Lundbeck and Merck have signed an agreement for the exclusive US development and commercialisation of gaboxadol Sleep disorders Insomnia is the most common type of sleep disorder and is considered to be a symptom rather than an actual disease or syndrome. Insomnia is one of the most complained about but least understood and misdiagnosed disorders known today. About 25% of adults complain of insomnia, however only one insomniac out of four mentions it to his doctor during a visit for another problem and only one in twenty actually seeks help for their specific sleep problem. Given these parameters, obtaining an accurate estimate of its burden on society is complicated. Although the data that exists concerning the economic consequences and effects of insomnia is from the mid 1990s, it clearly indicates that its total cost to society is profound. In the USA, estimates range between USD 92.5 and USD 107 billion for both the direct and the indirect economic consequences of insomnia. (Source: Economic effects of insomnia, 1994). There is a need for more epidemiological and socio-economic data to make more exact calculations of the economic burden of insomnia on society. Based on data from 1995, the latest and most recognised analysis of the economic burden of insomnia in the USA estimates the direct costs of insomnia to be USD 13.9 billion annually. This includes outpatient visits, sleep recordings, medications directly devoted to insomnia, and charges for medical care and/or treatment. It is noteworthy that only USD 809 million is spent on prescription medication used for insomnia whereas over USD 1.1 billion is spent on non-prescription remedies such as alcohol (USD 781 million), OTC medications (USD 326 million), and melatonin (USD 50 million). (Source: Sleep, 1999). The market for drugs to treat insomnia has undergone extensive development since then, and by comparison, sales of the three major drugs in the sleep market (Stilnox®/Ambien® (zolpidem) from Sanofi-Synthelabo, Imovane® (zopiclone) from Aventis and Sonata® (zaleplon) from Wyeth-Lederle) amounted to USD 1.3 billion in North America in 2002 (Source: IMS Health, IMS Dataview Q4 2002). The field of sleep disorder and economics remains largely unexplored and prospective studies should be made to compare treated and non-treated insomniacs in order to better grasp the burden of insomnia on public health and society. Prevalence Sleep disorders are prevalent among the general population. It is estimated that 19-36% of the adult population in the seven major What are sleep disorders? Sleep disorders cover a range of disorders, insomnia being by far the most prevalent. Other sleep problems include sleep apnoea and restless legs syndrome (RLS). Insomnia is characterised by one or more of the following symptoms: Patients have difficulty in falling asleep and in sleeping without interruption. They wake up frequently, or very early, and feel that they have slept lightly and do not feel rested after sleeping. Sleep apnoea is described as a period when there is no airflow at the nose and mouth for ten seconds or more, which typically stops when the patient awakens abruptly. Restless legs syndrome is characterised by a creeping or prickling sensation that primarily occurs in the calves. The feeling occurs when the patient lies down to rest or sleep, and it can only be alleviated by getting up and walking about. pharmaceutical markets (France, Germany, Italy, Japan, Spain, the UK and the USA) suffered from a sleep disorder in 2000. Sleep disorders cover a range of disorders, the best known types being insomnia, sleep apnoea and restless legs syndrome (RLS). Insomnia is the most prevalent sleep disorder, and there were an estimated 164 million insomniacs in 1998. Sleep apnoea, described as a period when there is no airflow through the nose and mouth for ten seconds or more, is a less prevalent disorder. It is estimated that close to 12 million people suffered from this disorder in the seven major pharmaceutical markets in 1998. Sleep apnoea is unevenly distributed among the sexes, with an estimated 4% of all adult men and 2% of all adult women suffering from the disorder. Close to 40 million people are believed to suffer from restless legs syndrome, which is characterised by a creeping, prickling sensation that primarily occurs in the calves. Although prevalent among the adult population, insomnia remains a highly underdiagnosed disorder. There are a number of reasons for this, but some of the key factors are unwillingness to see a doctor, self-medication or acceptance of the problem without taking any action. Epidemiological studies conducted in the USA show that only about 25-30% of patients who mention their insomnia to their doctor during a visit for another problem will be diagnosed with insomnia. More or less the same applies in Europe, where an estimated 20-30% of insomniacs are diagnosed correctly. R E P O RT 31 SD 107 billion for both the direct and the indirect economic consequences of insomnia It is estimate Contents A process of change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Sup 2 L U