#1Investor Presentation Horizon Therapeutics plc March 2020 H HORIZON Horizon Therapeutics.com#2Forward-Looking Statements This presentation contains forward-looking statements, including, but not limited to, statements related to Horizon's expected financial performance and operating results in future periods, including potential growth in net sales of certain of Horizon's medicines; development plans; expected timing of clinical trials, studies and regulatory submissions; potential market opportunity for and benefits of Horizon's medicines and medicine candidates; and business and other statements that are not historical facts. These forward-looking statements are based on Horizon's current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks that Horizon's actual future financial and operating results may differ from its expectations or goals; Horizon's ability to grow net sales from existing medicines; the availability of coverage and adequate reimbursement and pricing from government and third-party payers; risks relating to Horizon's ability to successfully implement its business strategies; risks inherent in developing novel medicine candidates, and existing medicines for new indications; risks associated with regulatory approvals; risks in the ability to recruit, train and retain qualified personnel; competition, including potential generic competition; the ability to protect intellectual property and defend patents; regulatory obligations and oversight, including any changes in the legal and regulatory environment in which Horizon operates and those risks detailed from time-to-time under the caption "Risk Factors" and elsewhere in Horizon's filings and reports with the SEC. Horizon undertakes no duty or obligation to update any forward-looking statements contained in this presentation as a result of new information. HORIZON 2#3Agenda Horizon Overview and Strategy TEPEZZA™: First and Only FDA-Approved Medicine for Patients with Thyroid Eye Disease KRYSTEXXAⓇ: Only Approved Medicine for Uncontrolled Gout with Significant Growth Potential Pipeline: Built with Purpose to Drive Long-Term Growth#4Horizon: A Differentiated Investment Opportunity We are a leading, high-growth profitable biopharma company ⚫ Differentiated commercial model; generating annual net sales of $1.3B only 8 years post IPO • • Focused on rare diseases and presence in rheumatology, nephrology, ophthalmology and endocrinology Two high-growth drivers with >$2B in combined peak U.S. annual net sales potential(1) 呂 Delivering innovative therapies to patients Deep development expertise with proven track record . Building a pipeline through M&A to support sustainable long-term growth 123.7% 85.3% $ Generating high returns for shareholders 38.7% 25.1% • Outperformed NBI for 1, 3, 5 years Our prospects position us with a top-tier growth profile 1-year 3-year HZNP (1) Horizon estimate. HI HORIZON 180.8% 21.9% 5-year NBI (Nasdaq Biotechnology Index) Total Shareholder Return through Dec. 31, 2019 4#5Today We Are in Our Strongest Position Ever Key Takeaways TEPEZZA U.S. commercial launch underway First and only FDA-approved medicine for patients with thyroid eye disease Highly experienced team working with stakeholders since July 2019 Encouraging early launch progress Advancing KRYSTEXXA immunomodulation strategy • OMIRROR OL trial demonstrated 79 percent of patients achieved complete response (1) MIRROR RCT underway to potentially expand prescribing information · Maximizing growth drivers through additional R&D programs • KRYSTEXXA shorter-infusion trial; designed to improve patient convenience TEPEZZA exploratory trial in diffuse cutaneous scleroderma Strongest position ever Peak U.S. annual net sales expectations for our key growth drivers KRYSTEXXA and TEPEZZA of >$1B each (2) • Strong capital structure; significantly reduced gross debt in 2019 with 0.7x net leverage; below target of 2.0x(3) • MIRROR OL: Open-label initial trial with 14 enrolled patients evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. MIRROR RCT: Registrational, randomized, placebo-controlled 135-patient trial evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. (1) MIRROR open-label response rate of 79 percent compared to Phase 3 blinded, placebo-controlled clinical trial data of 42 percent. (2) Horizon estimate. (3) Net leverage as of Dec. 31, 2019. HORIZON 5#6Our Unique Biopharma Model is Delivering on Our Third Phase of Growth and Evolution Our Strategy: Maximizing Key Growth Drivers While Expanding Pipeline for Sustainable Growth $1.30B(1) $297M(2) $7M(3) Net Sales (1) Net sales for year ended Dec. 31, 2019. (2) Net sales for year ended Dec. 31, 2014. (3) Net sales for year ended Dec. 31, 2011. HORIZON 2011-2013 2019+ Expanding Pipeline and Therapeutic Area Focus Maximizing KRYSTEXXA opportunity • • Reinvesting cash flow into TEPEZZA launch and growth • . Building pipeline and presence in core therapeutic areas 11 medicines; 7 for rare diseases Rare Disease Focus Reinvested cash flow into acquiring rare disease portfolio Invested in repositioning and rejuvenating KRYSTEXXA • Built out R&D capabilities 2014-2019 • Formation • Created sustainable, cash-flow positive company via initial portfolio • Built out commercial capabilities . IPO in 2011 with 2 medicines 6#7Our Prospects Position Us with a Top-Tier Growth Profile Net Sales Target Double-digit CAGR Non-GAAP Operating Income Target Strong Double-digit CAGR Growth Drivers KRYSTEXXA: Peak Net Sales >$1B(1) ↑ TEPEZZA: Peak Net Sales >$1B(1) Meaningful operating margin ↑ expansion, inclusive of increased R&D investment 2020 2021 2022 2023 2020 2021 2022 