HZNP - Horizon Therapeutics plc Reports Fourth-Quarter 2021 and Full-Year 2021 Financial Results; Announces Full-Year 2022 Guidance

Fourth-Quarter 2021 Results:
-- Net Sales of $1.01 Billion Increased 36% --
-- GAAP Net Income of $173.2 Million; Adjusted EBITDA of $416.0 Million --
-- TEPEZZA ^® (teprotumumab-trbw) Net Sales of $589.6 Million Increased 72% --
-- KRYSTEXXA ^® (pegloticase injection) Net Sales of $170.3 Million Increased 32%;
KRYSTEXXA Plus Immunomodulation Use Now Approaching 50% --
-- Cash Position of $1.58 Billion as of Dec. 31, 2021 --

Full-Year 2021 Results:
-- Record Net Sales of $3.23 Billion Increased 47% --
-- GAAP Net Income of $534.5 Million; Adjusted EBITDA of $1.28 Billion --
-- Record TEPEZZA Net Sales of $1.66 Billion, Representing Year-Over-Year Growth of 103% --
-- Record KRYSTEXXA Net Sales of $565.5 Million, Representing Year-Over-Year Growth of 39% --
-- Operating Cash Flow of More Than $1.0 Billion --

Full-Year 2022 Guidance:
-- Net Sales Guidance of $3.9 Billion to $4.0 Billion, Representing 22% Growth at the Midpoint --
-- Adjusted EBITDA Guidance of $1.63 Billion to $1.70 Billion, Representing
30% Growth and 230 Basis Points of Margin Expansion at the Midpoint --
-- Expect TEPEZZA Net Sales Percentage Growth in the Mid-30s --
-- Expect KRYSTEXXA Net Sales Growth of More Than 20% --

Company Highlights:
-- Initiated Four Clinical Trials, Including TEPEZZA Phase 3 Trial in Japan --
-- Submitted S upplemental Biologics License Application (sBLA) to the U.S. FDA to Expand Label for KRYSTEXXA to Include Co-Treatment with Methotrexate Based on Positive Data from MIRROR Trial --
-- Advanced Pipeline to Drive Long-Term Growth; Entered into Agreement with Alpine to
Develop Novel Therapies for Autoimmune and Inflammatory Diseases --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced fourth-quarter and record full-year 2021 financial results and provided full-year 2022 net sales and adjusted EBITDA guidance.

“2021 marked a year of tremendous growth for Horizon – we invested significantly in our research and development capabilities and talent, significantly expanded our pipeline, increased our manufacturing capacity to meet growing demand and achieved outstanding financial results,” said Tim Walbert, chairman, president and chief executive officer, Horizon. “I am very proud of what we have accomplished, but I am most excited about the potential for continued growth going forward as we leverage the strong foundation we have built over the past several years. We expect another year of strong double-digit net sales and adjusted EBITDA growth in 2022, as well as meaningful margin expansion, as we continue to execute commercially and build on our momentum in R&D to develop new approaches for patients with rare, autoimmune and severe inflammatory diseases.”

Financial Highlights

Fourth Quarter and Recent Company Highlights

• Submitted sBLA for Co-Treatment of KRYSTEXXA Plus Methotrexate: In January, the Company submitted an sBLA to the U.S. Food and Drug Administration (FDA) to expand the label for KRYSTEXXA to include co-treatment with methotrexate. The submission is based on results from the MIRROR Phase 4 randomized, placebo-controlled trial announced in October, which demonstrated that 71% of patients receiving KRYSTEXXA plus methotrexate achieved a complete response , a more than 30 percentage point improvement compared to patients who were randomized to receive KRYSTEXXA plus placebo (p<0.001). KRYSTEXXA plus immunomodulation is a core element of the Company’s strategy to maximize the value of KRYSTEXXA and enable more patients with uncontrolled gout to benefit from the medicine.

• Entered into Agreement with Alpine Immune Sciences to Develop Novel Therapies for Autoimmune and Inflammatory Diseases: In December, the Company entered into an exclusive license and collaboration agreement with Alpine for the development and commercialization of up to four fusion protein-based preclinical candidates, including multi-specific approaches, for autoimmune and inflammatory diseases. The Alpine collaboration is an example of how Horizon continues to execute on its research strategy to drive earlier-stage discovery through internal research and research-based partnerships and collaborations.

