UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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Horizon Therapeutics Public Limited Company

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HORIZON THERAPEUTICS PUBLIC LIMITED COMPANY

ANNUAL GENERAL MEETING OF SHAREHOLDERS

April 28, 2022

NOTICE AND PROXY STATEMENT

March 17, 2022

Dear Fellow Shareholder:

2021 was a milestone year for Horizon. We significantly expanded our pipeline, generated top-tier growth and continued to make a difference in the lives of people impacted by rare, autoimmune and severe inflammatory diseases. Our continued strong strategic execution resulted in record full-year total net sales of $3.2 billion, representing year-over-year growth of 47 percent, and record full-year adjusted EBITDA⁽¹⁾ of $1.3 billion, representing year-over-year growth of 33 percent. We ended 2021 with cash and cash equivalents of $1.6 billion, giving us the flexibility to pursue future business development initiatives, supporting our strategy to further expand our pipeline. Our strong performance translated into significant shareholder returns, with our one-, three- and five-year total shareholder returns of 47 percent, 451 percent and 566 percent, respectively, far exceeding those of our peer group⁽²⁾ and the Nasdaq Biotechnology Index.

One of our key strategic goals is to expand our pipeline, through business development as well as maximizing the potential of our existing medicines and candidates. 2021 was a year of tremendous progress on both fronts. Our acquisition of Viela Bio in March dramatically expanded our pipeline, with Viela’s mid-stage biologics pipeline of four candidates in nine development programs. We also welcomed Viela’s talented R&D team with deep early-stage research and clinical development capabilities. In September, at our inaugural R&D day, in addition to discussing our R&D strategy and showcasing our team, we announced new development programs in five additional indications for two of our candidates, further expanding our pipeline. In addition, during the year we announced two collaborations to advance our early-stage research and innovation capabilities. We successfully completed two clinical trials and initiated seven clinical trials. This year we plan to initiate seven clinical trials and have already initiated two of them, our Phase 2b trial for HZN-825 for the treatment of idiopathic pulmonary fibrosis, in January, and our Phase 3 clinical trial for TEPEZZA in thyroid eye disease (TED) in Japan (OPTIC-J), in February. Our pipeline, balanced across the development life cycle, now includes more than 20 programs, with the majority of them added in 2021. With a focus on addressing critical unmet needs for patients, our pipeline is designed to drive long-term sustainable growth for Horizon.

Our excellence in commercial execution is evidenced by the progress we made during the year with our three key growth drivers TEPEZZA^®, KRYSTEXXA^® and UPLIZNA^®. We more than doubled the full-year net sales of TEPEZZA, our biologic approved for the treatment of TED, to $1.7 billion in its second year post-launch, representing impressive growth of 103 percent. We achieved this strong performance, despite the continued impact of the COVID-19 pandemic, as well as a supply disruption that resulted from government-mandated COVID-19 vaccine production at our manufacturing partner’s facilities. The government-mandated order resulted in a total disruption of TEPEZZA supply from the end of 2020 to April 2021. Through the outstanding execution of our commercial team, we rapidly overcame the impact of the disruption with a highly successful relaunch beginning once supply resumed in April. We see strong growth prospects for TEPEZZA and we continue to invest to support that growth, from our initiatives to drive increased awareness of TEPEZZA and TED, to our clinical trials in chronic TED and TED in Japan. We are well on our way to achieve our projected peak global annual net sales of greater than $3.5 billion.

Record annual net sales for KRYSTEXXA, our biologic for uncontrolled gout, grew 39 percent year-over-year to $565.5 million – impressive growth for a 12-year-old medicine. Driving much of the growth is the increasing use of KRYSTEXXA plus immunomodulation. Since 2017, to make the medicine available to more patients, we focused on increasing the response rate to KRYSTEXXA through our clinical immunomodulation strategy. In 2021, we announced positive topline data from our MIRROR randomized controlled trial, which demonstrated that 71 percent of patients who received KRYSTEXXA plus the immunomodulator methotrexate achieved a complete response compared to 39 percent who received KRYSTEXXA plus placebo. In January we submitted a Supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) to expand the label for KRYSTEXXA to include co-treatment with methotrexate. We believe KRYSTEXXA plus immunomodulation is redefining the standard of care for KRYSTEXXA, which is on track to achieve our projected peak U.S. annual net sales estimate of greater than $1 billion.

UPLIZNA, our third key growth driver, came to us with the Viela acquisition. UPLIZNA, which was approved in 2020 by the U.S. Food and Drug Administration for neuromyelitis optica spectrum disorder (NMOSD), was launched by Viela during the peak of the COVID-19 pandemic in June 2020, with relatively minimal resources. We successfully relaunched the medicine in the fourth quarter of 2021, backed by our expertise in commercializing rare disease medicines. Internationally, we made strides in building out the infrastructure and capabilities necessary to support the potential 2022 launch of UPLIZNA in Europe, as well as other global markets in the coming years. We have Phase 3 clinical trials underway evaluating UPLIZNA for myasthenia gravis (MG) and IgG4-related disease. We estimate potential peak global annual net sales of greater than $1 billion for UPLIZNA in NMOSD, MG and IgG4-related disease.⁽³⁾

At Horizon, our mission is simple and powerful: to improve people’s lives. We go to incredible lengths to make the world a better place by addressing unmet medical needs; by building healthier communities, urgently and responsibly; and by giving back to our communities. Behind all of our efforts are the people who make up Horizon and their dedication to making a difference in the lives of others. Our employees are highly engaged, evidenced by the 15 workplace-related awards we received in 2021 – including ranking as the Number 1 Burlington Road,biotech/pharmaceutical company in FORTUNE’s 100 Best Companies to Work For^®. We believe our high employee engagement – important in an industry as competitive as ours – is partly due to the many ways we strive to make working at Horizon attractive and rewarding. We were very pleased in 2021 to demonstrate continued gender and ethnicity pay equity in the second study conducted by Aon, after the dramatic growth in our workforce since the 2019 study, including the addition of a significant number of employees with the Viela acquisition.

Horizon today is a leading, high-growth, innovation-driven, profitable biotech company. One of the people who has been instrumental in our transformation is Paul Hoelscher, our executive vice president, chief financial officer. In October 2021, Paul notified us of his intention to retire in May 2022, continuing on as an advisor through May 2023. Paul has served as our CFO since 2014 and has been a valued partner to me these past seven years. Speaking for all of us at Horizon, I thank him for his leadership, his dedication and his commitment to our mission – and especially for the many successful initiatives he has spearheaded to build Horizon’s strong financial position. Aaron Cox, executive vice president, finance, will succeed Paul as CFO. Aaron, with his extensive knowledge of the business and strong financial background, has been a leader in many of our major strategic efforts and has led our corporate development and capital markets initiatives. I am confident that Aaron, along with our deeply experienced financial leadership team that Paul put in place, will continue to support our long-term strategy.