N D B E C K A N N UA L R E P O RT 2 0 0 3 A process of change This is a time of change for Lundbeck ­ both inside the company and in the world Supervisory Board Flemming Lindeløv Lars Bruhn Peter Kürstein Mats Pettersson Jes Østergaard J Executive Management Claus Bræstrup Lars Bang Ole Chrintz Hans Henrik Munch-Jensen Stig Løkke P Financial performance in 2003 Group financial highlights 1999-2003 1999 DKKm Revenue 3,991 Research It is managements intention that the shareholders should benefit from the companys strong financial Financial performance in 2003 New dividend policy It is proposed to raise the dividend payment for t Audit committee In connection with the decision to set up an audit committee, the Supervisory Board Important events in 2003 In January, Lundbeck announced the results of phase III clinical studies wi In October, Lundbeck and Teva Pharmaceutical Industries Ltd. announced that a rasagiline regulatory Drugs in clinical development Compound Rasagiline Memantine Sertindole Escitalopram Bifeprunox Gabox Launched drugs Compound Escitalopram Citalopram Memantine Activity SSRI SSRI NMDA-antagonist Indicat Alzheimers disease Alzheimers disease, which is the most common cause of dementia, is a neurological It is estimated that roughly 37 million people around the world will suffer from a form of dementia Alzheimers disease It is estimated that about 30% of the patients treated with acetylcholine esteras Brand name Aricept® Exelon® Reminyl® Akatinol®* Axura®* Ebixa®* Active ingredient donepezil rivasti Depression and anxiety Depression is a disease that affects a large proportion of the population, an WHO estimates that depression will become the second-largest cause of the global health burden by 20 Depression and anxiety What is depression? Common symptoms of depression are: · Low mood · Loss of p Depression treatment options have improved dramatically since the 1950s, and today there are good po Parkinsons disease Parkinsons disease is a progressive neurodegenerative disruption of the central n It is estimated that close to 4 million people worldwide suffer from Parkinsons disease In October Parkinsons disease Market size The market for drugs for the treatment of Parkinsons disease was USD WHO estimates that approx. 1% of the worlds population at some point in life will be affected by sch Schizophrenia Drugs in clinical development Compound Sertindole Bifeprunox Lu 31-130 Launched drugs The latest generation of antipsychotic drugs were launched in the late 1990s. These drugs are charac Schizophrenia Symptoms of the disease Schizophrenia afflicts both sexes equally, and typically start Lundbeck and Merck have signed an agreement for the exclusive US development and commercialisation o Sleep disorders The sleep apnoea diagnosis rate in the USA is well above that for Europe. It is esti addiction. They each have different tolerability profiles, but typical side-effects are drowsiness, Know-how and competencies Lundbecks employees work to improve the quality of life for people sufferi Lundbecks success builds on research, development and marketing of unique pharmaceutical drugs. For Know-how and competencies Distribution by gender, worldwide, 2003 Geographic composition of employee Lundbeck received 3,100 unsolicited job applications during 2003 Age composition of Lundbecks emplo Environmental factors In 2003, Lundbeck focused on enhancing the in-house organisation of environmen The environmental approvals regulate the atmospheric emission of organic solvents. The field is also Summary for the Group 1994-2003 Income statement (DKKm) 1994 Revenue 1,336 Profit before research an Ratios ­ continued Capital employed (DKKm) Capital turnover (%) 1994 1,084 87.0 1995 1,507 91.0 26 Financial review The annual report of H. Lundbeck A/S has been presented in accordance with the prov On recognition of income from sales of citalopram and escitalopram to Forest, the quantities of cita Financial review restructuring and closing down the companys regional sales and administration offic The net currency expense included in net financials amounted to DKK 6 million compared to DKK 29 mil Financial review patents are amortised over the remaining patent period. In 2003, the patents were a Lundbecks total cash resources at 31 December 2003 appear from the table below. Cash resources 2003 Financial review According to the agreement with Forest, Lundbeck is guaranteed a minimum price. The Share price based plan for employees of foreign companies (1999 plan): In 1999, the employees of Lun Financial review Liability ­ 1999 plans Executive Management Executives Other Options employees not 2004 plans Warrants granted Stock Appreciation Rights granted to employees of American subsidiaries Financial review The return on the bond portfolio and money market deposits was DKK 21 million in 20 The companys USD income derives primarily from sales invoiced to Forest. According to the Groups acc Accounting policies The annual report of H. Lundbeck A/S has been presented in accordance with the p matically through the income statement based on an individual assessment of the