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March 22, 2018 – Canton plc (LSE: SHP, NASDAQ: SHPG) (the “Company”) announces that the afterward abstracts will today be acquaint to shareholders:

PDF) Cinacalcet Reduces Serum Calcium Concentrations in Patients ..
PDF) Cinacalcet Reduces Serum Calcium Concentrations in Patients .. | sensipar patient assistance form
Meeting Record - sensipar patient assistance form
Meeting Record – sensipar patient assistance form | sensipar patient assistance form
Intravenous Form of Sensipar® Has Been Approved by the FDA - sensipar patient assistance form
Intravenous Form of Sensipar® Has Been Approved by the FDA – sensipar patient assistance form | sensipar patient assistance form
PDF) Cinacalcet for Secondary Hyperparathyroidism in Patients ..
PDF) Cinacalcet for Secondary Hyperparathyroidism in Patients .. | sensipar patient assistance form

>      2017 Anniversary Abode >      Notice of the 2018 Anniversary Accustomed Meeting>      Form of Proxy

In accordance with Listing Rule 9.6.1R, a archetype of anniversary of these abstracts will be uploaded to the Civic Storage Mechanism and will be accessible for examination shortly.

The 2017 Anniversary Abode and Notice of the 2018 Anniversary Accustomed Meeting are additionally accessible on Shire`s website: www.shire.com

Disclosure & Transparency Rule (“DTR”) 6.3.5R requires the Aggregation to accede to the media assertive advice from its Anniversary Abode if that advice is of a blazon that would be adapted to be broadcast in a half-yearly report. The advice absolute in the Appendix to this announcement, calm with the Company`s unaudited abounding year after-effects for the year concluded December 31, 2017, issued on February 14, 2018, accumulated the abstracts adapted by DTR 6.3.5R to be appear to the media in unedited abounding argument through a Authoritative Advice Service. This complete is not a acting for anniversary the abounding 2017 Anniversary Report. Folio and agenda references in the Appendices beneath accredit to folio and agenda references in the 2017 Anniversary Report.

The advice included in the Appendix is extracted from the 2017 Anniversary Abode which is anachronous February 16, 2018. Authentic acceding acclimated in the Appendix accredit to acceding as authentic in the 2017 Anniversary Report, unless the ambience contrarily requires.

Shire is the all-around baton in confined patients with attenuate diseases. We strive to beforehand best-in-class therapies aloft a bulk of attenuate ache areas including hematology, immunology, abiogenetic diseases, neuroscience, and centralized anesthetic with growing ameliorative areas in ophthalmics and oncology. Our adapted capabilities accredit us to adeptness patients in added than 100 countries who are disturbing to alive their lives to the fullest.

We feel a able faculty of coercion to abode unmet medical needs and assignment endlessly to beforehand people`s lives with medicines that accept a allusive appulse on patients and all who abutment them on their journey.

Statements included herein that are not complete facts, including afterwards limitation statements apropos approaching strategy, plans, objectives, expectations and intentions, projected revenues, the advancing timing of analytic trials and approvals for, and the bartering abeyant of, inline or action products, are avant-garde statements. Such avant-garde statements absorb a cardinal of risks and uncertainties and are accountable to change at any time. In the accident such risks or uncertainties materialize, Shire`s after-effects could be materially abnormally affected. The risks and uncertainties include, but are not bound to, the following:

a added anniversary and description of risks, uncertainties and added diplomacy can be begin on pages 18 to 21 of the 2017 Anniversary Report.

All avant-garde statements attributable to us or any actuality acting on our anniversary are abnormally able in their absoluteness by this cautionary statement. Readers are cautioned not to abode disproportionate affirmation on these avant-garde statements that allege alone as of the date hereof. Except to the admeasurement contrarily required  by applicative law, we do not undertake any obligation to amend or alter forward- attractive statements, whether as a aftereffect of new information, approaching contest or otherwise.

In 2017, Canton started its aboriginal abounding banking year as a adapted company: the accustomed all-around baton in alleviative attenuate diseases.

As we began the year, the affiliation of Baxalta was able-bodied beneath way. A aggregation that had bartering operating units in 22 countries in 2013 is now in added than 60 countries. A analytic action with 20 programs in 2013, concluded 2017 with 40 such alive programs. And our ameliorative brand had broadcast into three new activating areas: immunology, hematology, and oncology.

Shire has adapted itself, but with this transformation came accessible challenges. We had a all-around accomplishment portfolio that adapted accurate pruning and disciplined, able management. In abounding countries we had to consolidate two offices into one, affective and reassigning able staff, while advancement bartering momentum. And we set advancing targets for our teams, blame ourselves to accommodated the able accessible banking goals, some of which were acutely aspirational.

At the end of 2017, the bodies of Canton could attending aback with pride. The accomplishing of our Adjustment Accomplishment Study laid the foundation for able and able accumulation operations. And at the aloft time, Canton exceeded its arduous affiliation synergy targets for the year, extenuative money and managing its all-around accretion systems in the best cost-effective and able manner.

Despite these abounding achievements, Shire`s allotment bulk accomplishment was disappointing. For a Board, administration team, and aggregation focused on convalescent actor value, the claiming is bright and we accept adequate our dness to beforehand and accomplish in 2018.

 For Shire, success agency accustomed added avant-garde solutions to the patients who depend on us. We apperceive that if patients, physicians, and caregivers accede and bulk our products, again shareholders will additionally benefit. In this way 2017 was not aloof a year of integration, but additionally one of alertness for the future.

In 2017, we launched 50 articles in 25 countries with therapies to amusement diseases such as abbreviate bowel syndrome, hypoparathyroidism and absorption arrears hyperactivity ataxia (ADHD). We decidedly avant-garde our Assay and Development (R&D) action with 54 aloft bazaar filings about the apple and connected to beforehand in areas breadth we see abundant charge and befalling such as immunology.

We maintained our adherence to our ambiance and the communities in which we serve. In 2017, Canton developed our new Albatross action with commitments and abiding goals to be able by 2025. We additionally captivated our third anniversary All-around Day of Service, during which added than 7,300 Canton advisers from about the apple committed added than 29,000 hours of their time to volunteering in their communities. A abundant description of Shire`s charge to Albatross can be begin on folio 35.

The accomplishments – focused absolutely on accustomed allowances to patients in charge and the communities in which we alive – came during a year of abundant alien authoritative and macroeconomic challenge. The hemophilia bazaar mural shifted, and continues to change rapidly. The all-around political, tax, and authoritative ambiance in which we accomplish is consistently in motion. And the biologic industry charge still administer civic challenges in funding, pricing, and anecdotic means to abutment approaching innovation.

These challenges will abide in 2018, authoritative it basic that Canton maintains its able and active business strategy. Appear that end, we abide to appraise the cardinal and operational administration of the Company, including an appraisal of our neuroscience business. While this assay continues, we are creating two audible business accommodation aural Shire: one focused on attenuate ache and the added focused on neuroscience. This will accredit bluff administration focus, greater cardinal clarity, and audible beforehand opportunities for both genitalia of the business. We apprehend the cessation of  our cardinal assay of these two business segments in the added bisected of 2018. Added accommodation on the accommodation can be begin on folio 12.

For our employees, 2017 was a aeon of claiming and change. But it was additionally a year in which they all showed their grit, resolve, and abiding adherence to the patients we serve. The Board and I would like to accede anybody at Shire, not aloof for their adamantine work, but additionally for their drive, focus, and charge during a aeon of transformation. We would additionally like to accede our CEO, Dr. Flemming Ornskov, who has led the Canton aggregation through this affiliation with abundant accomplishment and has kept anybody focused on the ambition of architecture a added airy Canton for the long-term.

Finally, I`d like to accurate my aboveboard acknowledgment to Bill Burns, Chief Absolute Director; Anne Minto, the antecedent Chairman of our Remuneration Committee; and Dominic Blakemore, antecedent armchair of the Audit, Acquiescence & Accident Committee, all of whom will be backward from the Board afterwards the 2018 AGM.

Thank you additionally to aloft Canton CFO Jeff Poulton who larboard the Aggregation at the end of 2017. The contributions of Bill, Anne, Dominic, and Jeff cannot be overstated. Canton is a bigger aggregation because of their work; we are beholden for their adherence and ambition them all the best in the future.

In closing, I am beholden of the contributions of our added than 23,000 advisers and our Board, and I am beholden to our accommodating communities for their partnership. And importantly, I abide aflame and optimistic about the approaching of our Company. It is our advantage to abide alive on anniversary of the patients who affect us every day.

Susan KilsbyChairman

2. Chief Controlling Officer`s Assay (Pages 6 – 9 2017 Anniversary Report)

2017 is the year Canton caked its position as the all-around baton in attenuate diseases. With about 70 percent of revenues advancing from attenuate ache products, and the best able-bodied action in Shire`s history -60 percent of which are biologic therapies we abide to accomplish cogent beforehand in the Company`s evolution.

As we evolved, we additionally put the Aggregation on solid banking footing. Key to Shire`s accomplishment has been the adeptness to accomplish able banking after-effects while managing our bigger integration. We grew by about 17,000 advisers and circumscribed 28 country sites globally – and abide on clue to bear on our Baxalta bulk synergy ambition of $700 actor by the third year post-close. We able sales beforehand of 33 percent and delivered a able operating banknote breeze of $4.3 billion enabling us to apprehend our 2017 advantage adjustment target.

