Summary Report Value through Innovation. nopq

Transcription

1 Summary Report 2009 Value through Innovation nopq

2 Financial Highlights Boehringer Ingelheim group of companies Amounts in millions of EUR, unless otherwise indicated change Net sales 12,721 11, % by region Europe 31 % 33 % Americas 49 % 48 % Asia, Australasia, Africa 20 % 19 % by business Human Pharmaceuticals 95 % 96 % Animal Health 5 % 4 % Research and development 2,215 2,109 5 % Personnel costs 3,221 3,004 7 % Average number of employees 41,534 41,300 1 % Operating income 2,239 1, % As % of sales 17.6 % 17.1 % Income after taxes 1,764 1, % As % of sales 13.9 % 12.3 % Shareholders equity 5,901 4, % Return on shareholders equity 37.4 % 42.2 % Cash flow 2,409 1, % Investments in tangible assets % Depreciation of tangible assets %

3 Contents 1 Value through Innovation 2 Key aspects At a glance 8 Corporate bodies 10 corporate responsibility 12 Living our Values 13 Our people 17 Sustainability 19 Corporate Citizenship 22 research & development 24 Our strategy in research and development 24 Our research areas 26 Our R&D pipeline growth in Partnering innovation 28 Access to new therapeutic concepts The Boehringer Ingelheim Venture Fund 28 Selected clinical trials 30 Oncology 32 Progress in female sexual health 34 our business 34 Human Pharmaceuticals 36 Prescription Medicines 40 Consumer Health Care 42 Biopharmaceuticals 46 Operations 50 Animal Health Boehringer Ingelheim is a research-driven company dedicated to researching and developing, manufacturing and marketing pharmaceuticals that improve health and quality of life. Our business areas consist of Human Pharmaceuticals and Animal Health. We have more than 41,500 employees in 142 affiliated companies worldwide, research and development (R&D) facilities at 12 sites in seven countries and production plants in 15 countries. R&D expenditure in Prescription Medicines corresponds to 21 % of its net sales. Our headquarters is at Ingelheim, the German town where the family-owned company was founded in imprint

4 Value through Innovation The objectives and beliefs of Boehringer Ingelheim can be summed up in a single vision: Value through Innovation. This has helped us to build on our strengths and make the most of our distinctive character. In a competitive and fast-changing world, the value of products, services and companies is constantly changing. Real customer value today can only be created by constantly developing new solutions and doing what we already do better.

5 Key aspects was again a successful year for Boehringer Ingelheim. Once more, the company, measured by net sales, and for the tenth year in a row, showed stronger growth than the pharmaceutical market worldwide. And in the 125th year of the company s history, it was the fastest growing of the 15 biggest companies. The Animal Health business was also the fastest growing of the 10 biggest companies in the industry. Hubertus von Baumbach, Wolfram Carius, Engelbert Tjeenk Willink, Andreas Barner (from left to right) It was a successful year for research and development purposes, as clinically relevant advances were delivered and new product registrations were achieved. The most important thing for us is that our innovative medicines are helping millions of patients. Our core products, such as spiriva, micardis, flomax /alna and mirapex /sifrol, showed distinct growth again and improved their market position once more. Our business performance In 2009, Boehringer Ingelheim increased its net sales by more than EUR 1 billion to EUR 12,721 million. This represents an increase of 9.7% on the previous year. In our Human Pharmaceuticals business, the development of Prescription Medicines maintained a good growth path. The business in Consumer Health Care products was impacted by the effects of the financial and economic crisis on consumer markets, e. g. in Eastern Europe and Spain. We strengthened our Animal Health business substantially with the acquisition of parts of Fort Dodge in the USA and by taking on employees in the Boehringer Ingelheim group of companies. In 2009, Animal Health significantly strengthened its position in vaccines, expanded its already strong product portfolio for small animals and cattle and maintained its growth path in Biopharmaceuticals showed technological leadership in biopharmaceutical development and performed exceptionally well in Clinical studies Clinical studies have produced very robust data for five therapeutically highly promising and innovative substances from our own research pipeline. These new medicines in new indication areas will offer distinct therapeutic progress for patients. Strategic goals Our goals directed at the pharmaceutical market are international launches of new compounds and thereby the positioning of the company with new, innovative medicines in therapeutic areas where it has so far not been represented. 2 Boehringer Ingelheim S U M M A R Y R E P O R T Key aspects 2009

6 These are, for example, oncology and metabolic diseases, with the indication area diabetes. Our goals are opening up new growth regions in emerging markets, such as Brazil, India, Russia and China. There is also the expansion of Consumer Health Care and the active positioning of our biopharmaceutical expertise. We are in the process of implementing the necessary structural changes to improve our organisational structure, productivity and flexibility. We expect the first new launches already in 2010, which, after only a one-year pause, will lead Boehringer Ingelheim once more into a successful growth phase with new, innovative medicines that offer patients convincing therapeutic advantage in the treatment of their diseases. Attractive employer The attractiveness of Boehringer Ingelheim as a preferred employer has long been acknowledged in many countries and has been confirmed many times in surveys by highly regarded, independent institutes. In 2009, Boehringer Ingelheim was No. 2 in the Top Employer ranking of the journal Science. Outlook The business environment in the pharmaceutical market will increasingly be impacted by volatility and by growing pressure on national healthcare systems. This will be compounded by higher spending to launch important medicines from our product pipeline will, see generic competition in the US pharmaceutical market for important turnover generators such as flomax, mirapex /sifrol and catapresan tts and will limit our growth. We expect net sales at the same level as the previous year. Investments in new product launches and the decision to sustain high research and development expenditure of more than 20% of net sales will lead to a burden on our operating profit. 4 Boehringer Ingelheim S U M M A R Y R E P O R T Key aspects 2009

