 Horizon Pharma plc October 13, 2014 Friedreich's Ataxia Analyst Day Presentation Exhibit 99.2 Non-Confidential Information – Horizon Pharma plc |
 Forward-Looking Statements 2 Non-Confidential Information – Horizon Pharma plc This presentation contains forward-looking statements, including, but not limited to, statements related to the consummated business combination transaction between Horizon Pharma, Inc. and Vidara Therapeutics International plc and the benefits thereof, the strategy, plans, objectives, expectations (financial or otherwise) and intentions, future financial results and growth potential of the combined company – Horizon Pharma plc, development programs and management structure, and other statements that are not historical facts. This presentation also includes forward-looking statements regarding results of the Phase 2 clinical trial of ACTIMMUNE and management expectations and plans regarding further study of ACTIMMUNE in Friedreich’s ataxia (FA) , related discussions with the FDA, the potential for ACTIMMUNE as a treatment for FA patients, and potential sales opportunity for ACTIMMUNE. The statements made by representatives of the Friedreich’s Ataxia Research Alliance and the Collaborative Clinical Research Network in Friedreich’s Ataxia represent their independent conclusions and recommendations. These forward-looking statements are based on Horizon Pharma plc’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 related to future opportunities and plans for Horizon Pharma plc, including uncertainty of the expected financial performance and results; disruption from the transaction, making it more difficult to conduct business as usual or maintain relationships with customers, employees or suppliers; and the possibility that if Horizon Pharma plc does not achieve the perceived benefits of the transaction as rapidly or to the extent anticipated by financial analysts or investors, the market price of its shares could decline, as well as other risks related to Horizon Pharma plc’s business, including whether results of subsequent studies will be consistent with results of the Phase 2 clinical trial of ACTIMMUNE; risks regarding timing and outcome of regulatory review and approval of product candidates; its dependence on sales of its existing products and its ability to increase sales of its existing products; Horizon Pharma plc’s ability to successfully execute its commercial strategy and achieve projected financial results in 2014 and 2015; the fact that past financial or operating results are not a guarantee of future results; competition, including potential generic competition; the ability of Horizon Pharma plc to protect its intellectual property and defend its patents; regulatory obligations and oversight; and those risks detailed from time-to-time under the caption “Risk Factors” and elsewhere in Horizon Pharma plc’s SEC filings and reports, including in its Annual Report on Form 10-K for the year ended December 31, 2013. Horizon Pharma plc undertakes no duty or obligation to update any forward-looking statements contained in this presentation as a result of new information, future events or changes in its expectations. For full prescribing information, please see product websites; www.DUEXIS.com www.ACTIMMUNE.com www.RAYOSrx.com www.VIMOVO.com , ; ; . |
 Non-Confidential Information – Horizon Pharma plc Forward-Looking Statements – Friedreich’s Ataxia Slides regarding the Friedreich’s ataxia population and market are from a report prepared by L.E.K. Consulting LLC (“L.E.K.”) and are being provided for informational purposes only. Recipients of such report and the information contained therein are not permitted to rely on the report, and their access to the report is not a substitute for the investigations and due diligence that any such recipient would ordinarily undertake. L.E.K. is not and shall not be responsible for decisions made by any such recipient of the report. L.E.K. owes no obligations or duties to recipients of this report in connection with the report, whether in contract, tort (including negligence), breach of statutory duty or otherwise. During the course of L.E.K.’s analysis, certain assumptions and forecasts may have been developed. These assumptions are inherently subject to uncertainties, and actual results may differ from those projected. While L.E.K. believes that the assumptions and forecasts are reasonably based, L.E.K. does not provide any assurance that these assumptions are correct, or that any forecasts will reflect actual results. Therefore, no representation is made or intended to be made, nor should be inferred, with respect to the likely occurrence of any particular future set of facts. L.E.K.’s analysis is based on information available at the time it prepared its analysis and on certain assumptions, including, but not limited to, assumptions regarding future events, developments and uncertainties and contains “forward-looking statements” (statements that may include, without limitation, statements about projected revenues, earnings, market opportunities, strategies, competition, expected activities and expenditures, and at times may be identified by the use of words such as “may”, “could”, “should”, “would”, “project”, “believe”, “anticipate”, “expect”, “plan”, “estimate”, “forecast”, “potential”, “intend”, “continue” and variations of these words or comparable words). L.E.K. is not able to predict future events, developments and uncertainties. Consequently, any of the forward-looking statements contained in this report may prove to be incorrect or incomplete, and actual results could differ materially from those projected or estimated in this report. L.E.K. undertakes no obligation to update any forward-looking statements for revisions or changes after the date of this report and L.E.K. makes no representation or warranty that any of the projections or estimates in this report will be realized. Nothing contained herein is, or should be relied upon as, a promise or representation as to the future. 3 |