2023 Well Positioned to Deliver Sustainable Top-Tier Growth and Enhanced Shareholder Value Note: Projections could change significantly as a result of any acquisitions or divestitures. (1) Horizon estimate. HORIZON 7#8We Employ a Holistic Approach to Maximize the Value of Our Medicines for Patients ||| མ་ We DEEPLY UNDERSTAND the medicine, the disease and the market dynamics, investing in clinical data to advance the science We develop the right COMMERCIAL STRATEGY, TEAM AND INFRASTRUCTURE to support our patients and drive uptake We develop the right CLINICAL STRATEGY to improve physician understanding and clinical conviction to benefit more patients and optimize growth • KRYSTEXXA exemplifies our industry-leading holistic approach; we are leveraging this expertise with TEPEZZA KRYSTEXXA was an underperforming and undervalued asset at acquisition in January 2016 • We transformed its growth trajectory through strong commercial execution, quintupling annual net sales in 4 years • We are driving continued growth opportunities for KRYSTEXXA; projecting peak U.S. annual net sales of >$1B(1) • We are further maximizing KRYSTEXXA through our immunomodulation clinical strategy so more patients can benefit (1) Horizon estimate. HORIZON 8#9Transformed Our R&D Organization to Deliver on Our Future Promise Tremendous Progress in Two Years 2018 2019 2020+ • . Built experienced R&D leadership team with deep drug development expertise; agile execution and proven track record Added leadership team with broad expertise and capabilities Experience across broad range of therapeutic areas and rare diseases • 100+ molecules developed across team . Opened new South San Francisco facility to support expanding organization Accelerated delivery on near-term transformative priorities including TEPEZZA development and improvement of KRYSTEXXA profile TEPEZZA: Accelerated development and BLA submission; 2020 FDA approval nearly 2 months before PDUFA date • KRYSTEXXA: Optimizing product profile targeting response rate • Initiated HemoShear collaboration to discover new targeted therapies for gout Maximizing and expanding pipeline of early and late stage medicines to drive sustainable growth ⚫ TEPEZZA: Evaluating additional indications, including a new program for diffuse cutaneous scleroderma • KRYSTEXXA: Continuing to optimize product • profile and convenience Growing pipeline through M&A FDA: U.S. Food and Drug Administration. BLA: Biologics License Application. PDUFA: Prescription Drug User Fee Act. HI HORIZON 9#10Expanding Our Pipeline Added Two Programs to Maximize Our Current Portfolio MEDICINE / PROGRAM KRYSTEXXA Immunomodulation DESCRIPTION MIRROR Randomized Controlled Trial KRYSTEXXA Nephrology KRYSTEXXA Shorter-Infusion Duration (1) TEPEZZA Thyroid Eye Disease TEPEZZA Diffuse Cutaneous Scleroderma (1) HZN-003 Next-Gen Uncontrolled Gout HZN-007 Next-Gen Uncontrolled Gout (2) HemoShear Gout Discovery Collaboration PROTECT trial in kidney transplant patients with uncontrolled gout Open-label trial • OPTIC-X: Phase 3 extension trial Exploratory trial • Optimized uricase and optimized PEGylation for uncontrolled gout Optimized uricase and PASylation for uncontrolled gout Exploration of novel approaches to treating gout (1) New trial expected to begin in 2020. (2) Being developed under a collaboration agreement with XL Protein GmbH. MIRROR: Trials evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. PROTECT: Clinical 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 the Phase 3 trial evaluating TEPZZA for the treatment of thyroid eye disease. HI HORIZON PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 PHASE 3b/4 10#11Significantly Strengthened Our Capital Structure in 2019 Reduced Gross Debt by $575M in 2019; Net Leverage of 0.7x at Dec. 31, 2019 $1,500M $1,000M Strong Cash Balance and Net Debt Position Managing Debt and Leverage Efficiently • Reduced gross debt by $575M to $1.418B at Dec. 31, 2019 • Extended maturities of $1B of debt to 2026/2027 • Reduced interest expense by more than 40 percent (1) $500M $959M $1,076M $751M $509M $OM • Net leverage ratio of 0.7x at Dec. 31, 2019, down from 2.3x at Dec. 31, 2018 (2) $342M $500M $1,034M $1,269M $1,435M $1,000M Dec. 31, 2018 Dec. 31, 2019 Target $1,500M 12/31/2016 12/31/2017 12/31/2018 12/31/2019 Gross Leverage (2) 4.4x 2.9x <3.0x Cash Net Debt Net Leverage(2) 2.3x 0.7x <2.0x Gross Leverage: Gross debt to last-12-months adjusted EBITDA. Net Leverage: Net debt to last-12-months adjusted EBITDA. (1) 2018 cash interest expense vs. annualized 2019 cash interest expense following debt refinancing and repayment transactions. (2) Net debt and LTM adjusted EBITDA are non-GAAP measures; see reconciliation slides at the end of the presentation for a reconciliation of GAAP to non-GAAP measures. HORIZON 11#12A Leading, High-Growth Biopharmaceutical Company Executing on Our Strategy • • Maximizing the value of our key growth drivers KRYSTEXXA and TEPEZZA Expanding our pipeline for sustainable growth • • • Significant Progress in 2019 Announced impressive TEPEZZA Phase 3 data; submitted BLA 12-0 FDA Advisory Committee vote for TEPEZZA Invested in TEPEZZA pre-launch activities Completed KRYSTEXXA MIRROR OL trial Initiated KRYSTEXXA MIRROR RCT Initiated KRYSTEXXA PROTECT trial Significantly strengthened capital structure Opened new South San Francisco R&D and manufacturing facility • . Progress and Expected Milestones in 2020 TEPEZZA Jan. 21 approval; continued launch execution Advance KRYSTEXXA immunomodulation strategy: - Announced 79% complete response rate in MIRROR OL Complete MIRROR RCT enrollment Complete KRYSTEXXA PROTECT trial