2014 Annual Responsibility Review

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2014 Annual

Responsibility Review

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CONTENTS

03 This is Shire

04 Chief Executive Officer’s Introduction 05 Our approach to responsibility 06 Focusing on what matters 07 Performance overview 09 Our Patients 16 Our People 20 Our Planet 24 Our Partners 27 Further Information Key

At Shire, we enable people with life altering

conditions to lead better lives. We focus

on developing and delivering innovative

treatments for patients with rare diseases

and other specialty conditions. Our

responsibility is to meet the current

and future needs of patients.

OUR GOALS

This symbol reflects our goals and what we strive for as an organization.

WHAT WE DID IN 2014

This symbol points to our accomplishments and accolades.

WHAT WE WILL DO IN 2015

This symbol shows our planned activities for the year ahead.

OUR PATIENTS OUR PARTNERS

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THIS IS SHIRE

Our Business Units: Conditions:

Neuroscience Attention Deficit Hyperactivity Disorder (ADHD); Acute Convulsive Seizures; Binge Eating Disorder (BED) Gastrointestinal

and Internal Medicine

Ulcerative Colitis; Chronic Constipation; Cholestatic Liver Diseases; Chronic Kidney Disease (CKD Stage 5); Essential Thrombocythemia (ET); Adrenal Insufficiency; Short Bowel Syndrome; Hypoparathyroidism

Rare disease Hunter syndrome; Hereditary Angioedema (HAE); Fabry Disease; Gaucher disease Ophthalmics* _{Dry Eye Disease; Retinopathy}

of Prematurity (ROP)

READ MORE AT SHIRE.COM/SHIREPLC/EN/PRODUCTS

OUR STRATEGIC DRIVERS

We focus on researching, developing and marketing innovative medicines that have the potential to transform the lives of people around the world with rare and other specialty conditions. To realize our aspiration to become a leading biotech, we will concentrate our efforts on four strategic drivers: growth, innovation, efficiency and people.

Growth

Growth is both a means and an end. Sustained high growth across all our business units enables us to fuel further R&D and in turn develop innovative new products for patients with unmet needs.

Innovation

Innovation is the lifeblood of our current and future success. We seek to focus our innovation across areas with high medical need. To this end, we aim to expand our rare disease expertise and offerings through research and partnerships, and to extend our existing portfolio of products to new indications and therapeutic areas.

People

Our people are at the heart of our journey to become a leading biotech delivering innovative global medicines to patients with rare diseases and other speciality conditions. We focus on attracting and retaining great people and giving them an environment where they are encouraged to excel.

Efficiency

Our ongoing focus on efficiency enables us to reinvest in continued growth. The leaner and more agile we are as an organization, the more able we are to fuel and fulfil our purpose to enable people with life altering conditions to lead better lives.

This is Shire

* Pipeline candidate

OUR GLOBAL REACH (AS AT 31 DEC 2014)

We have simplified our global footprint and have offices and facilities in 34 countries around the world. We employ more than 5,000 people and are committed to developing a diverse organization that values all genders, cultures, ages and experience.

Our operations (as at 31 December 2014) Key location: Lexington, MA US Operational Headquarters Key location: Zug, Switzerland International Operational Headquarters

OUR PATIENTS OUR PEOPLE OUR PARTNERS

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THIS IS SHIRE

Chief Executive Officer’s letter

Our purpose is to enable people

with life altering conditions to lead

better lives, and our approach

to Responsibility is fundamental

to fulfilling this purpose.

Taking an ethical and responsible approach that is in the best interest of our patients underpins our daily activities, and is core to how we approach our business. It always has been, and remains an important priority for us. One of the best examples of this can be seen in our efforts to improve access to our treatments. Particularly with rare disease therapies, this is a very complex and challenging area, but one that we recognize is critically important to us, to patients, and to physicians around the world. You can read more about these programs, including our work with Direct Relief, Project HOPE and AmeriCares, in this Annual Review. We were pleased to be recognized this year as a constituent of the 100 Most Sustainable Corporations in the World and the FTSE4Good Index. In addition, we received accolades from Newsweek as the 32nd “greenest” company in the world, and Transparency International identified Shire as one of the top 25 out of 60 best UK companies for transparency in corporate reporting.

We are proud of the progress we are making, but are not complacent. We will continue to strive towards greater transparency of our policies, goals and progress towards those goals. We will continue to work with governments, policymakers and payors to improve access to treatments in both developed and developing countries. And we will continue to invest in developing and marketing new treatments where the need is great and our skills and experience can help most.

Sincerely,

Dr Flemming Ornskov

Chief Executive Officer

RECOGNITION

In 2014, we remained a constituent of the FTSE4Good Index Series, a leading responsibility investment index. We are also proud to rank among the 100 Most Sustainable Corporations in the World in 2015 as determined by Corporate Knights with our inclusion for the first time in the “Global 100”.

In addition, we have earned the distinction from Newsweek as the 32nd “greenest” company in the world.

FTSE4GOOD.COM

CORPORATEKNIGHTS.COM/GLOBAL100 NEWSWEEK.COM

OUR PATIENTS OUR PEOPLE OUR PARTNERS

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Our approach to responsibility

At Shire, responsibility has always

been embedded in our business

– we have never separated it from

our daily activities, decisions and

relationships. Our responsibility is

to our patients and in developing

and helping them access the

medicines they need. Taking an

ethical and responsible approach

that is in the best interest of

our patients underpins our

daily activities.

