Creating the global leader
`in Rare Diseases
`Fourth quarter and full year results
`to December 31, 2015
`
`4
`
`Flemming Ornskov, M.D.
`CEO
`Jeff Poulton
`CFO
`Phil Vickers, Ph.D.
`Head of R&D
`
`February 11, 2016
`
`CFAD Exhibit 1063
`CFAD v. NPS
`IPR2015-01093
`
`

`
`“SAFE HARBOR” Statement Under the Private Securities
`Litigation Reform Act of 1995
`
`Forward-Looking Statements
`Statements included herein that are not historical facts, including without limitation statements concerning our proposed business combination with Baxalta Incorporated (“Baxalta”) and the timing and financial and
`strategic benefits thereof, our 20x20 ambition that targets $20 billion in combined product sales by 2020, as well as other targets for future financial results, capital structure, performance and sustainability of the
`combined company, the combined company’s future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline
`products 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 such risks or uncertainties materialize, Shire’s
`results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:
`• the proposed combination with Baxalta may not be completed due to a failure to satisfy certain closing conditions, including any shareholder or regulatory approvals or the receipt of applicable tax opinions;
`• disruption from the proposed transaction with Baxalta may make it more difficult to conduct business as usual or maintain relationships with patients, physicians, employees or suppliers;
`• the combined company may not achieve some or all of the anticipated benefits of Baxalta’s spin-off from Baxter International, Inc. (“Baxter”) and the proposed transaction may have an adverse impact on Baxalta’s
`existing arrangements with Baxter, including those related to transition, manufacturing and supply services and tax matters;
`• the failure to achieve the strategic objectives with respect to the proposed combination with Baxalta may adversely affect the combined company’s financial condition and results of operations;
`• products and product candidates may not achieve commercial success;
`• product sales from ADDERALL XR and INTUNIV are subject to generic competition;
`• the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payers in a timely manner for the combined company’s products may affect future revenues, financial condition
`and results of operations, particularly if there is pressure on pricing of products to treat rare diseases;
`• supply chain or manufacturing disruptions may result in declines in revenue for affected products and commercial traction from competitors; regulatory actions associated with product approvals or changes to
`manufacturing sites, ingredients or manufacturing processes could lead to significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
`• the successful development of products in various stages of research and development is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive
`regulatory approval;
`• the actions of certain customers could affect the combined company’s ability to sell or market products profitably, and fluctuations in buying or distribution patterns by such customers can adversely affect the combined
`company’s revenues, financial condition or results of operations;
`• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to the combined company’s activities in the highly regulated markets in which it operates may result in significant legal
`costs and the payment of substantial compensation or fines;
`• adverse outcomes in legal matters and other disputes, including the combined company’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material
`adverse effect on the combined company’s revenues, financial condition or results of operations;
`• Shire is undergoing a corporate reorganization and was the subject of an unsuccessful acquisition proposal and the consequent uncertainty could adversely affect the combined company’s ability to attract and/or retain
`the highly skilled personnel needed to meet its strategic objectives;
`• failure to achieve the strategic objectives with respect to Shire’s acquisition of NPS Pharmaceuticals Inc. or Dyax Corp. (“Dyax”) may adversely affect the combined company’s financial condition and results of
`operations;
`• the combined company will be dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks
`and other security breaches or data leakages that could have a material adverse effect on the combined company’s revenues, financial condition or results of operations;
`• the combined company may be unable to retain and hire key personnel and/or maintain its relationships with customers, suppliers and other business partners;
`• difficulties in integrating Dyax or Baxalta into Shire may lead to the combined company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at
`the time anticipated or at all; and
`other risks and uncertainties detailed from time to time in Shire’s, Dyax’s or Baxalta’s filings with the Securities and Exchange Commission (“SEC”), including those risks outlined in Baxalta’s current Registration
`Statement on Form S-1, as amended, and in “Item 1A: Risk Factors” in Shire’s Annual Report on Form 10-K for the year ended December 31, 2014.
`All forward-looking statements attributable to us or any person acting on our 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, we do not undertake any obligation to republish revised forward-looking statements to reflect
`events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
`
`2
`
`