 Non-Confidential Information – Horizon Pharma plc Note Regarding Use of Non-GAAP Financial Measures 4 Horizon provides certain financial measures such as adjusted non-GAAP net income (loss), adjusted non-GAAP net income (loss) per share, non- GAAP gross profit margins and non-GAAP cash from operations that include adjustments to GAAP figures. These adjustments to GAAP exclude acquisition transaction related expenses as well as non-cash items such as stock compensation, depreciation and amortization, accretion, non- cash interest expense, and other non-cash adjustments such as the increase or decrease in the fair value of the embedded derivative associated with the Company’s convertible senior notes. 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. EBITDA, or earnings before interest, taxes, depreciation and amortization, and adjusted EBITDA are also used and provided by Horizon as non-GAAP financial 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 performance. The non-GAAP financial measures are included with the intent of providing investors with a more complete understanding of the Company’s operational results, trends and expectations. 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. The Company has not provided a reconciliation of full year 2014 or 2015 adjusted EBITDA outlook to a net income (loss) outlook because certain items that are a component of net income (loss) but not part of adjusted EBITDA, such as the gain (loss) on derivative revaluation associated with the convertible senior notes, stock compensation, acquisition related expenses and certain purchase accounting items such as intangibles and step-up inventory, cannot be reasonably projected, either due to the significant impact of changes in Horizon’s stock price on derivative revaluation and stock compensation, or the variability associated with acquisition related expenses and purchase accounting items due to timing and other factors. |
 Friedreich’s Ataxia Analyst Day Agenda 5 Non-Confidential Information – Horizon Pharma plc Overview & Vision for ACTIMMUNE ® Timothy P. Walbert Chairman, President and Chief Executive Officer FA Overview & ACTIMMUNE Phase 2 Clinical Trial Results Jennifer Farmer, MS Certified Genetic Counselor Executive Director, FARA and Coordinator, Collaborative Clinical Research Network in FA FARA’s Mission and Strategy Ronald J. Bartek Co-Founder & President of FARA ACTIMMUNE Clinical & Regulatory Plan Jeffrey W. Sherman, M.D., FACP Executive Vice President, Research and Development, Chief Medical Officer FA Market Overview Brian Andersen Group Vice President and General Manager, Orphan Business Unit Business Development Strategy Robert F. Carey Executive Vice President, Chief Business Officer Q&A All |
 6 HZNP Overview and Vision for ACTIMMUNE® Timothy P. Walbert Chairman, President and Chief Executive Officer Non-Confidential Information – Horizon Pharma plc |
 Non-Confidential Information – Horizon Pharma plc (1) On a non-GAAP basis (2) RAYOS is known as LODOTRA outside the United States • Profitable (1) specialty biopharmaceutical company with accelerating growth • Integrated commercial model with track record of execution • Four products targeting unmet therapeutic needs in orphan diseases, primary care and specialty segments • Experienced, proven leadership team • Tax efficient corporate platform facilitating an aggressive business development strategy via product/company acquisitions Horizon Pharma plc Overview 7 (2) |
 Non-Confidential Information – Horizon Pharma plc Four U.S. Products in Three Market Segments 8 • 7 clinical science associates – Academic medical centers – Infectious disease and immunology Orphan Diseases Primary Care • 250 sales reps – Primary care – Orthopedic surgeons Specialty • 42 sales reps – Rheumatology |
 Non-Confidential Information – Horizon Pharma plc 2012 2013 2014E (1) 2Q 2013 2Q 2014 2015E (1) ~495% Year-over-Year Net Sales Growth 2Q13 vs. 2Q14 Accelerating Growth in Net Sales and EBITDA 9 $18.8 $74.0 $270 - $280 $380 - $405 $11.1 $66.1 $(73.3) $(33.5) $80 - $90 $(12.5) $23.8 $(150.0) $(50.0) $50.0 $150.0 $250.0 $350.0 $450.0 Net Sales Adjusted EBITDA $150 - $170 (1) Guidance provided on September 19, 2014 which included estimated ACTIMMUNE results and excluded transaction related expenses. By this presentation, Horizon is not confirming or updating September 19, 2014 financial guidance. |
 Non-Confidential Information – Horizon Pharma plc • Adjusted 2Q 2014 non-GAAP net income was $20.7 million, or $0.28 non-GAAP basic earnings per share and $0.21 non-GAAP diluted earnings per share (1) RAYOS is known as LODOTRA outside the United States Consistently Improving Quarterly Growth 10 $9 $11 $24 $30 $52 $66 $0 $10 $20 $30 $40 $50 $60 $70 1Q 2013 2Q 2013 3Q 2013 4Q 2013 1Q 2014 2Q 2014 LODOTRA (1) RAYOS (1) DUEXIS VIMOVO |