7 At a glance Boehringer Ingelheim/Corporation Net sales by businesses (in millions of EUR) Change Employees Average capacity of employees by region Human Pharmaceuticals 12,111 11, % Prescription Medicines 10,058 9, % Consumer Health Care 1,261 1, % Biopharmaceuticals % Pharma Chemicals and Pharmaceuticals Production % Animal Health % Americas 13,519 13,443 Europe 21,314 21,557 Asia, Australasia, Africa (AAA) 6,701 6,300 41,534 41,300 Human Pharmaceuticals Key products Net sales (in millions of EUR) Change Net sales by region (in millions of EUR) Change Americas 6,257 5, % Europe 3,980 3, % Asia, Australasia, Africa (AAA) 2,484 2, % Key financial figures (in millions of EUR) Change Net sales 12,721 11, % Operating income 2,239 1, % Return on net sales (as %) 17.6 % 17.1 % Spiriva 2,404 2, % Flomax 1,414 1, % Micardis 1,393 1, % Mirapex /Sifrol % Consumer Health Care Key products Net sales (in millions of EUR) Change Dulcolax % Mucosolvan % Pharmaton % Buscopan % Research and Development Key figures R&D Animal Health Key products Net sales (in millions of EUR) Change Expenditure in millions of EUR 2,215 2,109 1,900 1,574 1,360 - as% of net sales Prescription Medicines (PM) expenditure in millions of EUR 2,100 2,016 1,818 1,501 1,293 - as % of PM net sales Ingelvac CircoFLEX % Metacam % Ingelvac PRRS % Vetmedin % Average number of employees 6,934 6,788 6,405 6,003 5,678 6 Boehringer Ingelheim S U M M A R Y R E P O R T At a glance

8 Corporate bodies Shareholders Committee Advisory Board Board of Managing Directors Christian Boehringer Chairman of the Shareholders Committee Albert Boehringer Christoph Boehringer Erich von Baumbach Jr. Ferdinand von Baumbach Dr Mathias Boehringer Prof. Dr Michael Hoffmann-Becking Attorney at Law, Düsseldorf Chairman of the Advisory Board Egbert Appel Trustee, Martin Hilti Family Trust; Member of the Board and Managing Director, Hilti Foundation Dr Andreas Kreimeyer Member of the Board of Executive Directors and Research Executive Director BASF SE Prof. Dr Fredmund Malik Chairman of the Board Malik Management Zentrum St. Gallen AG Prof.* Dr Dr Andreas Barner Chairman of the Board Corporate Board Division Chairman of the Board and Pharma Research, Development and Medicine Hubertus von Baumbach Corporate Board Division Finance and Animal Health Prof. h. c. Dr Wolfram Carius Corporate Board Division Human Resources and Operations Engelbert Tjeenk Willink Corporate Board Division Marketing and Sales Human Pharma * Republic of Austria 8 Boehringer Ingelheim S U M M A R Y R E P O R T Corporate bodies

9 corporate responsibility Boehringer Ingelheim acts with long-term responsibility and in a value-based manner. 10 Boehringer Ingelheim S U M M A R Y R E P O R T

10 corporate responsibility Corporate Responsibility Living our Values Extracts from our Leitbild We are committed to serving humankind through research into diseases and the development of new drugs and therapies. We safeguard our employees, facilities and the environment from harmful influences, conserve natural resources and promote environmental awareness. We seek to foster economic and social wellbeing wherever we do business. Our people Responsibility for employees Our company s social responsibility was always expressed in the core business and social benefits have been an important part of the culture of the familyowned company Boehringer Ingelheim. During the company s early years, the founder, Albert Boehringer, introduced social measures for employees that were remarkably progressive and generous for that time. A special corporate culture and working environment has been developed built on mutual respect and fairness values that Boehringer Ingelheim has constantly fostered during its 125-year history. Value through Innovation Our objectives and beliefs can be summed up in a single vision: Value through Innovation. This has helped us to build on our strengths and make the most of our distinctive character. Our Leitbild (stated core principles) defines our corporate values and gives the direction for our businesses, innovation, technology, organisation and corporate culture. Our Value through Innovation vision is the driver and strength of our corporate principles and values. Our Lead & Learn principles are outline ways in which we want to deliver Value through Innovation. Employer of choice The attractiveness of Boehringer Ingelheim has for some years been widely acknowledged in highly regarded, independent surveys. Internal surveys, conducted on a global basis, also confirm the strong affinity that our more than 41,500 employees in 50 countries have for the company. External recognition Most prominent among the external recognition that the company received in 2009 was the No.2 place it secured on the Science 2009 Top Employer list. This survey, conducted by the prestigious Science journal and published by the American Association for the Advancement of Science, recognises our commitment to innovation at a time of change in the pharmaceutical and biotechnology industries. 12 Boehringer Ingelheim S U M M A R Y R E P O R T Our people