`
`“SAFE HARBOR” Statement Under the Private Securities
`Litigation Reform Act of 1995 (continued)
`
`Additional Information
`This communication does not constitute an offer to buy or solicitation of any offer to sell securities or a solicitation of any vote or approval. It does not constitute a prospectus or prospectus equivalent document. This
`communication relates to the proposed business combination between Shire and Baxalta. The proposed combination will be submitted to Shire’s and Baxalta’s shareholders for their consideration and approval. In connection
`with the proposed combination, Shire and Baxalta will file relevant materials with (i) the SEC, including a Shire registration statement on Form S-4 that will include a proxy statement of Baxalta and a prospectus of Shire, and
`(ii) the Financial Conduct Authority (FCA) in the UK, including a prospectus relating to Shire ordinary shares to be issued in connection with the proposed combination and a circular to the shareholders of Shire. Baxalta will
`mail the proxy statement/prospectus to its shareholders and Shire will mail the circular to its shareholders. This communication is not a substitute for the registration statement, proxy statement/prospectus, UK prospectus,
`circular or other document(s) that Shire and/or Baxalta may file with the SEC or the FCA in connection with the proposed transaction. INVESTORS AND SECURITY HOLDERS OF SHIRE AND BAXALTA ARE URGED TO
`READ CAREFULLY THE REGISTRATION STATEMENT,PROXY STATEMENT/PROSPECTUS AND OTHER DOCUMENTS FILED WITH THE SEC AND THE UK PROSPECTUS AND CIRCULAR WHEN THEY BECOME
`AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT SHIRE, BAXALTA AND THE PROPOSED TRANSACTION. Investors and security holders may obtain free copies of these documents
`(when they are available) and other related documents filed with the SEC at the SEC’s web site at www.sec.gov. Investors may request copies of the documents filed with the SEC by Shire by directing a request to Shire’s
`Investor Relations department at Shire plc, Attention: Investor Relations, 300 Shire Way, Lexington, MA 02421 or to Shire’s Investor Relations department at +1 484 595 2220 in the U.S. and +44 1256 894157 in the UK or
`by email to investorrelations@shire.com. Investors may request copies of the documents filed with the SEC by Baxalta by directing a request to Mary Kay Ladone at mary.kayklandone@baxalta.com or (224) 948-3371.
`
`The statements in this presentation are Shire’s statements and not those of Baxalta or any third party.
`
`Certain Information Regarding Participants
`Shire, Baxalta and their respective directors and executive officers may be deemed participants in the solicitation of proxies in connection with the proposed transaction. You can find information about Shire’s directors and
`executive officers in Shire’s Annual Report on Form 10-K for the year ended December 31, 2014, which was filed with the SEC on February 24, 2015. You can find information about Baxalta’s directors and executive officers
`in Baxalta’s registration statement on Form S-1, which was filed with the SEC on September 1, 2015.Additional information regarding the special interests of these directors and executive officers in the proposed transaction
`will be included in the registration statement, proxy statement/prospectus or other documents filed with the SEC if any when they become available. You may obtain these documents (when they become available) free of
`charge at the SEC’s web site at www.sec.gov and from Investor Relations at Shire or Baxalta as described above.
`
`This communication shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful
`prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act
`of 1933, as amended.
`
`Trademarks
`Shire owns or has rights to use the trademarks, service marks and trade names that it uses in conjunction with the operation of its business. Some of the trademarks that Shire owns or has the rights to use that are
`referenced in this communication include: ADDERALL XR, CINRYZE, ELAPRASE, FIRAZYR, GATTEX/REVESTIVE, INTUNIV, LIALDA, NATPARA, REPLAGAL, PENTASA, VPRIV, VYVANSE and XAGRID. Baxalta states
`that it owns or has the right to use certain trademarks referenced in this communication, including: ADVATE, ADYNOVATE, ARALAST, FEIBA, FLEXBUMIN, GAMMAGARD, GAMMAGARD LIQUID, GLASSIA, HYQVIA,
`OBIZUR, ONCASPAR, ONIVYDE, RECOMBINATE, RIXUBIS and SUBCUVIA, which may be registered or used in the United States and other jurisdictions.
`
`Basis of Forecasts
`The Shire forecasts included herein are derived from Shire’s Long Range Plan (the "LRP") and Shire papers subsequently produced as part of the business planning process. Shire produces a long range plan annually. The
`LRP was updated in March 2015, as part of Shire’s annual planning cycle, and was reviewed by the Board in April 2015. This LRP was subsequently adjusted to reflect revised expectations for SHP625 following trial results
`in the second quarter of 2015, the Dyax acquisition and other updates for 2015 actual performance.
`
`The forecast product sales in Shire’s January 11, 2016 announcement on the proposed combination with Baxalta are consistent with the LRP, which is at constant exchange rates, and reflects net sales for each product and
`key line extensions currently identified as in Phase III, Phase II and those in Phase I included in the LRP as launching before the end of 2020.
`
`The forecast product sales included in the LRP are risk-adjusted to reflect Shire’s assessment of the individual probability of launch of products in development, and the probability of success in further life cycle management
`trials. Estimates for these probabilities are based on industry wide data for relevant clinical trials in the pharmaceutical industry at a similar stage of development.
`
`For each pharmaceutical product, there is a range of possible outcomes from clinical development, driven by a number of variables, including safety, efficacy and product labelling. In addition, if a product is approved, the
`effect of commercial factors including the patient population, the competitive environment, pricing and reimbursement is also uncertain. As a result, the actual net sales achieved by a product over its commercial life will be
`different, perhaps materially so, from the risk adjusted net sales figures in this announcement and should be considered in this light.
`
`The forecast product sales for Baxalta’s included in this communication have been stated on a constant currency and risk adjusted basis.
`
`IMS information is an estimate derived from the use of information under license from the following IMS Health information service: IMS NPA Weekly for the period Jan 17, 2014 to Jan 22, 2016.
`IMS expressly reserves all rights, including rights of copying, distribution and republication.
`
`3
`
`

