otherwise) such Shire Shares represented by the Shire ADSs in respect of which instructions

have been received in accordance with those instructions.

The Shire Deposit Agreement provides that the Shire Depositary will not exercise any voting

discretion in respect of the Shire Shares represented by Shire ADSs. If the Shire Depositary does

not receive an ADS Voting Card (or instructions by internet or telephone) from a Shire ADS

Holder before 10.00 a.m. (New York time) on November 29, 2018 in respect of their entire holding

of Shire ADSs, then:

(i) in respect of the Shire General Meeting only, subject to the terms of the Shire Deposit

Agreement, such Shire ADS Holder shall be deemed to have instructed the Shire

Depositary to give a person designated by Shire a discretionary proxy to vote the Shire

Shares represented by the Shire ADSs in respect of which the Shire Depositary has not

received voting instructions. Any such Shire ADS Holder may be required, in accordance

with DTR 5 of the Disclosure Guidance and Transparency Rules, to notify Shire of their

relevant holding of Shire ADSs if the percentage of their voting rights falls below a

notifiable threshold as a result of a person designated by Shire having been so appointed.

In the event that a person designated by Shire is given such a discretionary proxy, it is the

intention of the Shire Board to direct such person to exercise such votes in line with the

voting recommendation of the Shire Board for each of the resolutions to be proposed at

the Shire General Meeting; and

(ii) in respect of the Court Meeting, such Shire ADS Holder shall not be deemed to have

instructed the Shire Depositary to give a person designated by Shire a discretionary proxy

to vote the Shire Shares represented by the Shire ADSs in respect of which the Shire

Depositary has not received voting instructions. Accordingly, the Shire Shares represented

by the Shire ADSs in respect of which the Shire Depositary has not received voting

instructions will not be represented at the Court Meeting and will not be voted at the Court

Meeting.

(b) Cancellation of Shire ADSs so as to become a Shire Shareholder

Shire ADS Holders who wish to attend the Court Meeting and/or the Shire General Meeting must

take steps to present their Shire ADSs (and, to the extent that such Shire ADSs are certificated,

the certificates evidencing such Shire ADSs) to the Shire Depositary for cancellation before 5.00

p.m. (New York time) on November 23, 2018 (subject to the relevant Shire ADS Holder’s

compliance with the terms of the Shire Deposit Agreement and payment of the Shire Depositary’s

fees), together with: (i) delivery instructions for the Shire Shares represented by such Shire ADSs

(including, if applicable, the name and address of the person who will be the registered holder of

such Shire Shares); and (ii) if the cancellation is to take place before the Shire Meetings, a

certification that the Shire ADS Holder: (x) beneficially owned the relevant Shire ADSs as at the

ADS Voting Record Time and has not given, and will not give, voting instructions to the Shire

Depositary in respect of such Shire ADSs in relation to the Shire Meetings (or has cancelled all

voting instructions previously given); (y) beneficially owned the relevant Shire ADSs as at the

ADS Voting Record Time and has given voting instructions to the Shire Depositary in respect of

such Shire ADSs in relation to the Shire Meetings, but undertakes not to vote the Shire Shares

represented by such Shire ADSs at the Shire Meetings; or (z) did not beneficially own the

relevant Shire ADSs as at the ADS Voting Record Time, but undertakes not to vote the Shire

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Shares represented by such Shire ADSs at the Shire Meetings. Shire ADS Holders who hold their

Shire ADSs in a brokerage, bank, custodian or other nominee account should promptly contact

their broker, bank or other nominee to find out what actions are required to instruct the broker,

bank or other nominee to cancel the Shire ADSs on their behalf. Shire ADS Holders who present

their Shire ADSs to the Shire Depositary for cancellation prior to 5.00 p.m. (New York time) on

November 23, 2018 in order to take delivery of Shire Shares will be responsible for the payment

of the Shire Depositary’s fees associated with such cancellation.

Shire ADS Holders will not be permitted to cancel their Shire ADSs from 5.00 p.m. (NewYork time) on November 23, 2018 until 8.00 a.m. (New York time) on December 4, 2018.Shire ADS Holders who take steps (as described in the paragraphs above) to cancel their Shire

ADSs before 5.00 p.m. (New York time) on November 23, 2018 and become Shire Shareholders

before the Voting Record Time will also have the right to attend the Court Sanction Hearing in

person and be represented by counsel to support or oppose the sanctioning of the Scheme.

Further details are set out in Part X (Further information for Shire ADS Holders) of this document.

9

ACTION TO BE TAKEN:

MAKING AN ELECTION IN RESPECT OF THE CONSIDERATION

This section should be read in conjunction with the rest of this document, the accompanying Forms of

Proxy and Form of Election (including the accompanying notes on how to complete the relevant Form

of Election) and any document incorporated by reference.