In summary, 2021 was a year of significant progress, multiple milestones and record financial results. With our highly focused strategy, strong execution and business development and R&D capabilities, we believe we are well positioned to deliver sustainable top-tier growth and shareholder value going forward.

You are cordially invited to attend our Annual General Meeting of Shareholders on Thursday, April 28, 2022, at 3:00 p.m. local time at our new corporate headquarters, located at 70 St. Stephen’s Green, Dublin 4, D04 C5Y6,2, D02 E2X4, Ireland. Whether or not you plan to attend, it is important that your shares be represented and voted. Please take a moment now to vote your shares using the instructions found in the Notice of Internet Availability of Proxy Materials and in this Proxy Statement. Your vote is important, and we appreciate your continued support.

Sincerely,

Timothy P. Walbert

Chairman, President and Chief Executive Officer

Horizon Therapeutics Public Limited Company

70 St. Stephen’s Green, Dublin 2, D02 E2X4, Ireland

NOTICE OF ANNUAL GENERAL MEETING OF SHAREHOLDERS TO BE HELD ON APRIL 29, 202128, 2022

Dear Shareholder:

We will be holding the Annual General Meeting of Shareholders of Horizon Therapeutics Public Limited Company on Thursday, April 29, 2021,28, 2022, at 3:00 p.m. local time at our corporate headquarters located at Connaught House, 1st Floor, 1 Burlington Road,70 St. Stephen’s Green, Dublin 4, D04 C5Y6,2, D02 E2X4, Ireland, for the following purposes:

These items of business are more fully described in the Proxy Statement accompanying this Notice.

The Board recommends that you vote FOR each of the nominees for director named herein and FOR Proposals 2, 3, 4 and 5.The accompanying Proxy Statement contains additional information and should be carefully reviewed by shareholders.

Our Irish statutory financial statements for the fiscal year ended December 31, 2020,2021, including the reports of the directors and statutory auditors thereon, will be presented at the Annual General Meeting. There is no requirement under Irish law that such statements be approved by the shareholders and no such approval will be sought at the Annual General Meeting.

For the purposes of our Articles of Association, Proposals 1 and 2 and the receipt and consideration of the Irish statutory financial statements by us at the Annual General Meeting are deemed to be ordinary business and Proposals 3, 4 and 5 are deemed to be special business. The Annual General Meeting will also include a review of the Company’s affairs. Shareholders of record as of February 24, 2021,2022, the record date for the Annual General Meeting, are entitled to notice of the Annual General Meeting and to vote at the Annual General Meeting or any adjournment or postponement thereof.

As permitted by the U.S. Securities and Exchange Commission, we are making this Proxy Statement and Horizon’s Annual Report to shareholders available to our shareholders electronically through the internet, accessible at http://materials.proxyvote.com/G46188and also on the Annual Reports/Proxy Statements page of our website at www.horizontherapeutics.com. We believe this electronic distribution model, known as Notice and Access, provides our shareholders a convenient and expedited method to access the proxy materials and vote, while allowing us to conserve natural resources and reduce the environmental impact of our Annual General Meeting. In addition, it reduces the costs of printing and distributing the proxy materials.

By Order of the Board of Directors

Jennifer T. LeeDavid Caraher

Company Secretary

Dublin, Ireland

March 17, 20212022

If you are a shareholder of record on February 24, 2021,2022, you are cordially invited to attend the Annual General Meeting in person. Whether or not you expect to attend the meeting, please complete, date, sign and return the proxy mailed to you, or vote over the telephone or the internet as instructed in these materials, as promptly as possible in order to ensure your representation at the meeting. Even if you have voted by proxy, you may still vote in person if you attend the meeting. Please note, however, that if your shares are held of record by a broker, bank or other nominee and you wish to vote at the meeting, you must obtain a proxy issued in your name from that record holder.

We are closely monitoring developments related to COVID-19. It could become necessary to change the date, time, location and/or means of holding the Annual General Meeting (including by means of remote communication). If such a change is made, we will announce the change in advance, and details on how to participate will be issued by press release, posted on our website and filed as additional proxy materials.

TABLE OF CONTENTS

PROXY STATEMENT SUMMARY

This summary highlights certain information contained elsewhere in this Proxy Statement and does not contain all of the information that you should consider. You should read the entire Proxy Statement carefully before voting. For more complete information regarding our business and 20202021 performance, please review our Annual Report on Form 10-K for the year ended December 31, 20202021 and our subsequent filings with the Securities and Exchange Commission (SEC).

Voting Items and Board Recommendations

Director Nominees and Continuing Directors

Horizon  |  2022 Proxy Statement 1

2020—2021 – Year at a Glance

Record Net Sales and Strong Shareholder Returns

Except for 1-, 3-Net sales and 5-year total shareholder return,adjusted EBITDA growth percentages represent comparisonyear-over-year growth over full-year 2020.

Prior TSR results are not intended to full-year 2019.forecast or be indicative of possible future performance of our ordinary shares.

EBITDA: Earnings before interest, taxes, depreciation and amortization. | TSR: Total shareholder return through December 31, 2020.2021. | NBI: Nasdaq Biotechnology Index.

A BannerMilestone Year for Horizonin Our Transformation

Horizon  |  2022 Proxy Statement 2

Business Overview

Horizon at a Glance

What Sets Us Apart

KRYSTEXXA exemplifies our excellence in commercial execution. An underperforming and undervalued medicine when we acquired it in 2016, with our investment, expertise and deep knowledge of the rheumatology space, we transformedexecuted on the right commercial strategy for KRYSTEXXA to jump start its growth trajectorytrajectory. We know how to help significantly more patients with uncontrolled gout andeffectively market rare disease medicines, demonstrated by the fact that we have increased itsthe annual net sales more than six-fold. We project more than $1 billion inof KRYSTEXXA nearly ten-fold since acquiring it, and we are well on our way toward our projected peak U.S. annual net sales for KRYSTEXXA, impressive growth for a 10-year-old medicine.of more than $1 billion.

WeThe returns we have a long and successful track record ingenerated to date also attest to the success of our business development (BD). TEPEZZA is an excellentefforts. For example, of significant value creation we have created for our shareholders through BD. We acquired TEPEZZA for an upfront payment of approximately $144$145 million plus milestones in 2017, and2017; in 2020,the two years since its launch, year, TEPEZZA achievedwe have generated cumulative net sales of $820 million,$2.5 billion, despite the negative impact of the COVID-19 pandemic. pandemic, representing exceptional value creation for our shareholders – and we see opportunities for continued growth for TEPEZZA, projecting peak global annual net sales of more than $3.5 billion. Importantly, TEPEZZA has brought hope for patients with thyroid eye disease (TED), who before TEPEZZA had no approved treatment options. Our strong business development acumen also resulted in the transformational acquisition of Viela Bio in 2021. It significantly expanded our pipeline with the addition of Viela’s four development candidates across nine development programs and three new therapeutic areas. It also expanded our commercial portfolio with the addition of UPLIZNA, a recently approved biologic for the treatment of neuromyelitis optica spectrum disorder (NMOSD).