• Added Second TEPEZZA Drug Product Manufacturer: In December, the U.S. FDA approved Horizon’s application for a second drug product manufacturer for TEPEZZA, Patheon (contract development and manufacturing organization services of Thermo Fisher Scientific). The addition of Patheon is part the Company’s long-term strategy adopted in early 2020 to support TEPEZZA supply, given the much stronger than expected demand since launch and planned expansion outside of the United States.

• Received CHMP Positive Opinion for UPLIZNA® (inebilizumab-cdon): In November, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending marketing authorization for UPLIZNA in adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+). The Company expects to launch UPLIZNA in Europe in 2022, beginning with Germany in the second quarter, as well as other international markets in the coming years.

• Presented Final Results from KRYSTEXXA PROTECT Trial at Key Medical Meeting: Final results from the PROTECT open-label trial evaluating KRYSTEXXA to improve management of uncontrolled gout in kidney transplant patients were presented at the American Society of Nephrology (ASN) Kidney Week in November. The data demonstrated that 89% (16 of 18 patients) achieved the primary endpoint at Month 6. The results are encouraging with respect to the ability of KRYSTEXXA to treat uncontrolled gout without compromising kidney function in this very sensitive transplant population.

• Presented New TEPEZZA Data at Key Medical Meetings: In February, multiple new data were presented at the 48 ^th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS 2022) , including new data from a post-marketing safety analysis of hearing-related events associated with TEPEZZA that showed rates were comparable to what was seen in the OPTIC Phase 3 and OPTIC-X open-label extension trials. In November, new TEPEZZA real-world data were presented at the American Academy of Ophthalmology Annual Meeting (AAO 2021) . The data showed that over 90% of TEPEZZA patients completed all eight infusions, indicating a high level of adherence to TEPEZZA in clinical practice.

• New TEPEZZA Chronic TED Data Published: In January, new data from an independent physician case study of six chronic thyroid eye disease (TED) patients who showed benefit after treatment with TEPEZZA were published in Eye , the official journal for the Royal College of Ophthalmologists. The case study adds to the growing body of evidence supporting the use of TEPEZZA in chronic TED patients, with nearly 60 chronic TED patients across multiple case studies who have demonstrated benefit.

• New UPLIZNA Data Published and Presented at Medical Meetings: New UPLIZNA data from the Phase 3 trial were presented at NANOS 2022 in February, showing treatment with UPLIZNA effectively reduced the severity of attacks in patients with NMOSD. In November, an analysis of UPLIZNA data from the Phase 3 trial was published in Multiple Sclerosis and Related Disorders showing that prior rituximab exposure did not impact the efficacy of UPLIZNA, and that UPLIZNA demonstrated comparable efficacy to trial participants without prior exposure to rituximab. Notably, all seven participants who had pre-study attacks despite rituximab use did not experience any attacks after being treated with UPLIZNA. In October, an analysis of data from the Phase 3 trial was published in the Multiple Sclerosis Journal highlighting a sustained effect on attack risk in people with NMOSD who were treated with UPLIZNA for four or more years. Multiple new data were also presented at the virtual 37 ^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October, including new data showing a link between the depth of b-cell depletion in the blood and long-term clinical outcomes.

• Initiated Enrollment in Four Clinical Trials:
  
  
  • In November, the first patient enrolled in a pivotal Phase 2b trial to evaluate HZN-825 in patients with diffuse cutaneous systemic sclerosis , a subset of systemic sclerosis (also known as scleroderma). Systemic sclerosis is a rare, chronic, autoimmune disease marked by fibrosis or skin thickening and can lead to internal organ damage.
    
    
  • In November, the first patient enrolled in a Phase 1 exploratory trial to evaluate TEPEZZA in patients with diffuse cutaneous systemic sclerosis.
    
    
  • In January, the first patient enrolled in a pivotal Phase 2b trial to evaluate HZN-825 in patients with idiopathic pulmonary fibrosis (IPF) , the most common form of interstitial lung disease. IPF is a rare, progressive lung disease caused by inflammation and fibrosis, or scarring, of the lungs.
    
    
  • In February, the first patient enrolled in a Phase 3 trial in Japan to evaluate TEPEZZA in patients with moderate-to-severe active TED , a serious, progressive and potentially vision-threatening rare autoimmune disease. TEPEZZA has not been approved for commercial use in Japan.

