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ACTELION LTD DELIVERING ON OUR STRATEGY Company Presentation February 2016 Copyright © 2016 Actelion Pharmaceuticals Ltd The following information contains certain “forward-looking statements”, relating to the company’s business, which can be identified by the use of forward-looking terminology such as “estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “will continue”, “should”, “would be”, “seeks”, “pending” or “anticipates” or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company’s investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company’s existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. 2 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TABLE OF CONTENTS Actelion at a Glance Actelion Today Strategy for Value Creation Sustain & Grow the PAH Franchise Build Additional Specialty Franchises Optimize Profitability Management & Board 3 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION AT A GLANCE 4 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION PHARMACEUTICALS LTD ACTELION IS A FULLY INTEGRATED BIOPHARMACEUTICAL COMPANY WITH INNOVATION AT ITS CORE Leader in the science and medicine of pulmonary arterial hypertension (PAH) Actelion Center, Allschwil FOUNDED IN 1997 IN ALLSCHWIL, SWITZERLAND Total employees (December ‘15) • Drug Discovery • Clinical Development • Marketing & Sales • Support Functions 2,547 371 422 1,425 329 Global reach with more than 30 affiliates worldwide 7 Products on the Market: Opsumit®, Tracleer®, Uptravi®, Veletri®, Ventavis®, Valchlor®, Zavesca® 2015 Sales: CHF 2.042 Billion Core earnings: CHF 814 million Over 65‘000 Patients currently treated with an Actelion medication Extensive Research & Development portfolio 5 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STAGES OF COMPANY DEVELOPMENT 2020 2014 2007 2001 1997 Build pipeline and commercial Company formed, infrastructure development & approval of Tracleer 6 © 2016 Actelion Pharmaceuticals Ltd February 2016 Commercial leverage and prepare for Tracleer LOE Company presentation Opsumit, Uptravi and development of new franchises PAH, Life Cycle Management and New Franchises ACTELION TODAY 7 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation 2 Fully integrated and global 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets 8 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation 2 Fully integrated and global ► Searching only for innovative products ► In-house research infrastructure from discovery to clinical development ► With a broad pipeline of interesting projects on novel targets 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets 9 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION TODAY FULLY INTEGRATED AND GLOBAL A UNIQUE COMPANY From Research to Commercialization More than 30 operative affiliates worldwide Product availability in >60 markets 1 Based on innovation 2 Fully integrated and global 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets Commercial Operations R&D Centers 10 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION TODAY A UNIQUE COMPANY CORE EARNINGS 1 Based on innovation 2 Fully integrated and global 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets 11 © 2016 Actelion Pharmaceuticals Ltd February 2016 900 800 700 600 500 400 300 200 100 0 Company presentation 2009 2010 2011 2012 2013 2014 2015 ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation ► Swiss company 2 Fully integrated and global ► One discovery center in Switzerland 3 Highly profitable ► Full global development capabilities ► Fully established infrastructure from process to buildings ► Focus on quality 4 Comprehensive infrastructure 5 Unencumbered assets 12 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation 2 Fully integrated and global ► Full rights to all products* ► Strong balance sheet and financing capacity ► No major alliances for own products 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets *Cooperation with Nippon Shinyaku in Japan for macitentan and selexipag 13 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 14 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRATEGIC PRINCIPLES FOUR GOALS FOR ACTELION Drive innovation forward Maximize the value of innovation Pursue top quality science, internally and externally, balanced with medical need and commercial potential Leverage our global presence Insist on the highest quality in all we do Expand innovative commercial capabilities to new customers and regions. Manage alliances putting the product first 15 © 2016 Actelion Pharmaceuticals Ltd February 2016 Develop projects ourselves and seek partners or out-license when necessary to maximize value Quality is crucial and needs to be ingrained across all functions Company presentation 2015 STRONG PERFORMANCE CONTINUES Operational Highlights – Strong, sustained Opsumit® launch trajectory across markets – Uptravi – Approved and launched in the US, EU filing resulted in positive CHMP opinion – Pipeline – Advancing late-stage assets – Pipeline – Significant progress in discovery and earlystage development 16 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation 2015 KEY FINANCIAL HIGHLIGHTS Core EPS PRODUCT SALES CHF 6.16 >CHF 2 BILLION CASH RETURNED TO SHAREHOLDERS CORE EARNINGS >CHF 800 MILLION 17 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ALMOST CHF 1 BILLION STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 18 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PULMONARY ARTERIAL HYPERTENSION A LIFE-THREATENING AND OFTEN MISUNDERSTOOD CONDITION Disease of the blood vessels carrying blood from the heart to the lungs - the pulmonary arteries