An example ofThe Viela acquisition also augmented our strong research and development capabilities. Viela’s talented R&D team, with its early-stage research and clinical development capability is the execution of the TEPEZZA Phase 3 clinical program and early regulatory approval. We continue to maximize value for patients through capabilities, highly complements our immunomodulation strategy for KRYSTEXXA, which has produced impressive results in completed studies – almost double the response rate of the KRYSTEXXA Phase 3 program, which means more patients may benefit from the medicine.proven late-stage development capabilities.

Horizon  |  2022 Proxy Statement 3

Leveraging our combined strengths has already driven innovation. In September 2021, we announced pipeline programs in five additional indications for two of the Viela biologic candidates. In addition to adding depth to our pipeline, these programs aim to address high unmet medical needs for patients living with the rare diseases the programs target. Our R&D capabilities also drive innovation of our on-market medicines to maximize their benefit. Our successful MIRROR registrational trial is a testament to this: 71 percent of patients receiving KRYSTEXXA plus the immunomodulator methotrexate achieved a complete response, a more than 30-percentage-point improvement compared to patients who received KRYSTEXXA plus placebo.

Our Pipeline: A Top Strategic Priority to Drive Long-Term Growth

Building a robust pipeline, primarily through business development,One of our key strategic goals to support our ambitious growth objectives is a top strategic priority for us. We are focused on rare diseases and attractive therapeutic areas, including rheumatology, nephrology, endocrinology and ophthalmology, and we continued to expand theour pipeline, which we are doing through internal investment and external business development. 2021 was a year of tremendous progress in 2020. With the April 2020 acquisition of Curzion Pharmaceuticals,this regard – we added development-stage candidate HZN-825, an oral selective LPAR₁ antagonist that has shown early signs of clinical impact in fibrotic diseases. We intend to launch two pivotal Phase 2b trials in HZN-825 in 2021, one in diffuse cutaneous systemic sclerosis and the other in idiopathic pulmonary fibrosis, an interstitial lung disease indication. Both indications represent high unmet medical needs. On March 15, 2021, we acquired Viela Bio, which further expandssignificantly expanded our pipeline with the additionViela acquisition, we added five new clinical programs and we augmented our early-stage discovery efforts with two collaborations for novel therapeutics.

A key part of our R&D strategy is maximizing the full potential of our pipeline. In determining new indications to pursue, we evaluate four development candidates in nine developmentmajor areas to identify the disease states that have the most overall potential for success: scientific rationale, unmet need, the competitive landscape and feasibility. We are also building out our discovery pipeline of novel programs in addition to adding early-stageby using a balanced approach of internal research and translational capabilitiesexternal collaborations while aligning with our core focus areas: rheumatology, nephrology, ophthalmology, endocrinology, neuroimmunology, dermatology and respiratory. Our goal is to generate high-quality investigational new drug applications (INDs) over the coming years.

Our pipeline is balanced across the development life cycle, with early- to late-stage programs. Currently with more than 20 programs – the majority of which were added in 2021 – the pipeline is designed to support sustainable growth over the long-term. We plan to initiate seven clinical trials this year, two of which have already been initiated.

Underscoring all of our already strong R&D organizationpipeline – and our commercial and business development – initiatives is our focus is on addressing the unmet medical needs of patients with Viela’s highly talented R&D teamrare, autoimmune and severe inflammatory diseases. This is part of our purpose – strengthening our position asto make a leading, innovation-driven biotech company.meaningful difference in the lives of patients, their caregivers, their physicians and the communities we serve.

Expected
(1)   Planned program expected to initiate in 2021. (1) Being developed under a collaboration agreement with XL Protein GmbH.2022. Of these programs, the HZN-825 IPF clinical trial initiated in January 2022 and the TEPEZZA TED in Japan (OPTIC-J) initiated in February 2022. We also have four Phase 4 programs: TEPEZZA chronic TED trial, KRYSTEXXA shorter infusion duration trial, KRYSTEXXA monthly dosing trial and KRYSTEXXA retreatment trial. | TED: Thyroid Eye Disease.

MIRROR: Trial evaluating

Horizon  |  2022 Proxy Statement 4

Our Key Growth Drivers: TEPEZZA, KRYSTEXXA and UPLIZNA

Our biologic TEPEZZA is the use of KRYSTEXXA in combination with methotrexate to increase the response rate. | PROTECT: Trial evaluating the effect of KRYSTEXXA on serum uric acid levels in kidney transplant patients with uncontrolled gout. | OPTIC-X: Open-label extension trial of Phase 3 trial evaluating TEPEZZA for the treatment of Thyroid Eye Disease. | IPF: Idiopathic pulmonary fibrosis. | TED: Thyroid Eye Disease

TEPEZZA: One of the Most Successful Rare Disease Medicine Launches Ever

We launched TEPEZZA, our biologicfirst and only medicine indicated for the treatment of Thyroid Eye Diseasethyroid eye disease (TED), with tremendous successa serious, progressive and potentially vision-threatening, rare autoimmune disease. Launched shortly after receiving FDA approval in January 2020, for the treatment of TED. TED is a rare, serious, progressive and vision-threatening autoimmune disease that significantly impacts patients and their quality of life. Overexpression of the insulin-like growth factor-1 receptor (IGF-1R) results in inflammation and expansion of the muscles and fatty tissue behind the eye, which can lead to proptosis, or eye bulging and other eye symptoms, such as diplopia, or double vision, and pain. With its broad label, TEPEZZA is indicated for all TED patients, including those with acute TED, the initial inflammatory phase, and chronic TED, when the disease is no longer changing but the debilitating symptoms may remain.

TEPEZZA is a fully human monoclonal antibody (mAb) and a targeted therapy that blocks IGF-1R, reducing proptosis – and it is the only medicine approved for the treatment of TED. Since the treatment path was not well defined before TEPEZZA, we invested in considerable market preparation initiatives in 2019 to drive awareness of TED in the medical and patient community and to establish a pathway for treatment. Our pre-launch initiatives proved highly effective: the launch of TEPEZZA significantly exceeded expectations, quickly becoming one of the most successful rare-disease-medicinerare disease medicine launches ever. To driveOur significant pre-launch investment in educating physicians and key stakeholders about TED, as well as our teams’ superlative execution, have driven cumulative net sales of $2.5 billion since launch, despite the impact of the COVID-19 pandemic and an over-three-month supply disruption in 2021 due to government-mandated COVID-19 vaccine production orders. We expect continued strong growth for TEPEZZA in the years ahead, driven by three key growth opportunities: increasing new prescribers while driving additional uptake in our existing prescriber base; increasing the use of TEPEZZA in patients with chronic TED; and adoption, we’re investing in multiple TEPEZZA expansion efforts:maximizing the medicine’s potential through global expansion. We are supporting our U.S. commercial and field-based organization, which we have doubled to approximately 200 employees; our marketing initiatives; our long-term supply capacity; and our expansion efforts in multiple geographies outsidechronic TED with a Phase 4 clinical trial and supporting global expansion with a Phase 3 trial in TED in Japan. We remain confident about the United States.prospects for helping more patients living with this debilitating disease and estimate TEPEZZA embodies our vision in action – making the world a better place through innovative medicines for patients with unmet needs – and it represents a significant growth opportunity with our projection for peak TEPEZZA global annual net sales of more than $3.5 billion.