Although we give the areas of responsibility related to our patients special attention, we have other important responsibilities, to our people, to our planet, and in our interactions with our partners. Together, these make up our four pillars of responsibility. We have set clear and ambitious goals for each and these are outlined in more detail in this review. We are committed to measuring and reporting progress against our goals regularly.

Governance

Our approach to responsibility is championed by our CEO. More than a dozen senior leaders from around Shire, serve as “sponsors” for our responsibility focus areas, with Shire’s Chief Human Resources Officer and member of our Executive Committee serving as executive sponsor. Sponsors are responsible for setting goals, maintaining high standards and ensuring progress across their functions. They help embed responsibility within our business.

In addition, our Responsibility team facilitates the activities of Responsibility working groups across our three material areas (access to medicines, disease awareness and transparency), oversees communications and works closely with sponsors to identify risks, opportunities, and potential areas for policy development.

Stakeholder Engagement

Many different groups take an interest in our work and the way we conduct our business. These include patients, physicians, investors and our own employees. We recognize the importance of staying close to these groups, so we can understand what matters most to them and how we can best address their needs and concerns. For that reason we consult and engage with our stakeholders on a regular basis including our environmental performance and reporting, our approach to clinical trials, and our role in providing access to medicines and raising awareness of health conditions.

Human Rights

The protection of human rights is another important area for our business. We recognize the need to observe the human rights and fundamental freedoms of all. We support the UN Universal Declaration of Human Rights and commit to the principles of the International Labour Organization’s (ILO) Declaration on Fundamental Principles and Rights at Work. It is also critically important that we safeguard the rights of those taking part in our clinical trials. We do this through the informed consent of trial participants and we adhere to the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. For more information on our approach to human rights, please go online to

SHIRE.COM/SHIREPLC/EN/ABOUT/POLICIES/ HUMAN-RIGHTS

OUR PLANET

We have a responsibility to protect the environment and the communities where we work and live. We are committed to effective environmental management as this is an important part of creating a sustainable business.

OUR PARTNERS

We believe that strong partnerships are a vital part of the way we do business. We have a responsibility to build and maintain positive, supportive relationships with our partners and suppliers, including the communities where we operate. OUR PEOPLE

We understand that our success as a business is dependent on a patient-focused high-performing workforce. With our increasing global footprint it is crucial that we create a safe and engaging culture that celebrates diversity and promotes the development and well-being of all our staff around the world. OUR PATIENTS

We put patients at the heart of everything we do. We are dedicated to improving the lives of those with rare diseases and other speciality conditions by developing and improving access to innovative treatments that meet their needs. We also have a responsibility to build awareness of the conditions we treat.

OUR FOUR PILLARS OF RESPONSIBILITY

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OUR APPROACH OUR PATIENTS OUR PARTNERS

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Focusing on what matters

While responsibility at Shire

covers a wide range of topics

within our four pillars, our 2014

materiality assessment points

to three primary areas where we

have the greatest responsibility

– access to medicines, disease

awareness and transparency.

Access to medicines

We have a responsibility to continually improve access to our therapies for patients around the world. We do this by focusing in three areas: availability, accessibility and affordability. For those with rare or specialist conditions, gaining the right treatment can be a challenge, even in more developed parts of the world. According to Shire’s 2013 RARE DISEASE INDEX REPORT, some 7,000 rare diseases have been identified yet treatment exists for less than 5% of them. Developing new treatments for unmet patient needs, where there currently may be little hope, is a major contribution to improving access.

It is for this reason that we see the development of new therapies for rare conditions as a core responsibility in itself. In 2014 we invested 18% of sales, or $840 million in research into new treatments and currently have 27 programs in our clinical development pipeline, the most in our history. In 2014 We also work to reduce barriers, such as affordability and geographic access to our existing treatments. We have several programs to remove these barriers and examples are shown in the section

OUR PATIENTS PG 09

Disease awareness

Disease awareness is especially important for Shire because the conditions our products treat are often extremely rare or not well understood. Without appropriate awareness, conditions often remain undiagnosed for long periods and this can impact on the patient, their family, the healthcare system and society. Our RARE DISEASE INDEX REPORT shows that it takes more than seven and a half years in the US to receive a proper diagnosis of a rare disease.

We believe that creating awareness based on facts and evidence is key to enabling proper diagnosis and treatment. It is our responsibility therefore to share our expertise and provide balanced, reliable and scientifically sound information to improve understanding and appreciation of difficult and life-altering conditions. Examples of how we do this are shown in the section OUR PATIENTS PG 09

Transparency

Transparency relates to many aspects of our business, but is a particular focus for our clinical trials. In 2014 we launched shiretrials.com which provides patients, physicians and researchers a single portal to access information on Shire’s trials – current and past. We also publish details regularly about our educational grants as well as donations made to patient groups and charitable organizations.

In 2014, Shire ranked in the top 25 of 60 companies in the UK evaluated by Transparency International. The study ranked companies based on their publication of anti-bribery and corruption efforts, disclosure of subsidiaries/ operations and disclosure of financial data on foreign operations.