We are beholden that we now accept bristles of our seven franchises accidental added than $1 billion in acquirement annually. Immunology delivered outstanding accomplishment in 2017, apprenticed by the success of our sub-cutaneous immunoglobulin articles and beforehand in All-embracing markets. Ophthalmics, our newest franchise, generated sales of $259 actor in 2017 as XIIDRA, the alone assay accustomed in the U.S. to amusement the signs and affection of dry eye ache (DED), able added than one actor prescriptions accounting back barrage in backward 2016. I am abundantly beholden of what our able and focused aggregation has delivered, in abounding cases, aloft our accomplishment expectations in 2017.

Two audible market-leading businessesSince I accustomed at Canton bristles years ago, we accept developed from an ADHD-focused aggregation to a all-around biotech with two audible market-leading businesses – attenuate ache and neuroscience. To accredit these two businesses to adeptness their abounding potential, in aboriginal 2018 we appear that the neuroscience business adequate added acicular focus and added beforehand and that there was a able cardinal anniversary for creating abstracted Attenuate Ache and Neuroscience divisions. For added advice about the two divisions, amuse see folio 12.

Innovation at the affection of our eyes and adeptness Our abiding eyes is to be an innovation- apprenticed biotech aggregation focused on attenuate diseases and specialized altitude aloft our bulk accurate platforms and ameliorative areas. Canton has an able almanac of accessing alien accession and accustomed late-stage articles to market. Activity forward, we plan to body on these capabilities by demography our centralized assay to a new level. To beforehand this goal, we accept appointed a new Head of Assay and Development and Chief Accurate Officer, Andreas Busch, PhD, an able scientist with an all-encompassing accomplishments and arresting clue almanac in research.

At the aloft time, we abide to accompaniment our R&D accession with new advances in bloom advice technologies and absorption medicine. Canton is utilizing bogus intelligence (AI) as able-bodied as advancing wearables and sensor technology, decidedly in analytic trials. We are partnering with new, cutting-edge companies to beforehand the time it takes for attenuate ache patients to accretion a diagnosis, clothier our assay options for abate accommodating groups, and advice us assay adamantine to accretion patients for analytic trials. Added advice about these efforts can be begin on folio 30.

We are additionally alive to enhance our accomplishment adjustment with an eye appear optimizing our believability and growth. We`re authoritative important changes to our centralized and alien networks to abate back-up while additionally ensuring accumulation continuity. Amid the allowances of these changes, we ahead accumulation of $100 actor annually alpha in 2019 and $300 actor annually by 2023. Additionally, we are modernizing the accomplishment adjustment with new accessories in Georgia (U.S.) and Dublin (Ireland). Our Georgia bulb will aggrandize accomplishment accommodation for our plasma-derived articles by about 30 percent, while our Dublin adeptness will focus on assembly of antibody-based therapies.

An industry-leading pipelineOur R&D alignment continues to ammunition our able-bodied action with avant-garde therapies.  In 2017, our R&D aggregation completed 54 aloft bazaar authoritative filings about the world. In addition, Canton accustomed two U.S. FDA Fast Clue Designations, two Orphan Biologic Designations, and one Breakthrough Assay Designation. We completed nine Appearance 3 analytic trials, and accustomed 126 artefact approvals globally. These accomplishments are aloft strides avant-garde on anniversary of our patients. Added accommodation about our action can be begin on folio 24.

New artefact launches fueled beforehand As we avant-garde programs through the pipeline, we additionally developed a aggregation that excels at artefact launches and ensures patients accept admission to these important therapies. We accomplished 50 artefact launches globally in 2017, including the antecedent barrage of MYDAYIS in the U.S. and broadcast into assorted new geographies for articles such as CUVITRU, NATPARA/N ATPAR, and GATTEX/REVESTIVE. In total, Canton generated $1.6 billion in sales in 2017 from articles launched back 2013. Our articles are now accessible in added than 100 countries enabling us to adeptness added patients than anytime before. For added accommodation about Shire`s barrage excellence, amuse see folio 28.

Patient and chump focusThe basic acumen I accept our Aggregation has performed so able-bodied is because the Canton aggregation is apprenticed by a bright mission, a accumulated purpose, and able values-all of which put the accommodating at the centermost of all that we do. We apperceive we are best accustomed back we accept patients advanced of mind, alarming our thinking, and allegorical our assignment every distinct day.

Central to our mission at Canton is actuality aing to our patients and our partners, which allows us to not alone serve them better, but additionally to innovate based on their insights. We are about with patients for the long-term, accustomed that bisected of attenuate diseases are diagnosed in childhood. From assay to award adapted assay options, accepting access, and acknowledging patients on treatment, we are committed to the wellbeing of our patients for life. The afflatus they accommodate to our aggregation is second-to-none. I`d like to booty this befalling to accede our patients, their families, and their healthcare providers for acceptance us to be allotment of their journey.

Navigating challengesWhile I am acutely beholden of Shire`s accomplishments in 2017, the year was  not afterwards its challenges. We faced all-encompassing antagonism for LIALDA (for the assay of ulcerative colitis) for the aboriginal time. We additionally faced a accumulation abeyance during the summer for CINRYZE (for the assay of ancestral angioedema (HAE)) accompanying to issues with a third-party manufacturer. We accede HAE patients and the HAE association for their backbone while we formed agilely to abode this affair and accept taken accomplish to abate this accident in the future, including bringing added accomplishment of biologic artefact centralized alpha in 2018.

We additionally able added antagonism in the Hematology franchise, but abide to be assured in our administration position. Canton is committed to innovating and architecture for the approaching – as it can be apparent with ADYNOVI accepting a complete appraisal and, aboriginal this year, the business allotment from the European Medicines Agency (EMA) and with the contempo approval of myPKFiT, a registered software-based medical accessory for alone hemophilia A dosing in the U.S. And, we abide to beforehand in and aggrandize our action of avant-garde Hematology programs.

While we are beholden of our accomplishments in 2017, we additionally accede that we charge to assignment akin harder on convalescent actor bulk throughout 2018.

Despite these challenges, Canton performed complete able-bodied financially in 2017 – accustomed 8% pro forma artefact sales beforehand to $14.4 billion, an admission of over $1 billion. We additionally bigger our operating allowance and operating banknote breeze of $4.3 billion which enabled us to adeptness our debt target.

Employees and cultureI would like to accede Canton advisers and the Board of Directors who has provided invaluable advice for the organization. We`ve developed from beneath than 6,000 advisers to added than 23,000, and anybody continues to focus on our mission to serve the needs of patients. The accomplishments able in 2017 are absurd and I attending avant-garde to an appropriately arresting 2018.

Outlook and summaryWe larboard 2017 stronger than we`ve anytime been afore with administration positions in abounding of the ameliorative areas in which we compete. In particular, we now accept a arch high-growth Immunology franchise, which will be the foundation of our attenuate ache business as we move into 2018. Our neuroscience business will anon anniversary from added beforehand and focus as we attending to augment our adeptness aloft ADHD.

2018 will be a year of connected focus on bartering beheading and targeted beforehand in our accomplishment infrastructure, new artefact launches, and action to drive approaching growth. We apprehend to bear mid-single chiffre artefact sales beforehand in 2018 afterwards arresting the advancing appulse of generics. Based on accustomed assumptions, we additionally apprehend margins to be impacted by the start-up of our new U.S. claret accomplishment site, accumulative genericization, and lower royalties. But, I abide assured that Canton will abide to body on our administration position in both attenuate ache and neuroscience and we are committed to accomplishing our 2020 ambition of $17-$18 billion in revenues and mid-forties Non GAAP EBITDA margin.

I am activated and aflame about Shire`s approaching as we attending avant-garde to growing our franchises, abnormally Immunology; active on our abounding launches; leveraging our able-bodied all-embracing brand in key markets such as China to aggrandize access  to our 40 marketed products; and, architecture an innovative, results-oriented, patient-centric culture. I am assured that our aggregation and our ally will abide to assassinate on our priorities and serve as champions for our patients.

Flemming Ornskov, MD, MPHChief Controlling Officer

Diagram on pages 8 – 9 of 2017 Anniversary Report:

Q1

             Q2

             Q3

             Q4

3. Banking Assay (Pages 44 – 55 2017 Anniversary Report)

Overview

The Aggregation has developed both organically and through acquisition, commutual a alternation of aloft diplomacy that accept brought therapeutic, geographic and action beforehand and diversification. The Aggregation will abide to conduct its own assay and development, focused on attenuate diseases and specialized conditions, as able-bodied as appraise companies, articles and action opportunities that action a cardinal fit and accept the abeyant to bear bulk to all of the Company`s stakeholders: patients, physicians, action makers, payers, partners, investors and employees.

The Company`s purpose is to accredit bodies with action altering altitude to advance bigger lives. The Aggregation will assassinate on its purpose through its action and business model. For added accommodation of Shire`s action and business model, accredit to pages 12 and 14.

Through abysmal compassionate of patients` needs, the Aggregation is able to:

Shire`s in-licensing and accretion efforts are focused on articles in specialist markets with able bookish acreage aegis or added forms of bazaar exclusivity and all-around rights. Canton believes that a anxiously called and counterbalanced portfolio of articles with strategically accumbent and almost small-scale sales armament will bear able results.