11 corporate responsibility Internal survey Your view on our culture The objective of our internal survey Your view on our culture was to measure how our company culture is seen by our employees worldwide, to evaluate similarities and differences between regions, countries and functions, and to identify areas for further developments. The survey showed a clearly improving trend compared to the initial survey in With responses from more than 80% of the workforce, participation was again very high. Awards 2009 Country Ranking Survey Brazil Best Companies to Work for in Brazil (Great Place to Work Institute) China Corporate Social Responsibility Award granted by the Pudong Government Finland 17 Best Place to Work Germany 1 Beliebtester Arbeitgeber (VAA Verband der angestellten Akademiker) 14 TOP Arbeitgeber Deutschland The survey confirmed that employees continue to see Boehringer Ingelheim as an ethical company with a strong performance focus. More than 80% of respondents again stated that they have a good knowledge of the company s business performance, its objectives and standards. In 2009, two new strengths were identified worldwide: the company s well-qualified employees and the good access to and relationship with supervisors. Some 84% of respondents said they would recommend Boehringer Ingelheim as a good place to work. Japan Mexico The Netherlands 1 Corporate Health Award 2009 (Initiative of Handelsblatt, EuPD Research and TÜV SÜD Life Service) Excellent Action Learning Program Award in 2009 (Japan Institute for Action Learning JIAL) Socially Responsible Company (Mexican Center of Philanthropy) Clean Industry Certification 2009 (Mexican Environmental Protection Federal Office) Best werkgever Nederland 2009 Best Employer the Netherlands 2009 (Corporate Research Foundation) Change management competitive workforce as a key success factor The external environment of the pharmaceutical market is changing with rapidly evolving market and competitive trends. The internal situation of Boehringer Ingelheim will also change with the patent expiry of important marketed products. Furthermore, we will have to invest in the launch of our new compounds in development. Our aim is to produce a new mindset that enables change to be successfully implemented throughout the company. This involves analysis and planning of change, communicating change, winning acceptance of new behaviours, changing Spain Family Award for Reconciliation between Work and Family Life UK Best Places to Work 2009 (Sunday Times) 1 Pharmafield Survey Employer of Choice USA Best Places to Work for LGBT Equality 100 % Corporate Equality Index Human Rights Campaign Diversity Council Honors Award (Association of Diversity Councils) Top 50 A Top 50 Employer, Reader s Choice: 2009 Workforce Diversity Magazine, Careers & the disabled Magazine Venezuela 4 Great Place to Work in Latin America 14 Boehringer Ingelheim S U M M A R Y R E P O R T Our people

12 corporate responsibility from the status quo to the desired state, and consolidating and institutionalising the new states. Talent management development of employees Talent management is about ensuring that the company has the best people in the right position at the right time. By adopting a global talent management approach as a strategic priority, with initial implementation in 2009, we aim for a competitive advantage. This will mean greater stringency in how we develop our people, sustain their employability and grow the capabilities of our high potential and high professional experts for current and future roles. Sustainability We safeguard our employees, facilities and the environment The manufacture of medicinal products inevitably has an impact on the environment. It is thus the express aim of our Leitbild (core principles) to keep such impact to a minimum. At the same time, we make every endeavour to guarantee the protection of our employees. Our worldwide fundamental standards for key environment, health and safety (EHS) issues and an EHS management system guarantees compliance with corporate and legal requirements. It also guarantees continual improvement in terms of the Responsible Care Initiative of the chemical industry and helps to meet the demands of our Principles for Safety, Quality and Environmental Protection. Regular corporate EHS audits ensure that we fulfil these requirements. Environment, Health and Safety Protection of employees health Protection of workers from highly potent compounds is a central issue, since substances that can help cure patients in low doses, can potentially put employees inhaling high concentrations at risk. This is why we calculate the limit values for all of our active ingredients and for years have been running a now well-advanced programme which, by enclosing critical equipment, helps us reduce dust exposure to such an extent that employees can work safely without additional respiratory protection. 16 Boehringer Ingelheim S U M M A R Y R E P O R T Sustainability

13 corporate responsibility To decrease the number of work-related accidents, large-scale initiatives to improve safety culture have been launched and clear objectives agreed for prevention. The safety of our field force is another key issue. Almost a third of our employees are working in the field. Pharmaceuticals in the environment Before market launch of new drugs, we investigate the potential environmental effects of active ingredients that could enter the surface water with human waste. The evidence to date confirms that none of the active substances examined have a negative impact on fish and water organisms. Reducing environmental emissions By far the highest percentage of environmental emissions is produced during the chemical production of medicinal substances. It is of paramount importance that the foundations are laid during chemical process development to ensure a minimum of waste, wastewater and emissions to the air and that use of critical hazardous substances are kept to a minimum. Focus on energy efficiency In environmental terms, the focus is on reducing energy consumption and thus in turn the production of carbon dioxide (CO₂). Heating, ventilation and air conditioning systems are the company s largest energy consumers. Corporate Citizenship We seek to foster economic and social well-being Corporate citizenship is an integral part of our corporate culture. Our activities emanate from our operating units and embrace patients, neighbouring communities and society at large. Fighting paediatric AIDS The Boehringer Ingelheim viramune Donation Programme was inaugurated in 2000 as a contribution to prevention of mother-to-child transmission of HIV-1 (pmtct) in developing countries. The programme provides single-dose nevirapine, our non-nucleoside reverse transcriptase inhibitor (viramune ), for mother and baby free of charge for pmtct. By 2009, it had extended to 170 schemes in 60 countries. The programme serves as a catalyst for building healthcare infrastructure. See Partnership with Elizabeth Glaser Pediatric AIDS Foundation Elizabeth Glaser Pediatric AIDS Foundation, a US national non-profit organization dedicated to prevent paediatric HIV infection and to eradicate paediatric AIDS, is the largest beneficiary of our viramune Donation Programme. 18 Boehringer Ingelheim S U M M A R Y R E P O R T Corporate Citizenship