enrollment Initiate KRYSTEXXA shorter- infusion duration trial Initiate TEPEZZA diffuse cutaneous scleroderma exploratory trial TEPEZZA permanent J-code Oct. 1 • Expected Milestones Beyond 2020 New KRYSTEXXA data • readouts: - MIRROR RCT PROTECT Advancing toward peak U.S. net sales expectations: KRYSTEXXA: >$1B (1) TEPEZZA: >$1B(1) Pre-clinical gout candidates advance into clinical development Potential upside from future pipeline assets BLA: Biologics License Application. FDA: U.S. Food and Drug Administration. MIRROR OL: Open-label initial trial with 14 enrolled patients evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. MIRROR RCT: Registrational, randomized, placebo-controlled 135-patient trial evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. PROTECT: Clinical trial evaluating the effect of KRYSTEXXA on serum uric acid levels in kidney transplant patients with uncontrolled gout. (1) Horizon estimate. HORIZON 12#13TEPEZZA First and Only FDA-Approved Medicine for Patients with Thyroid Eye Disease HORIZON 13#14TEPEZZA: First and Only FDA-Approved Medicine for Patients with Thyroid Eye Disease Significant Early Interest from Thyroid Eye Disease Community Received early U.S. FDA approval on Jan. 21, 2020 for patients with thyroid eye disease (TED) Impressive Phase 3 results show 82.9 percent of TEPEZZA patients with ≥2mm proptosis reduction • TED is a debilitating, vision-threatening, rare autoimmune disease that severely impacts quality of life • Inflammation and tissue expansion behind the eye cause proptosis (eye bulging) and diplopia (double vision) U.S. commercial launch underway following significant pre-launch market education efforts Multi-functional, highly experienced team has been working with stakeholders since July 2019 More than 500 patient enrollment forms (PEFS) submitted, significantly exceeding our expectations, with conversion subject to typical reimbursement dynamics and timelines $ Peak U.S. annual net sales estimate >$1B(1) HORIZON (1) Horizon estimate. Patient enrollment forms, which are similar to benefit investigations, are early indicators of demand. 14#15Progressive TED Becomes Fibrotic; Without Treatment Damage Becomes Permanent; May Require Surgery Signs and Symptoms Thyroid Eye Disease: Progressive Phase Evolves to Fibrotic Phase Complex and Multiple Surgeries, Including Decompression Surgery Progressive phase (inflammation, pain) Fibrotic phase (permanent damage and disfigurement) Ideal Therapy HI HORIZON Source: Smith & Douglas (2011). Natural course of the disease Time Progressive Fibrotic Exposing Orbit Surgery Removing Bone Removing Tissue and Bone 15#16Phase 3 Trial: 82.9 Percent of Patients Achieved Primary Endpoint of Proptosis Response Proptosis Response (Reduction of ≥2 mm) at Week 24 100 Proptosis Responders (%) 40 60 80 20 20 56.1 p<0.001 82.9 82.9 75.6 p<0.001 p<0.001 p<0.001 Difference: 73.45 (95%CI 58.89, 88.01) 14.3 14.3 9.5 7.1 0 Baseline Week 6 Week 12 Week 18 Week 24 TEPEZZA (N=41) Placebo (N=42) Proptosis Reduction of 3.32 mm at Week 24(1) Proptosis Reduction (mm) 0 -0.38 -0.64 -0.59 -0.53 2 3 -2.00 -2.70 Difference: -2.79 (95%CI -3.40, -2.17) -3.26 -3.32 -4 Week 0 Week 6 Week 12 Week 18 Week 24 TEPEZZA (N=41) Placebo (N=42) Note: Throughout the 24-week treatment period, patients treated with TEPEZZA had an average proptosis reduction of 2.82 mm compared with 0.54 mm for those who received placebo (p<0.001). (1) Change from baseline in proptosis as a continuous variable is based on Mixed-Model Repeated-Measures (MMRM) analysis of covariance (ANCOVA) model with an unstructured covariance matrix including the following terms: baseline score, tobacco use status (non-user, user), treatment group, visit, and visit-by-treatment and visit-by-baseline-score interactions. HORIZON 16#17TEPEZZA Data Published Twice in The New England Journal of Medicine One of Few Clinical Programs to Have Both Phase 2 and Phase 3 Clinical Results Featured in the Journal Phase 2 Results: May 2017 The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Phase 3 Results: January 2020 The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE HORIZON Teprotumumab for Thyroid-Associated Ophthalmopathy Terry J. Smith, M.D., George J. Kahaly, M.D., Ph.D., Daniel G. Ezra, M.D., James C. Fleming, M.D., Roger A. Dailey, M.D., Rosa A. Tang, M.D., Gerald J. Harris, M.D., Alessandro Antonelli, M.D., Mario Salvi, M.D., Robert A. Goldberg, M.D., James W. Gigantelli, M.D., Steven M. Couch, M.D., Erin M. Shriver, M.D., Brent R. Hayek, M.D., Eric M. Hink, M.D., Richard M. Woodward, Ph.D., Kathleen Gabriel, R.N., Guido Magni, M.D., Ph.D., and Raymond S. Douglas, M.D., Ph.D. "In conclusion, a 24-week course of teprotumumab therapy provided clinical benefit in patients with active, moderate- to-severe thyroid-associated ophthalmopathy by reducing proptosis and the Clinical Activity Score and by improving the patients' quality of life." (2) (1) Douglas Raymond S, The New England Journal of Medicine; 382 January 23, 2020, p341-352. (2) Smith Terry J, Hegedus Laszlo., Graves' disease, The New England Journal of Medicine; 375 July 3, 2016, p. 1552-1565. Teprotumumab for the Treatment of Active Thyroid Eye Disease R.S. Douglas, G.J. Kahaly, A. Patel, S. Sile, E.H.Z. Thompson, R. Perdok, J.C. Fleming, B.T. Fowler, C. Marcocci, M. Marinò, A. Antonelli, R. Dailey, G.J. Harris, A. Eckstein, J. Schiffman, R. Tang, C. Nelson, M. Salvi, S. Wester, J.W. Sherman, T. Vescio, R.J. Holt, and T.J. Smith "Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon." (1) Clinical Activity Score (CAS): a 7-point scale that measures change in orbital inflammation and pain; a score of >3 indicates active TED. 17#18Driving TEPEZZA Adoption: Our Commercialization Strategy Establish Market structure and simplify patient journey Educate All stakeholders about Thyroid Eye Disease and TEPEZZA Support TEPEZZA.M teprotumumab-trbw TEPEZZA launch with our comprehensive, high-touch, patient-centric model Facilitate Access to TEPEZZA by establishing an infusion site-of-care referral network HORIZON Note: For additional TEPEZZA safety information, please see end of presentation. 