Company revenues, expenditures and  net assets are attributable to the R&D, manufacture, auction and administration of biologic articles aural one reportable segment. The Aggregation additionally earns royalties and added revenues (where Canton has out-licensed articles to third parties) that are recorded as adeptness and added revenues.

Revenues are acquired primarily from two sources – sales of the Company`s own articles and royalties and added revenues:

The markets breadth the Aggregation conducts its business are acutely aggressive and awful regulated.

The healthcare industry is additionally experiencing:

Shire`s action has been developed to abode these industry-wide aggressive pressures. This action has resulted in a alternation of initiatives in the afterward areas:

MarketsShire`s accustomed portfolio of accustomed articles spans seven key ameliorative areas (TA): Immunology, Hematology, Neuroscience, Centralized Medicine, Abiogenetic Diseases, Oncology and Ophthalmics. In 2017, the accession of anniversary TA to all-embracing Artefact sales was as follows:

Shire has developed in allotment through accretion which has brought therapeutic, geographic and action beforehand and diversification.

The accretion of Baxalta in June 2016 added the Hematology, Immunology and Oncology franchises and enabled Canton to become the all-around baton in attenuate diseases and awful specialized conditions.

The accretion of Dyax in January 2016, with its advance action product, SHP643, and marketed artefact KALBITOR, broadcast and connected Shire`s industry-leading HAE portfolio (FIRAZYR and CINRYZE).

In July 2016, Canton accountant the all-around rights to all break for SHP647 from Pfizer Inc. SHP647 is an investigational biologic actuality evaluated for the assay of moderate-to- astringent anarchic bowel disease.

In 2015, Canton acquired NPS Pharma, Meritage Pharma, Inc. (Meritage Pharma) and Foresight Biotherapeutics Inc. (Foresight).

The accretion of NPS Pharma added all-around rights to an avant-garde artefact portfolio with assorted beforehand catalysts, including GATTEX/REVESTIVE and NATPARA/NATPAR. The accretion of Meritage Pharma provided all-around rights to SHP621, a Appearance 3 accessible asset for the assay of adolescents and adults with EoE, a rare, abiding anarchic GI disease. This builds aloft the Company`s attenuate ache and GI bartering basement and expertise. With the accretion of Foresight, Canton acquired the all-around rights to SHP640 (topical ophthalmic drops accumulation 0.6%  povidone iodine (PVP-I) and 0.1% dexamethasone), a assay in late-stage development for the assay of communicable conjunctivitis, an ocular apparent action frequently referred to as blush eye. This accretion has a bright cardinal fit with XIIDRA, which is accustomed in the U.S. for the assay of the signs and affection of dry eye disease, and added demonstrates Shire`s charge to architecture a administration position in ophthalmics.

In 2017, Canton acquired 34% (2016: 32%)   of Artefact sales from alfresco of the U.S. Canton has advancing commercialization and late-stage development activities, which are accustomed to added supplement the about-face of revenues in the future, including the following:·       the barrage of MYDAYIS in the U.S.;·       connected barrage of INTUNIV, REVESTIVE and ONIVYDE aloft Europe;·       the approvals of NATPAR and ADYNOVI in the EU; ·       acquiescence of SHP643 in the U.S.;·       acquiescence of CALPEG NDA for ALL in the U.S.;·       acquiescence of VONVENDI MAA in Europe; and·       geographic amplification of XIIDRA with the contempo approval in Canada and submissions in added key markets.

R&DShire`s R&D efforts are focused on bulk ameliorative areas including Immunology, Hematology, Neuroscience, Centralized Medicine, Abiogenetic Diseases, Oncology and Ophthalmics. Canton concentrates its assets on accepting authoritative approval for afterwards date action articles aural these ameliorative areas and focuses its early-stage assay activities in attenuate diseases.

Evidence of the accustomed progression of the backward date action can be apparent in the acceding of approval and associated launches of the Company`s articles over the aftermost three years. In this time, several articles accept accustomed authoritative approval including: in the U.S., MYDAYIS in 2017, XIIDRA and CUVITRU in 2016, NATPARA and VYVANSE for BED in 2015; in the EU, ONIVYDE and CUVITRU in 2016, ELVANSE/TYVENSE for adults, INTUNIV for accouchement and adolescents in 2015.

Shire`s administration reviews complete costs for all R&D projects by development phase.

Shire`s R&D costs in 2017 and 2016 accommodate costs on programs in all stages of development. The afterward table summarizes the Company`s complete R&D absorb categorized by development stage, based aloft the development date of anniversary diplomacy for the years concluded December 31, 2017 and 2016:

$M

$M

Early date programs additionally accommodate pre- analytic and assay programs. In accession to the above, the Aggregation recorded R&D agent costs of $506.9 actor in 2017 (2016: $431.9 million) and added aberrant R&D costs of $198.6 actor (2016: $153.0 million), complete mainly of abrasion and up-front and anniversary payments for in-licensed development projects.

For a altercation of the Company`s accustomed development projects see pages 24 and 25.

Patents and Bazaar Exclusivity The accident or cessation of apparent aegis or authoritative exclusivity with anniversary to any of the Company`s aloft articles could accept a complete adverse aftereffect on the Company`s revenues, banking action and after-effects of operations, as all-encompassing or biosimilar articles may admission the market. Companies diplomacy all-encompassing articles about do not charge to complete all-encompassing analytic studies back they seek allotment of a all-encompassing or biosimilar artefact and accordingly, are about able to advertise a all-encompassing adaptation of the Company`s articles at a abundant lower price.

In 2017, a all-encompassing adaptation of the Company`s LIALDA artefact was launched, which led  to lower sales of Shire`s LIALDA artefact compared to the aeon afore accident of exclusivity. In 2017, a all-encompassing adaptation of the Company`s FOSRENOL artefact was launched, which led to lower sales of FOSRENOL compared to the aeon afore accident of exclusivity.

Shire is affianced in assorted acknowledged diplomacy with all-encompassing manufacturers.For advice apropos accustomed apparent litigation, accredit to Agenda 25, Acknowledged and Added Proceedings, to the circumscribed banking statements.

Corporate DevelopmentShire focuses its accumulated developmentactivity on the accretion and in-licensing of businesses, articles or compounds that action a cardinal fit and accept the abeyant to bear ascertainable bulk to all of the Company`s stakeholders.

Results of operations for the years concluded December 31, 2017 and 2016Financial highlights for the year concluded December 31, 2017 are as follows:

Revenues

Operating results

Earnings per allotment (EPS)

Cash flows

Total revenuesThe afterward table provides an assay of the Company`s complete revenues by source. In 2017, Immunology includes HAE from Abiogenetic Diseases; above-mentioned year amounts accept been reclassified to accommodate with the accustomed year presentation.

Years concluded December 31

$`M

$`M

N/M: Circumscribed after-effects accommodate Baxalta sales as of June 3, 2016, the date of acquisition, or fractional year artefact launches; therefore, Artefact sales beforehand as a allotment is not meaningful.

ImmunologyImmunology artefact sales, which now accommodate HAE artefact sales, were $4,370.3 actor in 2017 compared to $2,827.0 actor in 2016, primarily apprenticed by the admittance of a abounding year of immunoglobulin therapies and bio assay artefact sales afterward the accretion of Baxalta in June 2016. Immunoglobulin and bio assay appear complete artefact sales of $2,940.7 million.

HAE artefact sales for the year concluded December 31, 2017 added to $1,429.6 actor or 9% from $1,310.9 actor in 2016, primarily apprenticed by FIRAZYR, up 15% to $663.0 and CINRYZE up 3% to $699.3 million. During the third division of 2017, CINRYZE had a accumulation coercion acquired by a accomplishment abeyance at a third-party supplier. The affair was addressed and assembly resumed in the fourth division of 2017. On January 24, 2018, FDA accustomed approval for the technology alteration of CINRYZE biologic artefact accomplishment action to the Vienna, Austria accomplishment site. The Aggregation expects to alpha accomplishment CINRYZE biologic artefact centralized in Vienna in the aboriginal division of 2018, accouterment an added accumulation antecedent to accommodated accommodating demand.

HematologyHematology, acquired with Baxalta in June 2016, included sales of recombinant and plasma-derived hemophilia articles (primarily Factor VIII and Factor IX) and inhibitor therapies. Hematology artefact sales were $3,785.6 actor in 2017 compared to $2,240.8 actor in 2016, primarily apprenticed by the admittance of a abounding year of Hematology artefact sales afterward the accretion of Baxalta.

NeuroscienceNeuroscience artefact sales for the year concluded December 31, 2017 added to $2,664.1 million, or 7%, from $2,490.5 actor in 2016, with beforehand primarily apprenticed by VYVANSE and the admittance of MYDAYIS.

VYVANSE artefact sales for the year concluded December 31, 2017 added to $2,161.1 million, or 7%, from $2,013.9 actor in  2016, due to the anniversary of a bulk increase1 taken back 2016, added appeal consistent from beforehand in the U.S. ADHD bazaar and able accomplishment in the Company`s all-embracing markets, partially anniversary by lower U.S. stocking.

1The complete net aftereffect of bulk increases on accustomed aeon net sales compared to the allusive aeon is difficult to quantify due to the assorted managed affliction rebates, Medicaid discounts, added abatement programs in which the Aggregation participates and fee for anniversary agreements with broad customers.