economic life of the Accounting policies future cash flows are recognised directly in equity (hedge accounting). Income a Development costs are capitalised if the criteria for capitalising these costs in the balance sheet Accounting policies Development projects Clearly defined and identifiable development projects are r Investments in subsidiaries and associates Investments in subsidiaries and associates are measured a Accounting policies Liabilities relating to share options and other employee plans Liabilities relat On acquisitions of companies provisions for restructurings in the acquiree are included in the calcu 66 L U N D B E C K A N N UA L R E P O RT 2 0 0 3 Income statement for the year ended 31 December 2003 PARENT 2002 DKKm 2003 DKKm Notes GROUP 2003 DKK Balance sheet at 31 December 2003 - assets PARENT 2002 DKKm 2003 DKKm Notes GROUP 2003 DKKm 2002 DKK Balance sheet at 31 December 2003 - liabilities PARENT 2002 DKKm 2003 DKKm Notes GROUP 2003 DKKm 200 Equity at 31 December 2003 ­ Group Share capital DKKm Share premium DKKm Retained earnings DKKm Tota Equity at 31 December 2003 ­ Parent 2002 Equity at 1.1.2002 Distribution of dividend 9.4.2002, gross 72 L U N D B E C K A N N UA L R E P O RT 2 0 0 3 Cash flow statement for the year ended 31 December 2003 GROUP Notes 2003 DKKm 2002 DKKm Profit from Management statement The Supervisory Board and the Executive Management have today considered and ad Auditors report To the shareholders of H. Lundbeck A/S We have audited the annual report of H. Lundb Notes 1. Revenue PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 2002 DKKm 284.3 2,976.7 3,172.3 461.0 6 2. Staff costs, continued Employees: PARENT 2002 2003 2003 GROUP 2002 2,015 2,129 Average number Notes 2. Staff costs, continued Share price based plan for employees in foreign subsidiaries (1999 p 3. Depreciation and amortisation PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 2002 DKKm 131.8 39.8 65 Notes 5. Net financials PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 2002 DKKm 37.7 31.7 13.4 5.8 10. 6. Tax on profit for the year PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 2002 DKKm 577.6 (17.5) 8.4 Notes 7. Intangible assets and property, plant and equipment GROUP Goodwill DKKm Patent rights1 DKKm 7. Intangible assets and property, plant and equipment, continued GROUP Land and buildings DKKm Plan Notes 8. Investments in subsidiaries Total DKKm Accumulated Cost revaluations DKKm DKKm Accumulated 8. Investments in subsidiaries, continued Lundbeck Argentina S.A., Argentina Lundbeck Australia Pty Notes 9. Investments in associates Accumulated revaluations/ impairment Cost losses DKKm DKKm Total 12. Share capital The share capital of DKK 1,168.7 million at 31 December 2003 is divided into 233,7 Notes 14. Provision for pensions and similar liabilities PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 14. Provision for pensions and similar liabilities, continued The UK defined benefit plan is funded Notes 15. Provision for deferred tax GROUP Temporary differences between assets and liabilities as s 15. Provision for deferred tax, continued PARENT Temporary differences between assets and liabilitie Notes 16. Other provisions PARENT 2002 DKKm 2003 DKKm 2003 DKKm GROUP 2002 DKKm - 199.7 199.7 Pro 18. Treasury shares PARENT AND GROUP Shares of DKK 5 nom. Number Nominal value DKKm Share of share c Notes 19. Contractual obligations Rental and lease obligations Lundbeck has obligations amounting to 20. Contingent liabilities Incentive plans The Group has an obligation relating to share options gra Notes 21. Financial instruments Currency risks Net forward exchange contracts and currency options o 21. Financial instruments, continued Trading part: Market value (forward exchange contracts) DKKm Lo Notes 21. Financial instruments, continued Interest rate risk The interest rate risk has been calcul 22. Related parties Lundbeck defines related parties as: - The companys principal shareholder, LFI A Notes 24. Earnings per share Earnings per share (EPS) is calculated on the basis of the average numb 27. Acquisitions of companies GROUP Acquisitions of companies: Intangible assets Property, plant and Shareholder information Lundbecks year on the stock exchange H. Lundbeck A/S shares are listed on th The Supervisory Board proposes payment of a dividend of DKK 1.77 per share. This corresponds to 30% Shareholder information Composition of the shareholder group Composition of the shareholder group ex Releases from H. Lundbeck A/S in 2003 No. 119 118 117 116 115 114 113 112 111 110 109 108 107 106 10 Shareholder information Analyst coverage Broker ABG Sundal Collier Analyst Alexander Lindström Peter S U P P L E M E N TA RY R E P O RT 109 Lundbeck worldwide Parent company Denmark H. Lundbeck A/S India Lundbeck Israel Lundbeck Japan Lundb Portugal Lundbeck Portugal - Produtos Farmacêuticos Lda Russia Lundbeck Russia Slovakia Lundbeck Slo H. Lundbeck A/S Annual General Meeting will be held on 30 March 2004 at 4 pm at Copenhagen Congress In the United States, estimates range between USD 92.5 an 37 million people around the According to