In 2014, Shire ranked in the top

25 of 60 companies in the UK

for transparency in reporting

by Transparency International.

OUR APPROACH Transparency Areas of the greatest responsibility Disease awareness Access to medicines

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Performance overview

Our Patients

Access to medicines Disease awareness Global patient advocacy Clinical trial conduct

OUR GOALS Improve patient access to medicines Increase awareness and education of

rare diseases and specialist conditions Strive to make a valued difference in patients’ lives Ensure clinical trials are conducted compliantly and transparently

WHAT WE DID

IN 2014 ∙Launched pilot humanitarian Enzyme Replacement Therapy (ERT) access program Assisted US patients with affordability issues through Shire Cares and OnePath programs ∙Supported Direct Relief and

AmeriCaresin their Ebola relief efforts

∙Presented the ADHD Alliance for Change “Real Voices” report to European policy makers in Brussels ∙Created the International Gaucher

Disease Ambassador Program ∙Launched partnership with CPAMM to

address abuse, misuse and diversion of ADHD medications

∙Established Shire Patient Advocacy Team

∙Launched working groups to seek advice from advocacy experts to inform our vision and strategy for patient advocacy

∙Improved disease awareness through patient-led presentations

∙Launched shiretrials.com, our dedicated clinical trials website ∙Established mechanism for sharing trial

data with independent researchers

OUR

PERFORMANCE INDICATORS

∙$840m invested in targeted R&D ∙43,000 patients receiving help with

access and affordability issues ∙$60,000 donated to Direct Relief

and AmeriCares

∙27 programs in our clinical development pipeline, 22 of which are unique

∙More than $6.6 million spent on educational grants

∙50 ADHD patients received $2,000 scholarship grant plus coaching ∙Awarded the Shire ACES scholarship

– a $5,000 grant to a rare disease patient

∙Worked with more than 50 patient advocacy organizations representing therapy areas across the Shire portfolio

∙18 trials recruited for and completed

WHAT WE PLAN TO DO IN 2015

∙Take learnings from 2014 pilot

humanitarian ERT access program and look to improve our approach to help even more patients, in more places, obtain access to these therapies ∙Continue to improve patient-led approach to product donations for entire product portfolio

∙Open up new channels to promote exchange of knowledge of ADHD and BED

∙Develop online resource centers for patients and caregivers to improve access to credible information ∙Partner with stakeholders

to promote appropriate use of stimulant medications ∙Create awareness of the need

for improved ocular care

∙Launch patient advocacy strategy to develop innovative ways to amplify the patient voice and influence product ∙development programs

∙Launch “Diagnosis Doesn’t Have to be Rare” campaign

∙Continue to develop and grow shiretrials.com as new studies are announced

∙Enhance shiretrials.com to improve the user experience

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Performance overview (continued)

Our People

Our Planet

Our Partners

OUR GOALS Have a high-performing, healthy organization Understand and reduce our environmental impact Enjoy mutually beneficial relationships with our partners and the communities in which we operate

WHAT WE DID

IN 2014 ∙Launched “Leading Through Ambiguity” leadership development program ∙Continued to reward performance with 2,300

employee recognition awards

∙Created internal ambassador program to help foster open communications and increase employee engagement

∙Completed One Shire program, to build a unified organization, while re-organizing and streamlining our internal operations

∙Conducted materiality assessment to identify our most critical environmental issues

∙Started to develop long-term plan for our environmental programs and identified key environmental metrics

∙Continued to encourage employees to identify environmental impacts and develop reduction plans ∙Started to develop a formal process to capture and

benchmark environmental data

∙Verified scope 1 and scope 2 GHG (Green House Gases) emissions for reporting to CDP

∙Provided two internships to students with learning, communication and physical disabilities

∙The Big Give in Chesterbrook, PA supported local charity, Cradles to Crayons, helping over 5,000 children with educational materials and clothing ∙Supported local charities in Zug, Switzerland through

employee and corporate fundraising initiatives

OUR

PERFORMANCE INDICATORS

∙More than 140 leaders took part in new 360-degree leadership assessment

∙ 49% of our workforce is female ∙ 30% of senior management is female ∙ 22% of our US employees come from

ethnic minorities

∙Total recordable incident rate: 0.59 ∙Lost time injury rate: 0.23

∙Reduction in energy consumption at our facilities since 2011: 27%

∙Climate disclosure score from CDP: 91% ∙Total waste diverted from landfill: 43%

∙Newsweek Green award, 32nd “greenest” company in the world

∙$158 million spent in US with small and diverse suppliers, exceeding spending goal for these groups ∙Seven HSE audits and one labor audit completed

with direct suppliers

WHAT WE PLAN TO DO

IN 2015 ∙Drive leadership and management excellence ∙Engage our colleagues to foster a high-performance organization

∙Enhance talent identification, development and acquisition programs

∙Implement new HR software platform ∙Complete the move to new US operational

headquarters and maximize opportunities for cross-team working

∙Set five-year reduction targets ∙Finalize our climate change policy ∙Establish a Global Sustainability Council ∙Begin to understand our water footprint ∙Add more fuel efficient car choices for sales fleet

∙Develop infrastructure to grow community-employee engagement

∙Strengthen relationships with strategic suppliers and work with them to create efficiencies

∙Conduct HSE and labor audits with suppliers to meet goal to have conducted audits with key suppliers by the end of 2018

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Our patients

We put patients at the heart of everything we do. We are dedicated to improving

the lives of those with rare diseases and other specialty conditions by developing

and marketing innovative treatments that meet their needs. Beyond this, we have

a responsibility to build awareness of the conditions we treat, improve access

to our treatments and be transparent in all areas of our business.