MYDAYIS, which was fabricated accessible to patients on August 28, 2017, contributed $21.6 actor of artefact sales in 2017.

Information about action accompanying to MYDAYIS can be begin in Agenda 25, Acknowledged and Added Proceedings, to the circumscribed banking statements.

Internal MedicineInternal Anesthetic artefact sales for the year concluded December 31, 2017 decreased to $1,670.3 million, or 5%, from $1,755.5 actor in 2016, primarily apprenticed by the appulse of LIALDA all-encompassing competition, partially anniversary by beforehand from GATTEX/ REVESTIVE and NATPARA.

LIALDA/MEZAVANT artefact sales decreased to $569.4 million, or 28%, for the year concluded December 31, 2017 from $792.1 actor in 2016, due to the appulse of all-encompassing antagonism in 2017.

Information about action accompanying to LIALDA can be begin in ITEM 3: Acknowledged Diplomacy and Agenda 25, Acknowledged and Added Proceedings, to the circumscribed banking statements.

GATTEX/REVESTIVE and NATPARA/NATPAR artefact sales added to $335.5 million, or 53%, and $147.4 actor or 73%, respectively, for 2017, compared to artefact sales in 2016 primarily due to an admission in the numbers of patients on assay and to  a bottom extent, the anniversary of bulk increases taken back 20161.

Genetic DiseasesGenetic Diseases artefact sales, which now excludes HAE artefact sales, for the year concluded December 31, 2017 added to $1,437.7 million, or 4%, from $1,387.1 actor in 2016, primarily due to ELAPRASE and REPLAGAL, as both articles benefited from an admission in the cardinal of patients on therapy.

OncologyOncology, acquired with Baxalta in June 2016, appear artefact sales of $261.7 actor for the year concluded December 31, 2017 compared to $130.5 actor for the year concluded December 31, 2016. Oncology includes sales of ONCASPAR and ONIVYDE. ONIVYDE was accustomed in the EU on October 18, 2016.

OphthalmicsOphthalmic artefact sales chronicle to XIIDRA, which was fabricated accessible to patients on August 29, 2016. XIIDRA artefact sales were $259.2 actor for the year concluded December 31, 2017 compared to $54.4 actor for the year concluded December 31, 2016.

Royalties and added revenuesRoyalties and added revenues added to $711.7 actor or 39% for the year concluded December 31, 2017 from $510.8 actor in 2016, primarily due to an upfront license  fee received, a abounding year of adjustment accomplishment acquirement acquired with Baxalta, admission in SENSIPAR royalties and an admission in adeptness streams acquired with Dyax.

Cost of salesCost of sales added by $884.3 actor to $4,700.8 actor for the year concluded December 31, 2017 (31% of Complete revenues) from $3,816.5 actor in 2016 (33% of Complete revenues), due to the admittance of a abounding year of bequest Baxalta costs. The abatement in Bulk of sales as a allotment of Complete revenues  for the year concluded December 31, 2016 to December 31, 2017 is primarily due to the appulse of lower bulk accompanying to the disentangle of anniversary fair bulk adjustments, partially anniversary by the admittance of a abounding year of lower allowance artefact franchises acquired with Baxalta.

For the year concluded December 31, 2017, Bulk of artefact sales included added abrasion accretion $276.1 actor (2016: $160.8 million), primarily due to the accretion of Baxalta.

R&DR&D bulk added by $323.5 million, or 22%, to $1,763.3 actor for the year concluded December 31, 2017 (12% of Complete revenues) from $1,439.8 actor in 2016 (13% of Complete revenues), primarily due to the admittance of a abounding year of bequest Baxalta costs.

R&D bulk for the year concluded December 31, 2017 included abrasion of $47.2 actor (2016: $34.1 million).

SG&ASG&A bulk added by $515.7 million, or 17%, to $3,530.9 actor for the year concluded December 31, 2017 (23% of Complete revenues) from $3,015.2 actor in 2016 (26% of Complete revenues), primarily due to  the admittance of a abounding year of bequest Baxalta costs.

For the year concluded December 31, 2017, SG&A bulk included abrasion of $172.5 actor (2016: $98.0 million).

Amortization of acquired abstract assetsFor the year concluded December 31, 2017, Canton recorded Acquittal of acquired abstract assets of $1,768.4 actor compared to $1,173.4 actor in 2016. The admission of $595.0 actor was primarily accompanying to a abounding year of acquittal of abstract assets acquired with Baxalta and the dispatch of CINRYZE acquittal afterward complete SHP643 Appearance 3 results.

Integration and accretion costsFor the year concluded December 31, 2017, Canton recorded Affiliation and accretion costs of $894.5 million, primarily apropos to the Baxalta acquisition. Costs included asset crime charges, agent severance and costs associated with adeptness consolidations.

For the year concluded December 31, 2016, Canton recorded Affiliation and accretion costs of $883.9 million, primarily apropos to the Baxalta and Dyax acquisitions. Costs included agent severance, dispatch of banal compensation, third-party able fees, adjustment terminations and added transaction-related fees.

Reorganization costsFor the year concluded December 31, 2017, Canton recorded Reorganization costs of $47.9 million, primarily accompanying to the cease of the Basingstoke, U.K. office.

For the year concluded December 31, 2016, Canton recorded Reorganization costs of $121.4 million, primarily accompanying to the cease of a adeptness at the Los Angeles, U.S. accomplishment site.

Other expense, netOther expense, net added by $85.0 actor to $561.8 actor for the year concluded December 31, 2017 from $476.8 actor in 2016, primarily due to a abounding year of absorption bulk incurred on borrowings acclimated to armamentarium the accretion of Baxalta, bargain by repayments of borrowings and partially anniversary by lower acquittal of ancient upfront borrowing costs for Baxalta and Dyax in 2017.

TaxationThe able tax bulk in 2017 was a tax acclaim of 125% (2016: tax acclaim of 26%). The able tax bulk in 2017 was lower due to the accomplishment of the U.S. Tax Cuts and Jobs Act (P.L. 115-97) (Tax Act), which was active into law on December 22, 2017. Amid the changes is a abiding abridgement in the federal U.S. accumulated assets tax bulk from 35% to 21% able January 1, 2018.

As a aftereffect of the abridgement in the U.S. accumulated assets tax rate, Canton revalued its net deferred tax positions for the year catastrophe December 31, 2017.

This resulted in a abatement to the net deferred tax accountability of about $2.5 billion, which was recorded as abridgement to assets tax bulk for the fourth division of 2017. In addition, Canton has estimated an assets tax accountability of $621.7 actor accompanying to the alteration tax which is applicative to assertive non U.S. antithesis ahead untaxed in the U.S. The Aggregation recorded a $90.1 actor assets tax bulk accompanying to the alteration tax and reclassified a deferred tax accountability which had been accrued for above-mentioned years` unremitted antithesis to assets tax payable for the actual amount. Canton continues to assay the Tax Act to actuate the abounding furnishings the new law will accept on its banking statements and all amounts recorded in the 2017 banking statements are conditional in nature.

Discontinued operationsThe accretion from discontinued operations for the year concluded December 31, 2017 was $18.0 million, net of taxes, primarily the acknowledgment of funds ahead captivated in escrow accompanying to the accretion of the DERMAGRAFT business. The accident from discontinued operations for the year concluded December 31, 2016 was $276.1 million, net of tax anniversary of $98.9 million, primarily due to the enactment of acknowledged contingencies accompanying to the bald DERMAGRAFT business.

Liquidity and Basic ResourcesGeneralThe Company`s allotment requirements depend on a cardinal of factors, including the timing and admeasurement of its development programs; corporate, business and artefact acquisitions; the akin of assets adapted for the amplification of assertive accomplishment and business capabilities as the artefact abject expands; increases in accounts receivable and anniversary which may appear with any admission in Artefact sales; aggressive and abstruse developments; the timing and bulk of accepting adapted authoritative approvals for new products; the timing and breakthrough of anniversary payments on business combinations, in-licenses and collaborative projects; the timing and breakthrough of tax and allotment payments; the timing and breakthrough of purchases by the Agent Anniversary Trust (EBT) of Canton shares in the bazaar to amuse awards accustomed beneath Shire`s agent allotment plans; the timing and accomplishment of its refinancing obligations; and the bulk of banknote generated from sales of Shire`s articles and adeptness receipts.

An important allotment of Shire`s business action is to assure its articles and technologies through the use of patents, proprietary technologies and trademarks, to the admeasurement available. The Aggregation intends to avert its bookish acreage and as a aftereffect may charge banknote for allotment the bulk of litigation.

The Aggregation diplomacy its activities through banknote generated from operating activities; acclaim facilities; clandestine and accessible offerings of disinterestedness and debt securities; and the gain of asset or beforehand disposals.

Shire`s Circumscribed Antithesis Sheets included $472.4 actor of Banknote and banknote equivalents as of December 31, 2017.

Shire has a revolving acclaim adeptness (RCF) of $2.1 billion which matures in 2021, $810.0 actor of which was activated as of December 31, 2017. The RCF incorporates a $250 actor U.S. dollar and Euro swingline adeptness operating as a sub-limit thereof.

In affiliation with the accretion of Dyax, Canton entered into a $5.6 billion amortizing appellation accommodation adeptness in November 2015. As of December 31, 2017, $1.2 billion of this appellation accommodation adeptness was outstanding. The adeptness matures on November 2, 2018.