14 corporate responsibility Cooperations Our activities cover many areas, including child protection, healthcare projects, educational programmes, environmental protection and emergency aid. These include cooperation with Health Partners International of Canada, AmeriCares Free Clinics in the USA and the AmeriCares disaster relief and humanitarian aid organisation as well as the Catholic Medical Mission Board in Latin America. We have an agreement with the Mexican Foundation for Children with Immunodeficiency Diseases, while in South Africa and Botswana we support health education and clinicals trials and the development of healthcare infrastructure. In India, the company supports the International Federation of Chemical, Energy, Mine and General Worker s Unions project on HIV/AIDS and Workplace in India. Boehringer Ingelheim Foundations: sustainable commitment to society The Boehringer Ingelheim Foundation and the Boehringer Ingelheim Fonds are non-profit organisations, which act independently from the company. Both foundations are dedicated to the exclusive and direct promotion of science and basic research. In 2009, the Boehringer Ingelheim Foundation decided to make a special EUR 100 million donation. The foundation will support over a ten-year period the scientific operations of the institute of molecular biology (IMB). Partnerships and Foundations Pharmaceutical Biotechnology cooperation with the University of Applied Sciences in Biberach Boehringer Ingelheim entered into a co-operation with the University of Applied Sciences in Biberach, Germany, on a bachelor of science programme specifically focused on the development and production of biopharmaceuticals. IMP the Boehringer Ingelheim life science think-tank The Vienna-based Research Institute of Molecular Pathology (IMP), a basic biomedical research institute sponsored mainly by Boehringer Ingelheim, has the primary goal of conducting innovative basic research and is committed to uncovering fundamental molecular and cellular mechanisms underlying complex biological phenomena. 20 Boehringer Ingelheim S U M M A R Y R E P O R T Corporate Citizenship

15 research & development We continue our research and development activities in order to discover new therapies for people with diseases with high medical need. 22 Boehringer Ingelheim S U M M A R Y R E P O R T

16 research & development Delivering Value through Innovation Research and Development (R&D) Research areas Respiratory diseases Examples of disease areas Asthma COPD Idiopathic pulmonary fibrosis Sites Biberach (Germany) Our strategy in research and development Our vision at Boehringer Ingelheim is Value through Cardiometabolic diseases Atherosclerosis Diabetes Metabolic syndrome Thrombo-embolic diseases Biberach (Germany) Ridgefield (USA) Innovation. As a family-owned company, we have built up a long-term commitment to R&D that is best suited to the unique challenges and long cycles of drug discovery and Oncology Lymphomas Leukaemias Solid tumours Vienna (Austria) development. Our investment in R&D is substantial and steady, and our ambition to bring innovative medicines to market for serious illnesses is equally great and persistent. Our 6,900 highly qual- Neurological diseases Alzheimer s disease Chronic pain Migraine Parkinson s disease Biberach (Germany) ified employees in drug discovery, research, non-clinical drug development and medicine strive to reach these goals. We also partner scientists at universities and research institutes world- Immunology Multiple sclerosis Psoriasis Rheumatoid arthritis Ridgefield (USA) wide, covering basic science and clinical research. Our research areas Infectious diseases Hepatitis C HIV/AIDS Laval (Canada) Our major drug discovery centres are located in Biberach (Germany), Ridgefield (USA), Vienna (Austria) and Laval (Canada), supported by units in Milan (Italy) and Kobe (Japan). 24 Boehringer Ingelheim S U M M A R Y R E P O R T Our research areas

17 research & development Our R&D pipeline growth in 2009 We work diligently to bring new drug candidates to market from our research teams, such as dabigatran etexilate (pradaxa ) for the treatment of venous thromboembolism and prevention of stroke in patients with atrial fibrillation, linagliptin, BI 1356 (intended brand name ondero ) in type 2 diabetes, flibanserin for the treatment of hypoactive sexual desire in women with associated distress, BIBW 2992 in lung cancer and BIBF 1120 (intended brand name vargatef ) in lung and ovarian cancer. In the area of cardiometabolic diseases, we in 2009 added to our DPP-4 and SGLT-2 phase II and phase III clinical programmes for diabetic patients, a development programme targeting the 11β-HSD-1 enzyme. This programme addresses several features of the metabolic syndrome, a combination of disorders, including abdominal obesity, high blood pressure and insulin resistance or glucose intolerance. Our oncology development programme comprises its current lead compounds: BIBW 2992, an oral next generation tyrosine kinase inhibitor, irreversibly blocking EGFR and HER2 receptors, BIBF 1120 (intended brand name vargatef ), an angiogenesis inhibitor, both in clinical phase III development, as well as BI 6727, a unique Pololike kinase inhibitor in phase II clinical development. Our current main focus is on lung cancer. Furthermore, to strengthen our oncology port folio, we have entered development programmes with a biotherapeutic targeting lymphoma cells in leukaemia, and a biotherapeutic targeting a key cell survival signal linked to advanced cancers. In neurological diseases, we conduct extensive research on new treatment modalities for Alzheimer s disease and have initiated a development programme targeting compromised glutamatergic neurotransmission to address memory loss and other cognitive deficits. In 2009, we initiated a new development programme for osteoarthritis and neuropathic pain. We started a development programme in 2009 of potential therapeutic value for patients with the autoimmune diseases rheumatoid arthritis and multiple sclerosis. We have also continued our drive to introduce new medicines for patients suffering from chronic and life-threatening infectious diseases. Our hepatitis C virus NS3 protease inhibitor BI advanced into clinical phase II studies in both treatment-naïve and treatment-experienced patients with chronic hepatitis C. Partnering innovation In our partnerships with biotech companies, we in 2009 issued joint statements on significant milestones, for example with Ablynx, nv (Ghent, Belgium), Vitae Pharmaceuticals, Inc. (Fort Washington, USA) and Evotec AG (Hamburg, Germany). New partnerships and initiatives were also announced, including agreements with Exelixis Inc. (San Francisco, USA), for a collaboration on S1P1 (sphingosine-1-phosphate type 1) receptor agonists to treat autoimmune diseases, with Develo- Gen AG (Göttingen, Germany) in the field of type 2 diabetes, with Vitae Pharmaceuticals, Inc. (Fort Washington, USA) in the field of beta-secretase inhibitors for the treatment of Alz heimer s disease, and with DxS Ltd. (Manchester, UK) on diagnostic kits to enable a personalised medicine approach with BIBW 2992 in oncology. 26 Boehringer Ingelheim S U M M A R Y R E P O R T Partnering innovation