Since acquiring KRYSTEXXA, our biologic medicine for uncontrolled gout, in 2016, we have transformed its growth trajectory through our strong strategic execution, our deep knowledge of both rheumatology and rare disease medicines, and by investing commercially to support future growth. We’ve also invested significantly to maximize the benefit of KRYSTEXXA so more patients can benefit from the medicine. We announced positive topline data in 2021 from our MIRROR randomized controlled trial, which evaluated KRYSTEXXA plus the immunomodulator methotrexate. We recently submitted a supplemental biologics license application (sBLA) to expand the label for KRYSTEXXA to include co-treatment with methotrexate. We expect the use of KRYSTEXXA plus immunomodulation, which has been steadily increasing, to redefine the standard of care. We see several additional growth opportunities for KRYSTEXXA: expanding uptake in rheumatology and nephrology; elevating the urgency to treat and investing to improve the patient experience. We are well on track toward achieving our projected KRYSTEXXA peak U.S. annual net sales of more than $1 billion.

Horizon  |  Proxy Statement 4

Our Total Shareholder ReturnReturns Significantly Surpassed Our Peers⁽¹⁾ and NBI

1, 1-, 3- and 5-Year Periods Ended December 31, 2021

Note: The peer group used for the TSR calculations for the 1-, 3- and 5-year periods ended December 31, 2020 is our peer group shown on page 42.

Board Highlights

The Nominating and Corporate Governance Committee of our Board examines multiple factors when evaluating directors, including their knowledge, skills and experience, including experience in our industry and with respect to clinical development, sales and marketing, business development, finance, management and public service. The Committee believes in an expansive definition of diversity that includes differences of experience, education, talents, geography, gender and race, among other things. The table below highlights the extensive experience of our directors as well as the balance of skills on our Board:

Our Board of Directors: Skills and Experience Matrix

Horizon  |  2022 Proxy Statement 56

Our Board is predominantly independent and includes a range of expertise, experience, diversity, as well as newer and longer-tenured directors. As is set forth in its diversity policy, the Board values diversity and believes that maintaining a diverse membership enhances the Board’s deliberations and enables it to better represent all of Horizon’s constituents. As such,the Nominating and Corporate Governance Committee works to ensure that the Board represents a diversity of experience and perspectives, as well as race, gender, geography and areas of expertise. A strong, annual director assessment process hasresulted in periodic refreshment, enhancing the Board’s effectiveness. As a result of the assessment process, since 2017, two prior directors did not stand for re-election and three new directors joined the Board. Board committee memberships are also refreshed periodically.

Our Board of Directors: Gender and Ethnicity Diversity Matrix

As of March 15, 2022

Horizon  |  2022 Proxy Statement 7

Corporate Governance Highlights

Horizon  |  Proxy Statement 6

With a strategic focus on growing the business over the long term, it is imperative that our executive compensation program motivates our talented management team in such a manner as to encouragethat encourages – and rewardrewards – successful execution of this business strategy. We utilize the following compensation elements to achieve this:

Please see our Compensation Discussion and Analysis on page 3639 for additional information on our compensation philosophy.

Horizon  |  Proxy Statement 7

During our shareholder engagement cycle before our Annual General Meeting in April 2020,2021, as well as during our off-season shareholder engagement cycle in late 2021/early 2022, we offered engagement opportunities to shareholders who represented approximately 60 percent of our shares outstanding. Our shareholders appreciated the outreach and theShareholder feedback from thisthe subsequent engagement was very positive. At our 20202021 Annual General Meeting, of Shareholders, our say-on-pay proposal received the support of approximately 96 percent of the shares voted. We believe this high level of support is partly a result of our comprehensive shareholder outreach and engagement program to solicit feedback, understand investor viewpoints and incorporate their feedback into future evaluations of our compensation programs.

In early 2021, during our shareholder engagement cycle before our upcoming Annual General Meeting in April, we offered engagement opportunities to shareholders who represented approximately 60 percent of our shares outstanding and are in the process of conducting calls with those shareholders who expressed interest.

In addition to our outreach on compensation and governance, we have also engaged with shareholders on environmental, social and governance (ESG)ESG matters. WeDuring this ongoing ESG-related outreach, which we started this outreach in the summer of 2019, discussingwe discuss ESG factors and matters of interest to our shareholders. The feedback we have received has informed and enhanced our ESG disclosures and initiatives.

We greatly value the dialogue we have with our shareholders and remain committed to continued engagement going forward.

Horizon  |  Proxy Statement 8

Summary of Voting Items and Board Recommendations

Horizon  |  Proxy Statement 11

Fostering a Sustainable Future for Horizon, Our Stakeholders and Communities: Key Environmental, Social and Governance (ESG) Factors

Making a difference is ingrained in our corporate culture and integral to our purpose – we go to incredible lengths at Horizon to impact lives and make the world a better place. What we do extends beyond the innovative medicines we deliver; we support patients and their caregivers, physicians, advocacy groups, our communities and beyond. We know that our efforts contribute not just to Horizon’s long-term success and sustainability but also to the broader world.

Key ESG factors that support Horizon’s long-term sustainability include: our governance; our purpose and our focus on ethics and integrity; access to medicines and our patient-centric focus; employee engagement and corporate culture; our product supply chain and environmental sustainability.

Our Governance:

We employ strong corporate governance principles and practices.

Our Purpose and Our Focus on Ethics and Integrity:

We build healthier communities, urgently and responsibly.

Horizon  |  2022 Proxy Statement 12

Access to Medicines and Our Patient-Centric Focus:

We make health a priority, not a privilege.

Our Employee Engagement and Corporate Culture:

For us it’s personal – we want to make a difference and are consistently recognized for our engaged employees.

Horizon  |  2022 Proxy Statement 13

Our Product Supply Chain:

We work stringently to ensure the safety and quality of our medicines.

Environmental Sustainability:

We aim to conduct our business in a responsible way that minimizes environmental impacts.

Horizon Is Consistently Recognized as a Best Place to Work

Horizon  |  2022 Proxy Statement 14

QUESTIONS AND ANSWERS ABOUT THESE PROXY MATERIALS AND VOTING

This Proxy Statement contains important information regarding the Annual General Meeting of Shareholders, the proposals on which you are being asked to vote, information you may find useful in determining how to vote and voting procedures. You are invited to attend the Annual General Meeting to vote on the proposals described in this Proxy Statement. However, you do not need to attend the meeting to vote your shares.