`
`Agenda
`
`Creating the global leader
`in Rare Diseases
`
`Progressing our innovative pipeline
`
`Financial review
`
`Summary
`
`Q & A
`
`Flemming
`Ornskov, M.D.
`
`Phil
`Vickers, Ph.D
`
`Jeff
`Poulton
`
`Flemming
`Ornskov, M.D.
`
`All
`
`4
`
`

`
`Our continuous transformation
`
`2013
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`2019
`
`2020+
`
`Investing to create
`further long-term value
`
`2014-2016
`Building a leading global biotech company
`Creating scale and momentum
`Culture of bold innovation – internal and external
`Patient-centric Rare Diseases mindset
`
`2016+
`Global Leadership in Rare Diseases
`Multiple, durable, best-in-class products
`Compelling financial profile
`Enhanced diversification and optionality
`
`2013-2015
`Becoming OneShire
`Step-change in performance
`Effective and efficient organization
`Established foundation for long-term growth
`
`5
`
`

`
`2015 & recent achievements:
`significant steps towards advancing our strategy
`
`• Closed NPS
`Pharma acquisition
`adding two new
`rare disease assets
`in GATTEX/
`REVESTIVE and
`NATPARA/NATPAR
`
`Lifitegrast
`for adults with
`Dry Eye Disease
`
`• Reported positive
`results from the
`OPUS-3 study
`
`• Resubmitted NDA
`on January 22,
`2016 for treatment
`of signs and
`symptoms of Dry
`Eye Disease
`
`• FDA acceptance of
`NDA and July 22,
`2016 PDUFA date
`
`• Closed Dyax Corp
`acquisition
`
`• SHP643 (DX2930)
`expands and
`extends Shire’s
`leading Hereditary
`Angioedema (HAE)
`portfolio
`
`• Announced
`combination with
`Baxalta, which would
`create the global
`leader in Rare
`Diseases
`
`6
`
`