In affiliation with the accretion of Baxalta, Canton afflicted $5.0 billion of apart chief addendum ahead issued by Baxalta, of which $750.0 actor is due aural the aing twelve months and issued $12.1 billion of apart chief addendum in September 2016, of which none are due for claim in the aing twelve months.

The accommodation of these debt agreements are declared beneath and in Agenda 18, Borrowings and Basic Leases, to the circumscribed banking statements.

In addition, Canton additionally has admission to assertive concise uncommitted curve of acclaim which are accessible to advance from time to time to accommodate concise banknote administration flexibility. As of December 31, 2017, these curve of acclaim were not utilized.

The Aggregation may additionally appoint in costs activities from time to time, including accessing the debt or disinterestedness basic markets.

Senior Addendum IssuanceOn September 23, 2016, SAIIDAC, issued chief addendum with a complete accumulated arch bulk of $12.1 billion (SAIIDAC Notes), affirmed by Canton plc and by Baxalta. SAIIDAC acclimated the net gain to absolutely accord amounts outstanding beneath the January 2016 Accessories Acceding (discussed below), which was acclimated to accounts the banknote application payable accompanying to the Company`s accretion of Baxalta. Beneath is a arbitrary of the SAIIDAC Addendum as of December 31, 2017:

The costs and abatement associated with this alms of $49.8 actor accept been recorded as a abridgement to the accustomed bulk of the debt on the Circumscribed Antithesis Sheets. These costs will be amortized as added absorption bulk application the able absorption bulk adjustment over the aeon from arising through maturity.

Baxalta NotesShire plc affirmed chief addendum issued by Baxalta with a complete accumulated arch bulk of $5.0 billion in affiliation with the Baxalta accretion (Baxalta Notes). Beneath is a arbitrary of the Baxalta Addendum as of December 31, 2017:

Variable-rate addendum due 2018

375.0

2.60

373.9

The able absorption ante aloft exclude the aftereffect of any accompanying absorption bulk swaps. The book ethics aloft accommodate any premiums and adjustments accompanying to ambiguity instruments. For added accommodation accompanying to the absorption bulk acquired contracts, amuse see Agenda 16, Banking Instruments, to the circumscribed banking statements.

Revolving Acclaim Accessories AgreementOn December 12, 2014, Canton entered into a $2.1 billion revolving acclaim accessories acceding with a cardinal of banking institutions. Canton plc and SAIIDAC are able to borrow beneath the RCF; Canton plc, SAIIDAC and Baxalta are guarantors beneath the RCF. As of December 31, 2017 SAIIDAC activated $810.0 actor of the RCF.

The RCF, which terminates on December 12, 2021, may be activated appear costs the accustomed accumulated purposes of Shire. The RCF incorporates a $250 actor U.S. dollar and Euro swingline adeptness operating as a sub-limit thereof.

Interest on any loans fabricated beneath the RCF is payable on the aftermost day of anniversary absorption period, which may be one anniversary or one, two, three or six months at the acclamation of Shire, or as contrarily agreed with the lenders. The absorption bulk for the RCF is: LIBOR (or, in affiliation to any revolving loan  in Euro, EURIBOR); added 0.30% per annum accountable to change depending aloft (i) the prevailing adjustment of Net Debt to EBITDA (each as authentic in the RCF) in anniversary of the best afresh completed banking year or banking bisected year and (ii) the accident and assiduity of an accident of absence in anniversary of the banking covenants or the abortion to accommodate a acquiescence certificate.

Shire additionally will pay (i) a charge fee according to 35% of the applicative allowance on accessible commitments beneath the RCF for the availability aeon applicative thereto and (ii) a appliance fee according to (a) 0.10% per year of the accumulated of all outstanding loans up to an accumulated abject bill bulk according to $700.0 million, (b) 0.15% per year of the bulk by which the accumulated abject bill bulk of all outstanding loans exceeds $700.0 actor but is according to or beneath than $1,400.0 actor and (c) 0.30% per year of the bulk by which the accumulated abject bill bulk of all outstanding loans exceeds $1,400.0 million.

The RCF includes accustomed representations and warranties, covenants and contest of default, including requirements that Shire`s (i) adjustment of Net Debt to EBITDA in anniversary of the best recently-ended 12-month accordant aeon (each as authentic in the RCF) charge not, at any time, beat 3.5:1 except that, afterward an accretion accomplishing assertive criteria, Canton may accept to admission this adjustment to (a) 5.5:1 for the accordant aeon in which the accretion was completed (b) 5.0:1 in anniversary of the aboriginal accordant aeon afterward the accordant aeon in which the accretion was completed and (c) 4.5:1 in anniversary of the added accordant aeon afterward the accordant aeon in which the accretion was completed and (ii) adjustment of EBITDA to Net Absorption for the best recently-ended 12-month accordant aeon (each as authentic in the RCF) charge not be beneath than 4.0:1. Canton adopted to admission the Net Debt to EBITDA adjustment in affiliation with the aeon catastrophe June 30, 2016, afterward the accomplishment of the accretion of Baxalta during the period. The final accordant aeon concluded June 2017.

The RCF restricts, accountable to assertive exceptions, Shire`s adeptness to access added banking indebtedness, admission aegis over its assets or accommodate loans/grant credit. Further, any lender may crave bounden accommodation of its accord if there is a change of ascendancy of Shire, accountable to assertive exceptions for schemes of adjustment and akin schemes.

Events of absence beneath the RCF include, accountable to accustomed adroitness periods and accomplishment thresholds: (i) non-payment of any amounts due beneath the accounts abstracts (as authentic in the RCF), (ii) abortion to amuse any banking covenants,(iii) complete bribery in any of the accounts documents, (iv) abortion to pay, or assertive added defaults, beneath added banking indebtedness, (v) assertive defalcation contest or proceedings, (vi) complete adverse changes in the business, operations, assets or banking action of Canton as a whole, (vii) if it becomes actionable for Canton (or any almsman ancestor company) or any of their corresponding subsidiaries that are parties to the RCF to accomplish their obligations thereunder or (viii) if Canton (or any almsman ancestor company) or any accessory thereof which is a affair to the RCF repudiates such acceding or added accounts document, amid others.

Term Accommodation Accessories Acceding November  2015 Facilities  Acceding On November 2, 2015, Canton entered into a $5.6 billion accessories acceding with assorted banking institutions (November 2015 Accessories Agreement). Canton plc, SAIIDAC and Baxalta are guarantors beneath the November 2015 Accessories Agreement. SAIIDAC is the borrower beneath the November 2015 Accessories Agreement. The November 2015 Accessories Acceding comprises three acclaim facilities: (i) a $1.0 billion appellation accommodation adeptness of which, afterward the exercise of the one year addendum advantage in the bulk of $400.0 million, $600.0 actor accomplished and was repaid on November 2, 2016 and $400.0 actor was repaid on July 31, 2017 (November 2015 Adeptness A), (ii) a $2.2 billion amortizing appellation accommodation adeptness which was absolutely paid during 2017 (November 2015 Adeptness B) and (iii) a $2.4 billion amortizing appellation accommodation adeptness which matures on November 2, 2018 (November 2015 Adeptness C), of which $1.2 billion charcoal outstanding as of December 31, 2017.

Interest on any loans fabricated beneath the November 2015 Accessories Acceding is payable on the aftermost day of anniversary absorption period, which may be one anniversary or one, two, three or six months, or as contrarily agreed with the lenders. The absorption bulk applicative is LIBOR plus, in the case of the November 2015 Adeptness A, 0.55% per annum, in the case of the November 2015 Adeptness B, 0.65% per annum and, in the case of the November 2015 Adeptness C, 0.75% per annum, in anniversary case accountable to change depending on (i) the prevailing adjustment of Net Debt to EBITDA (each as authentic in the November 2015 Accessories Agreement) in anniversary of the best afresh completed banking year or banking bisected year and  (ii) the accident and assiduity of an accident of absence in anniversary of the banking covenants or abortion to accommodate a acquiescence certificate.

The November 2015 Accessories Acceding includes accustomed representations and warranties, covenants and contest of default, including requirements that Shire`s (i) adjustment of Net Debt to EBITDA in anniversary of the best afresh concluded 12-month accordant period, (each as authentic in the November 2015 Accessories Agreement), charge not, at any time, beat 3.5:1, except that afterward an accretion accomplishing assertive criteria, Canton may accept to admission this adjustment to (a) 5.5:1 for the accordant aeon in which the accretion was completed, (b) 5.0:1 in anniversary of the aboriginal accordant aeon afterward the accordant aeon in which the accretion was completed, and (c) 4.5:1 in anniversary of the added accordant aeon afterward the accordant aeon in which the accretion was completed and (ii) adjustment of EBITDA to Net Absorption in anniversary of the best afresh concluded 12 ages accordant period, (each as authentic in the November 2015 Accessories Agreement), charge not be beneath than 4.0:1. Canton adopted to admission the Net Debt to EBITDA adjustment in affiliation with the aeon catastrophe June 30, 2016, afterward the accomplishment of the accretion of Baxalta during the period. The final accordant aeon concluded June 2017.

The November 2015 Accessories Acceding restricts, accountable to assertive exceptions, Shire`s adeptness to access added banking indebtedness, admission aegis over its assets or accommodate loans/grant credit. Further, any lender may crave bounden accommodation of its accord if there is a change of ascendancy of Shire, accountable to assertive exceptions for schemes of adjustment and akin schemes.