When PAH develops, blood circulating through these vessels becomes restricted, and the right side of the heart is put under increasing strain to pump blood through the lungs Normal artery 19 © 2016 Actelion Pharmaceuticals Ltd Artery showing vasoconstriction February 2016 Company presentation Diseased artery showing tissue thickening and fibrosis CLINICAL SEVERITY OF PAH CLASSIFIED BY WORLD HEALTH ORGANIZATION (WHO) This system grades PAH severity according to the functional status of the patient FUNCTIONAL CLASS SYMPTOMATIC PROFILE I Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause dyspnoea or fatigue, chest pain, or near syncope. II Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope. III Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnoea or fatigue, chest pain, or near syncope. IV Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. 20 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TREATMENT PATHWAYS IN PAH ENDOTHELIN RECEPTOR ANTAGONISTS (ERA) PHOSPHODIESTERASE-5INHIBITORS (PDE-5i) PROSTACYCLIN RECEPTOR AGONISTS IP RECEPTOR AGONIST 21 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PGI2 ANALOGUES SIGNIFICANT PROGRESS IN THE FIELD OF PAH PAH targeted therapies Multiple approved 1st 1st PGI2 1990 INCREASING DISEASE AWARENESS PRECLINICAL/ CLINICAL RESEARCH 22 Oral PDE-5i 2000 IMPROVEMENT IN SYMPTOMS, MEASURED BY 6MWD ERA: PDE-5i: PGI2: Oral ERA 1st NATIONAL NETWORKS endothelin receptor antagonist phosphodiesterase-5 inhibitor prostacyclin © 2016 Actelion Pharmaceuticals Ltd February 2016 2010 DISEASE WORSENING, MEASURED BY TIME TO CLINICAL WORSENING REFERENCE CENTERS PATIENT ASSOCIATIONS DISEASE REGISTRIES therapies in 2010 CONTROLLED CLINICAL TRIALS EVIDENCE-BASED GUIDELINES PROCEEDINGS FROM 3RD WORLD CONGRESS 2003 ESC 2004 GUIDELINES Company presentation DISEASE PROGRESSION OVER YEARS, MEASURED BY MORBIDITY/MORTALITY SCREENING HIGH-RISK GROUPS PROCEEDINGS FROM 4TH WORLD CONGRESS 2008 ESC/ERS 2009 GUIDELINES ORAL THERAPIES IN PAH RANDOMIZED CONTROLLED TRIALS Drug Study Duration Primary endpoint No. of patients Study-3511,2 12 weeks 6-MWD 32 BREATHE-13 16 weeks 6-MWD 213 EARLY4 24 weeks PVR, 6-MWD 185 Sildenafil SUPER-15 12 weeks 6-MWD 277 Tadalafil PHIRST6 16 weeks 6-MWD 405 ARIES-17,8 12 weeks 6-MWD 202 ARIES-27,9 12 weeks 6-MWD 192 AMBITION10 78.6 weeks Clinical failure 610 Macitentan SERAPHIN11 103.9 weeks Morbidity/Mortality 742 Selexipag GRIPHON12 76.4 weeks Morbidity/Mortality 1,156 Bosentan Ambrisentan Short-term fixed treatment period trial design 1. Channick RN, et al. Lancet 2001. 2. Badesch D, et al. Curr Ther Res 2002. 3. Rubin LJ, et al. N Engl J Med 2002. 4. Galiè N, et al. Lancet 2008. 5. Galiè N, et al. N Engl J Med 2005. 6. Galiè N, et al. Circulation 2009. 7. Galiè N, et al. Circulation 2008. 8. Oudiz R, et al. Chest 2006. 9. Oudiz RJ, et al. J Am Coll Cardiol 2009. 10. Galiè N, et al. Eur Respir J 2014. 11. Pulido, et al. N Engl J Med 2013. 12. Sitbon O et al. N Engl J Med 2015. 23 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation EVOLUTION OF THE TREATMENT GUIDELINES FROM RANDOMISED CONTROLLED TRIALS TO EVIDENCE-BASED GUIDELINES A wealth of data concerning PAH management has emerged in recent years – Not only from RCTs, but also clinical practice, including disease registries – This has led to published management guidelines1, updated recommendations2, and approval of multiple therapies 1. Galiè N, et al. Eur Heart J 2009. 2. Galiè N, et al. J Am Coll Cardiol 2013. 24 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TRACLEER: OUR FIRST SUCCESS 25 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TRACLEER®: FIRST ORAL PRODUCT IN PAH THE FIRST DECADE OF SHAPING PAH TREATMENT Tracleer (bosentan) is an orally available endothelin receptor antagonist (ERA) approved for the treatment of PAH in over 60 countries, including the United States in November 2001, the European Union in May 2002 and Japan in April 2005 26 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TRANSITION TO OPSUMIT – RESILIENCE vs. GENERICS CHF million - 6% in Units -11% at CER(1) ~ 7,000 DU patients (+9%) 1,418 1,212 ~ 39,000 PAH patients (-9%) FY 2014 (1) Excluding 27 FY 2015 impact of prior-year US rebate reversals © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION’S PAH PORTFOLIO 28 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION’S PAH FRANCHISE 29 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TRANSFORMING OUR PAH PORTFOLIO MOVING TO OUTCOME-BASED THERAPY 30 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation UNIQUELY POSITIONED TO BUILD & SERVE PAH COVERING CONTINUUM OF CARE WITH OUTCOME-BASED MEDICINES FC II FC III +/- PDE-5 inhibitor 31 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FC IV ENGINE OF TRANSFORMATION 32 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OPSUMIT® ENGINE OF TRANSFORMATION Opsumit (macitentan) is an orally available endothelin receptor antagonist (ERA) approved for the treatment of PAH in over 35 countries, including the United States in October 2013, the European Union in December 2013 and Japan in March 2015 33 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OPSUMIT: A LANDMARK IN PAH The effect of macitentan to reduce combined morbidity/mortality events 34 – a multi-center, event driven long-term, placebo controlled study – average duration of exposure approximately 2 years, – in 742 patients – with symptomatic PAH – WHO functional class (FC) II-III – who were randomized to placebo (n=250), 3mg macitentan (n=250), or 10mg macitentan (n=242) once daily – Patients were treated with Opsumit® monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRONG LAUNCH DYNAMICS SUSTAINED Strong launch trajectory sustained CHF million across markets 2015: CHF 516 million 147 95 59 162 113 68 38 Q2 2014 35 Q3 2014 Q4 2014 Q1 2015 © 2016 Actelion Pharmaceuticals Ltd Q2 2015 Q3 2015 February 2016 Q4 2015 Company presentation Commercially available in over 35 countries OPENING THE PROSTACYCLIN PATHWAY TO MANY MORE PATIENTS 36 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OPENING THE PROSTACYCLIN PATHWAY TO MANY MORE PATIENTS US: FDA APPROVAL 21 DEC 2015 US: LAUNCH 04 JAN 2016 EU: CHMP POSITIVE OPINION 29 JAN 2016 Uptravi® (selexipag) is an orally available, selective IP prostacyclin receptor agonist, targeting and activating the prostacyclin pathway. 