 Non-Confidential Information – Horizon Pharma plc 11 ACTIMMUNE – Making a Difference in Patients’ Lives See full prescribing information at www.ACTIMMUNE.com |
 ACTIMMUNE - $500M Product Opportunity* 12 ACTIMMUNE in CGD/SMO + • ACTIMMUNE (interferon gamma-1b) • Indications – Reduction of the frequency and severity of serious infections associated with Chronic Granulomatous Disease (CGD) – Delaying time to disease progression in patients with severe, malignant osteopetrosis (SMO) • 270 CGD/SMO patients on drug ACTIMMUNE in FA • Friedreich's ataxia is a debilitating, life-shortening, ultra-orphan disorder • Prevalence of 1 in 50,000 people in U.S. or ~3,700 U.S. patients • No FDA approved treatment for patients • Strong efficacy signal in Phase 2 study • Plan to partner with FARA and rapidly move into Phase 3 registration program * Subject to approval in Friedreich’s ataxia + See full prescribing information at www.ACTIMMUNE.com Non-Confidential Information – Horizon Pharma plc |
  Non-Confidential Information – Horizon Pharma plc • $73.6 million annual sales and $39.1 million operating income run-rate based on 2Q 2014 performance • Q2 2014 ACTIMMUNE sales of $18.4M, an increase of $4.9 million from 2Q 2013 ACTIMMUNE Financial Overview – Q2 2014 13 ($ in millions) 2014 2013 2014 2013 Product Sales, net 18.4 $ 13.5 $ 35.7 $ 25.9 $ Cost of product sales 0.8 1.7 1.7 3.2 Gross Profit 17.6 11.8 34.1 22.7 Gross Margin 96% 87% 95% 88% Operating Expenses 7.8 6.1 17.1 12.6 Income from Operations 9.8 5.7 17.0 10.1 Operating Margin 53% 42% 47% 39% Other Expenses 0.2 0.6 0.5 1.6 Income Taxes 0.4 (0.8) 0.7 (1.5) Net Income 9.2 $ 5.9 $ 15.7 $ 10.1 $ Net Margin 50% 44% 44% 39% (Unaudited) (Unaudited) Three Months Ended June 30, Six Months Ended June 30, |
 Non-Confidential Information – Horizon Pharma plc Drive market penetration in CGD (currently < 30%) Meet with FDA and finalize Phase 3 program in Friedreich’s ataxia Identify further potential indications with proven science Rapidly understand opportunity in Cutaneous T-cell lymphoma and Eczema Herpeticum ACTIMMUNE Strategy Drive CGD Penetration and Rapidly Expand Market Opportunity 14 |
 Non-Confidential Information – Horizon Pharma plc 15 FA & ACTIMMUNE Phase 2 Clinical Trial Results Jennifer Farmer, MS, Certified Genetic Counselor Executive Director, FARA Coordinator, Collaborative Clinical Research Network in FA |
 Friedreich Ataxia (FA) • A rare, genetic condition that is a progressive degenerative disease of children, adolescents and adults • Affects 1 in 50,000 • Estimated 4-5,000 individuals in US and 15,000 worldwide • Nicolaus Friedreich first described in 1860’s based on 6 patients from 2 families • Typically thought of as a neurodegenerative disease as this is the most visible and common symptom; however FA is a multi-system disease • Genotypic and phenotypic heterogeneity 16 – Childhood onset is associated with more rapid progression. • Onset/symptoms appear between ages of 5-15 years • Late teens – early twenties most individuals are wheelchair-bound and require assistance with ADLs – Late onset (diagnosed after age 20) is associated with slower progression and overall more mild phenotype |
 FA – Clinical Features Clinical features: Neuro • Loss of large sensory neurons - proprioception – Loss of balance and coordination – Loss of reflexes • Loss of spinocerebellar tracts – Loss of balance and coordination • Loss of motor tracts to a lesser degree • Loss of dentate nucleus of the cerebellum – Dysarthria (slurred speech), modest eye movement abnormalities • Loss of a few other specific sites. – Vision, hearing loss • Sparing of cerebellar cortex, cerebral cortex – Normal cognition • Overall loss of relatively few neurons, modest number of axonal tracts----MRI scans are normal or almost normal in early disease 17 |
 FA – Not just Neuro but Multi-system condition • Heart: Cardiomyopathy and arrhythmia – Hypertrophic cardiomyopathy can be progressive and severe and early morbidity and mortality – Clinically significant arrhythmia • Endo: Diabetes –10-20%; >65% Insulin resistance • ENT – Swallowing difficulty in later stage patients – Hearing loss – 10-15% of patients • Ophthal – Optic atrophy – present in 10% of pts – Fixation abnormalities common (square wave jerks, ocular flutter) • Skeletal: Scoliosis -Corrective surgery required in up to 50% of patients -Pes cavus • Fatigue: Nearly all patients experience significant fatigue that impacts quality of life. • Cognition remains normal 18 |
 Friedreich’s Ataxia: Management • No treatment to stop progression of disease • Most individuals take vitamins and antioxidants • Annual Echocardiogram and EKG – Treat cardiac symptoms as they appear – No clinical treatment guidelines • Annual glucose • Annual scoliosis screening (especially kids ages 7-18) – Spinal fusion – as needed • Annual vision and hearing screening • Annual PT/OT/Speech 19 |
 Diagnosis - FXN gene identified in 1996 Exon 1 2 3 4 5 4 GAA FXN Gene 5 Transcription Translation Frataxin: highly conserved; functions in mitochondria 20 |
 Diagnosis - FXN gene identified in 1996 Exon 1 2 3 4 GAA 5 Exon 1 2 3 4 GAA 5 GAA repeats 3-33 – normal GAA repeats 66-1700 - abnormal Frataxin 21 |
