Company presentation
ACTELION LTD DELIVERING ON OUR STRATEGY Company Presentation February 2015 Copyright © 2015 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ACTELION AT A GLANCE 4 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 (Dec 14) • Drug Discovery • Clinical Development • Marketing & Sales • Support Functions 2,470 371 611 1,066 422 Global reach with more than 30 affiliates worldwide 6 Products on the Market: Opsumit®, Tracleer®, Veletri®, Ventavis®, Zavesca®, Valchlor® 2014 Sales: CHF 1.95 Billion Core earnings: CHF 743 million Over 50‘000 Patients currently treated with an Actelion medication Extensive Research & Development portfolio 5 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STAGES OF COMPANY DEVELOPMENT 2020 2014 2007 1997 2001 Build pipeline and commercial Company formed, infrastructure development & approval of Tracleer 6 © 2015 Actelion Pharmaceuticals Ltd February 2015 Commercial leverage and prepare for Tracleer LOE Company presentation Opsumit, selexipag and development of new franchises PAH, Life Cycle Management and New Franchises ACTELION TODAY 7 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation ► 2 Fully integrated and global ► 3 Highly profitable 4 Comprehensive infrastructure ► Searching only for innovative products In-house research infrastructure from discovery to clinical development With a broad pipeline of interesting projects on novel targets 5 Unencumbered assets 9 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation FULLY INTEGRATED AND GLOBAL From Research to Commercialization More than 30 operative affiliates worldwide Product availability in >55 markets 2 Fully integrated and global 3 Highly profitable 4 Comprehensive infrastructure 5 Unencumbered assets Commercial Operations R & D Centers 10 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ACTELION TODAY A UNIQUE COMPANY CORE EARNINGS 800 1 Based on innovation 700 2 Fully integrated and global 600 500 3 Highly profitable 400 4 Comprehensive infrastructure 200 300 5 Unencumbered assets 11 © 2015 Actelion Pharmaceuticals Ltd February 2015 100 0 Company presentation 2008 2009 2010 2011 2012 2013 2014 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 4 Comprehensive infrastructure ► 5 Unencumbered assets 12 © 2015 Actelion Pharmaceuticals Ltd February 2015 ► Fully established infrastructure from process to buildings Focus on quality Company presentation ACTELION TODAY A UNIQUE COMPANY 1 Based on innovation 2 Fully integrated and global 3 Highly profitable ► Full rights to all products* ► Strong balance sheet and financing capacity ► No major alliances for own products 4 Comprehensive infrastructure 5 Unencumbered assets *Cooperation with Nippon Shinyaku in Japan for macitentan and selexipag 13 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 14 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STRATEGIC PRINCIPLES FOUR GOALS FOR ACTELION Drive innovation forward Pursue top quality science, internally and externally, balanced with medical need and commercial potential Leverage our global presence Expand innovative commercial capabilities to new customers and regions. Manage alliances putting the product first 15 © 2015 Actelion Pharmaceuticals Ltd February 2015 Maximize the value of innovation Develop projects ourselves and seek partners or out-license when necessary to maximize value Insist on the highest quality in all we do Quality is crucial and needs to be ingrained across all functions Company presentation KEY HIGHLIGHTS OF 2014 ONCE AGAIN WE DELIVERED Strong operating performance leading to 25% core earnings growth at CER* Core earnings growth of 20% at CER - Excluding US rebate reversals Successful launch of Opsumit in 18 countries Opsumit filing in Japan in June Selexipag (Uptravi) positive morbidity/mortality Phase III Selexipag (Uptravi) filing in US and EU end of 2014 Tracleer – PIP Compliance Statement and Commission Decision issued in Europe *CER = constant exchange rates 16 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 17 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 18 © 2015 Actelion Pharmaceuticals Ltd Artery showing vasoconstriction February 2015 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. 