37 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation GRIPHON STUDY PUBLISHED 24 DECEMBER 2015 38 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation KEY US PRESCRIBING INFORMATION UPTRAVI is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH Source: US Prescribing Information, December 2015 39 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Adverse reactions occurring more frequently (>5%) on UPTRAVI compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing LAUNCH PRIORITIES Prostacyclin Market Development LAUNCH 3 Expand prescriber base 3 Establish as prostacyclin of 1st choice 2 2 Expand prostacyclin therapy patients base 2 2 Expand prostacyclin prescriber base 11st Establish as prostacyclin therapy of 1st choice 40 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation 11st Expand prostacyclin therapy patient base I.V. THERAPY MADE A LITTLE EASIER 41 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation VELETRI® I.V. THERAPY MADE A LITTLE EASIER Veletri (Epoprostenol for Injection) is intravenous prostacyclin. Unlike other epoprostenol formulations approved for PAH, Veletri is stable at room temperature (77 F, 25 C) for up to 48 hours when administered immediately upon reconstitution and dilution, making the use of frozen gel packs unnecessary. Approved in 15 countries including the United States since 2010 and some European markets since 2013 42 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CONTINUED SIGNIFICANT GROWTH +37% CER Growth(1) Available in 15 markets CHF million > 1,900 patients on drug Dec 2015 (> 50% from US) Growth momentum due to: 83 – Launch in France – > 80% new i.v. Epo patient share in US and EU 62 – Japan performance FY 2014 (1) Excluding 43 FY 2015 impact of prior-year US rebate reversals © 2016 Actelion Pharmaceuticals Ltd February 2016 *Trade name Epoprostenol “ACT” Company presentation SUSTAINING OUR BUSINESS MARKETED BY ACTELION IN THE US ONLY 44 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation VENTAVIS® Ventavis (inhaled iloprost) is an inhaled formulation of iloprost, a synthetic compound that is structurally similar to prostacyclin (PGI2), a naturally occurring molecule that causes blood vessels to dilate, limits cellular hypertrophy, and inhibits platelet aggregation. MARKETED BY ACTELION IN THE US ONLY 45 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation WELL MANAGED PERFORMANCE -7% CER Variance(1) CHF million 20% decline in units shipped due to competitive pressure Volume decline expected to accelerate due to competitive situation (1) Excluding 46 106 105 FY 2014 FY 2015 impact of prior-year US rebate reversals © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation EXPANDING THE CLINICAL UTILITY OF MACITENTAN MACITENTAN 47 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OBJECTIVES OF MACITENTAN CLINICAL PROGRAM Better characterize macitentan in specific PAH patient population Extend use beyond PAH in other forms of Pulmonary Hypertension Develop for diseases beyond PH 48 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CLINICAL CLASSIFICATION OF PULMONARY HYPERTENSION (PH) – 2015 1. PAH 1.1 Idiopathic PAH (iPAH) 1.2 Heritable PAH 1.3 Drugs and toxin induced 1.4 Associated with (APAH): 1.4.1 Connective tissue disease 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 CHD 1.4.5 Schistosomiasis 1.4.6 Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 1’. Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis 1”. Persistent PH of the newborn (PPHN) Galiè et al. Eur Heart J 2015 © 2016 Actelion Pharmaceuticals Ltd February 2016 2. PH due to left heart disease 3. PH due to lung disease and/or hypoxemia 4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions 5. PH with unclear and/or multifactorial mechanisms 5.1 Hematological disorders 5.2 Systemic disorders 5.3 Metabolic disorders 5.4 Other EXPANDING THE CLINICAL UTILITY OF OPSUMIT MANAGING THE LIFE CYCLE OPUS (US observational, drug registry of Opsumit new users in clinical practice) SYMPHONY (psychometric validation of QoL questionnaire – USA) ORCHESTRA (psychometric validation of QoL questionnaire – FR, IT, ES) MAESTRO (Eisenmenger Syndrome) MERIT (CTEPH - Chronic Thromboembolic Pulmonary Hypertension) MELODY (CpcPH-LVD - Combined Pre- and Post-capillary Pulmonary Hypertension due to Left Ventricular Dysfunction) SOPRANO (PH after left ventricular assist device implantation) 50 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation EXTEND USE IN PULMONARY HYPERTENSION CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (MERIT STUDY) Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by old blood clots in the lungs (pulmonary embolism) Goal is assessment of efficacy and safety of macitentan in CTEPH Results should be available later this year. 51 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation EXTEND USE IN PULMONARY HYPERTENSION COMBINED PRE- AND POST-CAPILLARY PULMONARY HYPERTENSION DUE TO LEFT VENTRICULAR DYSFUNCTION (CpcPH) CpcPH is pulmonary hypertension secondary to