Why did I receive a notice regarding the availability of proxy materials on the internet?

We have sent you a Notice of Internet Availability of Proxy Materials (the Notice) because our Board is soliciting your proxy to vote at the Annual General Meeting, including at any adjournments or postponements of the meeting. As permitted by the U.S. Securities and Exchange Commission, we are making this Proxy Statement, Horizon’s Annual Report to shareholders, and our Irish statutory financial statements available to our shareholders electronically via the internet. We believe that using this form of distribution provides a convenient and expedited method for our shareholders to access the proxy materials and vote, while allowing us to conserve natural resources and reduce the environmental impact of our Annual General Meeting. In addition, it reduces the costs of printing and distributing the proxy materials. Accordingly, we have sent a Notice to our shareholders of record. All shareholders can access the proxy materials on the website referred to in the Notice or may request a printed set of the proxy materials. Instructions on how to access the proxy materials over the internet or to request a print or email copy may be found in the Notice. We intend to mail the Notice on or about March 17, 20212022 to all shareholders of record as of February 24, 2021,2022, who are entitled to vote at the Annual General Meeting.

How do I attend the Annual General Meeting?

The meeting will be held on Thursday, April 29, 2021,28, 2022, at 3:00 p.m. local time at our corporate headquarters located at Connaught House, 1^st Floor, 1 Burlington Road,70 St. Stephen’s Green, Dublin 4, D04 C5Y6,2, D02 E2X4, Ireland. Directions to the Annual General Meeting may be found at https://www.google.com/maps/place/Connaught+House,70+St+Stephen’s+Green,+Burlington+Rd,Saint+Kevin’s,+Dublin+4,Dublin,+Ireland. Information on how to vote in person at the Annual General Meeting is provided below. However, you do not need to attend the Annual General Meeting to vote your ordinary shares.

We are closely monitoring developments related to COVID-19. It could become necessary to change the date, time, location and/or means of holding the Annual General Meeting (including by means of remote communication). If such a change is made, we will announce the change in advance, and details on how to participate will be issued by press release, posted on our website and filed as additional proxy materials.

Who can vote at the Annual General Meeting?

Only shareholders of record at the close of business on February 24, 2021,2022, will be entitled to vote at the Annual General Meeting. On this record date, there were 224,074,399229,167,259 of our ordinary shares outstanding and entitled to vote.

Shareholder of Record (shares registered in your name). If on February 24, 20212022 your shares were registered in your name in our Register of Members, which is maintained by our transfer agent, Computershare Shareowner Services LLC, then you are a shareholder of record. As a shareholder of record, you may vote in person at the meeting or vote by proxy. Whether or not you plan to attend the meeting, we urge you to vote by proxy over the telephone or on the internet as instructed in the Notice or as discussed below to ensure your vote is counted, or if you request a printed copy, vote by completing and returning the proxy card.

Beneficial Owner (shares registered in the name of a broker or bank). If on February 24, 2021,2022, your shares were not registered in your name in our Register of Members, but rather held in an account at a brokerage firm, bank, dealer or other similar organization, then you are the beneficial owner of shares held in “street name” and the Notice is being forwarded to you by that organization. The organization holding your account is considered to be the shareholder of record for purposes of voting at the Annual General Meeting. As a beneficial owner, you have the right to direct your broker or other agent regarding how to vote the shares in your account. You are also invited to attend the Annual General Meeting. However, since you are not the shareholder of record, you may not vote your shares in person at the meeting unless you request and obtain a valid proxy from your broker or other agent.

What am I voting on?

There are five matters scheduled for a vote:

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What if another matter is properly brought before the meeting?

The Board knows of no other matters that will be presented for consideration at the Annual General Meeting. If any other matters are properly brought before the meeting, it is the intention of the persons named in the accompanying proxy to vote on those matters in accordance with their best judgment.

How do I vote?

You may vote “For” or “Against” each Class III director nominee or you may abstain from voting for all or any of the nominees. For each of the other matters to be voted on, you may vote “For” or “Against” or abstain from voting.

The procedures for voting are fairly simple:

Shareholder of Record. If you are a shareholder of record, you may vote in person at the Annual General Meeting, by electronic proxy over the telephone or the internet as instructed below, or by proxy using the proxy card you receive if you request a set of printed materials. Whether or not you plan to attend the meeting, we urge you to vote by proxy to ensure your vote is counted. You may still attend the meeting and vote in person even if you have already voted by proxy.

We provide internet proxy voting to allow you to vote your shares online, with procedures designed to ensure the authenticity and correctness of your proxy vote instructions. However, please be aware that you must bear any costs associated with your internet access, such as usage charges from internet access providers and telephone companies.

Beneficial Owner. If you are a beneficial owner of shares registered in the name of your broker, bank or other agent, you should have received a Notice containing voting instructions from that organization. Simply follow the voting instructions in the Notice to ensure that your vote is counted. Alternatively, you may vote by telephone or through the internet as instructed by your broker, bank or other agent. To vote in person at the Annual General Meeting, you must obtain a valid proxy from your broker, bank or other agent. Follow the instructions in the Notice you receive from your broker, bank or other agent, or contact that organization to request a proxy form.

Joint Holders. In the case of joint holders of record, any one of such holders may vote either in person or by proxy in respect thereof as if he or she were the sole holder thereof, but the vote of the senior holder who tenders a vote, whether in person or by proxy, shall be accepted to the exclusion of the votes of the other joint holders, and for this purpose seniority shall be determined by the order in which the names stand in our Register of Members.

How many votes do I have?

On each matter to be voted upon, you have one vote for each ordinary share you own as of February 24, 2021.2022.

What happens if I do not vote?

Shareholder of Record. If you are a shareholder of record and do not vote by completing your proxy card, by telephone, through the internet or in person at the Annual General Meeting, your shares will not be voted.

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Beneficial Owner. If you are a beneficial owner and do not instruct your broker, bank, or other agent how to vote your shares, the question of whether your broker or nominee will still be able to vote your shares depends on whether the New York Stock Exchange (NYSE) deems the particular proposal to be a “routine” matter. Brokers and nominees can use their discretion to vote “uninstructed” shares with respect to matters that are considered to be “routine,” but not with respect to “non-routine”“non-routine” matters. Under the rules and interpretations of the NYSE, “non-routine”“non-routine” matters are matters that may substantially affect the rights or privileges of shareholders, such as mergers, shareholder proposals, elections of directors (even if not contested), executive compensation (including any advisory shareholder votes on executive compensation) and certain corporate governance proposals, even if management-supported. We have been advised by the NYSE that your broker or nominee may not vote your shares on Proposals 1, 3 or 5 without your instructions, but may vote your shares on Proposals 2 and 4.

What if I return a proxy card or otherwise vote but do not make specific choices?