18#19Horizon is Simplifying the Process for Patients, Physicians and Sites of Care Patient Journey Before TEPEZZA Primary Care Progressive Phase (inflammation, pain) Fibrotic Phase (permanent damage, disfigurement) Ophthalmologist Allergist or Optometrist Patient finally diagnosed with TED Severity increases Steroids up to 8 grams Steroids fail Surgeries Endocrinologist Optic nerve compromised Surgery Repeat Doctor Visits and Tests Before, During and After Diagnosis Endocrinologist Recognizes TED symptoms and refers to ophthalmologist "Watch and Wait" Approach Simplifying the Patient Journey Ophthalmologist / Oculoplastic Surgeon / Neuro-Ophthalmologist Confirms diagnosis and refers patient to site of care TEPEZZA Infused at Site of Care HORIZON 19#20We Have Established a Robust Infrastructure to Support All Aspects of the Patient Journey Approximately 100-Person Highly Experienced Field Team Physicians ~50-person sales force with buy-and-bill experience; 14+ medical scientific liaisons ⚫ Disease and treatment education Referral facilitation Reimbursement support Patient Education & Support Leveraging Horizon's extensive experience in patient services and dedicated marketing efforts ⚫ 1-to-1 patient support from diagnosis through treatment Direct-to-patient digital • disease awareness campaign Grassroots advocacy efforts • • • Site of Care (Infusion Centers) National and regional teams supporting infusion centers Logistical support Referral network build out Site-of-care identification and segmentation Disease and treatment education Reimbursement education • Payers Reimbursement team supporting access • Disease, unmet need and treatment education Value proposition education to ensure optimal patient access HI HORIZON 20#21TEPEZZA: A Compelling Value Proposition Addressing a Significant Unmet Need Unmet Need No prior treatments for thyroid eye disease Rare Disease U.S. addressable incidence of 15K to 20K patients (1) (1) Horizon estimate of patients eligible for TEPEZZA each year. HI HORIZON Efficacy 82.9 percent achieved proptosis reduction of ≥2mm Acute Treatment 6-month course of therapy with long-term durability Safety Significant benefits outweigh manageable risks Compelling Value Proposition 21#22HORIZON KRYSTEXXA Our Biologic Medicine for Uncontrolled Gout with Significant Growth Potential 22#23Gout: A Systemic Disease Often Associated with Multiple Negative Consequences • Gout Most common inflammatory arthritis (1) Characterized by multiple comorbidities, including chronic kidney disease and hypertension Systemic disease; uric acid deposits can occur almost anywhere in the body 9.5M U.S.gout patients; growing low-single digits (2) 3.5M Uncontrolled Gout Chronic gout refractory (unresponsive) to conventional therapies U.S. gout patients seeking treatment (2) ~100K Uncontrolled gout patients ~4K Treated with (1) Zhu Y, Pandya BJ, Choi HK. (2) Prevalence of gout and hyperuricemia in the U.S. general population: The National Health and Nutrition Examination Survey (NHANES) 2007-2016. Arthritis Rheum. 2019 Jun;71(6):991-999. HI HORIZON KRYSTEXXA in 2019 23#24KRYSTEXXA: The Only Medicine Approved for Uncontrolled Gout Rapidly Reverses Disease Progression (2) KRYSTEXXA Mechanism of Action (1) Urate Before and After KRYSTEXXA 10 Allantoin Converts urate to water-soluble allantoin; Renal excretion of allantoin is up to 10x more efficient than excretion of uric acid(3) (1) Uncontrolled gout is chronic gout refractory (unresponsive) to conventional therapies. (2) Sundy JS, Baraf HSB, Yood RA, et al. Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients. (3) McDonagh EM, Thorn CF, Callaghan JT, Altman RB, Klein TE. Pharmacogenet Genomics. 2014;24(9):464-476. HORIZON 24#25KRYSTEXXA: Our Commercial Strategy Has Accelerated Volume Growth Increasing Our Peak U.S. Annual Net Sales Expectations to >$1B" (1) KRYSTEXXA Net Sales Driven by Vial Growth Growth Drivers >$1B(1) Growth in New and 1 Existing Accounts Accelerating 2 Nephrology Growth 32% 65% 72% $342M $259M $91M $157M 3 2016 2017 2018 2019 Peak U.S. Annual Net Sales (1) Horizon estimate. HORIZON Growth in use of KRYSTEXXA plus Methotrexate 25#26} KRYSTEXXA: MIRROR Open-Label Trial Data Support Our Immunomodulation Strategy 79 Percent Complete Response Rate Achieved in MIRROR Open-Label Trial 79% MIRROR OL complete response rate VS. 42% Phase 3 complete response rate Well tolerated Response Rate Based on sUA <6mg at Month 6 Response Rate of KRYSTEXXA plus Methotrexate Dramatically Higher than KRYSTEXXA Alone KRYSTEXXA Alone KRYSTEXXA plus Methotrexate 100% 79% 80% 100% 90% 80% 70% 60% 50% 40% 30% 20% 42% 10% 0% Phase 3 Clinical Trials n=85 MIRROR OL Albert Peterson Botson n=14 n=10 n=10 Phase 3 Clinical Trials (blinded, placebo-controlled): 36 out of 85 patients achieved a complete response. MIRROR OL (open-label): 11 out of 14 patients enrolled achieved a complete response. Albert Case Series (open-label): 8 out of 10 patients achieved a complete response. Arthritis & Rheumatology, 2019;71(S10): Abstract 1236. Peterson Botson Case Series (open-label): 10 out of 10 patients achieved a complete response. Annals