left ventricular dysfunction based on the difference between the diastolic pulmonary artery pressure (dPAP) and the pulmonary artery wedge pressure (PAWP), or diastolic pulmonary vascular pressure gradient (DPG). Phase II “MELODY” study complete Goal is assessment of efficacy and safety of macitentan in CpcPH 52 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 53 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE MARKETED BY ACTELION IN THE US ONLY 54 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation VALCHLOR® Valchlor (mechlorethamine) gel 0.016% is applied topically once-a-day and dries on the skin. Valchlor is the only US FDA approved topical formulation of mechlorethamine, a chemotherapeutic agent for the treatment of early stage mycosis fungoides, a type of Cutaneous T-Cell Lymphoma. Launched in the US in November 2013 55 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation MYCOSIS FUNGOIDES EXPANDING OUR SPECIALTY BUSINESS Mycosis fungoides is the most common type of Cutaneous T-Cell Lymphoma (CTCL), a rare form of non-Hodgkin's lymphoma The cause of mycosis fungoides remains unknown and there is no known cure Unlike most non-Hodgkin's lymphomas, mycosis fungoides is caused by a mutation of T-cells. The malignant T-cells in the body initially migrate to the skin, causing various lesions to appear These lesions typically begin as what appears to be a rash and may progress to form plaques and disfiguring tumors 56 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CONSISTENT PROGRESS CHF million Sales of CHF 27 million Focused strategy to shape the space for Valchlor in patients with lower disease burden 7.4 3.5 4.1 7.1 8.0 underway* - approval anticipated by Q1 2017 4.6 Q3 2014 Q4 2014 Q1 2015 Q2 2015 Q3 2015 Q4 2015 57 © 2016 Actelion Pharmaceuticals Ltd February 2016 Registration process with the EMA Company presentation *Trade name Ledaga® BUILD ADDITIONAL SPECIALTY FRANCHISE 58 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ZAVESCA® Miglustat, the active ingredient of Zavesca, is an orally available molecule with a large volume of distribution Zavesca is approved for the treatment of Niemann-Pick type C disease in 45 countries, including the European Union since 2009 and Japan since 2012. Zavesca is approved for the treatment of mild to moderate type 1 Gaucher disease in 47 countries, including the US and the European Union since 2003 59 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation NIEMANN-PICK TYPE C DISEASE (NP-C) A RARE AND DIFFICULT TO DIAGNOSE GENETIC LYSOSOMAL STORAGE DISORDER Devastating neurological genetic disorder which is ultimately fatal Onset from early childhood until adult age Pathophysiology – Abnormal intracellular lipid transport – Cytotoxic accumulation of glycosphingolipids in neurons Symptoms become progressively more severe and include: 60 – Severe disabilities in swallowing, ambulation, eye movements, language, cognition, muscle control – Lipid accumulation can also lead to an enlarged liver and/or spleen. © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation TYPE 1 GAUCHER DISEASE (GD1) A RARE GLYCOSPHINGOLIPID DISORDER An inherited metabolic lysosomal storage disorder Characterized by an accumulation of lycosphingolipids The accumulation leads to multiple clinical manifestations: – an enlarged spleen and liver – anemia and a low platelet count – bone pain and bone deterioration Symptoms can appear at any age 61 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CONTINUED GROWTH IN NP-C Increasing generic competition for type 1 Gaucher disease CHF million -3% CER Variance(1) Underlying volume remained flat due to strong growth in NP-C patients outside of US Positive price in US but generic 102 driven erosion in some EU markets (i.e. ES) 92 Potential miglustat generic entry in US during H2 2016 FY 2014 (1) Excluding 62 FY 2015 impact of prior-year US rebate reversals © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE CADAZOLID CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA 63 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation International, Multi-center Program Assessing Cadazolid Treatment in patients suffering from Clostridium difficile-associated diarrhea (CDAD) mpact 64 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CADAZOLID: OUR NOVEL ANTIBIOTIC Investigated for the treatment of Clostridium difficile-associated diarrhea (CDAD) Clostridium difficile is a spore-forming bacteria that is best known for causing antibiotic-associated diarrhea Cadazolid: – Strong inhibitor of Clostridium difficile protein synthesis leading to strong suppression of both toxin and spore formation – Narrow spectrum – very limited effect on normal gut microflora – potential for selective treatment for Clostridium difficile in the gut = less recurrence – In vitro tests demonstrate low propensity for resistance development – Early results indicate it may be safe and well tolerated with negligible absorption – US FDA designated cadazolid as both a Qualified Infectious Disease Product (QIDP) and a Fast Track development program Cadazolid is investigational, in development and not approved or marketed in any country. 65 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CADAZOLID SHOWS MINIMAL EFFECTS ON THE GUT MICROFLORA QRT-PCR QUANTIFICATION OF BACTERIAL NUMBERS IN STOOL SAMPLES FROM PHASE II (T. LOUIE) C. leptum C. difficile 10.0 Bifidobacterium 10.0 * * 8.0 * 8.0 8.0 6.0 * 6.0 6.0 Prevotella Bacteroidetes 4.0 4.0 4.0 10.0 10.0 2.0 2.0 8.0 0.0 6.0 CFU/g stool 10.0 * 2.0 8.0 8.0 0.0 0.0 6.0 6.0 4.0 4.0 4.0 2.0 2.0 2.0 0.0 0.0 0.0 Cadazolid is an investigational drug in development and not approved or marketed in any country 66 Lactobacillus © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHASE II EFFICACY ENDPOINTS MODIFIED CURE RATE, RECURRENCE RATE, SUSTAINED CURE (MITT) 100.0 Cadazolid 250mg bid 94 86 Vancomycin 125mg qid 80.0 77 60.0 55 37 40.0 19 20.0 N= 17 22 16 19 17 22 0.0 Clinical Cure Recurrence Louie T. et al., Antimicrob Agents Chemother. 