FLOWCHARTS HAVE BEEN INCLUDED ON PAGES 16 TO 18 IN ORDER TO ASSIST YOU IN MAKING AN ELECTION IN RESPECT OF THE CONSIDERATION.

Background

Under the terms of the Acquisition, the holders of Shire Shares whose names appear on the register of

members of Shire at the Scheme Record Time will be entitled to receive for each Shire Share: (i) $30.33

in cash; and (ii) either 0.839 New Takeda Shares or 1.678 New Takeda ADSs in accordance with the

terms of the Scheme.

The New Takeda Shares will be listed and traded on the Tokyo Stock Exchange and the Local Japanese

Stock Exchanges. All shares of Japanese listed companies, including those of Takeda, are

dematerialised and are held in uncertificated form through an entry in the record maintained by Japan

Securities Depository Center, Inc. (“JASDEC”). In order to hold and trade listed Japanese shares,investors must have an account with either JASDEC or an account management institution (“AMI”) thathas been admitted to JASDEC pursuant to Japanese law. Further details are set out in paragraph 19.1

of Part II (Explanatory Statement) of this document.

New Takeda Shares are not capable of being held in certificated form, or transferred or settled directly

through the CREST settlement system. For this reason, Shire Shareholders have a number of options

to hold their New Takeda Shares indirectly.

Each Shire Shareholder (other than a Restricted Shire Shareholder) who holds Shire Shares in

certificated form at the Scheme Record Time, in respect of each Shire Share which they hold:

(a) may make a Currency Election in respect of the cash portion of the Consideration payable to

them under the Scheme; and

(b) should make at least one of four possible Securities Elections in respect of the non-cash portion

of the Consideration which they are entitled to receive under the Scheme.

Each Shire Shareholder (other than a Restricted Shire Shareholder) who holds Shire Shares in

uncertificated form (that is, in CREST) at the Scheme Record Time, in respect of each Shire Share

which they hold:

(a) may make a Currency Election in respect of the cash portion of the Consideration payable to

them under the Scheme; and

(b) should make at least one of three possible Securities Elections in respect of the non-cash portion

of the Consideration which they are entitled to receive under the Scheme.

In certain cases, Shire Shareholders are permitted to split their holding of Shire Shares such that they

may make multiple Securities Elections in relation to their holding. Further details are set out in

paragraph 5 of Part IX (Notes for making Elections) of this document.

Elections by Shire Shareholders holding Shire Shares in certificated form

(a) Currency Election

Shire Shareholders who hold Shire Shares in certificated form and have a registeredaddress in the United Kingdom, Channel Islands or Isle of Man as at the Scheme Record

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Time will be deemed to have elected for the Currency Conversion Facility and will receivethe entire cash portion of the Consideration payable to them under the Scheme in poundsSterling (net of any applicable customary transaction and dealing costs associated withthe conversion) at the applicable market exchange rate on the latest reasonablypracticable date for fixing such rate before the relevant payment date under the CurrencyConversion Facility. Such Shire Shareholders may opt out of the Currency Conversion Facility,which would result in such Shire Shareholders receiving the cash portion of the Consideration in

US Dollars, by completing and returning an Opt-out Form (a copy of which may be obtained by

contacting the Shareholder Helpline).

Unless they elect otherwise, each Shire Shareholder who holds Shire Shares incertificated form and does not have a registered address in the United Kingdom, ChannelIslands or Isle of Man as at the Scheme Record Time will receive the cash portion of theConsideration which is payable to them under the Scheme in US Dollars. Such ShireShareholders may elect to have the US Dollar cash portion of the Consideration which is payable

to them under the Scheme instead paid in pounds Sterling (net of any applicable customary

transaction and dealing costs associated with the conversion) at the applicable market exchange

rate on the latest reasonably practicable date for fixing such rate before the relevant payment

date under the Currency Conversion Facility (by completing Part 3 on the WHITE Certificated

Form of Election).

Each Shire Shareholder who has set up a standing electronic payment mandate with the Shire

Registrar for the purpose of receiving dividend payments from Shire in pounds Sterling will,

subject to such Shire Shareholder having made (or being deemed to have made) a valid

Currency Election to receive the cash portion of their Consideration in pounds Sterling, receive

the cash portion of the Consideration payable to them pursuant to the Scheme by way of an

electronic BACs transfer to the account indicated in such mandate. In the absence of a standing

electronic payment mandate held by the Shire Registrar for receiving dividend payments from

Shire in pounds Sterling, a cheque will be issued and despatched to each relevant Shire

Shareholder at their registered address.