`
`2015: Recent & full-year highlights
`
`GROWTH
`Double-digit CER(1)(4) product sales
`growth excluding INTUNIV in FY 2015
`
`Double-digit Non GAAP diluted
`earnings per ADS(2)(4) growth in FY 2015
`
`Strong performance driven by VYVANSE,
`LIALDA/MEZAVANT, CINRYZE, FIRAZYR,
`and the inclusion of GATTEX/REVESTIVE
`and NATPARA
`
`NPS assets continue to benefit from
`Shire’s GI and Rare Disease expertise
`
`Announced combination with Baxalta,
`which would create a global
`biotechnology company with leadership
`in Rare Diseases
`
`INNOVATION
`Closed Dyax acquisition, reinforcing
`Shire’s leadership in HAE
`
`PDUFA date for lifitegrast of July
`22, 2016; launch anticipated Q3
`2016(3)
`
`Initiated three Phase 3 studies :
`
`CINRYZE for AMR
`
`CINRYZE subcutaneous (SC) for HAE
`
`SHP621 for eosinophilic esophagitis
`
`Completed Phase 3 enrollment of
`SHP465 ahead of schedule; results
`expected H1:16
`Completed Phase 2 enrollment of
`SHP607 for retinopathy of prematurity;
`results expected mid-2016
`
`(1) Constant exchange rates (“CER”), a Non GAAP financial measure. CER performance is determined by comparing 2015 performance (restated using 2014
`exchange rates) to actual 2014 reported performance.
`(2) This is a Non GAAP financial measure. The most directly comparable measure under U.S. GAAP is EPS-ADS (FY 2015: $6.59, FY 2014: $17.28).
`(3) Subject to regulatory approval.
`(4) See slide 39 for a list of items excluded from the U.S. GAAP equivalent used to calculate all Non GAAP measures detailed above. A reconciliation of Non GAAP
`financial measures to the most directly comparable measure under U.S. GAAP is presented in Shire's Q4 2015 earnings release on pages 24 to 30.
`
`7
`
`

`
`Delivering robust top and bottom line growth
`while investing in the future
`Product Sales
`
`-$260m
`
`-5%
`
`-$257m
`
`-4%
`
`+$787m
`
`+14%
`
`$5,830m
`
`$6,100m
`
`GROWTH
`GROWTH
`• Core product sales excluding
`INTUNIV growing 14% on a CER
`basis(1)(2)(6)
`• Continued investment in new product
`launches and delivery of a 43% Non
`GAAP EBITDA margin(3)(4)(6)
`• FY 2015 Non GAAP diluted earnings
`per ADS(5)(6) up 10% on a reported
`basis; 14% on a CER basis(2)(6)
`
`FY 2014
`
`Core
`products(1)
`
`INTUNIV
`
`FX
`
`FY 2015
`
`Double-digit Non GAAP diluted earnings per ADS growth exceeded guidance
`
`(1) Results include NPS Pharmaceuticals Inc. in 2015 (acquired on February 21, 2015). Core product sales exclude INTUNIV and are stated at constant exchange rate (“CER”).
`(2) CER is a Non GAAP financial measure. CER performance is determined by comparing 2015 performance (restated using average 2014 foreign exchange rates for the relevant period) to
`actual 2014 reported performance.
`(3) This is a Non GAAP financial measure. The most directly comparable measure under US GAAP is Net Income margin (FY 2015: 20%, FY 2014: 57%).
`(4) Non GAAP earnings before interest, tax, depreciation and amortization (“EBITDA”) as a percentage of product sales, excluding Royalties and Other Revenues.
`(5) This is a Non GAAP financial measure. The most directly comparable measure under U.S. GAAP is EPS-ADS (FY 2015: $6.59, FY 2014: $17.28).
`(6) See slide 39 for a list of items excluded from the U.S. GAAP equivalent used to calculate all Non GAAP measures detailed above. A reconciliation of non-GAAP financial measures to the
`most directly comparable measure under U.S. GAAP is presented in Shire's Q4 2015 earnings release on pages 24 to 30.
`
`8
`
`