2015;59(10):6266-73 Cadazolid is an investigational drug in development and not approved or marketed in any country 67 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Sustained Cure CADAZOLID: PROGRESSING AS PLANNED PHASE III PROGRAM Two identical multi-center, randomized, double-blind studies designed to demonstrate: – Non-inferior clinical response with cadazolid compared to vancomycin – Superior sustained clinical response with cadazolid compared to vancomycin – Efficacy on hypervirulent strains Completion of enrollment is expected by the end of 2016 Cadazolid is investigational, in development and not approved or marketed in any country. 68 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE S1P1 RECEPTOR IMMUNOMODULATION 69 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PONESIMOD KEY PROPERTIES Profile suitable for once-daily oral dosing Selective S1P1 receptor modulator Prevents lymphocytes from leaving lymph nodes Lymphocyte reduction is rapid and dose- dependent Lymphocyte reduction is rapidly reversible upon discontinuation Potential in multiple immunological diseases 70 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRONG PHASE II DATA IN MULTIPLE SCLEROSIS PONESIMOD Ponesimod is investigational, in development and not approved or marketed in any country. 71 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHASE II DOSE FINDING STUDY IN MS STUDY DESIGN Randomization Placebo (n=121) 10 mg o.d. ponesimod (n=108) 20 mg o.d. ponesimod (n=116) Baseline 40 mg o.d. ponesimod (n=119) Treatment Screening Follow-up Follow-up 24 weeks Core Ponesimod is investigational, in development and not approved or marketed in any country. 72 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Extension PRIMARY ENDPOINT: CUMULATIVE NUMBER OF NEW T1 GD+ LESIONS FROM WEEK 12 TO WEEK 24 Cumulative new T1 Gd+ lesions from week 12 to week 24 (Mean ± SE) Per-protocol population 43% reduction * 77% reduction 83% reduction *** *p<0.05, ***p<0.0001 vs placebo Ponesimod is investigational, in development and not approved or marketed in any country. 73 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation *** SECONDARY ENDPOINT: ANNUALIZED RELAPSE RATE UP TO WEEK 24 All-treated population 0.9 Annualized relapse rate (+ 95% CI) 0.8 52% 0.7 0.6 p<0.05 0.5 0.4 0.3 0.2 0.1 0 • 0.525 0.332 0.417 0.251 Placebo Ponesimod 10 mg Ponesimod 20 mg Ponesimod 40 mg Annualized confirmed relapse rate estimated from negative binomial regression model Ponesimod is investigational, in development and not approved or marketed in any country. © 2016 Actelion Pharmaceuticals Ltd February 2016 Investor Webcast ADVERSE EVENTS OBSERVED IN ≥5% OF PATIENTS All-treated population n (%) Placebo (n=121) Ponesimod 10 mg (n=108) Ponesimod 20 mg (n=114) Ponesimod 40 mg (n=119) Patients with ≥1 AE 90 (74.4) 83 (76.9) 88 (77.2) 88 (73.9) 310 275 304 325 Headache 18 (14.9) 15 (13.9) 15 (13.2) 15 (12.6) Nasopharyngitis 17 (14.0) 16 (14.8) 11 (9.6) 13 (10.9) Upper RTI 11 (9.1) 4 (3.7) 9 (7.9) 11 (9.2) Diarrhoea 8 (6.6) 3 (2.8) 3 (2.6) 2 (1.7) Fatigue 7 (5.8) 7 (6.5) 9 (7.9) 6 (5.0) Arthralgia 7 (5.8) 2 (1.9) 1 (0.9) 1 (0.8) Back pain 6 (5.0) 2 (1.9) 5 (4.4) 6 (5.0) Nausea 6 (5.0) 2 (1.9) 3 (2.6) 4 (3.4) UTI 6 (5.0) 2 (1.9) 1 (0.9) 3 (2.5) Oral herpes 6 (5.0) 1 (0.9) – 2 (1.7) Sinusitis 5 (4.1) 4 (3.7) 5 (4.4) 6 (5.0) Dyspnoea 4 (3.3) 5 (4.6) 7 (6.1) 17 (14.3) Dizziness 3 (2.5) 8 (7.4) 7 (6.1) 11 (9.2) Peripheral oedema 2 (1.7) 2 (1.9) 3 (2.6) 13 (10.9) Cough 2 (1.7) 1 (0.9) 3 (2.6) 8 (6.7) Increased ALT 1 (0.8) 5 (4.6) 7 (6.1) 7 (5.9) Total number of AEs Ponesimod is investigational, in development and not approved or marketed in any country. AE, adverse event; ALT, alanine aminotransferase; RTI, respiratory tract infection; UTI, urinary tract infection 75 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OVERALL SAFETY SUMMARY No increase in the proportion of patients with infection-associated AEs (placebo 45.5%; ponesimod 10 mg, 37.0%; 20 mg, 32.5%; 40 mg, 36.1%) Two malignancies were reported: one case of breast cancer in the ponesimod 10 mg group and one case of cervix carcinoma in the placebo group The proportion of patients with respiratory AE was higher in the ponesimod than in the placebo group (placebo, 6.6%; ponesimod 10 mg, 9.3%; ponesimod 20 mg, 16.7%; ponesimod 40 mg, 31.9%) No cases of total bilirubin elevation ≥2× ULN and no cases of Hy’s law One case of macular edema confirmed by optical coherence tomography resolved after treatment discontinuation Ponesimod is investigational, in development and not approved or marketed in any country. 76 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation MAXIMUM EFFECT ON LYMPHOCYTES AT 20 MG Ponesimod is investigational, in development and not approved or marketed in any country. 77 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Week 24 Week 20 Week 16 Week 12 Week 8 Week 4 Day 13 Day 8 Mean change from baseline in lymphocyte count (%) All-treated set EFFECT ON LYMPHOCYTES IS RAPIDLY REVERSIBLE Ponesimod is investigational, in development and not approved or marketed in any country. 78 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FU2 FU 1 Week 24 / Week 20 Week 16 Week 12 Week 8 Week 4 Day 13 Day 8 Mean change from baseline in lymphocyte count (%) All-treated set – subset of patient with follow-up visit DOUBLE-BLIND EXTENSION OF THE PHASE II STUDY PONESIMOD Ponesimod is investigational, in development and not approved or marketed in any country. 