18 research & development Access to new therapeutic concepts The Boehringer Ingelheim Venture Fund The aim of this fund, which will invest an initial EUR 100 million, is to create options for the future by investing in biotech companies with innovative concepts and/or technologies that present opportunities to Boehringer Ingelheim to expand into new therapeutic approaches and businesses. Investments will intentionally extend beyond our current therapeutic area focus and our existing therapeutic modalities and technologies. Our sole focus is medical innovation, which may include new therapeutic modalities (e.g. regenerative medicine, silencing RNAs), new generation vaccines, new generation protein and antibody technologies, new molecular mechanisms, personalised medicine or disease-related biomarkers. Selected clinical trials Prophylaxis and treatment of thrombo-embolic diseases We continue to evaluate the efficacy and safety of dabigatran etexilate in a broad range of additional disease conditions in the global re-volution clinical trial programme which involves over 38,000 patients worldwide. This includes: Treatment of acute venous thrombo-embolism (VTE) in the re-cover and re-cover ii trials Secondary prevention of VTE in the re-medy and re-sonate trials Stroke prevention in atrial fibrillation: the ongoing rely-able trial is the long-term extension of re-ly. rely-able evaluates dabigatran etexilate in patients who completed the re-ly trial The RE-LY study In summary, patients with atrial fibrillation treated with dabigatran etexilate 150 mg BID (twice daily) had a significantly reduced risk of stroke and systemic embolism compared to well-controlled warfarin without increasing the risk of major bleeding. Patients with atrial fibrillation treated with dabigatran etexilate 110 mg BID (twice daily) clearly demonstrated similar reductions in stroke and systemic embolism compared to well-controlled warfarin while delivering an impressive 20% reduction in major bleeding rates compared to warfarin. Similarly impressive were the results in key secondary and other outcomes, including superior reduction in hemorrhagic strokes with both 150 mg and 110 mg BID (twice daily) doses, and a reduction in vascular mortality with the 150 mg BID (twice daily) dose. The data confirm that dabigatran etexilate can overcome the limitations of the current treatment with vitamin K antagonists, such as warfarin or phenprocoumon, thereby possibly revolutionising therapy for patients with atrial fibrillation. Only taking into consideration the potential of stroke reduction, dabigatran etexilate 150 mg BID (twice daily) could prevent more than 1,000 strokes per day worldwide compared to wellcontrolled warfarin. Results of the RE-DEEM trial The study convincingly demonstrated that dabigatran etexilate can be used on top of dual anti-platelet therapy without excessive bleeding and that it decreased coagulation activity markers. re-deem demonstrated a significant reduction in coagulation activity with all doses (110 mg and 150 mg twice daily) of dabigatran etexilate. 28 Boehringer Ingelheim S U M M A R Y R E P O R T Selected clinical trials

19 research & development Results of the RE-COVER study With re-cover it was evaluated whether oral dabigatran etexilate (150 mg, twice daily) is as effective and safe (noninferior) to warfarin for six months treatment of acute symptomatic VTE, following initial treatment with a parenteral anticoagulant. Dabigatran etexilate (150 mg, twice daily) showed equal efficacy compared to well-controlled warfarin in preventing recurrent VTE. It demonstrated a 37% reduction in major or clinically relevant non-major bleeding. Major bleeding was comparable between dabigatran etexilate and warfarin. For any bleeds, dabigatran etexilate showed a 29% reduction compared to warfarin. These results were achieved without any evidence of liver problems. re-cover demonstrated that dabigatran etexilate was as effective as well-controlled warfarin, with less bleeding in treatment of acute VTE. Oncology Our search for new cancer treatments is currently focused on three main areas, signal-transduction inhibitors, angiogenesis inhibitors and cell-cycle kinase inhibitors. Signal transduction inhibitor BIBW 2992 BIBW 2992 is being investigated as a novel, potent inhibitor of EGFR/HER1 and HER2 that irreversibly binds to both receptors, inhibiting signalling via the EGFR/HER2 pathway. BIBW 2992 is believed to inhibit all cancer-relevant receptor dimers from the erbb kinase family. Angiogenesis inhibitor BIBF 1120 BIBF 1120 (intended brand name vargatef ) is a novel triple angiokinase inhibitor that simultaneously inhibits three growth factor receptors (VEGFR, PDGFR and FDFR) all crucially involved in the formation of blood vessels. As these growth factors and receptors play an important role in angiogenesis, inhibition of them may play a critical role in the prevention of tumour growth and spread. Cellcycle kinase inhibitor / Pololike kinase 1 specific inhibitor We are investigating the potentially first-in-class Plk-1 inhibitor BI 6727 for the treatment of various cancer types independent of oncogenome signature. Preclinical data show that the compound inhibits Plk-1, resulting in disruption of the spindle assembly, mitotic arrest and induction of apoptosis leading to growth inhibition and tumour regression. Clinical trials Our studies in lung cancer With the introduction of the lume Lung 1 and lume Lung 2 trials the first phase III clinical trial programme has commenced for BIBF 1120 (intended trade name vargatef ). The trials will assess BIBF 1120 in combination with standard chemotherapy agents docetaxel and pemetrexed in patients with relapsed, advanced non-small cell lung cancer (NSCLC). Some 2,600 patients will be enrolled, making this one of the largest phase III study programmes to date in this NSCLC patient population. Both trials are currently recruiting patients. As angiogenesis plays a pivotal role in the growth of all solid tumours, BIBF 1120 is being investigated in a number of additional indications including ovarian cancer, colorectal cancer and hepato-cellular cancer. A phase III clinical trial in ovarian cancer with planned enrolment of 1,400 patients has started in the fourth quarter of Boehringer Ingelheim S U M M A R Y R E P O R T Oncology