`
`Multiple drivers of robust topline growth
`
`
`
`GROWTHROWT
`
`VYVANSE sales $1,722M; +21%(1)
`• Vyvanse performing strongly, particularly in the adult market which includes both ADHD and BED
`• U.S. growth driven by volume gains (TRx up 8% YoY), price, and favorable stocking patterns
`•
`International growth continues to benefit from gains in established markets
`• VYVANSE patents held to be valid and infringed on appeal; patents expire in 2023
`LIALDA sales $684M; +10%(1)
`• U.S. prescription growth of 10%
`• Market share gains driven by consistent messaging from highly specialized salesforce
`•
`Improved access to physicians as we increase awareness of GATTEX with gastroenterologists
`
`CINRYZE sales $618M; +24%(1)
`• Sales growth driven primarily by an increase in the number of new physicians prescribing for the first time,
`driving more patients on therapy, combined with a modest price increase
`• Strengthened our manufacturing position through renegotiation of agreement with Sanquin; Shire now in a
`position to seek a second source of supply
`FIRAZYR sales $445M; +25%(1)
`• Continued double digit growth primarily driven by new patient additions
`• Sales also benefitted from a price increase taken since Q3 2014
`GATTEX sales $142M; +53%(2)
`• Strong performance since NPS acquisition; 639 patients on therapy worldwide as of 12/31/15(3)
`• Leveraging LIALDA salesforce to aid patient identification
`•
`International roll out on track; favorable reimbursement obtained in France and Germany, launched in
`Nordics and Canada, encouraging early reception from patients and physicians
`NATPARA sales $24M
`• Strong U.S. launch in April 2015
`• 695 patients on therapy worldwide as of 12/31/15(3)
`
`(1) Growth rates are at Constant exchange rates (“CER”), a Non GAAP financial measure. CER performance is determined by comparing 2015 performance (restated using 2014 exchange rates for the relevant period) to
`actual 2014 reported performance. See slide 39 for a list of items excluded from the U.S. GAAP equivalent used to calculate all Non GAAP measures detailed above. A reconciliation of Non GAAP financial measures to the
`most directly comparable measure under U.S. GAAP is presented in Shire's Q4 2015 earnings release on pages 24 to 30.
`(2) GATTEX refers to pro-forma growth including product sales recorded by NPS prior to acquisition by Shire on a CER basis.
`(3) Patients on therapy include those on commercial supply, patient assistance, and compassionate-use programs
`
`9
`
`

`
`Outperformance of Vyvanse continues
`
`Year-to-date 2016 weekly TRx volume Vyvanse growth of 16.8% versus 9.9%
`for adult ADHD market
`
`Rolling 4-week YoY
`adult TRx growth
`
`VYVANSE
`ADHD
`
`19.2%
`
`17.2%
`
`12.3%
`
`10.1%
`
`19.6%
`19.6%
`
`16.8%
`16.8%
`
`11.2%
`11.2%
`
`9.9%
`9.9%
`
`6
`8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 2
`4
`2016
`Vyvanse BED launch
`Week
`
`Vyvanse above-market performance driven by uptake in the adult ADHD market
`and in adults with Binge-Eating Disorder since launch in Q1:15
`
`Source: This information is an estimate derived from the use of information under license from the following IMS Health information
`service: IMS NPA Weekly for the period Jan 17, 2014 to Jan 22, 2016. IMS expressly reserves all rights, including rights of copying,
`distribution and republication.
`
`10
`
`

`
`GATTEX; growth in patient start forms, treated
`patients continues to rise
`
`U.S. patient start forms
`
`2014
`420
`
`2015
`467
`
`-19%(1)
`
`+11%(2)
`
`Shire acquires NPS Q1:15
`and combines
`GATTEX/LIALDA sales team
`efforts in Q3:15 to drive
`disease awareness and
`patient identification
`
`600
`
`500
`
`400
`
`300
`
`200
`
`100
`
`0
`
`U.S. patients on therapy(3)
`Gattex/Lialda
`combined sales
`efforts
`
`Q1/14 Q2/14 Q3/14 Q4/14 Q1/15 Q2/15 Q3/15 Q4/15
`
`Physicians/patients becoming
`more experienced in
`managing SBS and using
`GATTEX
`
`Source: Shire
`(1) Year-over-year change in U.S. patient start forms from 2013 to 2014
`(2) Year-over-year change in U.S. patient start forms from 2014 to 2015
`(3)
`Includes patients on commercial supply and patient assistance programs
`
`11
`
`

`
`NATPARA; treated patients increasing
`9 months post launch
`U.S. NATPARA patients on therapy(1)
`
`Shire capabilities
`• 55 experienced, dedicated
`Rare Disease sales
`specialists/ managers
`• Shire OnePath patient
`services support including
`field-based Patient Access
`Managers support every
`patient
`• Access team; enabled
`coverage of >80% commercial
`lives in first 9 months of
`launch
`
`12
`
`694
`
`419
`
`196
`
`Q2 2015
`
`Q3 2015
`
`Q4 2015
`
`Source: Shire
`(1) Includes patients on commercial supply and patient assistance programs
`
`

`
`Progressing Shire’s
`Innovative Pipeline
`
`Phil Vickers, Head of R&D
`
`Our purpose
`We enable people with life-altering conditions to lead better lives.
`
`