OUR GOALS

1. Improve patient

access to medicines

2. Increase awareness and

education of rare diseases

and specialist conditions

3. Strive to make a valued

difference in patients’ lives

4. Ensure clinical trials are

conducted compliantly

and transparently

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WHY IT MATTERS

Improving access to our

medicines is the number one

expectation of our stakeholders.

However, providing access to

medical treatment for rare and

specialist conditions can be a

big challenge, even in developed

parts of the world. We want to

use our specialist knowledge

and expertise to help patients

access the medical treatment

they need.

OUR GOALS

1.Improve patient access to medicines

OUR APPROACH

Our vision is to transform the lives of those whose health is impaired by rare diseases and other specialized conditions. We therefore have a responsibility to continually improve access to our therapies for patients around the world. We do this by focusing on three critical areas: availability, accessibility and affordability.

Availability

At Shire, we develop innovative treatments and therapies that fulfill unmet patient needs. Making these treatments available is not just central to our business activities, we also see it as a core responsibility in itself. Availability in this sense isn’t just about providing access to existing treatments. It’s also about developing new medicines for rare conditions and disorders. In 2014, Shire invested $840 million into targeted Research & Development, and have 60 preclinical and clinical investigational programs in our pipeline.

Accessibility

To improve accessibility, we work to remove the barriers that prevent medicines being delivered to patients. Barriers can include a lack of suitable transport and medical infrastructure or the absence of trained personnel which can lead to late diagnosis. We work with NGOs, government bodies and other organizations across the world to overcome such hurdles.

Affordability

Affordability is another barrier to patients accessing medicine that we aim to address. We believe that the costs associated with medical treatments should not be a barrier to patient access. We have several US patient assistance programs to help those struggling to afford the treatments their physicians have prescribed.

2014 INDICATORS

$840m

$840 million invested in targeted R&D during 2014

43,000

43,000 patients receiving help with access and affordability issues

$60,000

Shire and our employees donated approximately $60,000 to Direct Relief and AmeriCares to help combat Ebola

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Accessibility

Providing humanitarian care – a pilot

Like most medical conditions, lysosomal storage disorders (LSDs) affect people all around the world – not just in countries where Enzyme Replacement Therapy (ERTs) are available. Individuals with these conditions have real and urgent needs and Shire has a history of supporting patients in countries where access is limited. In 2014, we started to formalize our humanitarian program by launching a pilot process designed to ensure a consistent and ethical approach to humanitarian requests for ERTs.

As part of the 2014 pilot, an independent medical expert committee reviewed all requests for therapy. The committee, made up of seven leading physicians from around the world, donated their time. Our humanitarian program is a partnership between NGO Direct Relief, patient advocacy organizations, and Shire who bring their expertise and resources together. In addition to the program with Direct Relief, we continue to partner with Project HOPE to donate ERT to Gaucher disease patients in Egypt. The program provides help through donated medicine, disease awareness initiatives and training to local healthcare providers. We continued to take an active role as a board member of the Partnership for Quality Medical Donations (PQMD), a global alliance of non-profit and corporate organizations whose aim is to enhance access to health care in underserved communities and in areas affected by disaster.

Affordability

Shire Cares

Shire Cares is an initiative in the US dedicated to helping patients with limited financial

resources. If a patient doesn’t have prescription insurance or is having trouble affording their medicines, Shire Cares may be able to help.

OnePath

OnePath is a US program to help people gain access to rare disease treatment by providing support through case management. The one-to-one support can range from helping navigate insurance or coverage to providing access to a larger community of support.

WHAT WE DID IN 2014 Availability

Our priority is to our patients and ensuring they have access to therapies. This year, we have continued to develop our pipeline; we currently focus on five therapeutic areas and now have 27 programs in clinical development, 22 of them unique. Furthermore, our commitment to innovation was reflected in our $840 million investment in R&D.

Continue to refine and roll out an operating model that promotes access, through various pathways, to Shire’s rare disease therapies. Continue to improve our patient-led approach to product donations for our entire product portfolio.

OUR GOALS

1.Improve patient access to medicines

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WHY IT MATTERS

Many of the diseases and

conditions for which we

develop treatments are not

widely understood. We see

it as a core responsibility to

increase understanding and

raise awareness by sharing

our specialist knowledge.

OUR GOALS

2.Increase awareness and education

of rare diseases and specialist conditions

OUR APPROACH

Understanding and awareness is vitally important for patients, particularly for rare and misunderstood conditions. Low levels of understanding and awareness can lead to misdiagnosis, social stigma, long delays for treatment, and misuse of treatments, which can lead to unnecessary stress for patients and their families.