20 research & development Boehringer Ingelheim s lux -Lung trial programme currently includes two phase III trials assessing the efficacy and safety of BIBW 2992 in various NSCLC patient populations. BIBW 2992 is currently in phase III clinical development in NSCLC, the most common type of lung cancer. lux -Lung 1 is a randomised, double-blind study of BIBW 2992 versus placebo in NSCLC patients. These patients included in the study suffered from disease progression after treatment with first-generation EGFR tumour kinase inhibitors (i.e. erlotinib or gefitinib). To investigate BIBW 2992 as a potential first-line treatment for NSCLC patients with EGFR mutations, we are conducting another phase III clinical trial, lux -Lung 3. This study is comparing the efficacy and safety of single-agent BIBW 2992 to that of standard chemotherapy (cisplatin/pemetrexed). With this, we are continuing to work towards providing personalised medicine for patients with lung cancer. As EGFR and HER2 play a pivotal role in many solid tumours, BIBW 2992 is also being investigated in additional indications including breast, colorectal and head and neck cancers. Current medical research suggests that diminished sexual desire may occur due to an imbalance in certain chemical pathways in the brain. Preclinical research has shown that flibanserin, a new, non-hormonal investigational compound from our own research and development pipeline, binds to certain serotonin receptors with preferential affinity to selective brain areas. This leads to region-specific modulations of chemical factors essential to sexual function. We believe that by modulating these neurotransmitter systems, flibanserin helps to restore a balance between inhibitory and excitatory factors. Results of the Bouquet trial programme Boehringer Ingelheim has conducted a number of pivotal studies in the flibanserin clinical programme bouquet, including over 5,000 pre-menopausal women from North America and Europe. Results of the pivotal phase III clinical trials demonstrated that flibanserin 100 mg, taken once daily at bedtime, significantly increased the number of satisfying sexual events (SSEs) and sexual desire while significantly decreasing the distress associated with HSDD. Progress in female sexual health Hypoactive sexual desire disorder of women with associated distress Hypoactive sexual desire disorder (HSDD) with associated distress is a condition that has been recognised for over 25 years and epidemiologic studies show that nearly one in ten women suffer from decreased sexual desire and associated distress. Boehringer Ingelheim is committed to progressing the understanding of the science in HSDD and to the development of a potential new treatment option for pre-menopausal women suffering from this condition. 32 Boehringer Ingelheim S U M M A R Y R E P O R T Progress in female sexual health

21 human pharmaceuticals With the oral thrombin inhibitor, I did not need any injections for thrombosis prevention, says Brasilina M. 34 Boehringer Ingelheim S U M M A R Y R E P O R T

22 human pharmaceuticals Human Pharmaceuticals Serving patients Human Pharmaceuticals is our prime business area and accounts for 95% of our net sales. All our drugs in various therapeutic areas are of special medicinal importance for our patients and thereby of great significance to Boehringer Ingelheim. Prescription Medicines Within our Human Pharmaceuticals business, Prescription Medicines represents the focus of our activities. Our key products, such as pradaxa, spiriva, micardis, flomax and mirapex /sifrol, made a significant contribution to our growth in Venous thrombo-embolism Pradaxa pradaxa (dabigatran etexilate) is a once-daily oral direct thrombin inhibitor from our own research and development. It prevents thrombus formation by specifically and selectively inhibiting free and clot-bound thrombin, the central and essential enzyme in the coagulation cascade. pradaxa is available in more than 50 countries for the primary prevention of venous thrombo-embolic events in adults who have undergone elective total hip or knee surgery. pradaxa is taken as an oral capsule and does not require coagulation monitoring. It has a favourable efficacy and safety profile, both in and out of hospital. Cardiovascular diseases Micardis Boehringer Ingelheim offers innovative options for the treatment of essential hypertension with micardis (telmisartan 20/40/80mg), our angiotensin II receptor blocker (ARB), micardisplus /micardis hct (telmisartan in fixed dose combination with the diuretic hydrochlorothiazide 40/12.5; 80/12.5; 80/25 mg). Hypertension is one of the most important, but modifiable, risk factors for cardiovascular disease. The organ systems most affected from end organ damage are the heart, the main blood vessels, the brain and the kidneys. The primary goal of any antihypertensive treatment is to prevent cardiovascular (CV) events, such as heart attacks or stroke, and finally to reduce CV mortality. Micardis cardiovascular risk reduction In 2009, micardis 80 mg was approved for reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease or type 2 diabetes mellitus with documented target organ damage by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). It is the first and only treatment in its class approved in this indication and offers a much needed alternative to ramipril, a widely used angiotensin converting enzyme inhibitor, the previous gold standard for cardiovascular risk reduction. micardis is better tolerated and associated with higher treatment adherence than ramipril. The new indication for micardis is based on the results of the landmark ontarget trial programme. It included more than 31,000 high-risk cardiovascular patients with a history of coronary heart disease, stroke, transient ischaemic attack, peripheral vascular disease or diabetes with target organ 36 Boehringer Ingelheim S U M M A R Y R E P O R T Prescription Medicines