of the Rheumatic Diseases, 2019;78(2):SAT0404. Note: Data from separate clinical trials may not be directly comparable due to differences in trial protocols, conditions and patient populations. HORIZON 26#27HORIZON Our Pipeline Built with Purpose 27#28Expanding Our Pipeline Added Two Programs to Maximize Our Current Portfolio MEDICINE / PROGRAM KRYSTEXXA Immunomodulation DESCRIPTION MIRROR Randomized Controlled Trial KRYSTEXXA Nephrology KRYSTEXXA Shorter-Infusion Duration (1) TEPEZZA Thyroid Eye Disease TEPEZZA Diffuse Cutaneous Scleroderma (1) HZN-003 Next-Gen Uncontrolled Gout HZN-007 Next-Gen Uncontrolled Gout (2) HemoShear Gout Discovery Collaboration PROTECT trial in kidney transplant patients with uncontrolled gout Open-label trial • OPTIC-X: Phase 3 extension trial Exploratory trial • Optimized uricase and optimized PEGylation for uncontrolled gout Optimized uricase and PASylation for uncontrolled gout Exploration of novel approaches to treating gout (1) New trial expected to begin in 2020. (2) Being developed under a collaboration agreement with XL Protein GmbH. MIRROR: Trials evaluating the use of KRYSTEXXA in combination with methotrexate to increase the response rate. PROTECT: Clinical 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 the Phase 3 trial evaluating TEPZZA for the treatment of thyroid eye disease. HI HORIZON PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 PHASE 3b/4 28#29KRYSTEXXA: MIRROR RCT Underway to Potentially Expand Prescribing Information Immunomodulation has potential to significantly increase KRYSTEXXA response rate Increase physician MIRROR Randomized Clinical Trial Design 135 Patients Evaluated for 24 Weeks KRYSTEXXA + methotrexate (n=90) 12 infusions: 1 every two weeks confidence Allow patients to stay on therapy longer . Following MIRROR RCT readout, potential to expand prescribing information RCT: Randomized controlled trial. HI HORIZON KRYSTEXXA + placebo (n=45) 12 infusions: 1 every two weeks Day 1 Initiated Q2 2019; Data Readout Expected in 2021 Week 24 Primary Endpoint Primary Endpoint at Week 24: Proportion of serum uric acid (SUA) responders (sUA <6 mg/dL) at Month 6 29#30KRYSTEXXA: PROTECT Trial Designed to Support Nephrologists' Understanding of Efficacy Evaluating KRYSTEXXA to Improve Management of Uncontrolled Gout in Kidney Transplant Patients Gout is 10 times more frequent in kidney transplant patients ⚫ PROTECT is designed to provide data for most severe chronic kidney disease patients PROTECT Trial Design 20 Kidney Transplant Patients with Uncontrolled Gout Evaluated for 24 Weeks KRYSTEXXA (n=20) 12 infusions: 1 every two weeks Day 1 Week 24 Initiated Q3 2019; Data Readout Expected in 2021 Primary Endpoint Primary Endpoint at Week 24: Proportion of serum uric acid (SUA) responders (SUA <6 mg/dL) at Month 6 PROTECT: Clinical trial evaluating the effect of KRYSTEXXA on serum uric acid levels in kidney transplant patients with uncontrolled gout. HORIZON 30#31KRYSTEXXA: Improving the Patient Experience through a Shorter-Infusion Trial HORIZON Current state KRYSTEXXA infusion duration currently 2+ hours Opportunity Open-label trial evaluating the impact of administering KRYSTEXXA over a significantly shorter infusion duration Potential to meaningfully improve the experience and convenience for patients, physicians and sites of care 31#32} • • TEPEZZA: New Development Program Evaluating Diffuse Cutaneous Scleroderma No Approved Therapies for this Rare Autoimmune Disease Diffuse Cutaneous Scleroderma Chronic autoimmune disease marked by fibrosis, including hardening of skin and internal organ involvement Rare disease with no approved or effective treatments Patients typically suffer extensive fibrosis that can progress to internal organ damage Primarily managed by rheumatologists (1) Horizon estimate. IGF-1R: Insulin-like growth factor 1 receptor. HORIZON . BED Epidemiology ☑ Scientific Rationale ~100K patients in U.S. diagnosed with scleroderma (1) Of U.S. diagnosed patients, ~30K patients are diagnosed with diffuse cutaneous scleroderma (1) Evaluating efficacy based on TEPEZZA mechanism of action, which is to block IGF-1R Literature suggests that targeting IGF-1R could have an impact on the fibrotic process Initiating exploratory trial to evaluate objective biomarker and clinical endpoints 32#33New Programs to Build on Our Market Leadership Position in Uncontrolled Gout Next-Generation Uncontrolled Gout Programs Potential to improve response rate and duration of treatment, and provide more convenient administration through subcutaneous dosing Novel Gout Discovery Program HZN-003 Optimized uricase and optimized PEGylation for uncontrolled gout Potency allowing potential for subcutaneous dosing HZN-007(1) Optimized uricase and PASylation for uncontrolled gout PASylation as a new approach to increasing half-life and reducing immunogenicity Potency allowing potential for subcutaneous dosing • (1) Being developed under a collaboration agreement with XL Protein GmbH. HI HORIZON HemoShear Collaboration Strong capability to identify and validate novel biological targets Exploring novel approaches to treating gout 33#34HORIZON Additional Information 34#35We Have Rapidly Evolved into a Company Focused on Rare Disease Medicines 2013: Net sales of $74 Million 2 Medicines DUEXIS (ibuprofen and famotidine) Tablets 800 mg/26.6 mg HORIZON 2019: Net sales of $1.3 Billion Diversified Portfolio; 6 for Rare Diseases RAVICTI (glycerol phenylbutyrate) Oral Liquid RAYOS® (Prednisone) Delayed-release Tablets KRYSTEXXA! pegloticase 12-HOUR PROCYSBI (cysteamine bitartrate) delayed-release capsules ACTIMMUNE (Interferon