 Diagnosis - FXN gene identified in 1996 Exon 1 2 3 4 GAA 5 Exon 1 2 3 4 GAA 5 Mat Pat Low frataxin 22 |
 Frataxin Correlates with GAA repeat length Deutsch et al., Mol Genet Metab. 2010 Measured frataxin levels inversely correlates with GAA repeat length, suggesting that the assay is useful for assessing severity of disease in buccal cells. 23 |
 p <<< 0.0001 p <<< 0.0001 p <<< 0.0001 p <<< 0.0001 p <<< 0.0001 p <<< 0.0001 Two Encouraging Learnings: 1) Individuals with FA make some Frataxin; 2) One does not need 100% 24 |
 Low frataxin = mitochondrial dysfunction and energy deprivation Frataxin: highly conserved; functions in mitochondria 25 |
 Why Interferon gamma for FA? 26 |
 Why Interferon gamma for FA? 27 |
 Why Interferon gamma for FA? • FRDA mice improve both locomotor activity and motor coordination, when treated with IFN , and that this is paralleled by both frataxin upregulation and neuronal preservation in DRG. 28 |
 Pilot Study of IFN in Children with FA • Investigator-initiated study; IND waiver – Goals • Safety and tolerability of IFN • Effect on frataxin protein levels • Effect on neurologic function • Design: Small, open-label pilot study • 12 Individuals with genetic confirmation of FA, ages 5-17 • Dose-escalation (10mcg/m2, 25mcg/m2, 50mcg/m2 – 3xwk) every two weeks based on tolerability • Overall treatment phase was 12 weeks • Reevaluation 1 month post treatment 29 |
 Study Outcome Measures 30 • Primary outcome measure – Effect of IFN- on frataxin mRNA and protein levels in whole blood (primary) and buccal cells after 12 weeks of treatment. • Secondary outcome measures • Pharmacokinetic: in vivo and in vitro levels of IFN- , whole blood • Neurologic: Friedreich’s Ataxia Rating Scale (FARS), Timed 25 Foot Walk Test (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Sloan Letter Acuity (LCSLA), Listening in Spatialized Noise – Sentences (LiSN-S) • Overall clinical measures: Global Impression of Clinical Severity, Modified Fatigue Impact Scale, Activities of Daily Living, Pediatrics Quality of Life scales • Safety and Tolerability: Clinical safety lab testing, electrocardiogram, assessment of adverse events, flu-like symptoms (FLS), injection-site reactions (ISR) |
 Demographics 31 8-17 years old, mean age of 12 Mean GAA repeat length 835 Mean age of onset was 6 12 of 12 subjects screened met criteria Two subjects did not follow dose escalation protocol due to adverse events Two subjects withdrawn from the study for inability to complete study procedures |
 No drug-related serious adverse events (SAE) occurred 11 of 12 subjects experienced at least 1 AE Low grade, not dose related Largely known side-effects of IFN- Two subjects were unable to continue with dose- escalation of IFN- due to moderate to severe flu-like symptoms Safety and tolerability 32 |
 Frataxin Measurements A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia, Deutsch EC 1 , Santani AB, Perlman SL, Farmer JM, Stolle CA, Marusich MF, Lynch DR. Mol Genet Metab. 2010 Oct-Nov;101(2-3):238-45. Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia, Deutsch EC 1 , Oglesbee D , Greeley NR , Lynch DR, J Neurol Neurosurg Psychiatry. 2014 Sep;85(9):994-1002. Validation in whole blood and buccal cells Exploratory – RBCs, platelets and WBCs – While there was statistically significant change it was not at a level or magnitude that could be clinically meaningful – Unaffected tissue 33 2 3 |
 34 |
 Friedreich Ataxia Rating Scale (FARS) 35 Clinical neurological exam and ADL based scale developed by S. Subramony • Good inter-rater reliability; correlates with duration, disability and ADL • Bulbar – speech, facial strength, cough • Upper Extremity – finger to nose, dysmetria, finger taps • Lower Extremity – heel to shin – slide and tap • Peripheral Nerves – reflexes, proprioception, sensation • Upright Stability – sitting, standing, walking • FARS, Functional Disability Rating Scale – 0-6 • Clinician grading • FARS, Activities of Daily Living 0-36 • Patient response • FARS Neuro, 5 separate subscores (0-125) |
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 FARS: Clinical Outcome Measure 37 |
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 Performance Measures 39 |
 Conclusions IFN- was safe and well-tolerated No overt significant increase in frataxin levels – Presence of increased levels through treatment – Sampling limited to unaffected tissue – Timing of sampling - short half life of gamma interferon – Limited to FDA approved dose for other diseases Clinically significant neurologic improvement magnitude 40 |
 Limitations • The small size of the study • Absence of a placebo group • One site 41 |
 Future Directions • Double-blind, placebo-controlled trial • Larger number of subjects • Frataxin measurements more consistently timed with dosing • Frataxin measurement in affected tissue – Muscle • Explore higher-dose 42 |
 43 Non-Confidential Information – Horizon Pharma plc Ronald J. Bartek Co-Founder & President of FARA FARA’s Mission and Strategy |
 FARA Mission & Strategy Mission is to marshal and focus the resources and relationships needed to cure FA Guiding Principle - Collaboration and Partnership • As a rare disease we can not afford to seek progress in isolation Strategy • Growing the scientific community • Diverse and Deep Pursuit of Treatments • Focus on Infrastructure needs • Public-Private Partnership • Advocacy 44 |