79 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation DOUBLE-BLIND PHASE II EXTENSION STUDY DESIGN Randomization 10 mg ponesimod Placebo 20 mg ponesimod 40 mg ponesimod 10 mg ponesimod 20 mg ponesimod 40 mg ponesimod Treatment Treatment Period 1 24 weeks Up to 96 weeks Core Extension Ponesimod is investigational, in development and not approved or marketed in any country. 80 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation DOUBLE-BLIND PHASE II EXTENSION STUDY DESIGN End of Treatment Randomization Randomization 10 mg ponesimod Placebo 20 mg ponesimod 10 mg ponesimod 40 mg ponesimod 20 mg ponesimod 10 mg ponesimod 20 mg ponesimod 10 mg ponesimod 40 mg ponesimod 20 mg ponesimod Treatment Treatment Period 1 Treatment Period 2 24 weeks Up to 96 weeks Up to 432 weeks Core Extension Ponesimod is investigational, in development and not approved or marketed in any country. 81 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Followup EXTENSION STUDY: ARR REDUCTION OVER ~2 YEARS Annualized Relapse Rates (ARR) (Confirmed Relapses) Negative Binominal Regressions – All-Randomized Set ,0.60 Annualized Relapse Rate ,0.50 RR = 42.3% p=0.045 RR = 22.5% p=0.322 ,0.40 V 10mg V 10mg 40 mg (n=119) 20 mg (n=116) ,0.30 ,0.20 ,0.10 ,0.00 10 mg (n=108) Ponesimod is investigational, in development and not approved or marketed in any country. 82 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Pla/40 mg (n=32) Pla/20 mg (n=31) Pla/10 mg (n=31) EXTENSION STUDY: CURRENT STATUS Safety profile consistent with the safety profile from the core study Continuing in a blinded fashion with two dose groups – 10 and 20 mg More than 4 years of exposure – drop-out rate minimal Long-term data with 10 and 20mg will be very useful for registration and launch High value of the study due to length, blinded fashion, size, and safety and efficacy endpoints collected at regular intervals Ponesimod is investigational, in development and not approved or marketed in any country. 83 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation NEW TITRATION SCHEME PONESIMOD Ponesimod is investigational, in development and not approved or marketed in any country. 84 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHARMACODYNAMIC STUDY New titration schemes to mitigate first dose effect Simulation work based on PK and PD data used to determine optimal titration scheme Confirmed in a specific trial comparing new vs. previous titration scheme Results presented at the European Association for Clinical Pharmacology and Therapeutics (EACPT) Congress in June 2015 Ponesimod is investigational, in development and not approved or marketed in any country. 85 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHASE III OPTIMUM STUDY IN MULTIPLE SCLEROSIS PONESIMOD Ponesimod is investigational, in development and not approved or marketed in any country. 86 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STUDY OVERVIEW OPTIMUM: A Multicenter, randomized, double-blind, parallel-group, active-controlled, superiority study to compare the efficacy and safety of ponesimod to teriflunomide in subjects with relapsing multiple sclerosis Pivotal Phase III study – ∼ 200 centers in North America, Latin America, Eastern and Western Europe, Pacific (planned) – ∼ 1100 patients randomized in 2 groups in a 1:1 ratio to receive either ponesimod 20 mg or teriflunomide 14 mg – New titration scheme implemented – Recruitment should finish in 2016 Ponesimod is investigational, in development and not approved or marketed in any country. 87 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STUDY OBJECTIVES Primary objective – To determine whether ponesimod is more efficacious than teriflunomide in terms of reducing relapses in subjects with relapsing multiple sclerosis Secondary objectives – To assess the effect of ponesimod on disability progression and on other aspects of multiple sclerosis disease control; – To assess the safety and tolerability of ponesimod in subjects with relapsing multiple sclerosis Ponesimod is investigational, in development and not approved or marketed in any country. 88 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CHOICE OF ACTIVE CONTROL Ponesimod compared to Teriflunomide 14 mg – Oral comparator facilitates recruitment and blinding – Recently approved first-line therapy for relapsing multiple sclerosis – Superiority study possible given incomplete effect of teriflunomide on ARR – 14 mg but not 7 mg approved in EU and Australia Ponesimod is investigational, in development and not approved or marketed in any country. 89 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PONESIMOD DIFFERENTIATION MAXIMIZE OPPORTUNITY WITH PONESIMOD OPTIMUM study is enriched with additional endpoints aiming at further differentiation: – PRO, MRI endpoints, disease activity, prospectively included in protocol – Compliance enhancement and monitoring tool using electronic device Additional study in multiple sclerosis to further characterize: – Clinical utility – Differentiation – Discussed with Health Authorities Ponesimod is investigational, in development and not approved or marketed in any country. 90 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHASE II STUDY IN GRAFT VS. HOST DISEASE PONESIMOD Ponesimod is investigational, in development and not approved or marketed in any country. 