`
`R&D Pipeline most robust in Shire’s history
`
`INNOVATION
`
`Phase 2
`
`Phase 3
`
`Registration
`
`Preclinical
`
`27 Research
` Programs
`
`
`
`TH / GCH1 TH / GCH1 TH / GCH1
`
`GenePod GenePod
`
`
` Parkinson’s Subset Parkinson’s SubsetParkinson s Subset
`
`SHP608
`Dystrophic E.Bullosa
`
`(clinical hold) (clinical hold)
`
`SHP630
`adRP
`
`SHP637
`MRT for CF
`
`SHP639
`Glaucoma
`
`SHP641
`MRT for UCD
`
`Phase 1
`
`SHP611
`MLD
`(Ph 1/2)
`
`
`
`SHP622 SHP622SHP622
`Friedreich’s Ataxia
`
`
`
`SHP623 SHP623SHP623
`(rC1-INH)
`HAE prophylaxis
`
`
`SHP627 SHP627
`
`Focal Segmental l S l
`
`
`Glomerulosclerosis Glomerulosclerosis
`
`SHP631
`Hunter Syndrome
`
`SHP626
`Non-Alcoholic
`Steatohepatitis
`
`SHP607
`Prevention of ROP
`
`SHP625
`Primary Biliary Cirrhosis
`
`SHP609
`Hunter IT
`(Ph 2/3)
`
`
`
`SHP610 SHP610SHP610
`Sanfilippo A
`
`
`SHP616 (CINRYZE)* SHP616 (CINRYZE)*( )
`
`
` Acute Neuromyelitis
`
`
`Optica (Ph2/3) Optica (Ph2/3)Optica (Ph2/3)
`
`SHP620 (maribavir)*
`CMV in transplant
`patients
`
`
`
`SHP625 SHP625 SHP625
`Progressive Familial
`
`
`
`Intrahepatic Cholestasis Intrahepatic CholestasisII
`
`SHP625
`Alagille Syndrome
`
`SHP625
`Primary Sclerosing
`
`Cholangitis Cholangitis
`
`SHP640 (FST-100)*
`Infectious Conjunctivitis
`
`
`LDX (Japan) LDX (Japan)
`ADHD (Ph2/3)
`
`NATPAR (EU)
`
`
`Hypoparathyroidism yp p y
`
`SHP606
`(lifitegrast)
`
`
`Dry eye disease Dry eye diseasey y
`
`INTUNIV (Japan)
`ADHD
`
`FIRAZYR
` (Japan)
`
`
`HAE (Ph2/3) HAE (Ph2/3)HAE (Ph2/3)
`SHP616 (CINRYZE)
`(Japan)*
`HAE prophylaxis
`
`SHP616 SHP616
`
`
`(CINRYZE SC) (CINRYZE SC)(CINRYZE SC)
`
`
`HAE Prophylaxis HAE ProphylaxisHAE Prophylaxis
`
`SHP616 (CINRYZE)
`Acute Antibody
`
`
`Mediated Rejection Mediated RejectionMediated Rejection
`
`SHP621 (Former
`Meritage OBS)
`
`Eosinophilic esophagitis Eosinophilic esophagitisEosinophilic esophagitis
`
`
`SHP643 (DX2930)
`
`Prophylaxis of HAE Prophylaxis of HAE
`
`
`GATTEX (Japan)
`Short bowel syndrome
`
`
`
`SHP465 SHP465SHP465
`ADHD
`
`SHP555 (US)
` Chronic Constipation
`
`14
`
`Rare Diseases ProgramsR
`
`Programs are Phase 3 ready
`
`*
`
`Changes since Q3 2015
`• CINRYZE SC, CINRYZE AMR, SHP621 and SHP643 (DX2930) have entered
`Phase 3 studies.
`INTUNIV (Japan) moved into registration.
`•
`• Totality of SHP625 data being assessed; programs under review.
`
`