We have expert knowledge about the conditions we help to treat. We are committed to sharing our expertise to help improve understanding and awareness of these conditions among physicians, patients, caregivers and policymakers. We seek to provide balanced and scientifically sound information in a number of ways, for example, by sponsoring new research and through education. We focus our efforts in our main areas of expertise – neuroscience, gastrointestinal and internal medicine, rare diseases, and ophthalmics.

2014 INDICATORS

$6.6 million

More than $6,600,000 spent on educational grants

We are committed to sharing

our expertise to help improve

understanding and awareness

of these conditions

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International Gaucher Disease Ambassador Program

As part of our commitment to the Gaucher community, we have created the “International Gaucher Disease Ambassador Program”. Building on the success of our US initiative set up in 2012, the new program has six ambassadors from Israel, Germany and the UK. The program allows those living with type 1 Gaucher disease to hear from ambassadors

who have personal experience with the disease. Sharing personal stories with those facing the same situations can help inspire and lift the burden of the disease.

International Awareness Events

To help improve awareness about rare diseases and specialty conditions, we support a range of disease awareness days/months annually. These include ADHD Awareness Month, Digestive Disease Awareness Month, Fabry Awareness Month and Gaucher Disease Awareness Month. For International Gaucher Day we produced awareness-raising materials including an infographic on the impact and burden of Gaucher and an in-depth factsheet. These were made available to Patient Advocacy Groups, healthcare providers and media to help inform and educate about this rare disease.

ACES Scholarship

As part of our commitment to the rare disease community in US, we offer the Shire ACES (Award for Collegiate Education from Shire) Scholarship. The scholarship provides a $5,000 grant, which may be renewed annually for up to three years, to cover educational expense at an undergraduate college or vocational school. Recent high school graduates and equally qualified students with a rare disease may apply. In 2014, the beneficiary of our $5,000 scholarship used the award to help support her further education at John Hopkins University, Maryland (US).

WHAT WE DID IN 2014

Real Voices

In order to help people with Attention Deficit Hyperactivity Disorder (ADHD) in Europe, in 2014 Shire developed and funded the ADHD Alliance for Change. To support and unite people affected by ADHD, the Alliance compiled stories from 120 ADHD sufferers and created the “Real Voices Report”. The report was reviewed by a steering committee of European ADHD experts who provided recommendations for changes to European and national policy to improve support options for people living with ADHD. The report was presented to 26 European policy and patient stakeholders and MEPs in Brussels during European ADHD Awareness Week. It also appeared in five pan-European policy and medical publications.

ADHD Scholarship

We continue to provide annual scholarships to support individuals with ADHD in the US who are pursuing higher education. Fifty recipients received the scholarship in 2014 which includes a $2,000 bursary and a year of ADHD coaching from the Edge Foundation to help meet the challenges of higher education.

OUR GOALS

2.Increase awareness and education of rare diseases and specialist conditions

Open up new channels to promote the exchange of knowledge and educational resources on rare diseases and

specialist conditions.

Improve our online resource centers for patients and caregivers to enhance the accessibility of credible information on rare diseases and specialist conditions.

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WHY IT MATTERS

Patients and their caregivers

are at the heart of all we do at

Shire. Understanding the unmet

needs of patients and families

affected by rare and specialist

conditions is essential to

making a valued difference

in their lives. Interacting with

patient advocacy organizations

improves our understanding

and helps these important

organizations give patients

a voice.

OUR GOALS

3.Strive to make a valued

difference in patients’ lives

OUR APPROACH

We have established a patient advocacy team that works directly with patient groups and organizations. The team supports patient organizations in a true partnership model, focusing on shared objectives to improve the lives of patients with life-altering conditions.

WHAT WE DID IN 2014 Shire Patient Advocacy Team

Established the Shire Patient Advocacy Team in 2014 to build and maintain mutually beneficial relationships that bring value to patients, patient advocacy organizations and to Shire.

Working groups

Launched working groups to seek advice from advocacy experts to inform our patient advocacy vision and strategy.

Disease Awareness

We also promoted disease awareness internally, as well as externally, through patient led speaking engagements at Shire sites and meetings, and at the patient ambassador programs.

We will launch a cohesive patient advocacy strategy in 2015 that will develop innovative ways to bring the patient voice into Shire and influence product development programs in all phases of development.

We have worked with more

than 50 patient advocacy

organizations representing

therapeutic areas across

the Shire portfolio

50+

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WHY IT MATTERS

We believe that conducting

clinical trials openly and

transparently is in the best

interest of patients and

healthcare as a whole. We’re

committed to disclosing our

current and future trials by

registering them publicly and

making the results available

to everyone.

OUR GOALS

4.Ensure clinical trials are conducted

compliantly and transparently

OUR APPROACH

We are committed to implementing the EFPIA1_/

PhRMA joint Principles for Responsible Clinical Trial Data Sharing. Establishing appropriate processes, training, and compliance programs is essential to ensuring trial transparency. All information regarding current and future Shire-sponsored clinical trials that are registered with Health Authorities and an external Ethics Committee will be listed and searchable on shiretrials.com.

The synopses of Clinical Study Reports for registered clinical trials completed after January 1, 2014 will be available on shiretrials.com within or before the required timeframes.