 FARA Research and Clinical Programs Grant Program Scientific Conference Program Patient Registry & Education Program Collaborative Clinical Research Network Advocacy •24/7/365 •Peer-reviewed •Basic, Translational and Clinical Research • > $25 Million in research funding to scientists in both public and private organizations. •Facilitating rapid and open sharing research •Promoting collaboration •Nurturing young investigators •Patient Recruitment •2200 Registrants •Athena Diagnostics sends letter to referring physicians alerting them to the FARA Patient Registry when an individual is diagnosed. •10 Network Sites Worldwide •>750 Individuals seen on an annual •Infrastructure for clinical research, including natural history, outcome measures, biorepository, biomarker studies and trials. •Trained physicians and coordinators •Promote public- private partnership. •Government (NIH &FDA) •Pharmaceutica l Industry •Other advocacy organizations 45 |
 FARA Patient Registry • The FARA Patient Registry is the only worldwide registry of FA patients • Web-based, patient entered demographic and basic clinical data • Proven successful for clinical research and trial recruitment. – 7 clinical trials; 9 clinical research studies – Recruiting subjects in hours and days not weeks and months • Providing good evidence for geographic distribution and population data 46 |
 FARA Patient Registry Over 2000 Patients Active Enrollment From 65 Countries Top Five Countries – United States (64%), Canada, United Kingdom, Australia, Spain 47 |
 FARA Patient Registry Average 200 new registrants per year 48 0 500 1000 1500 2000 2500 2006 2008 2010 2012 2014 >2400 individuals with FA Enrolled New Enrollment /YR Existing |
 Collaborative Clinical Research Network in FA (CCRN in FA) • Established 10 years ago - 10 sites in U.S., Australia and South America • Goals • Provide quantitative serial clinical data on patients – natural history • Design improved clinical measures for use in trials • Build a clinical database in parallel with a biorepository for use in translational research including modifier gene studies and biomarker studies • Create a mechanism for sharing data and resources • Facilitate the implementation and conduct of clinical trials • Define best practices for FA and provide the highest level of clinical care for patients 49 |
 CCRN in FA Cohort Assessment N Mean SD Age of Onset 746 13.7 10.03 Age at Baseline 746 26.2 15.17 Shorter GAA repeat 746 632.7 241.14 50 Gender Male 50% Female 50% |
 Advocacy • NIH – Member NINDS Council, Steering Committee NINDS non-profit forum, Rare Disease Patient Registry Advisors – 1 NIH RAID grant for non-cancer condition • Partnership – Industry, Academia, Advocacy • Raising awareness and knowledge at FDA – 2013 & 2014 – Invited speakers at FDA training – FA community members on FDA Advisory panels • Institute of Medicine – Accelerating Drug Development for Rare Diseases – Independent Review of the RAC 51 st |
 Researchers & Physicians Government NIH, FDA Pharma & Biotech Patients and Families FARA FARA 52 |
 53 Clinical and Regulatory Plan Clinical and Regulatory Plan Jeffrey W. Sherman, M.D., FACP Executive Vice President, Research and Development, Chief Medical Officer Non-Confidential Information – Horizon Pharma plc |
 Clinical/Regulatory Considerations for FA Clinical/Regulatory Considerations for FA • FA is a debilitating, life-shortening, ultra orphan disorder (prevalence of 1 in 50,000 people in U.S.) • No treatment for patients only monitored for symptoms • Increase in initiatives and incentives from FDA to expedite treatments for conditions such as FA – Rare and orphan disease programs – Expedited programs for serious conditions – Best Pharmaceuticals for Children Act (BPCA) • ACTIMMUNE already FDA approved for two debilitating, orphan diseases • Supplement approval pathway typically more straightforward than new entity approval 54 Non-Confidential Information – Horizon Pharma plc |
 Non-Confidential Information – Horizon Pharma plc Potential to Address an Unmet Medical Need Potential to Address an Unmet Medical Need Before Treatment 55 Source: Patient Blog http://fafysio.wordpress.com/2014/08/21/amazing-ilva/#comments |
 Potential to Address an Unmet Medical Need Potential to Address an Unmet Medical Need On Treatment (200mcg 3x/week [2x CGD Dose]) after 6 months 56 Non-Confidential Information – Horizon Pharma plc Source: Patient Blog http://fafysio.wordpress.com/2014/08/21/amazing-ilva/#comments |
 57 Anticipated ACTIMMUNE FA Clinical/Regulatory Timeline Anticipated ACTIMMUNE FA Clinical/Regulatory Timeline October 2014 November 2014 October 2014 Q1 2015 Received Orphan Drug Designation for ACTIMMUNE to treat FA Pre-IND meeting with FDA Planning ongoing in collaboration with CCRN in FA and FARA for FDA Pre-IND meeting and next-step development activities leading to clinical study and supplemental BLA Phase 3 clinical trial start pending FDA Pre-IND meeting feedback and IND submission IND Submission: Also planning a submission at the same time to FDA expedited programs for serious conditions (e.g., Fast Track Designation) pending Pre-IND meeting feedback Q2 2015 Non-Confidential Information – Horizon Pharma plc |
