Adderall XR Defence Status: 9th January 2003

Adderall XR Defence

    Status: 9th January 2003

Comment on the “Safe Harbor” Statement under the Private
 Securities Litigation Reform Act of 1995

The statements made during today’s presentation, or in response to questions during the Question
& Answer period, that are not historical facts are forward-looking statements. Such forward-looking
statements involve a number of risks and uncertainties and are subject to change at any time. In
the event that such risks or uncertainties materialise, Shire’s results could be materially affected.
The risks and uncertainties include, but are not limited to, risks associated with the inherent
uncertainty of pharmaceutical research, product development and commercialisation, the impact of
competitive products, including but not limited to the impact of same on Shire’s ADHD franchise,
patents, government regulation and approval, including but not limited to the expected approval
date of lanthanum carbonate (Fosrenol/Fosnol) and other risks and uncertainties detailed from time
to time in periodic reports produced by Shire, including the Annual Report filed on Form 10K by
Shire with the Securities and Exchange Commission.

Trademark Information:
Unless otherwise indicated, certain product names set out in this document are trademarks of the Shire Group,
many of which are the subject of trademark registrations in certain territories. These names include, but are not
limited to, Adderall, Adderall XR, Agrylin, Colazide, Carbatrol, DextroStat, Dirame, Fluviral S/F, Fosrenol, Foznol,
MMX, Pacis, Pentasa, ProAmatine, Solaraze, Troxatyl, EnSoTrol, Microtrol, OptiScreen, ProScreen, and Solutrol.
3TC, Epivir, Combivir, Trizivir, and Zeffix are trademarks of GlaxoSmithKline. Reminyl and Concerta are
trademarks of Johnson & Johnson. Aricept is a trademark of Pfizer / Eisai. Exelon is a trademark of Novartis.
NeisVac-C is a trademark of Baxter International. Adept is a trademark of ML Laboratories.

Introductory Comments

 We were informed late on 8.1.2003 that the FDA is showing on one of their
 websites that they have received an ANDA for a generic copy of Adderall XR.
 However Shire has not received a paragraph IV declaration or any other formal
 advice on the above.
 Shire has regularly maintained that it was highly likely that generic companies
 would submit such an ANDA attempting to receive an FDA approval.
 Our strategy to defend our leadership position in the US ADHD market is
 explained in the enclosed slides.
 The statements on these slides are based on information currently available to
 us and as currently understood.
 It is our intention to update this document or issue separate statements as
 appropriate, when important, new information becomes available.

Adderall versus Adderall XR

 Adderall*
      no exclusivity or patent protection in recent years
      no reporting requirement from a generic applicant to Shire at the time of an
      ANDA submission
      no knowledge when a competitor submitted an ANDA

 As the following slides explain, Adderall XR is in a totally different and
 stronger position!

* 1997 to 2001 perspective

Adderall versus Adderall XR (cont.)

        As with Adderall, we have planned
         our future ADHD strategy carefully.

Adderall XR: Patent status

  Adderall XR based on paediatric indication has Hatch-Waxman
 exclusivity until October 2004 and
  Adderall XR is protected by a valid, pharmaceutical composition patent
     The patent extends until 2018
 It will be difficult for a generic company to develop a similar product that
    receives AB rating that could be substituted for Adderall XR and
    does not infringe our patent and
    offers similar patient benefits including
        capsule presentation, sprinkle form
        speed of onset, duration of action and effect size

ANDA application for generic version of Adderall XR

 Once a generic company submits an ANDA:
    They must provide a paragraph IV certification to the FDA and supply notice
    to Shire if they are seeking to market before expiry of Shire’s patent (2018)
    Shire has 45 days from the notice to decide whether to initiate legal action
    against the ANDA applicant for potential patent infringement
    It is our policy, to rigorously defend our IP
    While the potential legal action is pending, the FDA will not approve the
    ANDA. The approximate duration of such legal actions is 30 months
    If Shire succeeds in the infringement action, the FDA will not approve the
    ANDA and Shire’s rights through the life of the patent remain
    If Shire loses, the FDA may approve the ANDA
        Based on 30 months litigation, currently, the earliest entry would
        be mid 2005.

sNDA for adult indication of Adderall XR

 Shire submitted on 18.12.2002 a supplementary NDA for the use of
 Adderall XR in adults.
 This submission is for specific strengths for use in adults, is supported
 by clinical data and is expected to attract its own 3 year Hatch-Waxman
 protection
 Subject to FDA approval and the assumption that this approval would be
 received by early 2004, this additional Hatch-Waxman protection would
 extend to early 2007.

Paediatric Extension

 Subject to the FDA and Shire agreeing an appropriate clinical trial
 programme for Adderall XR, Shire could receive a 6 months extension to
 the Hatch-Waxman protection period for its Adderall XR approvals.
 It is our current understanding that, if agreed with FDA, such an
 extension would add 6 months of protection both to the paediatric and
 the adult Hatch-Waxman protection periods.
 This would extend the Hatch-Waxman paediatric protection from
 October 2004 to April 2005 and for the adult indication from potentially
 early 2007 (subject to FDA approval) to mid 2007.