23 human pharmaceuticals damage. ontarget showed that micardis 80 mg can prevent one in five serious CV events or deaths from cardiac causes and is better tolerated and associated with higher treatment adherence than ramipril. Twynsta Increasingly, the hallmark of modern high blood pressure treatment are combinations, such as twynsta, the latest addition to the telmisartan family, as the majority of patients do not achieve blood pressure control on one therapeutic agent alone. in all EU/EEA countries as a new prolonged-release, oncedaily tablet for the treatment of early and advanced idiopathic PD. A new drug application for a once-daily formulation of pramipexole is also in review with the FDA for the treatment of PD. The new formulation, mirapexin /sifrol Prolonged- Release, causes less frequent fluctuations in the plasma concentration over 24 hours compared to the three times daily administration of the immediate release formulation. In October 2009, the FDA approved twynsta (telmisartan in a fixed dose combination with amlodipine (40/5, 40/10, 80/5, 80/10 mg), a convenient, well-tolerated once-daily, single pill combination. twynsta delivers highly effective blood pressure reductions and a 24-hour blood pressure response rate of up to 98% for hypertensive patients at risk of CV events. twynsta is available in the USA in a flexible range of dosing regimens (40/5 mg, 40/10 mg, 80/5 mg, 80/10 mg). It has also been submitted for approval in Europe and Japan, and is on schedule to be submitted in other countries (intended additional brand names twinsta, micamlo, micardis amlo, micardis anlo ). Diseases of the central nervous system Mirapex /Sifrol For more than a decade patients suffering from Parkinson s disease (PD) were successfully treated with mirapex / sifrol /mirapexin /pexola (pramipexole) with the immediate release tablet (three times daily). Worldwide the treatment exposure so far comprises more than 5 million patientyears. In October 2009, mirapex /sifrol /mirapexin / pexola (pramipexole) was granted marketing authorisation mirapexin /sifrol is licensed for the symptomatic treatment of idiopathic Parkinson s disease. It may be used as mono therapy or in combination with levodopa. Furthermore, it is licensed for the symptomatic treatment of idiopathic restless legs syndrome. Respiratory diseases Spiriva spiriva (tiotropium), an inhaled, long-acting anticholinergic, is the first and only once-daily medication for chronic obstructive pulmonary disease (COPD) that maintains 24-hour bronchodilation, resulting in significant and sustained long-term improvements in lung function and quality of life. It belongs to the group of long-acting bronchodilators recommended as a first-line maintenance treatment option for patients with moderate to sever COPD (GOLD stages II IV) in international guidelines developed by the Global Initiative for Obstructive lung Disease (GOLD). The world s most prescribed brand for COPD in the world, it is available to COPD patients in 35 countries and is marketed jointly by Boehringer Ingelheim and Pfizer, Inc. 38 Boehringer Ingelheim S U M M A R Y R E P O R T Prescription Medicines

24 human pharmaceuticals Spiriva HandiHaler In December 2009, the FDA also approved SPIRIVA Handi- Haler (tiotropium bromide inhalation powder) for the reduction of exacerbations in patients with COPD, a key goal of COPD disease management. Spiriva improvements in lung function A new analysis of the landmark UPLIFT trial, published by Decramer in the Lancet (Online, August 28, 2009), showed that tiotropium (spiriva HandiHaler 18 μg) administered to COPD patients with moderate disease severity (GOLD stage II) produced significant and sustained improvements in lung function for up to four years. This analysis involved 2,739 patients the largest group of early stage COPD patients treated with a long-acting anticholinergic in a randomised, placebo-controlled study. The launch of a heartburn-relief product under the buscopan umbrella brand marks a major milestone. Argentina, Germany and the Netherlands are among the first countries with buscogast /buscasan 24 (omeprazole 20mg) on the market. New buscogast offers targeted relief from heartburn for a full 24 hours with just one capsule per day. Gastrointestinal diseases Dulcolax Balance Following the launch of dulcolax Balance in Germany in 2007, the international roll-out began in 2009 with launches in South Korea and the USA. As the first macrogol-based laxative to be communicated directly to consumers, it has been important to firmly establish dulcolax Balance as a new option in relieving constipation, clearly distinguishing it from the traditional contact laxatives. Consumer Health Care Our Consumer Health Care (CHC) business segment is one of our core activities and strives to serve consumers worldwide with top-quality pharmaceuticals for self-medication. Gastrointestinal diseases Buscopan buscopan is the leading over-the-counter (OTC) antispasmodic brand worldwide and is marketed in over 100 countries. Expanding the buscopan brand into a franchise encompassing different sub-brands within abdominal categories is the key strategic objective. This means that the buscopan franchise in some key countries not only consists of antispasmodic products but also, for example, of medications against menstrual pain (buscofem ). Urological diseases Flomax Relief flomax relief, used to manage the symptoms of benign prostatic hyperplasia (BPH), has become our first prescriptiononly medicine (POM) switch to pharmacy (P) in the UK. The flomax relief launch represents the biggest opportunity for Boehringer Ingelheim to gain significant new growth in the UK market. In 2010, flomax relief will be made available at pharmacies to suitable men between 45 and 75 years of age. Leg vein health Antistax The antistax tablet (active ingredient: red vine leaf extract AS 195) for treatment of chronic venous insufficiency (CVI), has been very successful in South Africa since its launch in We have expanded the product range in 2009, launching the antistax leg chilling gel in February and the antistax leg cooling spray in July. 40 Boehringer Ingelheim S U M M A R Y R E P O R T Consumer Health Care