 Additional Potential ACTIMMUNE Indications Additional Potential ACTIMMUNE Indications 58 • Autosomal Dominant Osteopetrosis (ADO) – 1 in 250,000 in the U.S. (1) • Severe Atopic Dermatitis (AD) - 3.4 million (2) – Methicillin Resistant Staphylococcus aureus (MRSA) infection - colonization up to 11% (3) – Eczema Herpeticum (EH) - < 3%; ~102,000 (4) • Cutaneous T-Cell Lymphoma (CTCL) – 6 in 1 million in the U.S. (5) Non-Confidential Information – Horizon Pharma plc (1) Shaw, Tatyana E, Gabriel P Currie, Caroline W Koudelka, and Eric L Simpson. Eczema Prevalence in the United States: Data from the 2003 National Survey of Children’s Health. The Journal of Investigative Dermatology 131 (1): 67–73. doi:10.1038/jid.2010.251. (2) Hanifin, Jon M, Michael L Reed, and Eczema Prevalence and Impact Working Group. 2007. “A Population-Based Survey of Eczema Prevalence in the United States.” Dermatitis: Contact, Atopic, Occupational, Drug 18 (2): 82–91. (3) Huang, Jennifer T., Melissa Abrams, Brook Tlougan, Alfred Rademaker, Amy S. Paller. Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity. Pediatrics Vol. 123 No 5 May1, 2009 pp. e808-e814 (dol:10,152/peds/2008-2217). (4) Leung, Donald Y M. 2013. “Why is Eczema Herpeticum Unexpectedly Rare? “ Antiviral Research 98 (2): 153-57 . Doi:10.1016/j.anitivral.2013.02.010. (5) Cutaneous T-Cell Lymphoma Facts. Leukemia & Lymphoma Society. June 2014 . |
 59 ACTIMMUNE Market Overview ACTIMMUNE Market Overview Brian Andersen Group Vice President and General Manager, Orphan Business Unit Non-Confidential Information – Horizon Pharma plc |
 60 ACTIMMUNE Impacts Patients’ ACTIMMUNE Impacts Patients’ Lives Lives Non-Confidential Information – Horizon Pharma plc |
 Chronic Granulomatous Disease (CGD) Overview • CGD was identified in the 1950’s • Survival has improved over time and most patients are able to manage their disease and can live well into adulthood • CGD is a disease of the immune system and described as a primary immunodeficiency disorder • CGD is the most common disorder of phagocytes making up 6% of primary immune deficiencies • ~1 in every 200,000 babies are born with CGD. There are estimated to be ~1,600 CGD patients in the U.S. 61 Non-Confidential Information – Horizon Pharma plc |
 Non-Confidential Information – Horizon Pharma plc 62 Common Presentation Indicating CGD Common Presentation Indicating CGD In the U.S., the majority of CGD-related infections are caused by: * This is not a complete list of pathogens. Infections may also be caused by other species of bacteria, fungi, and yeast not listed here. Pathogen* Type of Infection Common Presentation Aspergillus species Fungal Pneumonia, lymphadenitis, osteomyelitis, brain abscess Burkholderia species Bacterial Pneumonia, sepsis Nocardia species Bacterial Pneumonia, osteomyelitis, brain abscess Serratia marcescens Bacterial More common: Osteomyelitis, soft tissue infections Less common: Pneumonia, sepsis Staphylococcus aureus Bacterial Soft tissue infections, lymphadenitis, liver abscess, osteomyelitis, pneumonia, sepsis Most frequent sites of infection and common inflammatory complications resulting from CGD |
 van den Berg JM, et al. (2009) Chronic Granulomatous Disease: The European Experience. PLoS ONE 4(4): e5234. Typically Diagnosed Before the Age of Five • CGD may become apparent any time from infancy to late adulthood • >75% are diagnosed before the age of five years • CGD is under-diagnosed and can be misdiagnosed • Diagnostic testing is readily available 63 Non-Confidential Information – Horizon Pharma plc |
 64 ACTIMMUNE Clinical Benefit in CGD ACTIMMUNE Clinical Benefit in CGD Fewer Days of Hospitalization Reduction in Relative Risk of Serious Infections Non-Confidential Information – Horizon Pharma plc * Serious infection was defined as an infection requiring hospitalization and parenteral antibiotics **The beneficial effect of ACTIMMUNE was demonstrated throughout a 12 month study • 67% reduction in relative risk of serious infection* in patients receiving ACTIMMUNE (p=0.0006) • 64% reduction in total number of serious infections* (p<0.0001) • Placebo patients required 3x as many inpatient hospitalization days for treatment of clinical events compared to patients receiving ACTIMMUNE (p=0.02) • 77% of patients receiving ACTIMMUNE were free of serious infections vs. 30% receiving placebo. ** (P= 0.0006). The mean duration of therapy for these patients was 8.9 months • A long-term observational follow-up study of patients who received adjunctive prophylactic therapy with ACTIMMUNE demonstrated an incidence of 0.30 serious infections* per patient-year |
 Severe Malignant Osteopetrosis (SMO) Overview • SMO is a one form of osteopetrosis and is sometimes referred to as marble bone disease or malignant infantile osteopetrosis (MIOP) • Often misdiagnosed as hematologic cancer • ~1 in every 250,000 babies are born with SMO • There are estimated to be ~200 SMO patients in the U.S. 65 Non-Confidential Information – Horizon Pharma plc |
 Non-Confidential Information – Horizon Pharma plc 66 • Most severe form and diagnosis usually in first months of life • Clinical Presentation – Failure to thrive – Impaired vision or blindness – Hearing loss – Fractures, frontal bossing, macrocephaly, hydrocephalus, hypocalcaemia – Infections – Absence of the bone marrow cavity results in severe anemia and thrombocytopenia • If left untreated, generally lethal < 10 years old due to severe anaemia, bleeding or infections associated with bone marrow failure Severe Malignant Osteopetrosis (SMO) Severe Malignant Osteopetrosis (SMO) Clinical Presentation Clinical Presentation Sobacchi et al. Nature Rev Endocrinology. 2013 (9) 522-36 |