gamma-1b) BUPHENYL® (sodium phenylbutyrate) Quinsair aerosolized form of levofloxacin Non-Rare Disease Medicines 35#36U.S. Indication Market Growth Strategy HORIZON Durable Orphan Franchise RAVICTI® (glycerol phenylbutyrate) Oral Liquid Urea cycle disorders (UCDs) UCDs are rare and life-threatening genetic diseases resulting in the body's inability to remove ammonia from the blood stream(1) UCDs cause hyperammonia that can lead to intellectual disability, seizures, coma or death(2)(3) ~2,600 people with UCDS ~1,000 diagnosed population (4) Conversion from older-generation nitrogen- scavengers to RAVICTI Increase awareness of label expansion to position RAVICTI as first-line therapy Increase awareness and diagnosis of UCDS ° PROCYSBI® (cysteamine bitartrate) delayed-release capsules Nephropathic cystinosis (NC) NC is a rare and life-threatening, progressive, multisystem metabolic disorder (1) Without cysteamine-depleting treatment, high intracellular cystine concentrations can occur in virtually all organs and tissues, leading to irreversible cellular damage, progressive multi-organ failure and death ~500-600 diagnosed patients ~400-450 diagnosed patients on cystine-depleting therapy (4) Conversion from older-generation cysteamine- depleting therapy to PROCYSBI Increase awareness of label expansion to position PROCYSBI as first-line therapy Increase persistence of and adherence to treatment ACTIMMUNE (Interferon gamma-1b) Ⓡ Chronic granulomatous disease (CGD) CGD is a life-threatening inherited primary immunodeficiency disease that limits the body's ability to fight off certain pathogens (1) Patients have increased susceptibility to severe and recurrent bacterial and fungal infections, along with the formation and development of granulomas in most organs ~1,600 people with CGD(4) Increase awareness and diagnosis of CGD Drive adoption of "triple prophylaxis" therapy - immunomodulation (IFNg) + antifungal + antibiotic Increase persistence of and adherence to treatment (1) See full prescribing information at www.RAVICTI.com, www.PROCYSBI.com and www.ACTIMMUNE.com. Information found on or accessible through these websites is not a part of or incorporated by reference in this presentation. (2) Summar, 2001. (3) Haeberle, 2019. (4) Horizon estimate. 36#37Inflammation Segment: Provides Cash Flow to Support Investments in Our Orphan and Rheumatology Medicines . Four medicines: - PENNSAIDⓇ 2%: indicated for treatment of OA of the knee RAYOS® indicated for treatment of multiple conditions, including rheumatoid arthritis (RA) and polymyalgia rheumatica DUEXISⓇ and VIMOVO®: indicated for treatment of osteoarthritis (OA) and RA PENNSAID (diclofenac sodium topical solution) 2% w/w RAYOS® (Prednisone) Delayed-release Tablets DUEXIS (ibuprofen and famotidine) Tablets 800 mg/26.6 mg HORIZON VIMOVO® (naproxen/esomeprazole magnesium) 37#38We Have Transformed into a Rare Disease Focused Company through Acquisitions 2014 September 2014 Acquisition of Vidara Therapeutics Intl. ACTIMMUNE™ (Interferon gamma-1b) HORIZON RAVICTI (glycerol phenylbutyrate) Oral Liquid May 2015 Acquisition of Hyperion Therapeutics, Inc. 2015 January 2016 Acquisition of Crealta Holdings LLC 2016 KRYSTEXXA! pegloticase 12-HOUR PROCYSBI (cysteamine bitartrate) delayed-release capsules HZN-003 and HZN-007 for uncontrolled gout October 2016 Acquisition of Raptor Pharmaceutical Corp. January 2018 • Acquisition of HZN-003 from MedImmune LLC • Partnered with XL-protein GmbH on HZN-007 (PASylated Uricase) 2016 2017 2018 2019 May 2017 January 2019 Acquisition of River Vision Development Corp. Collaboration with HemoShear Therapeutics LLC TEPEZZA.M teprotumumab-trbw Gout Discovery Collaboration 38#39Our Portfolio Is Supported by Our Intellectual Property Expertise KRYSTEXXA pegloticase • Orphan 18 U.S. patents extending to 2030; composition of matter to 2026 Biologic Exclusivity to 2022 PENNSAID (diclofenac sodium topical solution) 2% w/w • Inflammation Settled Teligent, Amneal, Paddock (Perrigo), Taro and Lupin litigations by granting a right to market no sooner than Oct. 17, 2027 ⚫ In May 2017, U.S. District Court upheld '913 patent (extends to 2027) in case against Actavis TEPEZZA™ teprotumumab-trbw RAVICTI® (glycerol phenylbutyrate)OralLiquid 12-HOUR PROCYSBI (cysteamine bitartrate) delayed-release capsules Orphan Drug Exclusivity: U.S. 2020-2027 Biologic Exclusivity to 2032 Settled Par (first-filer) litigation with right to market July 1, 2025 Settled Lupin litigation with right to market 180 days after Par 9 OB-listed patents extending to 2036 Orphan Drug Exclusivity: U.S. 2020-2022 DUEXIS® (ibuprofen and famotidine) Tablets 800 mg/26.6 mg RAYOSⓇ (Prednisone) Delayed-release Tablets ACTIMMUNE (Interferon gamma-1b) 2 U.S. patents extending to 2022 HORIZON • • Settled Par (first-filer) litigation with right to market Jan. 1, 2023 Settled Actavis (first-filer) litigation with right to market Dec. 23, 2022 VIMOVO (naproxen/esomeprazole magnesium) On-going litigation with Dr. Reddy's Laboratories Although Dr. Reddy's Laboratories received FDA approval of its ANDA in February 2020, a launch while patent litigation is ongoing constitutes an at-risk launch ⚫ Settled litigation with the following parties: Mylan, Actavis and Lupin with right to market Aug. 1, 2024 39#40Fourth-Quarter and Full-Year 2019 Financial Results Driven by Strong Orphan and Rheumatology Segment Growth ($M, except for per share amounts) Net sales Net income (loss) Non-GAAP net income Adjusted EBITDA Earnings (loss) per share - diluted Non-GAAP earnings per share - diluted Q4 2019 Q4 2018 % Change FY 2019 FY 2018 % Change $363.5 $355.5 2 $1,300.0 $1,207.6 8 592.8 101.6 483 573.0 (38.4) NM 116.6 116.8 390.2 314.7 24 24 139.9 151.1 (7) 482.8 451.4 7 $2.84 $0.58 390 $2.90 ($0.23) NM $0.56 $0.67 (16) $1.94 $1.83 6 Note: Non-GAAP net income, adjusted EBITDA and non-GAAP earnings per share are non-GAAP measures; see reconciliations at the end of the presentation for a reconciliation of GAAP to non-GAAP measures. HI HORIZON 40#41Fourth-Quarter and Full-Year 2019 Orphan and Rheumatology Segment Results Driven by Strong KRYSTEXXA Growth ($M) KRYSTEXXAⓇ RAVICTIⓇ(1) PROCYSBIⓇ ACTIMMUNE® RAYOS® BUPHENYLⓇ(1) QUINSAIR™ LODOTRA®(1) Orphan and rheumatology segment net sales Q4 2019 Q4 2018 % Change FY 2019 FY 2018 % Change $110.7 $83.3 33 $342.4 $258.9 32 32 68.5 60.2 14 228.8 226.6 1 40.8 40.1 2 161.9 154.9 5 28.4 27.5 3 107.3 105.6 2 19.5 19.8 78.6 61.1 29 1.6 6.4 (75) 9.8 21.8 (55) 0.3 0.2 68 0.8 0.5 62 0.1 NM 2.1 NM $269.8 $237.6 14 $929.6 $831.5 12 Orphan and rheumatology segment operating income $95.4 $84.8 13 $306.3 $290.0 6 NM: Not meaningful. (1) Beginning in 2019, the Company no longer recognizes revenue from RAVICTI and AMMONAPS sales outside of North America and Japan, nor from sales of LODOTRA. On Dec. 28, 2018, the Company divested the rights to RAVICTI and AMMONAPS outside of North America and Japan. AMMONAPS is known as BUPHENYL in the United States. In addition, effective Jan. 1, 2019, the Company transferred the rights to LODOTRA to Vectura Group plc. LODOTRA is known as RAYOS in the United States. HORIZON 41#42Fourth-Quarter and Full-Year 2019 Inflammation Segment Results ($M) PENNSAIDⓇ 2% DUEXISⓇ VIMOVO® MIGERGOTⓇ(1) Inflammation segment net sales Q4 2019 Q4 2018 % Change FY 2019 FY 2018 % Change $57.0 $64.3 (11) $200.8 $190.2 6 26.3 34.0 (23) 115.7 114.7 1 10.4 18.8 (45) 52.1 67.6 (23) 0.8 NM 1.8 3.6 (49) $93.7 $117.9 (21) $370.4 $376.1 (2) Inflammation segment operating income $44.0 $66.2 (33) $174.9 $160.4 9 (1) In June 2019, the Company divested the rights to MIGERGOT. HORIZON 42#43HORIZON Reconciliations of GAAP to Non-GAAP Measures 43#44Note Regarding Use of Non-GAAP Financial Measures EBITDA, or earnings before interest, taxes, depreciation and amortization, and adjusted EBITDA are used and provided by Horizon as non-GAAP financial measures. Horizon provides certain other financial measures such as non-GAAP net income, non-GAAP diluted earnings per share, non-GAAP gross profit and gross profit ratio, non-GAAP operating expenses, non-GAAP operating income, non-GAAP tax rate, non-GAAP operating cash flow, net leverage ratio and net debt, each of which include adjustments to GAAP figures. These non-GAAP measures are intended to provide additional information on Horizon's performance, operations, expenses, profitability and cash flows. Adjustments to Horizon's GAAP figures as well as EBITDA exclude acquisition and/or divestiture-related expenses, charges related to the discontinuation of ACTIMMUNE development for Friedreich's ataxia, gain or loss from sale of assets, upfront, progress and milestone payments related to license and collaboration agreements, litigation settlements, loss on debt extinguishment, costs of debt refinancing, drug manufacturing harmonization costs, restructuring and realignment costs, as well as non-cash items such as share-based compensation, depreciation and amortization, non-cash interest expense, long-lived asset impairment charges and other non-cash adjustments. Certain other special items or substantive events may also be included in the non-GAAP adjustments periodically when their magnitude is significant within the periods incurred. Horizon maintains an established non-GAAP cost policy that guides the determination of what costs will be excluded in non-GAAP measures. Horizon believes that these non-GAAP financial measures, when considered together with the GAAP figures, can enhance an overall understanding of Horizon's financial and operating performance. The non-GAAP financial measures are included with the intent of providing investors with a more complete understanding of the Company's historical and expected 2020 financial results and trends and to facilitate comparisons between periods and with respect to projected information. In addition, these non-GAAP financial measures are among the indicators Horizon's management uses for planning and forecasting purposes and measuring the Company's performance. For example, adjusted EBITDA is used by Horizon as one measure of management performance under certain incentive compensation arrangements. These non-GAAP financial measures should be considered in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The non-GAAP financial measures used by the Company may be calculated differently from, and therefore may not be comparable to, non-GAAP financial measures used by other companies. HORIZON 44#45GAAP to Non-GAAP Reconciliation EBITDA and Adjusted EBITDA - Three and Twelve Months Ended December 31 HORIZON $ in thousands Three Months Ended December 31, 2019 2018 2019 Twelve Months Ended December 31, 2018 GAAP net income (loss) Depreciation Amortization and step-up: $ 592,769 2,159 $ 101,648 1,499 $ 573,020 $ 6,733 (38,380) 6,126 Intangible amortization expense Inventory step-up expense 57,662 61,125 99 230,424 243,634 89 17,312 Interest expense, net (including amortization of debt discount and deferred financing costs) 17,098 Benefit for income taxes EBITDA Other non-GAAP adjustments: Acquisition/divestiture-related costs (555,885) $ 113,803 $ 29,771 (49,054) 145,088 87,089 121,692 (593,244) (44,752) $ 304,111 $ 305,632 Restructuring and realignment costs 942 204 (1,710) 462 3,556 4,396 237 15,350 Impairment of