19 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation TREATMENT PATHWAYS IN PAH ENDOTHELIN RECEPTOR ANTAGONISTS (ERA) 20 © 2015 Actelion Pharmaceuticals Ltd February 2015 PHOSPHODIESTERASE-5INHIBITORS (PDE-5i) Company presentation PROSTACYCLIN RECEPTOR AGONISTS SIGNIFICANT PROGRESS IN THE FIELD OF PAH PAH targeted therapies 1st 1st PGI2 1990 INCREASING DISEASE AWARENESS PRECLINICAL/ CLINICAL RESEARCH 21 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 PATIENT ASSOCIATIONS DISEASE REGISTRIES therapies in 2010 2010 DISEASE WORSENING, MEASURED BY TIME TO CLINICAL WORSENING REFERENCE CENTERS Multiple approved 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. Actelion press release, June 2014. 22 © 2015 Actelion Pharmaceuticals Ltd February 2015 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. 23 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation TRACLEER SUCCESS CONTINUES 24 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 25 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation TRACLEER® SOLID VOLUME GROWTH IN NON-OPSUMIT MARKETS Solid growth ex-US – driven by Digital Ulcer indication in Europe and PAH emerging markets (China, Russia, Asian and Latin America business) Global units sales -2% due to erosion in Opsumit markets and increasing Gx competition Positive impact of US rebate reversals and 2013/2014 US price increases Successful Gx defense in Canada, Turkey, Mexico Stayveer launched by Marklas in Poland and Czech Republic CHF million -1% at CER 1,532 2013 26 © 2015 Actelion Pharmaceuticals Ltd 1,481 2014 February 2015 Company presentation ACTELION’S PAH PORTFOLIO 27 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ACTELION’S PAH FRANCHISE * Selexipag (Uptravi) is an investigational drug submitted to health authorities but not approved for use. 28 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation TRANSFORMING OUR PAH PORTFOLIO MOVING TO OUTCOME-BASED THERAPY * Selexipag (Uptravi) is an investigational drug submitted to health authorities but not approved for use. 29 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation UNIQUELY POSITIONED TO SERVE PAH COVERING CONTINUUM OF CARE WITH OUTCOME-BASED MEDICINES FC II FC III * Selexipag (Uptravi) is an investigational drug submitted to health authorities but not approved for use. 30 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FC IV ENGINE OF TRANSFORMATION 31 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation OPSUMIT® ENGINE OF TRANSFORMATION Opsumit (macitentan) is an orally available endothelin receptor antagonist (ERA) approved for the treatment of PAH in over 30 countries, including the United States in October 2013 and the European Union in December 2013 32 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation OPSUMIT: A LANDMARK IN PAH The effect of macitentan to reduce combined morbidity/mortality events 33 – 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation IMPORTANT DATA CONFIRMING THE CLINICAL UTILITY OF OPSUMIT Macitentan efficacy in incident & prevalent patients Change in 6MWD vs. long-term outcomes Change in WHO FC vs. long-term outcomes & WHO FC subgroup analysis Macitentan and PAH related hospitalization All cause hospitalization Macitentan and quality of life in PAH Macitentan hemodynamic sub-study Macitentan in patients with and w/o anticoagulant Macitentan in patients with and w/o RV function 34 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation Oral presentations 9 Poster presentations 8 OPSUMIT® STRONG LAUNCH TRAJECTORY ENGINE OF TRANSFORMATION Strong launch momentum maintained – 2014 sales of CHF 180 million Over 6,300 patients benefiting from Opsumit Global roll-out update: CHF million – 59 68 38 5 Q4 2013 35 15 Q1 2014 Launched in: US, Germany, Austria, Switzerland, Canada, UK, Ireland, Denmark, Norway, Sweden, NL, Italy, Belgium, Luxembourg, Australia, Mexico*(private market), Iceland and Finland Registration process proceeding well in Japan; filed in other markets * Trade name Zependo Q2 2014 © 2015 Actelion Pharmaceuticals Ltd Q3 2014 February 2015 Q4 2014 Company presentation I.V. THERAPY MADE A LITTLE EASIER 36 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 37 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation VELETRI® BECOMING A TRULY GLOBAL ASSET CHF million +84% CER Growth Accelerated growth trajectory Global asset – available in 14 markets around the globe Continued strong uptake in Japan* - adversely affected going forward by price reduction March 01 2014 64 37 2013 38 © 2015 Actelion Pharmaceuticals Ltd 2014 February 2015 * Trade name Epoprostenol “ACT” Company presentation OPEN THE PROSTACYCLIN PATHWAY TO MORE PATIENTS Selexipag (Uptravi) is an investigational drug submitted to health authorities but not approved for use 39 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation PROSTACYCLINS ARE UNDER UTILIZED TODAY