25 biopharmaceuticals Biopharmaceuticals A flexible technology portfolio Our Biopharmaceuticals business is committed to extending its technological leadership in biopharmaceutical development and manufacturing for in-house research projects and for its Industrial Customer business with third parties. Our aim is to develop a technology portfolio flexible enough to react to external competition as well as to business needs, at the same time enabling long-term orientated technology development. Cell culture upstream technology In recent years, we have seen enormous product titer increases in recombinant mammalian cell culture with, for example, titer clearly above 5 g/l for monoclonal antibodies manufactured on an industrial scale with recombinant Chinese hamster ovary (CHO) cells. scientists created powerful computational workflows that allow fast processing of these large amounts of data and established a Boehringer Ingelheim CHO gene expression data base. RAPPTor platform Key to rapptor (Rapid Automated Protein Purification Technology), a novel multi-parallel screening and analytical platform, is the co-development of screening and automated analytical methods, enabling it to eliminate bottlenecks and deliver a complete data set for all process parameters. rapptor data can therefore directly impact development decisions, improve timelines and process quality. Microbial platform technology In 2007, Boehringer Ingelheim and Ablynx nv agreed to discover and develop Nanobodies, small antibody fragments, as biopharmaceuticals. In the last two years several expression systems and fermentation conditions for different Nanobody formats were developed and applied for more than 60 different molecules. Expression titers of up to 15 g/l were achieved in E. coli in combination with high refolding yields above 90% for different Nanobody formats. By combining our upstream expertise, our Process Science department has even reached product titers beyond 8g/L using our proprietary bi-hex platform technology with a productivity of 100 pg/cell/day. Next-generation media design Technologies, such as gene expression profiling, as well as large-scale analysis of hundreds of metabolites and proteins, today open up a new chapter in mammalian bioprocess development. A current example is gene expression profiling for advanced and rational media design. For this purpose, our 42 Boehringer Ingelheim S U M M A R Y R E P O R T Biopharmaceuticals

26 operations Farsightedness, project management that sees itself as oil in the engine, as well as technical know-how, are the guarantors for the successful production of Pradaxa, Falk March (left) and Dr Michael Wedy. 44 Boehringer Ingelheim S U M M A R Y R E P O R T

27 operations Operations Pharma Chemicals and Pharmaceuticals Production Operations is a key function at Boehringer Ingelheim that ensures reliable supplies of top-quality active pharmaceutical ingredients (APIs) and advanced intermediates. In Operations, drug substances and drug products are manufactured for captive use by our Human Pharmaceuticals business as well as for external partners for the global markets (contract manufacturing). The aim is to offer added value to customers ranging from research-led start-ups to the major pharmaceutical groups. Operations accomplishes this global mission through two specialised units: Pharmaceuticals Production and Pharma Chemicals. These specialised units form a worldwide pharmaceutical network whose combined expertise, experience and service quality is a benchmark in the industry. The Pharma Chemicals network The APIs of pharmaceutical products are synthesised in our Chemicals network. Boehringer Ingelheim has a network of four sites for active ingredient production that are closely linked to each other: Ingelheim (Germany), Petersburg (Virginia, USA), Malgrat (Spain) and Fornovo (Italy). The Ingelheim plant has two roles: the process development site and launch site. The Pharmaceuticals Production launch sites For captive use, innovative drugs are launched from our manufacturing sites in Ingelheim and Columbus (Ohio, USA). These sites have the mission of ensuring the production and reliable supply of our own drug products, such as our (COPD) medication spiriva, and to launch innovative products, such as our oral direct thrombin inhibitor pradaxa. These launch sites interact closely with development and marketing to ensure that the manufacturing processes are dependable and efficient, but also to provide appropriate manufacturing capacity. Pradaxa manufacturing active ingredients in Fornovo In order to meet market demand for pradaxa a new facility in Fornovo was inaugurated in mid In this facility five steps of dabigatran etexilate, the active ingredient of pradaxa, are produced. Only the last step of production, milling to very fine particles (micronisation) is undertaken at our production plant in Ingelheim. Boehringer Ingelheim invested EUR 60 million in this new plant. This will increase the number of employees at Fornovo from 120 to 170. In the production building numerous reactors have been installed with a reactor volume of nearly 60 cubic metres (60,000 litres) and a facility for hydrogenation has been built. The building has four bays, each of them containing two reactors, a centrifuge to segregate the solid products from the liquids, and a dryer to finally dry the product. 46 Boehringer Ingelheim S U M M A R Y R E P O R T Operations