`
`Multiple Phase 3 programs underway
`
`INNOVATION
`
`• 14 programs in Phase 3, or Phase 3 ready
`• Three programs recently advanced into Phase 3:
`
`SHP616
`(AMR)
`CINRYZE (SHP616)
`for Antibody Mediated
`Rejection (AMR) in
`patients receiving
`kidney transplants
`
`SHP616 SC
`
`Subcutaneous (SC)
`CINRYZE (SHP616)
`for the prophylaxis of
`hereditary
`angioedema (HAE)
`
`SHP621
`
`SHP621 for
`eosinophilic
`esophagitis
`(EoE)
`
`• Dyax acquisition adds another Phase 3 asset SHP643 (DX2930)
`to our growing HAE franchise
`• Phase 3 study of SHP620 (maribavir) in CMV infection in
`transplant patients planned to start Q2 2016
`
`15
`
`

`
`Key clinical and regulatory milestones in 2016
`
`Firazyr
`HAE Japan
`Top-line data
`
`SHP610
`SanFilippo A Disease
`Phase 2 data
`
`NATPAR
`Anticipated EU
`approval(2)
`
`INNOVATION
`
`Clinical trial results
`
`Regulatory filing or
`anticipated approval
`
`Q1
`
`Q2
`
`Q3
`
`Q4
`
`Lifitegrast
`Adult Dry Eye Disease
`FDA refiled Jan 22, 2016
`
`SHP607
`Retinopathy of
`Prematurity
`Phase 2 data
`
`Lifitegrast
`PDUFA date:
`July 22, 2016
`
`SHP465
`Pediatric ADHD
`Phase 3 data(1)
`
`SHP465
`FDA refiling(1)
`
`SHP465 is currently being developed for use in adults. The ongoing pediatric trial is to generate data in support of an adult indication
`1
`Subject to approval by regulatory authorities
`2
`Note: Timings are approximated to the nearest quarter
`
`16
`
`

`
`Shire’s commitment to becoming a leader in ophthalmics
`
`PRECLINICAL
`
`PHASE 1
`
` PHASE 2
`
` PHASE 3
`
`• Acquired in 2013
`•
`If approved, lifitegrast will be first new
`prescription drug for DED in the US in over
`10 years with the potential to be the first
`indicated to treat both signs and symptoms
`
`• Acquired in 2015
`•
`If approved, has potential to treat both
`bacterial and viral eye infections
`
`Lifitegrast: Dry Eye Disease (DED)
`
`SHP640: Viral/Bacterial Conjunctivitis
`
`• Acquired in 2013
`• First-in-class investigational treatment that
`may prevent ROP
`
`SHP607: Retinopathy of Prematurity (ROP)
`
`• Acquired in 2014
`• Potential treatment for rare and visually
`debilitating genetic disease where there
`are no current treatments
`
`SHP630: Autosomal
`Dominant Retinitis
`Pigmentosa
`
`•
`
`Internal pipeline program acquired
`through Jerini acquisition
`
`SHP639:Glaucoma
`
`17
`
`

`
`Lifitegrast PDUFA date: July 22, 2016
`
`INNOVATION
`
`• NDA resubmission package included results from the positive Phase 3,
`OPUS-3 study as well as product quality information
`
`• Largest clinical trial program for an investigational-stage compound for
`dry-eye disease (>2,500 patients(1))
`
`• Prescription Drug User Fee Act (PDUFA) date July 22, 2016
`
`Anticipate potential approval and launch in Q3 2016(2)
`
`(1) Includes one Phase 2 study, three Phase 3 safety and efficacy studies (OPUS-1, -2, -2) and one long-term (one year) Phase 3 safety study (Sonata)
`(2) Subject to regulatory approval
`
`18
`
`

`
`Financial Review
`
`Jeff Poulton, Chief Financial Officer
`
`Our purpose
`We enable people with life-altering conditions to lead better lives.
`
`