PROSTACYCLIN MARKET US VS EU5 * Inhaled (no US EU 5 Intravenous & Sub-Cutaneous patients) (no patients) Total: ~ 4’500 Total: ~ 770 US Total: ~ 4’000 EU 5 Total: ~ 1’000 Only about 20% of European patients and 50% of US patients initiated in FC II - III receive a prostacyclin at some point in their PAH treatment** * Source: Actelion Assessment based on Decision Resources Forecast, IMS sales data, CIA Worldfact book accessed in 2014 ** Source: Actelion 2014 Quantitative Physician Survey 40 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation WHAT DRIVES PROSTACYCLIN UTILIZATION TODAY? ACTELION 2014 QUANTITATIVE PHYSICIAN SURVEY EFFICACY TREATMENT BURDEN PATIENT REFUSAL PATIENT ATTRIBUTES 41 © 2015 Actelion Pharmaceuticals Ltd “ Prostacyclins are the most potent drug class. “ The administration is a burden. There is the risk of line infections. “ Patients sometimes resist [PC] therapy because they view it as a last resort that signals the end is near. “ If a patient does not follow the hygiene rules you cannot give them parenteral therapy. Infections are a severe threat. ” Cardiologist, Italy ” Consultant for PH and Rheumatology, UK ” February 2015 Cardiologist, US ” Pulmonologist, France Company presentation WHAT CAN CHANGE THIS DYNAMIC? OPENING THE PROSTACYCLIN PATHWAY TO MORE PATIENTS Are prostacyclin's more than a “last resort” option? Is there an easy way to determine the best effective dose for each individual patient? Can an effective dose be reached with acceptable tolerability? Is there long-term outcome data – including in double and triple combination therapy? 42 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation SELEXIPAG (UPTRAVI) RESULTS FIRST SELECTIVE ORAL IP PROSTACYCLIN RECEPTOR AGONIST Positive study – decreased the risk of a morbidity/mortality event versus placebo by 39% (p<0.0001) Efficacy observed was consistent across key subgroups, ie. age, gender, WHO Functional Class, PAH etiology and background PAH therapy The most common adverse events in GRIPHON that occurred with higher frequency on selexipag than placebo were in-line with those known in prostacyclin therapies First regulatory filings with US FDA & EMA initiated in December 2014 Data to be presented at American College of Cardiology Congress (ACC.15) – 12:00 hrs, 15 March 2015 – San Diego, California * Selexipag (Uptravi) is an investigational drug submitted to health authorities but not approved for use. 43 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation SUSTAINING OUR BUSINESS MARKETED BY ACTELION IN THE US ONLY 44 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation VENTAVIS® SUSTAINING OUR BUSINESS CHF million 46 +3% CER Variance 110 112 2013 2014 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation Increasing competitive pressure 17% decline in units shipped Top line maintained through price increase and positive effects of US rebate accrual reversals Ready to defend our position in the US market EXPANDING THE CLINICAL UTILITY OF MACITENTAN MACITENTAN 47 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation CLINICAL CLASSIFICATION OF PULMONARY HYPERTENSION (PH) – 2009 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 Galiè et al. Eur Heart J 2009 © 2015 Actelion Pharmaceuticals Ltd February 2015 2. PH due to left heart disease 3. PH due to lung disease and/or hypoxemia 4. Chronic thromboembolic pulmonary hypertension 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) Phase I program in new and recurring glioblastoma 50 © 2015 Actelion Pharmaceuticals Ltd February 2015 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) Phase II study “MERIT-1” initiated Goal is assessment of efficacy and safety of macitentan in CTEPH 51 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 enrolling patients Goal is assessment of efficacy and safety of macitentan in CpcPH 52 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation MACITENTAN - POTENTIAL INDICATIONS BEYOND PH GLIOBLASTOMA: AREA OF HIGH UNMET MEDICAL NEED Glioblastoma (GBM) most common and aggressive malignant brain tumor, with approximately 5 cases per 100’000 Macitentan in GBM (with TMZ) Phase I tolerability study ongoing (dose of 150 mg reached), no safety issues raised to date Further steps to be discussed with Health Authorities 53 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 54 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE MARKETED BY ACTELION IN THE US ONLY 55 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 56 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 57 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation VALCHLOR® A YEAR OF EXTENSIVE LEARNING USD million 3.9 1.2 58 Q2 2014 Q3 2014 © 2015 Actelion Pharmaceuticals Ltd February 2015 FY 2014 sales: CHF 11 million For topical treatment of mycosis fungoides–type cutaneous t-cell lymphoma (a rare form of non-Hodgkin’s lymphoma) in patients who have received prior skindirected therapy Approx. 