For trials completed after January 1, 2014, where patient confidentiality can be assured and there is a proven scientific rationale, we will make patient-level data available to independent researchers.

As new clinical trials are initiated and more study reports announced, shiretrials.com will have even more depth.

We will continue to register trials with official websites such as

CLINICALTRIALS.GOV EUDRACT.EMA.EUROPA.EU.

We plan to enhance shiretrials.com to improve the user experience for our patients and others seeking more information about our trials.

LEARN MORE AT SHIRETRIALS.COM

1 _{EFPIA = European Federation of Pharmaceutical Industries and Associations}

PhRMA = Pharmaceutical Research and Manufacturers of America

WHAT WE DID IN 2014 Shire Trials

In January 2014, we launched shiretrials.com, our own dedicated clinical trials website. Delivering on our commitment to responsibly sharing clinical trials data, the site lists our current clinical studies, trial results and synopses of Clinical Study Reports. The site is publically available and fully searchable. It also includes study site location information, information for patients, detail on our approach to trials, and useful FAQs.

Enhancing Trial Transparency

In addition to our commitment to the EFPIA/ PhRMA joint Principles for Responsible Clinical Trial Data Sharing, we continued posting clinical trial results to EudraCT, the European Union clinical trials database, for trials conducted in EFPIA member countries. We also established a mechanism for sharing trial data with independent researchers.

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Our people

At Shire, we understand that our success as a business depends on

having a patient-focused high-performing workforce. We employ over 5,000

talented people in 34 countries. With such an increasing global footprint it is

crucial that we create a safe and engaging culture that celebrates diversity

and promotes the development and well-being of all our staff.

OUR GOAL

Have a high-performing,

healthy organization.

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WHY IT MATTERS

Our success depends on the

commitment of our employees.

We strive to maintain a

motivated workforce that brings

a diversity of experience, skills

and perspectives to enrich

our business. We have a

responsibility to provide a safe

and engaging environment that

nurtures talent and rewards

achievement.

OUR GOAL

Have a high-performing,

healthy organization

OUR APPROACH

To achieve our goal of a high-performing organization, we focus on four distinct areas:

1. Culture and engagement

We aim to create a culture that inspires, motivates and rewards our people. We believe that by building an engaged workforce we will improve loyalty, generate better ideas and encourage stronger performance from our employees. These things will help us provide a better service to our patients.

2. Leadership, development and training

Our long-term success depends on having the right people with the right skills to fill our roles. Where possible, we aim to fill vacant roles with internal candidates – as well as helping to develop our people, it helps us to retain valuable knowledge and experience. We invest in training and development, identifying and nurturing top talent and helping all our employees to realize their full potential.

3. Health and safety

We want all of our employees to be healthy and safe at work. This means providing a safe work environment as well as promoting healthy lifestyles and behavior. We take health and safety factors into consideration when working with our partners and suppliers.

2014 INDICATORS Injury and Illness Rates

TRIR: Number of recordable incidents per 200,000 hours worked (industry standard is 1.4)

LTIR: Number of recordable incidents resulting in lost time per 200,00 employee hours (industry standard is 0.5) 2010 2011 2012 2013 2014 1.2 1.0 0.8 0.6 0.4 0.2 0 OUR PEOPLE

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4. Diversity and inclusion

We believe that diversity gives us strength. Shire will benefit from a broad range of viewpoints and perspectives and we welcome and value all genders, ages, cultures and backgrounds. Our growing global reach gives us the opportunity to develop an even richer variety of experiences and capabilities.

2014 INDICATORS OUR GOAL

Have a high-performing,

healthy organization

Age 20 – 30 (10%) 30 – 40 (35%) 40 – 50 (35%) 50+ (20%)

30%

As of December 31 2014,

women represented 30% of

senior management at Shire

(up from 28% in 2013).

US ethnic minorities Minority (23%) Non-minority (77%) Senior management Female (30%) Male (70%) Overall gender

Employee breakdown by region

North America 70% Europe 23% Latin America 4% Other 3% Female Male 2011 2012 2013 2014 6,000 5,000 4,000 3,000 2,000 1,000 0 2, 73 6 2, 48 9 _2,778 2, 555 2, 60 0 2, 29 6 2, 618 2, 46 1 OUR PEOPLE

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Rewarding performance

All of our employees are eligible for

performance-based incentives and our long-term incentive stock program. 2,300 recognition awards were granted in 2014.

Simplifying our organization

Our One Shire program is nearing completion. This program helped us to build a unified organization, while reorganizing and streamlining our internal operations. As part of this program, we announced the consolidation of our US operations into a single US operational headquarters in Lexington, MA and began planning for this move.

Developing our organization

More than 140 leaders have taken part in our new 360-degree leadership assessment.

Enhancing our culture

We created an internal ambassador program with 100 enthusiastic and influential ambassadors

who help foster open communications with leadership and increase employee engagement. We also held a number of patient speaker and disease awareness events to build knowledge and engagement in our work.

WHAT WE DID IN 2014

Equipping our leaders to manage change

In 2014 we developed and launched a new leadership development program, “Leading Through Ambiguity”. Based on a well-respected model for managing through transition, the interactive program provided managers with tools to manage the process and lead colleagues through periods of uncertainty. More than 800 leaders from around our global operations took part and helped us to maintain high-performing operations during an unsettled time.