`
`Strong performance drives delivery of double digit
`Non GAAP diluted EPS growth
`
`FY 2015
`$m(1)
`
`FY 2014
`$m(1)
`
`Reported
`Growth
`
`CER
`Growth(2)(8)
`
`FY Guidance Actual vs.
`Guidance
`
`(cid:17951) (cid:17951)
`
`+4-5%
`
`Low double
`digit
`
`+45-55%
`
`6,100
`
`5,830
`
`6,035
`
`5,503
`
`317
`
`192
`
`6,417
`
`2,924
`
`6,022
`
`2,756
`
`+5%
`
`+10%
`
`+65%
`
`+7%
`
`+6%
`
`+9%
`
`+14%
`
`+70%
`
`+11%
`
`+10%
`
`43%
`
`44%
`
`-1% point
`
`-2% points
`
`11.68
`
`10.60
`
`2,422
`
`2,402
`
`+10%
`
`+1%
`
`+14%
`
`Mid-to-high
`single digit
`
`Product Sales
`Product Sales excluding
`INTUNIV
`Royalties and Other
`Revenues
`Total Revenue
`
`Non GAAP EBITDA(3)(8)
`Non GAAP EBITDA
`margin(4)(5)(8)
`Non GAAP diluted EPS –
`ADS(6)(8)
`Non GAAP Cash
`Generation(7)(8)
`
`(1) Results from continuing operations including NPS Pharmaceuticals Inc. in 2015 (acquired on February 21, 2015) and ViroPharma Inc. in 2014 (acquired on January 24, 2014) and excluding DERMAGRAFT in 2014 (treated as a discontinued operation
`following divestment on January 17, 2014).
`(2) This is a Non GAAP financial measure. Constant exchange rates ("CER") performance is determined by comparing 2015 performance (restated using average 2014 foreign exchange rates for the relevant period) to actual 2014 reported performance.
`(3) This is a Non GAAP financial measure. The most directly comparable measure under US GAAP is Net Income (FY 2015: $1,303m, FY 2014: $3,406m).
`(4) This is a Non GAAP financial measure. The most directly comparable measure under US GAAP is Net Income margin (FY 2015: 20%, FY 2014: 57%).
`(5) Non GAAP EBITDA as a percentage of product sales, excluding royalties and other revenues.
`(6) This is a Non GAAP financial measure. The most directly comparable measure under US GAAP is EPS-ADS (FY 2015: $6.59, FY 2014: $17.28).
`(7) This is a Non GAAP financial measure. The most directly comparable measure under US GAAP is Net Cash provided by operating activities (FY 2015: $2,337m, FY 2014: $4,228m).
`(8) See slide 39 for a list of items excluded from the US GAAP equivalent used to calculate all Non GAAP measures detailed above. A reconciliation of Non GAAP financial measures to the most directly comparable measure under US GAAP is presented
`in Shire's Q4 2015 earnings release on pages 24 to 30.
`
`20
`
`

`
`Growth across the portfolio and the inclusion of NPS drives
`product sales up 14% (excluding INTUNIV and at CER)
`
`INTUNIV generic entry holds back
`reported product sales by $260m or 5%
`
`CER(3)(4): Core product sales up $787m or 14%
`
`FX headwinds holds back reported
`product sales by $257m or 4%
`
`
`(1) Results from continuing operations including NPS Pharmaceuticals Inc. in 2015 (acquired on February 21, 2015) and ViroPharma Inc. in 2014 (acquired on January 24, 2014) and excluding DERMAGRAFT in 2014 (treated as a discontinued operation (1) Results from continuing operations including NPS Pharmaceuticals Inc. in 2015 (acquired on February 21, 2015) and ViroPharma Inc. in 2014 (acquired on January 24, 2014) and excluding DERMAGRAFT in 2014 (treated as a discontinued operation
`
`following divestment on January 17, 2014).following divestment on January 17, 2014).
`
`(2) Gattex growth on a pro-forma basis, including product sales recorded by NPS prior to acquisition by Shire. (2) Gattex growth on a pro-forma basis, including product sales recorded by NPS prior to acquisition by Shire.
`(3) This is a Non GAAP financial measure. Constant exchange rates ("CER") performance is determined by comparing 2015 performance (restated using average 2014 foreign exchange rates for the relevant period) to actual 2014 reported performance.
`(4) See slide 39 for a list of items excluded from the US GAAP equivalent used to calculate all Non GAAP measures detailed above. A reconciliation of Non GAAP financial measures to the most directly comparable measure under US GAAP is presented in
`Shire's Q4 2015 earnings release on pages 24 to 30.
`
`21
`
`

`
`Strong Non GAAP EBITDA margin in 2015 whilst
`investing for future growth
`
`Year on Year Change:
`Product Sales
`Product Sales excluding INTUNIV
`Non GAAP R&D(2)(10)
`Non GAAP SG&A(3)(10)
`Combined Non GAAP R&D and SG&A(4)(10)
`
`Ratios:
`% of Product Sales
`Non GAAP Gross Margin(5)(10)
`Non GA