 67 ACTIMMUNE Clinical Benefit in SMO ACTIMMUNE Clinical Benefit in SMO • Median time to disease progression was significantly delayed in the ACTIMMUNE plus calcitriol arm (165 days) vs. calcitriol alone (65 days) • When combined with data from a second study, 19 of 24 patients on ACTIMMUNE therapy (+/- calcitriol) for at least 6 months had reduced trabecular bone volume compared to baseline Delays the time to disease progression (1) in patients with SMO (1) Disease progression is defined by death, significant reduction in hemoglobin or platelet counts, a serious bacterial infection requiring antibiotics, a 50 dB decrease in hearing, or progressive optic atrophy. Non-Confidential Information – Horizon Pharma plc (1) |
 Non-Confidential Information – Horizon Pharma plc Weekly CGD/SMO SP Vials Dispensed up 73% Weekly CGD/SMO SP Vials Dispensed up 73% Likely impacted by lack of patient support programs and promotion +73% Jun-12: Vidara acquires ACTIMMUNE ® Sep-12: COMPASS HUB launched Apr-13: Launched patient ed. brochure & HCP detailer Jan-13: New brand launched with COMPASS brochure Jan-14: Launched new ACTIMMUNE.com website Note: 8-week moving average CGD/SMO vials dispensed per SP data. Excludes OptumRx, CignaTel Drug, Aetna SP and FEP. ~200+ new CGD patients have initiated ACTIMMUNE therapy since July 2012 68 |
 Non-Confidential Information – Horizon Pharma plc Our Commercial Effort is Focused Solely on CGD Our Commercial Effort is Focused Solely on CGD and SMO Patients and SMO Patients 69 CGD / SMO Other ICD-9 CGD / SMO Other ICD-9 % of ACTIMMUNE® Specialty Pharmacy Vials Dispensed 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 55% 60% 65% 70% Note: 8-week moving average vials dispensed per specialty pharmacy data. Excludes OptumRx, CignaTel Drug, Aetna SP and FEP. |
 Non-Confidential Information – Horizon Pharma plc ACTIMMUNE CGD/SMO Patient Increase of 74% ACTIMMUNE CGD/SMO Patient Increase of 74% Note: Active Patient defined as a patient that has shipped in the last 120 days. Grossed up by 10% to account for restricted data from OptumRx, CignaTel, Aetna SP and FEP patients. 70 0 25 50 75 100 125 150 175 200 225 250 275 300 Active CGD/SMO Specialty Pharmacy Patients 155 CGD/SMO Pts 270 CGD/SMO Pts |
 Non-Confidential Information – Horizon Pharma plc 71 ACTIMMUNE COMPASS Program ACTIMMUNE COMPASS Program COMPASS Advocacy & Support Services) *SP= Specialty Pharmacy, **SD= Specialty Distributor, † For FDA approved indications • Benefits Investigation • Prior Authorization Support † • Appeals Support † • Co-Pay Assistance (Private Insurance) • Patient Assistance Program (Uninsured) • Foundation Referral (Public Insurance) • StarterRX (Private insurance) • BridgeRX (Private insurance) • Sharps Container Program/Syringe Disposal – Improved Patient Safety – Environmentally-friendly • Clinical Support Program – Improve persistency – Improve compliance SP* SP* SD** SD** Patient Support Patient Support (Comprehensive Personalized Patient Prescription |
 FA Population Overview: ~3,700 in the U.S. U.S. Population X % Caucasian* X Diagnosed FA prevalence in Caucasians = Diagnosed FA prevalence in Caucasians ~320M X 78% X ~1.5/100,000 = ~3,700 72 Total estimated diagnosed FA prevalence is ~3,700 in the U.S. Methodology Non-Confidential Information – Horizon Pharma plc |
 85% of Diagnosed Patients are Early Onset Patients 73 Source: FARA, L.E.K. interviews and analysis • The vast majority (~85%) of diagnosed patients are early onset patients (i.e., exhibit symptoms before age 25) and are typically diagnosed by age 12 Age of FA onset and current age among diagnosed prevalent FA patients (2014) Adult ( 25 years) Percent of Patients) Adolescent (12-17 years) Non-Confidential Information – Horizon Pharma plc 0 10 20 30 40 50 60 70 80 90 100 Late onset (>25 years) Early onset Age of onset Current age of patient (N=8) ( 25 years) Pre-adolescent (12-17 years) ) |
 Non-Confidential Information – Horizon Pharma plc Neurological Examinations and Genetic Testing Lead to Specialized Care Centers 74 • Patients are typically referred by their primary provider to neurologists (including pediatric neurologists) for evaluation and diagnosis of FA • FA is typically suspected after a neurological exam, though genetic testing of frataxin is needed for definitive diagnosis • KOLs estimate two thirds of FA patients will eventually receive care at a center that specializes in muscular dystrophies, FA or general ataxias Source: L.E.K. interviews and analysis FA patient journey Pediatrician / PCP Neurological (including pediatric neurologist) FA or ataxia center neurologist MDA clinic neurologist Pediatric Cardiologist Clinical geneticist Specialized care centers 33% of patients are managed by general neurologists only Return to primary neurologist 100% 20-40% 60-80% 33% Return for Regular care 33% FA or ataxia centers are the primary care center for ~50% of FA patients DIRECTIONAL based on small N |