18,000 patients in US of which 30-40% considered candidates for Valchlor treatment Sales force expansion complete The registration process for other countries is under evaluation 4.2 2.3 Q1 2014 Q4 2014 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE 59 © 2015 Actelion Pharmaceuticals Ltd February 2015 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 43 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 43 countries, including the US and the European Union since 2003 60 © 2015 Actelion Pharmaceuticals Ltd February 2015 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: 61 – Severe disabilities in swallowing, ambulation, eye movements, language, cognition, muscle control – Lipid accumulation can also lead to an enlarged liver and/or spleen. © 2015 Actelion Pharmaceuticals Ltd February 2015 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 62 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation ZAVESCA® NIEMANN-PICK TYPE C INDICATION DRIVING GROWTH EX-US CHF million +11% CER Growth 96 2013 63 © 2015 Actelion Pharmaceuticals Ltd 103 2014 February 2015 Underlying volume growth +14% Driven by continued growth in the Niemann-Pick Type C (NP-C) indication outside US and new markets (i.e. Japan*) US growth driven by positive price effect Generic miglustat approved in several European markets for GD1 indication only * Trade name Brazaves Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE CADAZOLID CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA Cadazolid is investigational, in development and not approved or marketed in any country. 64 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation International, Multi-center Program Assessing Cadazolid Treatment in patients suffering from Clostridium difficile-associated diarrhea (CDAD) mpact 65 © 2015 Actelion Pharmaceuticals Ltd February 2015 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. 66 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation 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 Enrollment of >1,250 patients worldwide commenced in Q4 2013 Results expected in 2016 Cadazolid is investigational, in development and not approved or marketed in any country. 67 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation BUILD ADDITIONAL SPECIALTY FRANCHISE PONESIMOD S1P RECEPTOR IMMUNOMODULATION Ponesimod is investigational, in development and not approved or marketed in any country. 68 © 2015 Actelion Pharmaceuticals Ltd February 2015 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, dose- dependent and reversible Rapidly reversible upon discontinuation Potential in multiple autoimmune diseases 69 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation PONESIMOD IN MULTIPLE SCLEROSIS Long-term treatment in the multiple sclerosis Phase II extension study under evaluation Opportunity to proceed with an innovative treatment paradigm under assessment Any further development will carefully balance: – Clinical risk and investment – Medical need and commercial opportunity – Incorporating health authority input 70 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation S1P RECEPTOR MODULATORS: FOLLOW UP IMMUNOLOGICAL DISORDERS Currently evaluated in Phase I Tolerability data in human volunteers suggest differentiation from products on the market or compounds in development – After Phase I program is completed, decision on future direction will be made 71 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation EXTENSIVE RESEARCH & DEVELOPMENT 72 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation A CHAIN OF EXPERTISE 356 PROFESSIONALS (SEPT. 2014) Pharmacologists Toxicologists Cell Biologists Molecular Biologists DRUG DISCOVERY ORGANIZATION Biochemists Process Research Chemists © 2015 Actelion Pharmaceuticals Ltd Formulation Specialists Clinical Scientists Medicinal Chemists 73 Pharmacokineticists February 2015 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) 74 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation THE BASE FOR HIGH DISCOVERY EFFICIENCY CULTURE OF INNOVATION • • • • • • 75 Single-center approach Fully integrated research informatics Focus on small molecules Few platforms