Continue to drive leadership and management excellence.

Continue to engage our colleagues to foster a high-performance organization.

Enhance talent identification, development and acquisition programs.

Implement an enterprise level software solution to more effectively manage our human resources.

Initiate the transition to a single US operational headquarters, taking actions to maximise the benefits of co-location through increased opportunities for collaboration and improved cross-functional teamwork.

Continue to reduce Total Recordable Incident Rates (TRIR).

OUR GOAL

Have a high-performing, healthy organization

2,300

recognition awards

were granted in 2014

OUR PEOPLE

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Launching Excellence

in ADHD Patient Group

Awards 2014

Our planet

At Shire, we have a responsibility to protect our employees, the environment

and the communities where we work and live. We are committed to

effective environmental management and believe that this is an important

part of creating a successful, sustainable business.

OUR GOAL

Understand and reduce

our environmental impact

OUR PLANET

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WHY IT MATTERS

We are committed to building

a sustainable business that

protects our employees,

the environment and the

communities in which we

work so that we can continue

to operate in the future.

Understanding and improving

our impact on the environment

is an important part of

what it means to be a

sustainable business.

OUR GOAL

Understand and reduce

our environmental impact

OUR APPROACH

Compliance with environmental regulations is the minimum standard wherever we operate. Beyond this we strive to minimize our environmental impact and mitigate environmental risks associated with our business. We are committed to conserving natural resources, recycling, reducing waste, energy efficiency, and responsible product stewardship. Most of our environmental impacts are from local facilities and we believe they are most effectively addressed locally.

WHAT WE DID IN 2014

In 2014, we worked on developing a better understanding of our environmental impacts and on formulating a plan for future reporting and improving our performance.

Specifically, we:

Conducted a materiality assessment to identify our most critical environmental issues. The results show that energy and greenhouse gas (GHG) emissions, waste, and responsible use of water and materials are the areas we need to work on over the next few years.

Now that we know these focus areas, we started to develop a long-term plan for our environmental programs. This included the development of a climate change policy. The policy will be launched in 2015.

We identified key environmental metrics with the aim of establishing intensity reduction targets by the end of 2015.

We started to develop a formal process to capture and benchmark environmental data. We verified our scope 1 and scope 2 GHG emissions for the purpose of reporting to CDP.

OUR PLANET

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OUR GOAL

Understand and reduce our environmental impact

2014 INDICATORS

Environmental performance

Total waste/waste recycled

Total waste (metric tonnes)

Waste recycled/reused/recovered (metric tonnes)

Carbon Offsets Purchased

Carbon offsets purchased (tonnes CO2e)

Carbon Footprint disclosure score

Carbon footprint disclosure score

Energy consumption and credits purchased

Facility energy consumption (MWh) Renewable energy credits purchased (MWh)

Global Videoconference Hours

Global video conference hours

Volatile Organic Compounds

Volatile organic components (tonnes/year)

Water usage and effluent discharge

Water usage (m3 000s) Industrial effluent (m3 000s)

140,848

Energy consumption (MWh)

91%

Climate disclosure score from CDP

43%

Total waste diverted from landfill

374 m

3

Water usage

104.6 m

3

Effluent discharge

200 tonnes

Carbon offsets purchased

52,612

Global videoconference hours

200 150 100 50 0 2010 2011 2012 2013 2014 100 90 80 70 60 2010 2011 2012 2013 2014 3,000 2,000 1,000 0 2010 2011 2012 2013 2014 200k 150k 100k 50k 0 2010 2011 2012 2013 2014 60,000 50,000 40,000 30,000 20,000 10,000 0 2010 2011 2012 2013 2014 12 9 6 3 0 2010 2011 2012 2013 2014 200 150 100 50 0 2010 2011 2012 2013 2014

For more information on our environmental performance data please visit

SHIRE.COM/SHIREPLC/EN/RESP/CR-PLANET/ HEALTH_SAFETY_DATA

OUR PLANET

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Helping our employees SAVE the environment

Tapping into the enthusiasm of our employees, we have created an employee initiative called SAVE – Shire’s Actions and Value for the Environment. Through this initiative, employees play a key role in identifying environmental impacts and developing plans to reduce them.

SAVE initiatives and results:

We offer free “eco” driver training to employees in our Basingstoke, UK office partnering with My Journey, provided by Hampshire County Council and funded by the Department of Transport. We offer a shuttle services to/from train stations in our larger locations to help increase the use of mass transit.

We offer preferred parking for Low Emitting and Fuel Efficient (LEFE) vehicles at our larger sites.

Carbon Disclosure Project (CDP)

In 2014, we achieved our highest CDP score ever and one which is well above both the pharmaceutical industry average and the FTSE average. Shire’s disclosure score of 91% – compared with a 78% pharmaceutical industry average and 77% FTSE average – demonstrates our unique standing and ongoing motivation to reduce our carbon footprint and impact on natural resources.

Shire’s performance score was also higher than the FTSE average, solidifying our commitment to environmental sustainability, with a risk and opportunity management score of 100% and a governance and strategy score of 85% compared with industry averages of 75% for both categories. Emissions management and verification scores also scored above and on par with industry averages.