Events of absence beneath the November 2015 Accessories Acceding include, accountable to accustomed adroitness periods and accomplishment thresholds: (i) non-payment of any amounts due beneath the accounts abstracts (as authentic in the November 2015 Accessories Agreement), (ii) abortion to amuse any banking covenants, (iii) complete bribery in any of the accounts documents, (iv) abortion to pay, or assertive added defaults, beneath added banking indebtedness, (v) assertive defalcation contest or proceedings, (vi) complete adverse changes in the business, operations, assets or banking action of Canton as a whole, (vii) if it becomes actionable for Canton (or any almsman ancestor company) or any of their corresponding subsidiaries that are parties to the November 2015 Accessories Acceding to accomplish their obligations thereunder or (viii) if Canton (or any almsman ancestor company) or any accessory thereof which is a affair to the November 2015 Accessories Acceding repudiates the November 2015 Accessories Acceding or any added accounts document, amid others.

January 2016 Accessories AgreementOn January 11, 2016, Canton (as aboriginal angel and aboriginal borrower), entered into an $18.0 billion arch accessories acceding with assorted banking institutions (the January 2016 Accessories Agreement). The January 2016 Accessories Acceding comprised two acclaim facilities: (i) a $13.0 billion appellation accommodation adeptness originally crumbling on January 11, 2017 (January 2016 Adeptness A) and (ii) a $5.0 billion revolving accommodation adeptness originally crumbling on January 11, 2017 (January 2016 Adeptness B). On April 1, 2016, SAIIDAC became an added borrower and added angel beneath the January 2016 Accessories Agreement. The January 2016 Adeptness A was absolutely repaid in September 2016. The January 2016 Adeptness B was canceled able July 11, 2016, in accordance with its terms.

Short-term uncommitted curve of acclaim (Credit lines)Shire has admission to assorted Acclaim curve from a cardinal of banks which are accessible to be activated from time to time to accommodate short- appellation banknote administration flexibility. These Acclaim curve can be aloof by the banks at any time. The Acclaim curve are not relied aloft for bulk liquidity. As of December 31, 2017, these Acclaim curve were not utilized.

FinancingShire anticipates that its operating banknote breeze calm with accessible cash, banknote equivalents, and the RCF will be adequate to accommodated its advancing approaching operating expenses, basic expenditures, tax and absorption payments, charter obligations, debt repayments and anniversary payments as they become due over the aing twelve months.

If the Aggregation decides to access added businesses, it expects to armamentarium these acquisitions from banknote resources, the RCF and through new borrowings (including issuances of debt securities) or the arising of new equity, if necessary.

Sources and uses of cashThe afterward table provides an assay of the Company`s gross and net banknote (excluding belted cash):

$`M

$`M

             Cash breeze activityNet banknote provided by operating activities for the year concluded December 31, 2017 added 60% to $4,256.7 actor (2016: $2,658.9 million), primarily due to admittance of a abounding year of Baxalta operating banknote flows, added banknote receipts from college sales and operating profitability, partially anniversary by a acquittal of $351.6 actor associated with the adjustment of the DERMAGRAFT action and college absorption payments.

Net banknote provided by operating activities for the year concluded December 31, 2016 added 14% to $2,658.9 actor (2015: $2,337.0 million), primarily due to added banknote receipts from college sales, partially anniversary by college tax and absorption payments, costs accompanying to the Baxalta affiliation and a acquittal associated with the abortion of a biosimilar accord acquired with Baxalta.

Net banknote acclimated in advance activities was $700.9 actor for the year concluded December 31, 2017, primarily accompanying to acquirement of $798.8 actor of PP&E due to connected investments in accomplishment operations, anniversary by $88.6 actor of gain from the auction of investments.

Net banknote acclimated in advance activities was $18,092.2 actor for the year concluded December 31, 2016, primarily accompanying to the banknote paid for the acquisitions of Baxalta ($12,366.7 million, beneath banknote acquired of $583.2 million) and Dyax ($5,934.0 million, beneath banknote acquired of $241.2 million). The Company`s advance activities additionally included the acquirement of $648.7 actor of PP&E due to the connected beforehand in accomplishment operations.

Net banknote acclimated in costs activities was $3,619.3 actor for the year concluded December 31, 2017, principally due to repayments of November Accessories of $3,800.0 actor and allotment payments of $281.3 million, anniversary by monies adopted beneath the RCF of $360.0 actor and gain from the arising of banal and share-based advantage arrange of $134.1 million.

Net banknote provided by costs activities was $15,825.8 actor for the year concluded December 31, 2016, principally due to monies adopted beneath the January 2016 Accessories Acceding to partially armamentarium the accretion of Baxalta (repaid application the gain of the arising of the SAIIDAC Notes) and assets fabricated beneath the RCF and the November 2015 Accessories Acceding to armamentarium the accretion of Dyax (net of consecutive repayments). In addition, the Aggregation fabricated allotment payments of $171.3 million.

Outstanding Belletrist of creditAs of December 31, 2017, the Aggregation had assertive standby belletrist of acclaim and guarantees with assorted banks accretion $224.8 million, accouterment aegis for the Company`s accomplishment of assorted obligations. These obligations are primarily in anniversary of the recoverability of allowance claims, charter obligations and accumulation commitments.

Cash RequirementsAs of December 31, 2017, the Company`s banknote requirements for accustomed and non-current liabilities reflected on the Circumscribed Antithesis Sheets and added acknowledged obligations were as follows:

Payments due by aeon

Total$`M

1-3 years$`M

3-5 years$`M

The afterward items accept been afar from the table above:

Off-balance breadth arrange There are no asymmetric breadth arrangements, a from those categorical above, that have, or are analytic adequate to have, a accustomed or approaching complete aftereffect on the Company`s banking condition, revenues or expenses, after-effects of operations, liquidity, basic expenditures or basic resources.

Foreign bill fluctuationsA cardinal of the Company`s subsidiaries accept a anatomic bill added than the U.S. dollar. As such, the circumscribed banking after-effects are accountable to fluctuations in barter rates, decidedly in the Euro, Swiss franc, Japanese yen and Pound admirable adjoin the U.S. dollar.

Accumulated adopted bill adaptation differences of $1,279.6 actor are appear aural Accumulated added complete assets as of December 31, 2017. Adopted barter losses for the year concluded December 31, 2017 of $97.3 actor are appear in the Circumscribed Statements of Operations.

As of December 31, 2017, the Aggregation had outstanding adopted barter bandy and avant-garde diplomacy that administer the bill accident associated with intercompany transactions. As of December 31, 2017 the fair bulk of these diplomacy was a net asset of $11.4 million. For the year concluded December 31, 2017, net assets on adopted barter swaps and assiduously of $93.6 actor are appear in the Circumscribed Statements of Operations.

InflationAlthough at bargain levels in contempo years, aggrandizement continues to administer advancement burden on the bulk of appurtenances and casework which are acclimated in the business. However, the Aggregation believes that the net aftereffect of aggrandizement on its revenues and operations has been basal during the accomplished three years.

Treasury behavior and organizationThe Company`s arch treasury  operations are accommodating by its accumulated treasury function. All treasury operations are conducted aural a framework of behavior and procedures accustomed annually by the Board of Directors. As a amount of policy, the Aggregation does not undertake abstract diplomacy that would admission its credit, bill or absorption bulk exposure.

Interest bulk riskThe Aggregation is apparent to the accident that its antithesis and banknote flows could be abnormally impacted by fluctuations in criterion absorption ante apropos to its debt obligations on which absorption is set at amphibian rates.  The Company`s action is to administer this accident to an adequate level. The Aggregation is principally apparent to absorption bulk accident on any borrowings beneath the Company`s assorted debt accessories and on allotment of the chief addendum afflicted in affiliation with the accretion of Baxalta. Absorption on anniversary of these debt obligations is set at amphibian rates, to the admeasurement utilized. Shire`s acknowledgment beneath these accessories is to changes in U.S. dollar absorption rates. For accommodation accredit to Agenda 15, Banking Instruments, to the circumscribed banking statements.

The Aggregation is additionally apparent to absorption bulk accident on its belted cash, banknote and banknote equivalents and on adopted barter diplomacy on which absorption is set at amphibian rates. As the Aggregation maintains all of its cash, aqueous investments and adopted barter diplomacy on a concise base for clamminess purposes, this accident is not actively managed. For the year concluded December 31, 2017, the boilerplate absorption bulk accustomed on banknote and aqueous investments was beneath than 1.0% per annum. These banknote and aqueous investments were primarily invested in U.S. dollar appellation deposits with banks and money bazaar and clamminess funds or captivated as cash  on account.

As of December 31, 2017, Canton estimates that a academic admission and abatement of 100 base credibility in absorption ante would admission and abatement net absorption costs on borrowings by about $30.0 actor during 2018, and abatement and admission the fair bulk of continued appellation absorption bulk acute instruments by about $870.7 actor and $956.4 million, respectively, during the aloft period.

Foreign barter riskThe Aggregation operates in abundant countries and as a aftereffect has adopted barter exposure. The basic operating currencies of the Aggregation are the U.S. dollar, Pounds sterling, Swiss franc, Canadian dollar, Japanese yen and the Euro. It is the Company`s action that these exposures are minimized to the admeasurement accessible by denominating diplomacy in the subsidiary`s anatomic currency.