of expertise Multiple therapeutic areas High medical input © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation CLINICAL DEVELOPMENT ORGANIZATION 594 PROFESSIONALS (SEPT. 2014) Clinical Science Life Cycle Management Clinical Pharmacology CLINICAL DEVELOPMENT Global Drug Safety Global Drug Regulatory Affairs 76 © 2015 Actelion Pharmaceuticals Ltd February 2015 Biometry Global Clinical Operations Strategic Clinical Development Company presentation OUR CARDIOVASCULAR PIPELINE PROMISING PROJECTS TO DELIVER FUTURE SUCCESS Phase I Phase II Selexipag PAH Macitentan Eisenmenger syndrome Macitentan CTEPH Macitentan CpcPH Selexipag o Raynaud’s 2 to SSc New Chemical Entity Cardiovascular disorders 77 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation Phase III Filing OUR SPECIALTY PIPELINE PROMISING PROJECTS TO DELIVER FUTURE SUCCESS Phase I Phase II Cadazolid Clostridium difficile assoc. diarrhea Ponesimod Multiple Sclerosis Ponesimod Immunological Disorders Lucerastat Lipid storage disorders S1P1 follow-up Immunological Disorders Macitentan Glioblastoma 78 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation Phase III Filing 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 79 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation STRATEGY FOR VALUE CREATION SUSTAIN AND GROW THE PAH FRANCHISE BUILD ADDITIONAL SPECIALTY FRANCHISES OPTIMIZE PROFITABILITY 80 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FINANCIAL OVERVIEW BY REPORTING PERIOD 81 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FULL YEAR 2014 – FINANCIAL OVERVIEW Variance FY 2013 FY 2014 CHF CER Product sales 1,784 1,956 10% 12% Core earnings 619 743 20% 25% Operating income 482 570 18% 24% Core EPS 4.41 5.58 27% 33% CHF million CHF million CHF million CHF 82 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation CORE EARNINGS BY REPORTING PERIOD 83 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FY 2014 – CORE EARNINGS CHF million 800 743 66 619 32 600 677 588 400 2013 2014 Core earnings ex US rebate reversals 84 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation US rebate reversals EARNINGS PER SHARE (EPS) BY REPORTING PERIOD 85 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FY 2014 – EARNINGS PER SHARE Variance FY 2013 FY 2014 CHF CER Net income 453 594 31% 38% Basic EPS 4.06 5.34 Number of shares in calculation (m) 111.5 111.2 32% 39% Fully diluted EPS 3.92 5.11 115.4 116.2 30% 37% CHF million Number of shares in calculation (m) 86 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation SHAREHOLDER RETURNS 87 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation DELIVERING ON OUR STRATEGY CREATES VALUE SHARE PRICE PERFORMANCE CASH RETURNED TO SHAREHOLDERS 588 358 133 2012 2013 2014 2015 – CASH DISTRIBUTION New second-line share repurchase: up to 10 million shares within 3 years* Board proposal: Increased dividend to CHF 1.30 per share * Subject to regulatory approval 88 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation FINANCIAL GUIDANCE JANUARY 2015 89 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation 2015 FINANCIAL GUIDANCE AT CONSTANT EXCHANGE RATES From higher 2014 base (excluding US rebate reversals): Low-single digit core earnings growth 743 2014 inc US rebates 677 625 2014 ex US rebates 2014 ex US rebates at post SNB FX* * assumes USD 0.93, EUR 1.05, JPY 0.78, all other foreign currencies -5% 90 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation MANAGEMENT & BOARD 91 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation THE RIGHT PEOPLE FOR THE NEXT GROWTH PHASE ACTELION MANAGEMENT TEAM Jean-Paul Clozel Founder, CEO Joined in 1997 Martine Clozel Founder, CSO Joined in 1997 Otto Schwarz COO Joined in 2008 Nicholas Franco Chief BD Officer Joined in 2011 Marian Borovsky General Counsel Joined in 2003 92 © 2015 Actelion Pharmaceuticals Ltd February 2015 Christian Albrich Head of Global HR Joined in 2005 Company presentation André Muller CFO Joined in 2013 Guy Braunstein Head of Global CD Joined in 2009 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 Carl Feldbaum Joined in 2005 Robert J. Bertolini Joined in 2011 John J. Greisch Joined in 2013 Werner Henrich Joined in 2000 93 © 2015 Actelion Pharmaceuticals Ltd Michael Jacobi Joined in 2009 February 2015 Company presentation Jean-Paul Clozel Joined in 2000 Peter Gruss Joined in 2012 Jean Malo Joined in 2004 THANK YOU FOR YOUR INTEREST IN ACTELION 94 © 2015 Actelion Pharmaceuticals Ltd February 2015 Company presentation
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