These scores reflect our momentum and progress in identifying opportunities,

benchmarking performance, and monitoring our agenda toward environmental sustainability.

For more information on our environmental performance please visit

SHIRE.COM/SHIREPLC/EN/RESP/CR-PLANET

Set five-year reduction targets by end of 2015. Finalize our climate change policy.

Develop a plan to measure and report additional indirect GHG emissions (Scope 3).

Establish Global Sustainability Council. Begin to understand our water footprint – how we use, waste and conserve water – so that we can reduce our footprint in future.

Develop our understanding of our environmental impact so that we can continue to make improvements.

Continue to add more fuel efficient car choices for sales fleet.

OUR GOAL

Understand and reduce our environmental impact

We are collecting organic/

bio-degradable waste from our

cafeterias for compost creation

-0%

OUR PLANET

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Our partners

At Shire, we believe that how we manage our partnerships is a vital part

of the way we do business. We have a responsibility to build and maintain

positive and supportive relationships with our partners, which includes the

communities where we operate and our partners and suppliers.

OUR GOAL

Enjoy mutually beneficial

relationships with

our partners and the

communities in which

we operate.

OUR PARTNERS OUR PATIENTS

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WHY IT MATTERS

We recognize that our

impact goes beyond our

company and extends to the

communities in which we

operate and to organizations in

our supply chain and beyond.

We want to make sure that our

impact is positive and we work

in partnership with these

stakeholders to reduce

negative impacts.

OUR GOAL

Enjoy mutually beneficial relationships with our

partners and the communities in which we operate

OUR APPROACH

At Shire, we think about our responsibility to partners in two ways – how we engage with our local communities and our stewardship of partners and suppliers.

Community engagement

We have a responsibility to the communities where we live and work, as well as therapeutic communities such as the groups that represent patients and their families. We want to be an active partner to these communities, helping them to thrive and be healthy and sustainable in the long term. Our community program offers support to partners and organizations who are working to meet local needs. We have a particular focus on improving the well-being of disadvantaged children and their families.

Stewardship of partners and suppliers

When choosing suppliers and partners we take ethical and responsibility factors into account. We conduct health, safety, environment and labor standards assessments with our partners and suppliers where appropriate and expect them to commit to and uphold Shire’s ethical standards. We aim to cultivate strong

partnerships with suppliers involving long-term commitments that will provide jobs and revenue to local communities.

2014 INDICATORS

$158m

$158 million spent with small and diverse suppliers in the US during 2014, exceeding our spending goal for these supplier groups. This figure represents 11% of our budget and exceeds our target to spend over 10% of our budget with diverse supplier groups.

As part of our Responsible Supplier program, we completed HSE audits at seven direct suppliers and completed one labor audit.

We aim to cultivate strong

partnerships with select suppliers

involving long-term commitments

that will provide jobs and revenue

to local communities.

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WHAT WE DID IN 2014 Providing career inspiration for students with special needs

Cotting School is a special education school for students aged 3-22 with learning, communication and physical disabilities near our US operational headquarters in Lexington, MA. In 2014, we continued our support of Project Bridges, an established learning program run by the school. The program offers student placements in local businesses to explore realistic career options while gaining vocational experience and developing social skills. Building on the success of the program in 2013, we provided two more internships in 2014 for upper school students in Shire’s mailroom.

Develop infrastructure to grow community-employee engagement schemes in our principal operational locations in Zug and Lexington. Continue to develop and strengthen our relationships with strategic suppliers and work with them to identify innovative technologies and to create efficiencies.

Continue to conduct HSE and labor audits with our suppliers to meet our goal to have conducted audits with all direct suppliers by the end of 2018.

OUR GOAL

Enjoy mutually beneficial relationships with our partners and the communities in which we operate

Shire’s Big Give

Now it its seventh year, Shire’s Big Give is a collection initiative at our Chesterbrook, PA site. It supports local charity, Cradles to Crayons, which provides children in need with essential items they need to thrive. The theme for 2014 was “Caring Cover to Cover and Head to Toe” requesting donations of children’s books, socks and underwear, and batteries. We collected almost 5,000 books, more than 3,000 packs of socks and underwear and more than 2,000 batteries. Shire employees also sorted donations from the wider Chesterbrook community. Overall, 5,000 children were helped by the Big Give in 2014.

Community support at our new international HQ

In 2014, we opened our new international operational headquarters in Zug, Switzerland. As part of our commitment to the local community, we donated more than $16,000 to two family-support organizations in Zug – Kinderheim Lutisbach and Familienhilfe Kanton Zug. Our employees in Zug also got actively involved, cycling over 138km to raise funds to help young adults gain the skills needed to enter the world of work. The sponsored ride raised more than $18,000 which was donated to youth charities ProJet and Einstieg in die Berufswelt.

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ASSURANCE STATEMENT

We engaged Trucost to provide assurance of the GHG emissions data held within its 2014 CDP Climate Change Questionnaire Response. To view the full assurance statement please visit

SHIRE.COM

YOUR FEEDBACK COUNTS

We welcome your feedback on this review or on any aspect of our responsibility performance. Please contact us at:

[email protected]

Further information

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