Where cogent exposures remain, the Aggregation uses adopted barter diplomacy (spot, avant-garde and bandy contracts) to administer the acknowledgment for antithesis breadth assets and liabilities that are denominated in currencies altered to the anatomic bill of the accordant subsidiary. These assets and liabilities chronicle predominantly to inter-company financing. The Aggregation has not adopted barrier accounting for these transactions. Banknote flows from acquired instruments are presented aural net banknote provided by operating activities in the Circumscribed Statements of Banknote Flows, unless the acquired instruments are economically ambiguity specific advance or costs activities.

Translational adopted barter acknowledgment arises on the adaptation into U.S. dollars of the banking statements of non-U.S. dollar anatomic subsidiaries. For accommodation accredit to Agenda 16, Banking Instruments, to the circumscribed banking statements.

Foreign barter accident sensitivityThe afterward barter bulk acuteness assay summarizes the acuteness of the Company`s appear revenues and net assets to academic changes in the boilerplate anniversary barter ante of the Euro, Pound admirable and Swiss franc adjoin the U.S. dollar, (assuming a academic 10% deepening of the U.S. dollar adjoin anniversary of the aloft currencies in the year concluded December 31, 2017):

A 10% abrasion of the U.S. dollar adjoin the aloft currencies would accept an according and adverse effect.

For added detail of adopted barter avant-garde contracts, accredit to Agenda 16, Banking Instruments, to the circumscribed banking statements.

Concentration of acclaim riskFinancial instruments that potentially betrayal Canton to concentrations of acclaim accident abide primarily of concise banknote investments, acquired diplomacy and barter accounts receivable from Artefact sales and from  third parties from which the Aggregation receives royalties. Banknote is invested in concise money bazaar instruments, including money bazaar and clamminess funds and coffer appellation deposits or captivated on account. The money bazaar and clamminess funds breadth Canton invests are all amateur A rated by both Accustomed and Poor`s and by Moody`s acclaim appraisement agencies.

The Aggregation is apparent to the acclaim accident of the counterparties with which it enters into coffer appellation drop arrange and acquired instruments. The Aggregation banned this acknowledgment through a arrangement of centralized acclaim banned which alter according to ratings assigned to the counterparties by the aloft appraisement agencies. The centralized acclaim banned are accustomed by Shire`s Board of Directors and acknowledgment adjoin these banned is monitored by the Company`s accumulated treasury function. The counterparties to these derivatives diplomacy are aloft all-embracing banking institutions.

The Company`s revenues from Artefact sales in the U.S. are mainly complete by agreements with aloft biologic wholesalers and relationships with added biologic distributors and retail pharmacy chains. For the year concluded December 31, 2017, there were three barter in the U.S. that accounted for 26% of the Company`s Artefact sales. Such barter about accept cogent banknote assets and as such the accident from absorption of acclaim is advised acceptable. The Aggregation has taken complete accomplish to administer any acclaim accident associated with these diplomacy and operates acutely authentic acclaim appraisal procedures. However, an disability of one or added of these wholesalers to account their debts to the Aggregation could accept an adverse aftereffect on the Company`s banking action and after-effects of operations.

A abundant allocation of the Company`s accounts receivable in countries alfresco of the U.S. is acquired from Artefact sales to government-owned or government- accurate healthcare providers. The Company`s accretion of these accounts receivable is appropriately abased aloft the banking adherence and creditworthiness of the accordant governments. In contempo years all-around and civic bread-and-er altitude accept abnormally afflicted the growth, creditworthiness and accustomed bread-and-er action of assertive markets in which the Aggregation operates. As a result, in some countries alfresco of the U.S., specifically, Argentina, Brazil, Greece, Italy, Portugal  and Spain, the Aggregation is experiencing delays in the remittance of receivables due from government-owned or government- accurate healthcare providers. Of those, the alone cogent accounts receivable as of December 31, 2017 is $91.5 actor from Brazil.

The Aggregation will abide to appraise all its accounts receivable for abeyant accumulating risks and has fabricated accouterment for amounts breadth accumulating is advised to be doubtful. Any such accident could accept an adverse aftereffect on the Company`s banking action and after-effects of operations. The Aggregation does not accede it is currently apparent to cogent acclaim accident alfresco of the countries listed above.

Strategic reportThe Cardinal abode comprises pages 2 to 55 of this Anniversary Report.

Approved by the Board of Directors and active on its anniversary by:

Flemming Ornskov, MD, MPH

Chief Controlling Officer

February 16, 2018

4. Arch risks and uncertainties (Pages 18 – 21 2017 Anniversary Report)

Risk managementAs a awful adapted biopharmaceutical aggregation focused on confined bodies with attenuate diseases, Canton has implemented policies, processes and procedures advised to administer accident and ensure adapted and allowable conduct in the countries in which the Aggregation operates. Accustomed accident administration is of anniversary to shareholders and added stakeholders alike. Shire`s accident administration action is to identify, assess, manage, and adviser cogent risks that it faces. Despite this, no accident administration action can accommodate complete affirmation adjoin accident or abortive results.

Stakeholders in accident management, which is overseen by the Board of Directors and advised to accredit the able identification, assessment, management, and ecology of the Group`s risks, are abundant below.

Board of DirectorsThe Board of Directors is amenable for ensuring the development and aliment of complete systems of accident administration and centralized control. In accomplishing this responsibility, the Board oversees Action Accident Administration (ERM), determines the Company`s accident appetite, and ensures that an adapted accident adeptness is anchored throughout the Company. The Board additionally interacts with key accident and centralized ascendancy stakeholders on a common basis, enabling it to adviser and assay the Company`s arch risks and the adequacy of its accident administration and centralized ascendancy systems. During the accomplished year the Board conducted a able-bodied appraisal of the arch risks adverse the Company, including those that could abuse its business model, approaching performance, solvency, or liquidity.

Audit, Acquiescence & Accident Committee The Audit, Acquiescence & Accident Committee supports the Board by administering and reviewing accident management, compliance, and centralized ascendancy programs through its alternation with key stakeholders and alternate updates from management. The Committee reviews and monitors the arch risks adverse the Company, with anniversary accident adjourned on the likelihood of materialization, abeyant banking and non-financial impacts, and all-embracing accident acknowledgment effectiveness.

Executive CommitteeThe Controlling Committee oversees the accomplishing and operation of accident administration and centralized ascendancy systems aloft the Company. The Committee reviews and monitors arch risks articular during the action accident appraisal process, afore they are presented to the Audit, Acquiescence &Risk Committee. Committee associates additionally accept accustomed accident updates from anatomic and business assemblage stakeholders. Forth with both the Chief Acquiescence and Accident Officer and the Head of Centralized Audit, Committee associates are additionally amenable for ascent diplomacy of accident administration and centralized ascendancy to the Audit, Acquiescence & Accident Committee and/or the Board of Directors, as appropriate.

Chief Acquiescence and Accident Officer The Chief Acquiescence and Accident Officer leads the All-around Acquiescence and Accident Administration Department, and is amenable for administering acquiescence and accident administration systems and programs, including ERM aloft the Company, and accouterment the Controlling Committee, the Audit, Acquiescence & Accident Committee, and the Board with updates on accident administration and compliance.

Global Acquiescence and Accident Administration DepartmentThe All-around Acquiescence and Accident Administration Department, led by the  Chief Acquiescence and Accident Officer, is fabricated up of compliance, assurance, monitoring, privacy, and accident administration competencies. It is amenable for acknowledging the development, implementation, and aliment of accordant accident administration and acquiescence systems and programs aloft the Company. This is able through governance, policy, and procedures; awareness, training, and communications; as able-bodied as, audits, monitoring, and investigations. These activities accommodate for accident identification, assessment, management, and monitoring, as able-bodied as the accretion of accordant diplomacy to the Controlling Committee, Audit, Acquiescence & Accident Committee, and the Board of Directors as appropriate.

Enterprise Accident Administration Aggregation The ERM Team, led by the Chief Acquiescence and Accident Officer, includes the Head of All-around Accident and Acquiescence Assurance, and the Head of Accident Administration and Business Continuity, and is accurate by alien consultants as appropriate. The Aggregation is answerable with implementing and operating the ERM system. This consists of advancement the action accident cosmos and accident appraisal methodology, anecdotic anatomic and controlling accident owners, facilitating the action accident appraisal process, accouterment accident training and acquaintance to stakeholders aloft the Company, acceptable with accident reporting, and acknowledging the Controlling Committee and Audit, Acquiescence & Accident Committee as appropriate.

Internal AuditInternal Analysis provides absolute affirmation to the Audit, Acquiescence & Accident Committee that Shire`s accident management, governance, and centralized ascendancy processes are advised and operating effectively.

Business units, accumulated functions, and franchisesBusiness units, accumulated functions, and franchises participate in the action accident appraisal action by anecdotic and assessing their accordant risks. They are amenable for managing their risks; implementing controls, and monitoring, escalating, and advertisement risk.

Global Issues and Crisis Administration Canton operates a All-around Issues and Crisis Administration framework, which assists in planning for, and responding to, confusing contest that could potentially jeopardize  the Company`s acceptability and business operations, The allegorical attempt accent the bloom and assurance of patients, customers, employees, and the association at large; absorption the Company`s integrity, active strategy, and acknowledging business continuity.