 Significant Growth Opportunities for ACTIMMUNE • Significant expansion opportunity in CGD & SMO – CGD & SMO still under-diagnosed or misdiagnosed – Increasing focus on supporting patient and advocacy groups to help the CGD and SMO communities • We will continue to enhance the COMPASS program to serve patients – Scalable for new indications – Easily adapted for new orphan products 75 Non-Confidential Information – Horizon Pharma plc |
 76 Horizon Pharma plc Business Development Strategy Robert F. Carey Executive Vice President, Chief Business Officer Non-Confidential Information – Horizon Pharma plc |
 77 Business Development Strategy April 2010 Nitec Pharma acquisition November 2013 Acquired from AstraZeneca September 2014 Vidara Therapeutics acquisition Established track record of deal execution Non-Confidential Information – Horizon Pharma plc |
 (1) AstraZeneca Annual Reports (1) (1) Rapidly Successful VIMOVO Acquisition Perfect example of value arbitrage we intend to capture through our BD strategy Net Sales Product Highlights • Acquired November 18, 2013 from AstraZeneca • $35 million one-time payment • Leverages existing commercial infrastructure • Rapid growth in VIMOVO prescriptions and revenues • Maximizing value through price and lower patient co-pay • $76.4 million in 1H 2014 revenues 78 Non-Confidential Information – Horizon Pharma plc $25.0 $20.0 $34.0 $42.4 $- $5.0 $10.0 $15.0 $20.0 $25.0 $30.0 $35.0 $40.0 $45.0 2012 2013 1Q:14 2Q:14 |
 Plan to Execute Aggressive Acquisition Strategy • Executing on our aggressive business development strategy via product/company acquisitions to maximize shareholder value creation 79 Potential for attractive financial returns – rapid accretion, long-life assets Non-Confidential Information – Horizon Pharma plc Near term focus on U.S. marketed products/ companies to leverage core strengths Pursuing products with differentiated clinical benefits Differentiated and/or under appreciated assets regardless of therapeutic area Targeting products with potential annual revenues of $20 million to $200 million - - |
 80 Q&A Non-Confidential Information – Horizon Pharma plc |
 Non-Confidential Information – Horizon Pharma plc 81 Appendix Appendix |
 Non-Confidential Information – Horizon Pharma plc 2011 2012 2013 2014 2013 2014 2013 Adjusted Non-GAAP Net Income (Loss): GAAP Net Loss (113,265) $ (87,794) $ (149,005) $ (27,769) $ (18,441) $ (234,019) $ (40,612) $ Non-GAAP Adjustments: Change in estimate of VIMOVO royalties - - - 13,033 - 13,033 - Loss on derivative revaluation - - 69,300 10,965 - 214,995 - Vidara acquisition costs - - - 10,125 - 14,174 - Intangible impairment charge 69,621 - - - - - - Amortization and accretion: Intangible amortization expense (net of tax effect) 3,012 3,782 6,790 4,683 1,311 9,363 2,635 Amortization of debt discount and deferred financing costs 2,708 2,740 17,245 2,333 919 4,666 1,829 Accretion of royalty liability - - - 2,953 - 2,953 - Amortization of deferred revenue (166) (217) (930) (161) (147) (322) (215) Stock-based compensation 2,530 4,661 5,014 4,160 1,021 6,087 2,100 Depreciation expense 446 806 1,174 404 299 780 558 Total of non-GAAP adjustments 78,151 11,772 98,593 48,495 3,403 265,729 6,907 Adjusted Non-GAAP Net Income (Loss) (35,114) $ (76,022) $ (50,412) $ 20,726 $ (15,038) $ 31,710 $ (33,705) $ Weighted average shares - basic 9,014,968 38,871,422 63,657,924 73,384,801 62,872,173 70,164,267 62,339,285 Weighted average shares - diluted 9,014,968 38,871,422 63,657,924 98,073,812 62,872,173 93,119,769 62,339,285 Adjusted Non-GAAP net income (loss) per common share-basic 0.28 $ 0.28 $ 0.28 $ 0.28 $ (0.24) $ 0.45 $ (0.54) $ Adjusted Non-GAAP net income (loss) per common share-diluted 0.21 $ 0.21 $ 0.21 $ 0.21 $ (0.24) $ 0.34 $ (0.54) $ (Unaudited) (Unaudited) Three Months Ended June 30, Six Months Ended June 30, Fiscal Year Ended December 31, GAAP to Non-GAAP Reconciliation GAAP to Non-GAAP Reconciliation 82 |
 Non-Confidential Information – Horizon Pharma plc GAAP to Non-GAAP Reconciliation (continued) GAAP to Non-GAAP Reconciliation (continued) 83 2011 2012 2013 2014 2013 2014 2013 EBITDA and Adjusted EBITDA: GAAP Net Loss (113,265) $ (87,794) $ (149,005) $ (27,769) $ (18,441) $ (234,019) $ (40,612) $ Depreciation 446 806 1,174 404 299 780 558 Amortization and accretion: Intangible amortization expense 3,753 4,732 8,136 5,029 1,634 10,056 3,297 Accretion of royalty liability - - - 2,953 - 2,953 - Amortization of deferred revenue (166) (217) (930) (161) (147) (322) (215) Interest expense, net (including amortization of debt discount and deferred financing costs) 6,284 14,525 39,178 4,207 3,442 8,414 7,045 Expense (benefit) for income taxes (14,683) (5,171) (1,121) 880 (351) (225) (1,232) EBITDA (117,631) $ (73,119) $ (102,568) $ (14,457) $ (13,564) $ (212,363) $ (31,159) $ Non-GAAP adjustments: Change in estimate of VIMOVO reyalties - - - 13,033 - 13,033 - Intangible impairment charge 69,621 - - - - - - Loss on derivative revaluation - - 69,300 10,965 - 214,995 - Vidara acquisition costs - - 1,252 10,125 - 14,174 - Stock-based compensation 2,530 4,661 5,014 4,160 1,021 6,087 2,100 Total of Non-GAAP adjustments 72,151 $ 4,661 $ 75,566 $ 38,283 $ 1,021 $ 248,289 $ 2,100 $ Adjusted EBITDA (45,480) $ (68,458) $ (27,002) $ 23,826 $ (12,543) $ 35,926 $ (29,059) $ (Unaudited) (Unaudited) Three Months Ended June 30, Six Months Ended June 30, Fiscal Year Ended December 31, |
 Horizon Pharma plc October 13, 2014 Friedreich's Ataxia Analyst Day Presentation Non-Confidential Information – Horizon Pharma plc |