long-lived assets 10,847 46,096 (Gain)/Loss on sale of assets (30,682) 10,963 (42,985) Share-based compensation 24,149 27,878 91,215 114,860 Litigation settlements 1,000 5,750 Upfront, progress and milestone payments related to license and collaboration agreements 9,073 (10) Fees related to refinancing activities 855 854 2,292 937 Loss on debt extinguishment 58,835 Drug substance harmonization costs Charges relating to discontinuation of Friedreich's ataxia program 63 (145) 1,275 457 2,855 (2,940) 1,076 (1,464) Total of other non-GAAP adjustments Adjusted EBITDA 26,068 $ 139,871 $ 5,984 151,072 178,704 145,785 $ 482,815 $ 451,417 45#46GAAP to Non-GAAP Reconciliation Operating Income - Three and Twelve Months Ended December 31 HORIZON Three Months Ended December 31, 2019 2018 Twelve Months Ended December 31, 2019 2018 $ in thousands GAAP operating income Non-GAAP adjustments: Acquisition/divestiture-related costs Restructuring and realignment costs Amortization and step-up: Intangible amortization expense Inventory step-up expense $ 54,675 $ (200) 204 82,468 $ (1,972) 462 126,611 $ 37,911 1,032 237 3,989 15,350 57,662 61,125 230,424 243,634 99 89 17,312 Impairment of long-lived assets 10,847 46,096 (Gain)/Loss on sale of assets (30,682) 10,963 (42,985) Share-based compensation 24,149 27,878 91,215 114,860 Depreciation 2,159 1,499 6,733 6,126 Litigation settlements 1,000 5,750 Upfront, progress and milestone payments related to license and collaboration agreements 9,073 90 Fees related to refinancing activities 855 854 2,292 937 Drug substance harmonization costs 63 1,275 457 2,855 Charges relating to discontinuation of Friedreich's ataxia program (145) (2,940) 1,076 (1,464) Total of non-GAAP adjustments Non-GAAP operating income $ 84,747 139,422 68,445 354,591 412,550 $ 150,913 $ 481,202 $ 450,461 Orphan and Rheumatology segment operating income Inflammation segment operating income 95,388 44,034 Total segment operating income $ 139,422 $ 84,761 66,152 150,913 306,333 290,014 174,869 160,447 $ 481,202 $ 450,461 Foreign exchange (loss)/gain 58 (111) Other income, net Adjusted EBITDA 391 270 $ 139,871 $ 151,072 $ 33 1,580 482,815 (192) 1,148 $ 451,417 46#47GAAP to Non-GAAP Reconciliation Net Income (Loss) and Non-GAAP Net Income - Three and Twelve Months Ended December 31 HORIZON $ in thousands Three Months Ended December 31, 2019 2018 Twelve Months Ended December 31, 2019 2018 GAAP net income (loss) Non-GAAP adjustments: Acquisition/divestiture-related costs $ 592,769 $ 101,648 $ 573,020 $ (38,380) Restructuring and realignment costs 942 204 (1,710) 462 3,556 237 4,396 15,350 Amortization and step-up: Intangible amortization expense 57,662 61,125 230,424 243,634 Inventory step-up expense 99 89 17,312 Amortization of debt discount and deferred financing costs 5,533 5,872 22,602 22,752 Impairment of long-lived assets 10,847 46,096 (Gain)/Loss on sale of assets (30,682) 10,963 (42,985) Share-based compensation 24,149 27,878 91,215 114,860 Depreciation 2,159 1,499 6,733 6,126 Litigation settlements 1,000 5,750 Upfront, progress and milestone payments related to license and collaboration agreements 9,073 (10) Fees related to refinancing activities 855 854 2,292 937 Loss on debt extinguishment - 58,835 Drug substance harmonization costs 63 1,275 457 2,855 Charges relating to discontinuation of Friedreich's ataxia program (145) (2,940) 1,076 (1,464) Total of pre-tax non-GAAP adjustments 91,422 74,579 438,552 435,609 Income tax effect of pre-tax non-GAAP adjustments (14,277) (57,961) (66,568) (45,186) Other non-GAAP income tax adjustments (553,334) (1,499) (554,786) (37,392) Total of non-GAAP adjustments (476,189) 15,119 (182,802) 353,031 Non-GAAP Net Income $ 116,580 $ 116,767 $ 390,218 $ 314,651 47#48GAAP to Non-GAAP Reconciliation GAAP and Non-GAAP Earnings (Loss) Per Share - Basic and Diluted - Three and Twelve Months Ended December 31 $ in thousands, except share and per share data Non-GAAP Earnings Per Share: Weighted average ordinary shares - Basic Non-GAAP Earnings Per Share - Basic: Three Months Ended December 31, 2019 2018 Twelve Months Ended December 31, 2019 2018 187,421,561 168,126,924 182,930,109 166,155,405 GAAP earnings (loss) per share - Basic Non-GAAP adjustments Non-GAAP earnings per share - Basic $ 3.16 $ 0.60 $ 3.13 $ (0.23) (2.54) 0.09 (1.00) 2.12 $ 0.62 $ 0.69 $ 2.13 $ 1.89 Non-GAAP Net Income $ Effect of assumed conversion of Exchangeable Senior Notes, net of tax Numerator non-GAAP Net Income $ 116,580 $ 1,875 118,455 116,767 $ $ 116,767 $ 390,218 $ 7,500 397,718 314,651 $ 314,651 Weighted average ordinary shares - Diluted Weighted average ordinary shares - Basic Ordinary share equivalents Denominator - Weighted average ordinary shares - Diluted 187,421,561 23,532,018 210,953,579 168,126,924 6,103,787 174,230,711 182,930,109 22,294,112 205,224,221 166,155,405 5,393,514 171,548,919 Non-GAAP Earnings Per Share - Diluted GAAP earnings (loss) per share - Diluted $ 2.84 $ 0.58 2.90 $ Non-GAAP adjustments (2.28) 0.09 (0.96) (0.23) 2.12 Diluted earnings per share effect of ordinary share equivalents Non-GAAP earnings per share - Diluted (0.06) $ 0.56 $ 0.67 $ 1.94 $ 1.83 HORIZON 48#49GAAP to Non-GAAP Reconciliation Net Debt HORIZON $ in thousands December 31, 2019 As of December 31, 2018 Long-term debt, net of current $ 1,001,308 $ 1,564,485 Exchangeable notes, net 351,533 332,199 Total Debt 1,352,841 1,896,684 Debt discount 59,922 87,038 Deferred financing fees 5,263 9,304 Total Principal Amount of Debt 1,418,026 1,993,026 Less: cash and cash equivalents 1,076,287 958,712 Net Debt $ 341,739 $ 1,034,314 49#50HORIZON HORIZON Horizon Therapeutics.com