Principal areas of riskThe Aggregation is accountable to capricious degrees of accident and uncertainty. The table beneath accommodation the arch areas of accident that were articular and adjourned through the Company`s ERM arrangement in 2017.

These arch areas of accident are listed in no accurate adjustment and, forth with the abundant accident factors set out on pages 187 to 198 of this Anniversary Abode (the “Risk Factors”), should be anxiously advised afore any beforehand is fabricated in Shire. In addition, risks not anon accustomed to the Aggregation may additionally abnormally affect its business. If any of these aloft risks were to materialize, the business, banking condition, after-effects of operations, or diplomacy of the Aggregation could be materially harmed. In such circumstances, the bulk of the Company`s antithesis could abatement and an broker could lose allotment or all of his or her investment. In addition, avant-garde statements that are absolute in this Anniversary Abode or in the Company`s added reports, filings, or statements may be accountable to the arch areas of accident declared beneath and the Accident Factors.

The bazaar admission of adversary products, and accretion antagonism due to the accident of apparent exclusivity and artefact genericization, could advance to bargain revenue.

Shire continues to conduct accordant bazaar research, analysis, and artefact accident assessments. We adviser the regulatory, legal, and industry ambiance to proactively ahead and assay adversary articles and plan accordingly.

Failure to attach to accordant laws, regulations, and policies, including Shire`s Environment,

Health & Assurance Action and Supplier Code of Conduct, may aftereffect in fines, business disruptions, added operating costs, bargain revenue, interruption/postponement in research, delays of new artefact launches, and/or added ecology and reputational consequences.

Shire has accustomed a cross-functional Artefact Stewardship Alive Group that meets annual to assay any changes to the assorted complete acquiescence regulations and requirements as able-bodied as changes to the Company, products, and processes. Canton has implemented processes and acknowledging technology to accommodate a framework for blank and governance.

Failure to accede with anti-corruption/ anti-bribery laws, regulations, behavior and standards administering the manufacturing, sales, and business of Canton products, could abnormally appulse the Aggregation and/or its officers, Directors and employees, consistent in administration activity, civilian and/or bent liability, fines, penalties, imprisonment, business restrictions, or accident to our reputation.

Shire has a categorical Code of Ethics, a bright set of values, and pertinent policies/ procedures that adviser our access to Anti-Corruption/Anti-Bribery compliance, all of which are accessible Group-wide. Canton continues to review, audit, and adviser acquiescence with accordant policies, procedures, systems, and controls. We arrange all-around anti-corruption/ anti-bribery measures including training and acquaintance initiatives and a third-party due activity program.

In today`s circuitous and ever-changing environment, abortion to aegis information, systems, applications, databases, and networks could aftereffect in cyber breaches and violations of privacy/consumer aegis laws, business disruption, accident of bookish property, accident to our reputation, fines, penalties and/or accommodation of operations or banking condition.

We accept developed an centralized cyber aegis capability, that provides advice and abetment to the Aggregation apropos acquiescence with Canton cybersecurity policies, advice on cybersecurity standards, and recommendations on abeyant vulnerabilities.

We accommodate training, acquaintance and ecology of cybersecurity activities. We beforehand in cyber blackmail intelligence, aegis operations, and accident acknowledgment casework to proactively predict, prevent, ascertain and acknowledge to cyber risks.

Failure to finer identify, collect, and store, claimed (sensitive) advice in acquiescence with federal, state, and bounded laws, acknowledged obligations, and policies, could aftereffect in regulator-imposed fines/ administration actions, accident to our reputation, and/or civilian or bent liability.

Shire continues to apparatus a abstracts aegis and aloofness administration program,  including governance, policies, and procedures, to abode all-around abstracts aegis and aloofness requirements. Our acknowledgment strategies are evolving to accommodated a activating authoritative environment. We adviser regulatory, environmental, and accession key accident indicators, advance abstracts analytics, and advance agent acquaintance of abstracts aegis requirements.

Failure to proactively assay and accede with industry laws and biologic authoritative changes aloft our bulk alternation (including government allowable pricing), could aftereffect in fines, penalties, business disruption, bargain revenue, and/or abeyant exclusion from government programs.

Shire continues to adviser the authoritative ambiance at large, and proactively diplomacy for abeyant authoritative changes aural our industry. We coact internally aloft all-around functions and business units, and evidently with alfresco admonition and advisors, to accept abeyant industry reform, and its appulse on our strategy, operations  and performance.

Failure to authenticate assurance and efficacy  in planned and advancing analytic trials, bootless analytic research, and abortion to complete analytic assay in a adapted fashion, could aftereffect in penalties, fines, bargain revenue, and/or accident to our reputation.

We abide to accent accommodating assurance and a acclimatized access to assay and development. We accept babyminding structures in abode to adviser and appraise our accident acknowledgment in this area, and which additionally acquiesce for assurance in alien reviews with thought-leaders, key appraisal leaders and added stakeholders. Our accumulated portfolio is accountable to assay by Shire`s Quality Affirmation and Ascendancy action for analysis readiness. We conduct assorted operational reviews of the programs ensuring targeted reviews of assurance and adeptness profiles, including identification of programs breadth there is bound or no mechanistic, analytic or authoritative precedent.

Failure to obtain, maintain, accomplish or avert our patents, authoritative data, or added IP may advance to the accommodation of exclusivity periods and bargain revenue.

Shire works with centralized and alien admonition to adviser threats, avert our patents and IP and arraign violations.

Failure to finer administer third-party alliances, geopolitical uncertainty, technology expropriation, adopted barter exposure, payment/collections, and added accident areas could aftereffect in bargain revenue, accident to our reputation, and/or accident of “license to operate” in assertive jurisdictions.

Shire anxiously evaluates new PPP/JV opportunities afore entering into agreements.

We focus on abutment and alignment amid our patients, healthcare professionals, and anniversary PPP/JV. We oversee, monitor, audit, and abode on these PPP/JV relationships on a accustomed basis. We assay macroeconomic factors, administer accordant government relations, and accomplish acknowledged terms.

Failure to finer assassinate and win aloft tenders in key markets could aftereffect in bargain revenue.

We abide to administer breakable relationships and adviser the breakable mural about the world, adjusting our access as needed.

Risk of non-compliance in assurance advertisement and interpretation, and abridged assurance advice and affidavit about to Accommodating Abutment Programs (PSPs), could aftereffect in abeyant accommodation of accommodating safety, accident of arcane data, fines, penalties, business disruptions, and/or accident to our reputation.

Shire has implemented a assurance advertisement policy, allotment programs, cadre training, and abundant procedures for PSPs. We abide to beforehand and clarify our arrangement to ensure axial approval and blank of all all-around PSPs.

Failure to finer accommodate acquired products/companies, and accomplish projected bulk from added cardinal initiatives, could aftereffect in absent synergies, aberration of administration focus, time and resources, operational inefficiencies, added costs, bargain revenue, and/or accident to our reputation.

The Board has accustomed a babyminding framework to accredit the affiliation of Baxalta and the advancing cardinal assay of the organization. These initiatives are actuality led by senior, able leaders.

We abide to analysis and adviser Baxalta affiliation activities in all functions, franchises, and business units, with the Board advancement oversight. As of December 31, 2017, assertive Baxalta affiliation activities, decidedly in IT and Technical Operations, abide to progress, with the majority of affiliation assignment accepting been completed or actuality in the final phases of implementation. We abide to beforehand time, attention, and assets in the advancing cardinal assay of the business.

1 Illustrates all-embracing accident acknowledgment direction, based on an appraisal of abeyant accident impact, likelihood of materialization, and accident acknowledgment effectiveness

5. Directors responsibilities anniversary (Page 113 2017 Anniversary Report)

The Directors are amenable for advancing the Anniversary Abode and the banking statements in accordance with applicative law and regulations.

Company law requires the Directors to adapt banking statements for anniversary banking year. Beneath that law the Directors are adapted to adapt the Group banking statements in accordance with accounting attempt about accustomed in the United States of America. Beneath aggregation law the Directors charge not accept the accounts unless they are annoyed that they accord a accurate and fair appearance of the accompaniment of diplomacy of the Group and of the accumulation or accident of the Group for that period.

In advancing the Group banking statements, the Directors are adapted to:

The Directors are amenable for befitting able accounting annal that are adequate to appearance and explain the Group`s diplomacy and accede with reasonable accurateness at any time the banking position of the Group and accredit them to ensure that the banking statements accede with the Companies (Jersey) Law 1991. They are additionally amenable for absorption the assets of the Group and appropriately for demography reasonable accomplish for the blockage and apprehension of artifice and added irregularities.

Responsibilities statementsEach of the Directors confirms that to the best of their knowledge:

The Responsibilities Statements and the Directors` Report, which comprises pages 2 to 113 and pages 184 to 198 of this Anniversary Report, were accustomed by the Board of Directors and active on its anniversary by:

Flemming Ornskov, MD, MPH Chief Controlling Officer February 16, 2018

This advertisement is broadcast by Nasdaq Accumulated Solutions on anniversary of Nasdaq Accumulated Solutions clients.

The issuer of this advertisement warrants that they are alone amenable for the content, accurateness and dness of the advice absolute therein.Source: Canton plc via GlobeNewswireHUG#2178412

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