91 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation WHY PONESIMOD IN GRAFT VS. HOST DISEASE? UNMET MEDICAL NEED & SCIENTIFIC RATIONALE Unmet need – Patients with chronic GvHD have a 30-50% mortality during first 5 years of diagnosis – Currently no approved therapies for chronic GvHD in US – Glucocorticoids (with calcineurin inhibitors) are considered standard treatment – Half of patients receiving initial therapy do not have a sustained response Scientific rationale – T and B cells play a key role in pathogenesis – S1P1 receptor modulators have shown efficacy in models of GvHD Ponesimod is investigational, in development and not approved or marketed in any country. 92 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PONESIMOD IN GRAFT VS. HOST DISEASE PHASE II DOSE-ESCALATION STUDY DESIGN Open-label, single-arm, intra-subject dose-escalation study to investigate the biological activity, safety, tolerability, & pharmacokinetics of ponesimod in subjects with symptomatic moderate or severe chronic graft vs. host disease inadequately responding to first or second line therapy The study will also investigate the clinical response to ponesimod treatment in these patients ∼ 30 subjects enrolled to receive escalating doses of 5, 10 and 20 mg over the course of 24 weeks ∼ 10 sites in US expected to last approximately 18 months Enrollment imminent Ponesimod is investigational, in development and not approved or marketed in any country. 93 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation PHASE II STUDY IN SYSTEMIC LUPUS ERYTHEMATOSUS CENERIMOD An investigational compound, in development and not approved or marketed in any country. 94 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation ACTELION’S SECOND S1P1 MODULATOR: CENERIMOD KEY PROPERTIES Very potent S1P1 receptor modulator with highly selective profile O Prevents lymphocytes from leaving lymph nodes N Lymphocyte reduction is rapid, dose-dependent and reversible N Pharmacokinetic profile suitable for once-daily oral dosing with no need for up-titration regimen O Potential in multiple autoimmune diseases HO Cenerimod is investigational, in development and not approved or marketed in any country. 95 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OH O N WHY S1P1 MODULATOR FOR SYSTEMIC LUPUS ERYTHEMATOSUS? UNMET MEDICAL NEED & SCIENTIFIC RATIONALE Unmet need: – Severe organ damage and significant mortality in subset of patients – Impaired physical and mental QoL – Therapy is largely empirical with use of corticosteroids and other immunosuppressants – Only one biologic with limited efficacy gained approval Scientific rationale for S1P1 receptor modulation in SLE: – T and B cells play a key role in pathogenesis – S1P1 receptor modulators have shown efficacy in different preclinical models of SLE: MRL/lpr and BXSB mice Cenerimod is investigational, in development and not approved or marketed in any country. 96 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CENERIMOD IN SYSTEMIC LUPUS ERYTHEMATOSUS PHASE II DOSE-ESCALATION STUDY DESIGN Prospective, multicenter, multinational, randomized, double-blind, placebo- controlled, dose-response study to investigate the biologic activity, pharmacokinetics, safety, & tolerability of cenerimod in adult subjects with systemic lupus erythematosus ∼ 64 subjects enrolled to receive either 0.5, 1, 2 or 4 mg over the course of 12 weeks ∼ 20 sites and expected to last approximately 20 months Cenerimod is investigational, in development and not approved or marketed in any country. 97 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE CLAZOSENTAN CEREBRAL VASOSPASM POSTANEURISMAL SUBARACHNOID HEMORRHAGE (aSAH) Clazosentan is investigational, in development and not approved or marketed in any country. 98 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CLAZOSENTAN FOR CEREBRAL VASOSPASM POSTANEURISMAL SUBARACHNOID HEMORRHAGE (aSAH) Highly soluble ETA selective ERA ideal for intravenous administration >1’500 patients treated with clazosentan providing significant experience in vasospasm post aSAH and a well documented safety profile CONSCIOUS-2 aneurysm secured by clipping Lancet Neurology 2011;10(7):618-625 CONSCIOUS-3 aneurysm secured by coiling Stroke. 2012 Jun;43(6):1463-9 Clazosentan is an investigational drug in development and not approved or marketed in any country 99 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CONSCIOUS-3 STUDY - EVENT RATE FOR THE COMPONENTS OF THE 1o COMPOSITE ENDPOINT RRR (95% CI) 25 Clazosentan 5 mg/h Clazosentan 15 mg/h -21% (-97 to 26%) 15% (-28 to 44%) 29% (-9 to 54%) -34% (-211 to 42%) 44% (-5 to 70%) 54% (22 to 72%) 65% (38 to 80%) 21 20 Event rate (%) Placebo 35% (-79 to 76%) 21 18 16 15 15 13 10 10 5 5 6 7 7 3 0 Death (within 6 weeks) DIND = Delayed ischemic neurological deficits; Macdonald R et al. Stroke 2012. New cerebral infarct Vasospasm-related Clazosentan is an investigational drug in development and not approved or marketed in any country 100 © 2016 Actelion Pharmaceuticals Ltd February 2016 DIND Company presentation Rescue therapy ADAPTED STRATEGY: REVERSAL VS. PREVENTION Vasospasm reversal with clazosentan in humans Baseline Vasospasm 2 days of Tx Phase III study under discussion with HA’s Primary objective to determine whether clazosentan is an efficacious treatment of cerebral vasospasm Open question: How early is the effect of clazosentan on reversing vasospasm? REVERSE: Phase II study to evaluate whether clazosentan has an early effect in reversing angiographically-confirmed cerebral vasospasm in approximately 25 subjects Clazosentan is an investigational drug in development and not approved or marketed in any country 101 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation EXTENSIVE RESEARCH & DEVELOPMENT 102 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation A CHAIN OF EXPERTISE 371 PROFESSIONALS (DECEMBER 2015) Pharmacologists Toxicologists