If you return a signed and dated proxy card or otherwise vote without marking voting selections, then our designated proxy holders (one of the individuals named on your proxy card) will vote your shares in the manner recommended by our Board on all matters presented in this Proxy Statement and as the proxy holders may determine in their discretion regarding any other matters properly presented for a vote at the meeting. If any other matter is properly presented at the meeting, your proxy holder will vote your shares using his or her best judgment.

Who is paying for this proxy solicitation?

We have retained Alliance Advisors, a proxy solicitation firm, to solicit proxies in connection with the Annual General Meeting at a cost of approximately $22,500$23,500 plus expenses. The cost of soliciting proxies incurred by us and Alliance Advisors, including the preparation, assembly and mailing of the proxies and soliciting material, as well as the cost of forwarding such material to beneficial owners of our ordinary shares, will be borne by us. Our directors, officers and other employees may, without compensation other than their regular remuneration, solicit proxies personally or by telephone.

What does it mean if I receive more than one Notice?

If you receive more than one Notice, your shares may be registered in more than one name or in different accounts. Please follow the voting instructions on the Notices to ensure that all of your shares are voted.

Can I change my vote after submitting my proxy?

Shareholder of Record. Yes, you may revoke your proxy at any time before the final vote at the meeting. If you are the record holder of your shares, you may revoke your proxy in any one of the following ways:

Your most current proxy card or telephone or internet proxy is the one that is counted.

Beneficial Owner. If your shares are held by your broker or bank as a nominee or agent, you should follow the instructions provided by your broker or bank.

Do I need a ticket to attend the Annual General Meeting?

Yes, you will need an admission ticket or proof of ownership of ordinary shares to enter the Annual General Meeting. If you are a shareholder of record, your admission ticket is the Notice that was sent to you. Please bring your Notice and valid photo identification with you to the Annual General Meeting. If your shares are held in the name of a bank, broker or other holder of record, your admission ticket is your Notice, or if you are a beneficial owner, the ticket is on your voting instruction form. If you do not bring your admission ticket, you will need proof of ownership of ordinary shares to be admitted to the Annual General Meeting. A recent brokerage statement or letter from a bank or broker is an example of proof of ownership. If you arrive at the Annual General Meeting without an admission ticket or proof of ownership of ordinary shares, we will admit you only if we are able to verify that you are one of our shareholders.

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How are votes counted?

Votes will be counted by the inspector of election appointed for the meeting, who will separately count, with respect to the proposal to elect directors, votes “For,” “Against,” abstentions and broker non-votes; and, with respect to other proposals, votes “For” and “Against,” abstentions and, as applicable, broker non-votes. Abstentions and broker non-votes will be treated as shares present for the purpose of determining the presence of a quorum for the transaction of business at the Annual General Meeting. Abstentions and broker non-votes will not, however, be considered votes cast at the Annual General Meeting. Because the approval of all of the proposals is based on the votes cast at the Annual General Meeting, abstentions and broker non-votes will not have any effect on the outcome of voting on the proposals.

What are “broker non-votes”?

As discussed above, when a beneficial owner of shares held in “street name” does not give instructions to the broker or nominee holding the shares as to how to vote on matters deemed by the NYSE to be “non-routine,“non-routine,” the broker or nominee cannot vote the shares. These un-voted shares are counted as “broker non-votes.”

What is the quorum requirement?

A quorum of shareholders is necessary to hold a valid meeting. A quorum will be present if shareholders holding a majority of the issued and outstanding ordinary shares entitled to vote are present at the meeting in person or represented by proxy. On the record date, there were 224,074,399229,167,259 ordinary shares outstanding and entitled to vote. Thus, the holders of 112,037,200114,583,630 ordinary shares must be present in person or represented by proxy at the meeting to have a quorum.

Your shares will be counted towards the quorum only if you submit a valid proxy (or one is submitted on your behalf by your broker, bank or other nominee) or, provided that you are a shareholder of record, if you vote in person at the meeting. Abstentions and broker non-votes will be counted towards the quorum requirement. If there is no quorum, within one hour of the time appointed for the Annual General Meeting, the Annual General Meeting will stand adjourned to May 6, 20215, 2022 at 3:00 p.m. local time at the same location, or such other time or place as the Board may determine.

Assuming there is a quorum of shares present at the Annual General Meeting, how many votes are needed to approve each proposal?

How can I find out the results of the voting at the Annual General Meeting?

Preliminary voting results will be announced at the Annual General Meeting. In addition, final voting results will be published in a current report on Form 8-K that we expect to file within four business days after the Annual General Meeting. If final voting results are not available to us in time to file a Form 8-K within four business days after the meeting, we intend to file a Form 8-K to publish preliminary results and, within four business days after the final results are known to us, file an additional Form 8-K to publish the final results.

What are the Irish statutory financial statements?

We are presenting our Irish statutory financial statements, including the reports of the directors and the statutory auditors thereon, at the Annual General Meeting and are making a copy available for download on the Annual Reports / Proxy Statements page in the Investors section of our website (www.horizontherapeutics.com) on or before April 7, 2021.6, 2022. As an Irish company, we are required to prepare Irish statutory financial statements under applicable Irish company law and to deliver those accounts to shareholders of record in connection with our Annual General Meetings. The Irish statutory financial statements cover the results of our operations and financial position for the year ended December 31, 2020.2021.

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Irish law requires the directors to prepare financial statements for each financial year giving a true and fair view of the state of the group’s and parent company’s affairs at the end of the financial year and of the group’s profit or loss for the financial year. Under that law, the directors have prepared the group’s consolidated financial statements in accordance with U.S. accounting standards, as defined in Section 279 of the Irish Companies Act 2014, to the extent that the use of those accounting standards in the preparation of the consolidated financial statements does not contravene any provision of the Irish Companies Act 2014 or of any regulations made thereunder and have prepared Horizon’s parent company’s Irish statutory financial statements in accordance with accounting standards issued by the Financial Reporting Council and promulgated by the Institute of Chartered Accountants in Ireland (Generally Accepted Accounting Practice in Ireland).

What proxy materials are available on the internet?

The Proxy Statement and the Annual Report are available at https://materials.proxyvote.com/G46188. The Irish financial statements will be available in the Investors section of our website (www.horizontherapeutics.com) on or before April 7, 2021.6, 2022. We will mail without charge, upon written request, a copy of these materials to shareholders of record or beneficial owners of our ordinary shares. Requests should be sent to: Horizon Therapeutics plc, Attention: Company Secretary, Connaught House, 1st Floor, 1 Burlington Road,70 St. Stephen’s Green, Dublin 4, D04 C5Y6,2, D02 E2X4, Ireland.