• Expanding East Coast Hub Following Viela Bio Acquisition: In January, the Company entered into an agreement to lease a new 192,000-square-foot, state-of-the-art facility under construction in Rockville, Maryland that will serve as the Company’s primary East Coast research and development and technical operations hub. The Company is significantly expanding and consolidating its East Coast footprint with the new facility, nearly quadrupling its current Maryland footprint acquired in the acquisition of Viela and anticipates adding key R&D talent to support its growing research and development capabilities and expanded pipeline.

• Sean Clayton Appointed as General Counsel: In February, the Company named Sean Clayton as executive vice president and general counsel . Mr. Clayton brings nearly 20 years of legal experience and was previously a partner at Cooley LLP where he represented public and private biotechnology companies in general corporate matters and securities laws, as well as a wide range of transactions, including public and private financings. Mr. Clayton led the Cooley team that represented Horizon in its initial public offering in 2011 and has advised Horizon’s management team and board of directors on corporate and transactional matters since that time.

• Continued to Demonstrate Gender and Ethnicity Pay Equity: A second study conducted by Aon, a leading compensation consulting firm, showed that Horizon continues to demonstrate both gender and ethnicity pay equity. This study was a follow-on study to the gender and ethnicity pay equity study Aon conducted in 2019. The Company maintained its gender and ethnicity pay equity after having grown significantly in the two years since the first study, as well as having completed the acquisition of Viela, which included the addition of a significant number of employees.

• Received Continued Recognition as a Top Workplace: In 2021, the Company received 15 workplace-related recognitions, including six in the fourth quarter, reflecting the high level of engagement of its employees. Horizon was named to the following lists in the fourth quarter:
  
  
  • Newsweek’s inaugural Most Loved Workplaces ;
    
    
  • Great Place to Work’s 2021 Best Workplaces for Parents ;
    
    
  • Chicago Tribune Top Workplaces 2021 ;
    
    
  • National Association for Business Resources’ 2021 Best and Brightest Companies to Work For in the Nation;
    
    
  • San Francisco Bay Area’s 2021 Best and Brightest Companies to Work For ; and
    
    
  • Dave Thomas Foundation for Adoption’s Top 100 Best Adoption-Friendly Workplaces .

Key Clinical Development Programs

• Daxdilimab (HZN-7734) , an anti-ILT7 human monoclonal antibody that depletes certain dendritic cells. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, and a variety of other autoimmune conditions.
  
  
  • Systemic Lupus Erythematosus (SLE) Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate daxdilimab in patients with SLE, a disease in which the body's immune system attacks its own tissues and organs.
    
    
  • Alopecia Areata Trial: Phase 2 trial to evaluate daxdilimab in patients with alopecia areata, an autoimmune disorder characterized by nonscarring hair loss, expected to initiate in the second quarter of 2022.
    
    
  • Discoid Lupus Erythematosus (DLE) Trial: Phase 2 trial to evaluate daxdilimab in patients with DLE, a rare, chronic, inflammatory skin condition characterized by lesions that result in scarring, expected to initiate by mid-year 2022.
    
    
  • Lupus Nephritis Trial: Phase 2 trial to evaluate daxdilimab in patients with lupus nephritis, a rare, autoimmune and inflammatory condition of the kidney, expected to initiate in the third quarter of 2022.
    
    
  • Dermatomyositis Trial: Phase 2 trial to evaluate daxdilimab in patients with dermatomyositis, a rare, autoimmune disorder characterized by rashes, debilitating muscle weakness and interstitial lung disease, expected to initiate in the fourth quarter of 2022.

• Dazodalibep (HZN-4920) , a CD40 ligand antagonist that blocks T cell interaction with CD40-expressing B cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway.
  
  
  • Sjögren's Syndrome Trial: Phase 2b randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with Sjögren's syndrome, a chronic, systemic autoimmune condition that impacts exocrine glands, including the salivary and tear glands.
    
    
  • Rheumatoid Arthritis Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with rheumatoid arthritis.
    
    
  • Kidney Transplant Rejection Trial: Phase 2 open-label trial underway to evaluate dazodalibep in kidney transplant rejection patients.
    
    
  • Focal Segmental Glomerulosclerosis (FSGS) Trial: Phase 2 trial to evaluate dazodalibep in patients with FSGS, a rare kidney disorder characterized by scarring of glomeruli, expected to initiate in the fourth quarter of 2022.

• HZN-825 , an oral lysophosphatidic acid receptor 1 (LPAR ₁ ) antagonist that prevents gene activation.
  
  
  • Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial initiated in November 2021 to evaluate HZN-825 in diffuse cutaneous systemic sclerosis.
    