Cell Biologists Molecular Biologists DRUG DISCOVERY ORGANIZATION Biochemists Process Research Chemists © 2016 Actelion Pharmaceuticals Ltd Formulation Specialists Clinical Scientists Medicinal Chemists 103 Pharmacokineticists February 2016 Company presentation Structural Biologists ACTELION’S DRUG DISCOVERY STRATEGY All important research functionalities in-house (e.g. MedChem, AssayTech, DMPK, Pharmacology) Highly regulated service activities outsourced (e.g. Toxicology, Production, Formulation) 104 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation THE BASE FOR HIGH DISCOVERY EFFICIENCY CULTURE OF INNOVATION • • • • • • 105 Single-center approach Fully integrated research informatics Focus on small molecules Few platforms of expertise Multiple therapeutic areas High medical input © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation CLINICAL DEVELOPMENT ORGANIZATION 422 PROFESSIONALS (DECEMBER 2015) Clinical Science Life Cycle Management Clinical Pharmacology CLINICAL DEVELOPMENT Global Drug Safety Global Drug Regulatory Affairs 106 © 2016 Actelion Pharmaceuticals Ltd February 2016 Biometry Global Clinical Operations Strategic Clinical Development Company presentation EXTENDING THE CORE PAH FRANCHISE Phase I Phase II Macitentan OPUS Macitentan ORCHESTRA Macitentan SOPRANO Macitentan SYMPHONY Macitentan PORTICO Macitentan & Selexipag TRITON Selexipag GRIPHON Macitentan MAESTRO Macitentan MELODY Macitentan MERIT 107 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Phase III Phase IV DIVERSIFICATION Phase I Cadazolid Clostridium difficile assoc. diarrhea Ponesimod Multiple Sclerosis Clazosentan Reversal of vasospasm post-aSAH Ponesimod Graft vs. host disease Cenerimod Systemic lupus erythematosus Endothelin Receptor Antagonist Specialty cardiovascular disorders Lucerastat Fabry’s disease New Chemical Entity Neurological disorders New Chemical Entity Neurological disorders New Chemical Entity Cardiovascular disorders 108 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation Phase II Phase III OUR RICH DISCOVERY PIPELINE >15 promising projects advancing in Drug Discovery Focus towards specialty markets and rare diseases with high unmet medical need Current clinical pipeline to build solid portfolio for future revenue growth 109 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 110 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FINANCIAL OVERVIEW BY REPORTING PERIOD 111 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FY 2015 STRONG PERFORMANCE Variance FY 2015 CHF CER 1,956 2,042 4% 7% 11% 743 814 9% 14% 25% 5.58 6.16 10% 15% 26% 570 656 15% 21% - 5.11 4.91 -4% 1% - Product sales CHF million Core earnings CHF million Core diluted EPS CHF Operating income CHF million US GAAP diluted EPS CHF 112 © 2016 Actelion Pharmaceuticals Ltd CER FY 2014 February 2016 Company presentation Ex US rebate reversals CORE EARNINGS BY REPORTING PERIOD 113 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FY 2015 CORE EARNINGS – INTRINSIC GROWTH + 25% CHF million 32 168 66 814 743 FY '14 Core earnings as reported 114 US rebate reversals © 2016 Actelion Pharmaceuticals Ltd February 2016 677 677 FY'14 Core earnings excluding US rebate reversals FY '15 intrinsic growth Company presentation FX FY'15 Core earnings EARNINGS PER SHARE (EPS) BY REPORTING PERIOD 115 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation FY 2015 EARNINGS PER SHARE Variance FY 2014 FY 2015 CHF CER 648 693 7 11 Core Diluted EPS 5.58 6.16 Number of shares in calculation (m) 116.2 112.5 10 15 594 552 -7 -3 US GAAP Diluted EPS 5.11 4.91 Number of shares in calculation (m) 116.2 112.5 -4 1 Core Net income CHF million US GAAP Net income CHF million 116 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation SHAREHOLDER RETURNS 117 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation OUTSTANDING YEAR FOR SHAREHOLDERS SHARE PRICE PERFORMANCE CASH RETURNED TO SHAREHOLDERS 927 588 358 133 2012 2013 2016 – FURTHER RETURNS TO COME Second-line share repurchase continues Dividend: Board proposes increase to CHF 1.50 per share 118 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation 2014 2015 FINANCIAL GUIDANCE February 2016 119 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation 2016 FINANCIAL GUIDANCE Low single-digit percentage core operating income growth, at constant exchange rates and barring unforeseen events 120 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation MANAGEMENT & BOARD 121 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation THE RIGHT PEOPLE FOR THE NEXT GROWTH PHASE ACTELION MANAGEMENT TEAM Jean-Paul Clozel Founder, CEO Joined in 1997 Otto Schwarz COO Joined in 2008 Nicholas Franco Chief BD Officer Joined in 2011 Guy Braunstein Head of Global CD Joined in 2009 Martine Clozel Founder, CSO Joined in 1997 Christian Albrich Head of Global HR Joined in 2005 Rudi Frank Head of Global Quality Management Joined in 2000 Marian Borovsky General Counsel Joined in 2003 122 © 2016 Actelion Pharmaceuticals Ltd André Muller CFO Joined in 2013 February 2016 Company presentation Andrew Weiss Head of IR & CC Joined in 2014 THE RIGHT PEOPLE FOR THE NEXT GROWTH PHASE ACTELION BOARD OF DIRECTORS Jean-Pierre Garnier Chairman Joined in 2011 Juhani Anttila Joined in 2005 John J. Greisch Joined in 2013 Robert J. Bertolini Joined in 2011 Peter Gruss Joined in 2012 Jean Malo Joined in 2004 123 © 2016 Actelion Pharmaceuticals Ltd David Stout Joined in 2015 February 2016 Company presentation Jean-Paul Clozel Joined in 2000 Michael Jacobi Joined in 2009 Herna Verhagen Joined in 2015 THANK YOU FOR YOUR INTEREST IN ACTELION 124 © 2016 Actelion Pharmaceuticals Ltd February 2016 Company presentation