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PROPOSAL 1

ELECTION OF DIRECTORS

The Board is divided into three classes. Each class consists, as nearly as possible, of one-third of the total number of directors and each class has a three-year term. The Board currently consists of nine members, as follows:

The authorized number of directors may be changed only by resolution of the Board. Any additional directorships resulting from an increase in the number of directors will be distributed between the three classes so that, as nearly as possible, each class will consist of one-third of the directors. This classification of the Board may have the effect of delaying or preventing changes in our control or management. Our directors may be removed by ordinary resolution with majority vote of our shareholders at a general meeting provided that notice of such resolution has been given in accordance with Section 146 of the Irish Companies Act 2014. Vacancies on the Board may be filled only by persons elected by a majority of the directors then in office, provided that a quorum is present. A director elected by the Board to fill a vacancy in a class, including vacancies created by an increase in the number of directors, shall serve for the remainder of the full term of that class and until the director’s successor is duly elected and qualified.

Majority VotingVoting:: In order to be elected as a director, each nominee must receive the affirmative vote of a majority of the votes cast by the holders of ordinary shares represented at the Annual General Meeting in person or by proxy.

Directors Whose Term of Office Expires in 20212022:: There are currently three directors in Class III whose term of office expires in 2021.2022. Each of the nominees listed below in Class III is currently a director who was nominated for election by the Board, upon the recommendation of the Nominating and Corporate Governance Committee. If elected, each of these nominees would serve until the 20242025 Annual General Meeting of Shareholders and until his or her successor has been duly elected and qualified, or, if sooner, until the director’s death, resignation, disqualification or removal.

The biographical information for our directors that follows is as of March 15, 2021.2022.

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THE BOARD RECOMMENDS

A VOTE IN FAVOR OF EACH NAMED NOMINEE ABOVE

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THE BOARD OF DIRECTORS AND ITS COMMITTEES

In 2020,2021, the Board held ninesix meetings and acteddid not act by unanimous written consent at two sessions.without a meeting. Each Board member attended 98100 percent or more of the aggregate number of meetings of the Board and of the committees on which he or she served that were held during the portion of the last fiscal year for which he or she was a director or committee member, except for Michael Grey, who attended 82 percent of such meetings because he recused himself from three Transaction Committee meetings related to the acquisition of Curzion due to a conflict of interest. Excluding the recusals, Mr. Grey attended 100 percent of such Board and committee meetings.member. It is our policy to encourage directors and nominees for director to attend annual general meetings of shareholders. All current directors attended our 20202021 Annual General Meeting of Shareholders.

The Board is committed to exercising good corporate governance practices. As part of this commitment, the Board regularly monitors developments in corporate governance and reviews processes, policies and procedures in light of such developments. Key information regarding our corporate governance initiatives can be found on our website, www.horizontherapeutics.com, including our Memorandum and Articles of Association, Code of Conduct and Ethics, Corporate Governance Guidelines, and the charters for the Audit, Compensation, Nominating and Corporate Governance and Transaction Committees. The Board believes that its strong corporate governance policies and practices, including the substantial percentage of independent directors on the Board and the robust duties of its lead independent director, empower the Board to effectively oversee our chief executive officer and provide an effective and appropriately balanced Board governance structure.

Other than Mr. Walbert, our chairman, president and chief executive officer, all members of the Board are independent, and all members of committees of the Board are independent. The Board has affirmatively determined that the following eight directors are independent directors within the meaning of the applicable Nasdaq Stock Market (Nasdaq) listing standards: Mr. Daniel, Mr. Grey, Dr. Himawan, Dr. Mahony, Mr. Santini, Dr. Shannon, Mr. Watkins and Ms. Witz. In making these determinations, the Board found that none of these directors or nominees for director had a material or other disqualifying relationship with us. Mr. Walbert is not an independent director by virtue of his current employment with us. To determine independence, the Board reviewed all relevant identified transactions or relationships between each director, or any of his or her family members, and us, our senior management and our independent registered public accounting firm.

As required under applicable Nasdaq listing standards, our independent directors met four times in regularly scheduled executive sessions in 2020,2021, at which only independent directors were present.

We have adopted a Code of Conduct and Ethics (the Code) that applies to all officers, directors and employees, including our principal executive officer, principal financial officer, principal accounting officer orand persons performing similar functions. We introduced a revised, principles-based Code in 2021 that provides an instructive set of principles, guidelines and tools to operate our business in an ethical and compliant way. In addition to promptly publishing the revised Code on our website, we conducted employee training, including 45 live sessions, on the revised Code, with 100 percent participation. The Code is available onin the investor relations section of our website at www.horizontherapeutics.com. If we make any substantive amendments to the Code or grant any waiver from a provision of the Code to any executive officer or director, we will promptly disclose the nature of the amendment or waiver on our website or in a current report on Form 8-K.

The Board has determined that the current leadership structure, in which the offices of chairman and chief executive officer are held by one individual and an independent director acts as lead independent director, ensures that the appropriate level of oversight, independence and responsibility is applied to all Board decisions, including risk oversight, and is in our best interests and those of our shareholders.

Chairman/Chief Executive Officer

The Board is currently chaired by our president and chief executive officer, Mr. Walbert. We believe that combining the positions of chief executive officer and chairman of the Board helps to ensure that the Board and management act with a common purpose for the following reasons:

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Lead Independent Director

We require the election, by the independent directors of the Board, of a lead independent director to serve during any period when there is no independent chairman of the Board. Because Mr. Walbert is currently serving as chief executive officer and chairman of the Board, the independent directors of the Board elected Mr. Grey as the lead independent director. The lead independent director serves as the liaison between the chairman of the Board and the independent directors and hisdirectors. The responsibilities of the lead independent director include:

One of the Board’s key functions is informed oversight of our risk management process. The Board does not have a standing risk management committee, but rather administers this oversight function directly through the Board as a whole, as well as through various Board standing committees that address risks inherent in their respective areas of oversight. In particular, the Board is responsible for monitoring and assessing strategic risk exposure, including a determination of the nature and level of risk appropriate for the Company.Horizon.

Our Audit Committee has the responsibility to consider and discuss our major financial risk exposures and the steps our management has taken to monitor and control these exposures, including guidelines and policies to govern the process by which financial risk assessment and management is undertaken and provides oversight of the performance of our internal audit function and external auditors. The Audit Committee also reviews and receives regular briefings concerning information security and technology risks (including cybersecurity), including discussions of our information security and risk management programs.risks.

Our Nominating and Corporate Governance Committee reviews our key enterprise risks and risk-management strategies, as well as monitors the effectiveness of our corporate governance guidelines, including whether they are successful in preventing illegal or improper liability-creating conduct, and monitors compliance with legal, regulatory and ethical requirements.

Our Compensation Committee assesses and monitors whether any of our compensation policies and programs has the potential to encourage excessive risk-taking.

Our Transaction Committee evaluates potential strategic transactions and financing opportunities, including the risks that such transactions could pose to Horizon.

Cybersecurity

Horizon is committed to protecting our company’s information technology systems. We manage information technology (IT) systems that facilitate commercial, supply chain and regulatory activities; maintain our financial data; and store employee and customer data. We have protocols, policies and tools in place to mitigate cybersecurity risk. They also provide the administrative, technical, and physical safeguards to ensure the security, confidentiality, integrity and availability of confidential information and personal information from unauthorized access, use, disclosure, alteration, destruction or theft. In addition, we engage an independent third party annually to assess our IT general controls and IT security.