    
  • Idiopathic Pulmonary Fibrosis Trial: Pivotal Phase 2b trial initiated in January 2022 to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease.

• UPLIZNA , an anti-CD19 humanized monoclonal antibody that depletes B cells, including the pathogenic cells that produce autoantibodies.
  
  
  • Myasthenia Gravis Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with myasthenia gravis, a chronic, rare, autoimmune neuromuscular disease that affects voluntary muscles, especially those that control the eyes, mouth, throat and limbs.
    
    
  • IgG4-Related Disease Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with IgG4-related disease, which is a group of disorders marked by tumor-like swelling and fibrosis of affected organs, such as the pancreas, salivary glands and kidneys.

• TEPEZZA , an insulin-like growth factor type 1 receptor (IGF-1R) antagonist monoclonal antibody.
  
  
  • Chronic TED Trial: Phase 4 randomized, placebo-controlled trial underway to evaluate TEPEZZA in chronic TED.
    
    
  • TED in Japan (OPTIC-J) Trial: Phase 3 randomized, placebo-controlled trial in Japan initiated in February 2022 to evaluate TEPEZZA in patients with moderate-to-severe active TED.
    
    
  • Subcutaneous (SC) Administration Trial: Phase 1b trial to explore the pharmacokinetics, safety, tolerability, efficacy, and immunogenicity of subcutaneous administration of TEPEZZA in patients with TED, expected to initiate by mid-year 2022.
    
    
  • Diffuse Cutaneous Systemic Sclerosis Exploratory Trial: Phase 1 exploratory trial initiated in November 2021 to evaluate TEPEZZA in diffuse cutaneous systemic sclerosis.

• KRYSTEXXA , a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, that can be easily excreted from the body.
  
  
  • Shorter Infusion Duration Trial: Phase 4 open-label trial underway to evaluate the impact of administering KRYSTEXXA plus methotrexate over a shorter infusion duration in patients with uncontrolled gout.
    
    
  • Monthly Dosing Trial: Phase 4 open-label trial underway to evaluate monthly dosing of KRYSTEXXA plus methotrexate in patients with uncontrolled gout.
    
    
  • Retreatment Trial: Phase 4 open-label trial underway to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to KRYSTEXXA monotherapy.

• HZN-1116, a fully human monoclonal antibody that binds and neutralizes the function of the FLT3-ligand, thereby reducing both conventional and plasmacytoid dendritic cells.
  
  
  • Autoimmune Disease Trial: Phase 1 trial underway to evaluate HZN-1116 in patients with autoimmune diseases.

Fourth-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

• Net Sales: Fourth-quarter 2021 net sales were $1.014 billion, an increase of 36% compared to the fourth quarter of 2020.

• Gross Profit: Under U.S. GAAP, the fourth-quarter 2021 gross profit ratio was 76.2% compared to 78.2% in the fourth quarter of 2020. The non-GAAP gross profit ratio in the fourth quarter of 2021 was 86.5% compared to 87.1% in the fourth quarter of 2020.

• Operating Expenses: R&D expenses were 13.9% of net sales and SG&A expenses were 39.3% of net sales. Non-GAAP R&D expenses were 11.4% of net sales and non-GAAP SG&A expenses were 34.0% of net sales. Fourth-quarter 2021 GAAP and non-GAAP R&D expenses include $36.2 million of upfront and milestone payments primarily related to the collaboration agreement with Alpine. Beginning in the fourth quarter of 2021, the Company no longer excludes upfront and milestone payments related to license and collaboration agreements from non-GAAP financial measures and line item components.

• Income Tax Expense: On a GAAP basis in the fourth quarter of 2021, income tax expense was $37.9 million. Fourth-quarter non-GAAP income tax expense was $61.4 million.

• Net Income: In the fourth-quarter of 2021, net income on a GAAP and non-GAAP basis was $173.2 million and $334.0 million, respectively.

• Adjusted EBITDA: Fourth-quarter 2021 adjusted EBITDA was $416.0 million and includes $36.2 million of upfront and milestone payments primarily related to the collaboration agreement with Alpine. Beginning in the fourth quarter of 2021, the Company no longer excludes upfront and milestone payments related to license and collaboration agreements from non-GAAP financial measures.

• Earnings per Share: On a GAAP basis, diluted earnings per share in the fourth quarter of 2021 and 2020 were $0.73 and $0.82, respectively. Non-GAAP diluted earnings per share in the fourth quarter of 2021 and 2020 were $1.41 and $1.17, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the fourth quarter of 2021 were 236.8 million.