(b) Securities Election

Subject to the terms and conditions set out in this document, each Shire Shareholder (other than

a Restricted Shire Shareholder) who holds Shire Shares in certificated form at the Scheme

Record Time may, in relation to their holding of Shire Shares, make at least one of the following

Elections (each a “Securities Election”):

(a) elect to hold the New Takeda Shares which they are entitled to receive pursuant to the

Scheme in their own JASDEC Account (by completing Part 4A on the WHITE Certificated

Form of Election) (a “JASDEC Election”). Please refer to paragraphs 19.1 and 19.3(a) ofPart II (Explanatory Statement) of this document for a summary of the background to

holding New Takeda Shares through a JASDEC Account and for further information

concerning the making of a JASDEC Election;

(b) in the case of a Shire Shareholder who has a registered address in the EEA, Channel

Islands, Isle of Man, Switzerland or Gibraltar as at the Scheme Record Time, elect to have

the New Takeda Shares which they are entitled to receive pursuant to the Scheme held on

their behalf through the Corporate Nominee Facility, subject to the Corporate Nominee

Facility Terms and Conditions (by completing Part 4B on the WHITE Certificated Form of

Election) (a “Corporate Nominee Election”). Please refer to paragraph 19.3(b) of Part II(Explanatory Statement) of this document for further information concerning the making of

a Corporate Nominee Election and to paragraph 21 Part II (Explanatory Statement) of this

document for summary details of the Corporate Nominee Facility;

(c) elect to receive 1.678 New Takeda ADSs (each New Takeda ADS representing 0.5 New

Takeda Shares) for each Shire Share they hold instead of the 0.839 New Takeda Shares

11

per Shire Share they would otherwise have been entitled to receive pursuant to the

Scheme, subject to the terms and conditions applicable to the New Takeda ADSs (by

completing Part 4C on the WHITE Certificated Form of Election) (an “ADS Election”).Please refer to paragraph 19.3(c) of Part II (Explanatory Statement) of this document for

further information concerning the making of an ADS Election and to paragraph 5 of Part

V (Takeda Securities) of this document for summary details of the New Takeda ADSs; or

(d) in the case of a Shire Shareholder who holds 200 or fewer Shire Shares in certificated form

as at the Scheme Record Time and has a registered address in the EEA, Channel Islands,

Isle of Man, Switzerland or Gibraltar as at the Scheme Record Time, elect to have all (but

not some only) of the New Takeda Shares which they are entitled to receive pursuant to

the Scheme sold on their behalf under the Dealing Facility and to have the net proceeds

of such sale (after deduction of all expenses and commissions incurred in connection with

such sale) remitted to them in pounds Sterling (by completing Part 4D on the WHITE

Certificated Form of Election) (a “Dealing Facility Election”). Please refer to paragraph19.3(d) of Part II (Explanatory Statement) of this document for further information

concerning the making of a Dealing Facility Election.

Each Shire Shareholder who does not make a valid Securities Election in respect of all oftheir Shire Shares will receive 0.839 New Takeda Shares for each Shire Share they hold atthe Scheme Record Time in respect of which no such Securities Election has been made.Such New Takeda Shares will be held in the name of the Representative as bare trustee for such

Shire Shareholder until the earlier of: (i) the delivery of a valid Securities Election by such Shire

Shareholder to Equiniti in relation to the action which should be taken in respect of the New

Takeda Shares (in which case the Representative will procure that such action is taken as is

required in order to give effect to such Securities Election); and (ii) the date which falls three

months from the Effective Date (in which case the Representative will procure that such New

Takeda Shares are sold in the market in accordance with the Sales Policy and that the net

proceeds of sale (after the deductions specified in the Sales Policy) are paid to such Shire

Shareholder).

Flowcharts explaining the availability of the above Elections are included on pages 16 to 18 and

details of how to complete the Certificated Form of Election are included in the notes which

accompany the Certificated Form of Election.

Elections by Shire Shareholders holding Shire Shares in uncertificated form (that is, in CREST)

(a) Currency Election

Unless they elect otherwise, each Shire Shareholder who holds Shire Shares inuncertificated form (that is, in CREST) at the Scheme Record Time and does not make avalid Currency Election will receive the cash portion of the Consideration which is payableto them under the Scheme in US Dollars. Such Shire Shareholders may elect to have the USDollar cash portion of the Consideration which is payable to them under the Scheme instead paid

in pounds Sterling (net of any applicable customary transaction and dealing costs associated with

the conversion) at the applicable market exchange rate on the latest reasonably practicable date

for fixing such rate before the relevant payment date under the Currency Conversion Facility (by

making the relevant TTE Instruction through CREST).

Each Shire Shareholder who holds Shire Shares in uncertificated form at the SchemeRecord Time and does not make a valid Currency Election must ensure that an active USDollar Cash Memorandum Account is in place in CREST by no later than the SchemeRecord Time. In the absence of a US Dollar Cash Memorandum Account, the payment of thecash portion of the Consideration will not settle, resulting in a delay and the settlement of the

cash portion of the Consideration outside of CREST.

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(b) Securities Election

Subject to the terms and conditions set out in this document, each Shire Shareholder (other than

a Restricted Shire Shareholder) who holds Shire Shares in uncertific