The Audit Committee and full Board is briefed by our chief information officer at least twice a year on our cybersecurity risk management programs and the overall cybersecurity risk environment. The briefing includes discussions on topics such as information security and technology risks, cybersecurity, information risk management strategies and progress and cybersecurity and data protection training initiatives for employees, among others. To our knowledge, we have not experienced a material information security breach nor incurred any penalties or settlements regarding information security.

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The Nominating and Corporate Governance Committee believes that a strong director assessment process and periodic Board refreshment enhances the effectiveness of the Board and is an essential element of sound corporate governance.

Director assessment is conducted on an annual basis at both the full Board and individual director level:

Annual Board Member Self-Assessment: The director self-assessment process typically begins in August, when a telephonic survey is conducted with each director by a third party, generally a partner from our external legal counsel. The telephonic survey, which is updated annually, allows the interviewer to more fully assess and understand the needs, comments and patterns resulting from the individual conversations. This interview process elicits each director’s opinions on the overall effectiveness of the overall Board and its committees, the information the Board committees,receives, the conduct of Board meetings, communication among directors and communication,management, the director’s own participationoversight of key business risks and contributions, as well as those of

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In November 2021, Paul Hoelscher, our executive vice president, chief financial officer (CFO), notified us of his intention to retire in May 2022, continuing on as an advisor through May 2023 to ensure a smooth transition. Mr. Hoelscher, who has served as our CFO since 2014, will be succeeded by Aaron Cox, executive vice president, finance, who has been with Horizon since 2016. The process followed for Mr. Hoelscher’s leadership succession planning, as well as the transition period, illustrates the value of our robust succession planning process for the CFO role over the past several years. Mr. Cox, with his extensive knowledge of our business and his strong financial background, is well equipped to succeed Mr. Hoelscher: during his tenure with Horizon, he has been a leader in many of our major strategic efforts, including corporate development, and he has led our capital markets initiatives.

The Board is also regularly apprised of high-leadership potential candidates at Horizon and the plans for their development and potential roles. Board members have the chance to meet with these individuals at Board meetings, at dinners with Board members or in individual meetings as appropriate. We arrange for Board members to meet with key talent when they visit our offices. At each Board meeting, our chief human resources and chief diversity officer updates the Board on different key human capital management matters such as diversity, equity and inclusion, recruitment, development and retention. The Board also reviews our annual employee surveys and is briefed on the responses and targeted actions generated from the survey results.

The Board has four standing committees:

All committees comprise independent directors within the meaning of the applicable Nasdaq listing standards. A description of each committee of the Board is describedprovided below.

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Audit Committee

The Audit Committee assists the Board in fulfilling its oversight responsibility with respect to, among other things:

The independent registered public accounting firm, internal audit and management each periodically meet privately with the Audit Committee.

The Board has determined that each of Mr. Daniel, Mr. Grey, Dr. Mahony, Mr. Watkins and Ms. Witz qualify as “audit committee financial experts” within the meaning of applicable SEC rules. In making this determination, the Board has considered their formal education, the nature and scope of their previous experience and their financial and corporate governance expertise.

Report of the Audit Committee of the Board of Directors

The material in this report is not “soliciting material,” is not deemed “filed” with the SEC and is not to be incorporated by reference in any of our filings under the Securities Act of 1933, as amended (the Securities Act), or the Securities Exchange Act of 1934, as amended (Exchange Act), whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.

The Audit Committee has reviewed and discussed the audited financial statements for the year ended December 31, 2020,2021, with Horizon management. The Audit Committee has discussed with the independent registered public accounting firm the matters required to be discussed by Auditing Standard No. 1301, Communications with Audit Committees, as adopted by the Public Company Accounting Oversight Board (PCAOB). The Audit Committee has also received the written disclosures and the letter from the independent registered public accounting firm required by applicable requirements of the PCAOB regarding the

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The Compensation Committee may, at our expense, retain legal counsel (which may, but need not be, our regular corporate counsel) and other consultants and advisors, other than in-house legal counsel and certain other types of advisors, to assist it with its functions only after taking into consideration six factors, prescribed by the SEC and Nasdaq, that bear upon the advisor’s independence; however, there is no requirement that any advisor be independent. The Compensation Committee has authority to approve such advisors’ fees and other retention terms and to terminate its relationship with any advisor that it retains. In addition, the Compensation Committee has authority to delegate its responsibilities to subcommittees or individual committee members.

The Compensation Committee has engaged Radford, which is part of the RewardsAon’s Human Capital Solutions practice, ata division of Aon plc (Aon), as its independent consultant since 2016. For additional information regarding our processes and procedures for the consideration and determination of executive and director compensation, including the role of RadfordAon in determining and recommending executive and director compensation and the aggregate cost of Radford’sAon’s executive and director compensation consulting services during 2020,2021, see the sections of this Proxy Statement entitled “Compensation Discussion and Analysis – Compensation Determination ProcessProcess””and “Non-Employee Director Compensation.” With respect to non-employee director compensation matters, our Compensation Committee recommends to our Board and our Board determines and sets non-employee director compensation. Our compensation arrangements for our non-employee directors are described under the section of this Proxy Statement entitled “Non-Employee Director Compensation.”

Compensation Committee Interlocks and Insider Participation

No member of our Compensation Committee has ever been an executive officer or employee of Horizon. None of our executive officers currently serves, or has served during the last completed year, on the compensation committee or board of directors of any other entity that has one or more officers serving as a member of our Board or Compensation Committee.

Nominating and Corporate Governance Committee

The Nominating and Corporate Governance Committee oversees all aspects of our corporate governance functions on behalf of the Board, including, but not limited to:

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Shareholders who wish to communicate with the Board may do so by sending written communications addressed to the Company Secretary of Horizon Therapeutics plc at Connaught House, 1st Floor, 1 Burlington Road,70 St. Stephen’s Green, Dublin 4, D04 C5Y6,2, D02 E2X4, Ireland or by communicating online to the Board as a group. This information and an online communications form are available on our website at www.horizontherapeutics.com.Each communication will be reviewed by our Company Secretary to determine whether it is appropriate for presentation to the Board or such director on a periodic basis. Examples of inappropriate communications include advertisements, solicitations or hostile communications.

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NON-EMPLOYEE DIRECTOR COMPENSATION

Our directors perform a critical role in guiding Horizon’s strategic direction and overseeing management. Being a director entails many responsibilities and a substantial time commitment. Our compensation program for our non-employee directors reflects the critical function they perform and enables us to attract and retain highly qualified directors.

All current non-employee members of the Board are independent. Non-employee directors receive a combination of annual cash retainers and restricted stock unit (RSU) grants in amounts that correlate to their responsibilities and levels of Board participation, including service on Board committees. Our only employee director, Mr. Walbert, receives no separate compensation for his service as a director or chair.