Fourth-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results. The Company continues to exclude upfront and milestone payments related to license and collaboration agreements from its segment operating income.

Orphan Segment

• Fourth-quarter 2021 net sales of the orphan segment, the Company’s strategic growth segment, were $940.5 million, an increase of 50% over the prior year’s quarter, driven by the strong performance of TEPEZZA, KRYSTEXXA and RAVICTI. The orphan segment represented 93% of total company fourth-quarter net sales.
  
  
• KRYSTEXXA fourth-quarter 2021 net sales increased 32% year-over-year driven by increased adoption of KRYSTEXXA plus immunomodulation, which is now approaching 50%. In addition, the Company continues to see strong uptake of KRYSTEXXA from both rheumatologists and nephrologists.
  

• Fourth-quarter 2021 orphan segment operating income was $420.8 million, which includes additional investment associated with TEPEZZA, UPLIZNA and the Company’s pipeline programs.

Inflammation Segment

• Fourth-quarter 2021 net sales of the inflammation segment were $74.0 million, and segment operating income was $32.6 million.

Cash Flow Statement and Balance Sheet Highlights

• In the fourth-quarter of 2021, operating cash flow on a GAAP and non-GAAP basis was $538.6 million and $554.4 million, respectively. Full-year 2021 operating cash flow on a GAAP and non-GAAP basis was $1.035 billion and $1.190 billion, respectively.

• As of Dec. 31, 2021, the Company had cash and cash equivalents of $1.580 billion.

• As of Dec. 31, 2021, the total principal amount of debt outstanding was $2.606 billion.

2022 Guidance

The Company expects full?year 2022 net sales to range between $3.9 billion and $4.0 billion, representing 22% growth at the midpoint. The Company expects TEPEZZA full-year 2022 net sales percentage growth in the mid-30s and KRYSTEXXA full-year 2022 net sales growth of more than 20%. Full-year 2022 adjusted EBITDA is expected to range between $1.63 billion and $1.70 billion, representing 30% growth and 230 basis points of margin expansion at the midpoint.

Webcast

At 8 a.m. EST / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at http://ir.horizontherapeutics.com . Please connect to the Company's website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.

About Horizon

Horizon is focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter , LinkedIn , Instagram and Facebook .

Note 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 (benefit) and tax rate and non-GAAP operating cash flow, 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 Horizons GAAP figures as well as EBITDA exclude acquisition and/or divestiture-related costs, manufacturing plant start-up costs, drug substance harmonization costs, fees related to refinancing activities, restructuring and realignment costs and litigation settlements, as well as non-cash items such as share-based compensation, inventory step-up expense, depreciation and amortization, non-cash interest expense, long-lived assets impairment charges, loss on debt extinguishments, gain (loss) on sale of assets, gain on equity security investments 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 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. 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 has not provided a reconciliation of its full-year 2022 adjusted EBITDA and associated margin expansion outlook to an expected net income (loss) outlook because certain items such as acquisition/divestiture-related expenses and share-based compensation that are a component of net income (loss) cannot be reasonably projected due to the significant impact of changes in Horizon’s stock price, the variability associated with the size or timing of acquisitions/divestitures and other factors. These components of net income (loss) could significantly impact Horizon’s actual net income (loss).

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to Horizon’s full-year 2022 net sales, adjusted EBITDA and margin expansion guidance; expected financial performance and operating results in future periods, including potential growth in net sales of certain of Horizon’s medicines; development, manufacturing and commercialization plans; expected timing of clinical trials, availability of clinical data 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; impacts of the COVID-19 pandemic and actions taken to slow its spread, including impacts on supplies and net sales of Horizon’s medicines and potential delays in clinical trials; the fact that Horizon’s full-year 2022 net sales, adjusted EBITDA and TEPEZZA net sales guidance and the expected timing of certain TEPEZZA clinical trials assume that future committed manufacturing slots for TEPEZZA are not cancelled and are run successfully, which could be impacted by additional government-mandated COVID-19 vaccine production orders and other risks associated with the manufacture of biologic medicines; risks associated with acquisitions, such as the risk that the businesses will not be integrated successfully, that such integration may be more difficult, time-consuming or costly than expected or that the expected benefits of the transaction will not occur; 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, including its manufacturing and global expansion strategy; 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 press release as a result of new information.