It takes knowledge and experience to read the stones reactions when the rough cutting is done with drill, wedge and hammer. Before he starts, the sculptor has decided on an exact strategy that will ensure him the basic shape of what he is going to create. from Lund, Sweden, they were somehow more credible. But, in fact, what they were creating was an accumulation of dopamine in the brain and since it is an active compound that is obviously not good. Interestingly, even to this day, none of the people at that meeting has said or written anywhere that they were wrong. They just dont talk about it. So, this was the kind of resistance that we were up against and even if we did manage to change some peoples minds and advance the field in the right direction, there are still those who are not willing even to acknowledge our role at that time. Serotonin in Depression ­ birth of the SSRIs We also met with resistance towards the idea that serotonin could be important in depression. One reason was that the screening methods used at that time showed positive activity as soon as you had noradrenaline reuptake inhibition but they didnt show anything impressive for serotonin reuptake inhibition. But we didnt believe in the animal models at that time and to this day, they still have not been validated. We went with the biochemistry, which showed an important role for serotonin in depression. In fact, we shared our insights with P.V. Petersen of Lundbeck and other scientists at the company like Iver Møller Nielsen and Vagn Pedersen in the late 1960s since we had a collaboration with Lundbeck involving some of the antidepressant compounds that the Lundbeck chemists had developed. There were two key findings at that time that led us to believe in serotonin. One was Paul Kielholzs clinical scheme where he listed all the tricyclics, and on one side he had a spectrum of mood elevating effects and on the other, a spectrum of restoration of drive. The other finding was our discovery that in addition to noradrenaline, serotonin was also inhibited by antidepressants and more so by the tertiary than by the secondary amines. We put these findings together and concluded in an article that appeared in European Journal of Pharmacology in 1969 that noradrenaline is activating and serotonin is mood elevating. And so the race to develop a new class of antidepressants, the selective serotonin reuptake inhibitors (SSRI), was on. After discovering the effects of the antidepressant clomipramine on serotonin reuptake, I even went down to Basel to Geigy, which had not yet merged with Ciba, to see if they might be interested in developing this compound further as an SSRI but they were not very interested at first. We had also noted that certain antihistamines exhibited serotonin uptake inhibitory properties, as well as working on noradrenaline. So, we focused on pheniramine and diphenhydramine, the most potent serotonin uptake inhibitors among the antihistamines, and together with the Swiss organic chemist, Hans Corrodi, of the Astra subsidiary Hässle, we discovered zimeldine in 1972, which was the first SSRI antidepressant to hit the market. Incidentally, I believe that it was around that time that the chemical engineer, Klaus P. Bøgesø, joined Lundbeck and worked on turning talopram, Lundbecks selective noradrenaline reuptake inhibitor into the selective serotonin reuptake inhibitor or SSRI, citalopram. During one of our earlier meetings with P.V. Petersen and the Lundbeck people, we had talked about the possibility of turning a noradrenaline reuptake inhibitor into a serotonin reuptake inhibitor by making it more lipophilic. Apparently, Klaus, who is now head of medicinal chemistry at Lundbeck, cleverly applied this approach and the end result was citalopram. On a sad note, Astra decided to withdraw zimeldine from the market in all countries in 1983 due to the fact that patients treated with the drug had an incidence of approximately 1 in 10,000 of Guillain-Barré syndrome (a serious, but nonfatal, type of generalised weakness or paralysis) compared to 1 in 50,000 in the general population. After this unfortunate event, Astra decided to withdraw from this field of research altogether and not to pursue development of diphenhydra- 17 Årsberetning 1999 Annual Report 2000 2000 was a very satisfactory year for H. Lundbeck A/S. In the year 2000 the company achieved its bes Supervisory Board 1 2 3 4 5 6 7 8 9 1 ARNE V. JENSEN (Chairman) Directorships Lundbeckfonden Corporate Management Group 1 3 4 5 2 6 7 8 Board of Management 1 Senior Vice Presidents 3 ER Contents CHANGE REPORT GROUP FINANCIAL 5 6 7 2000 HIGHLIGHTS 1996-2000 MEMORIES OF A PSYCHOPHARMA In Northern Italy, on the boundary between Liguria and Toscana, lies the port of Carrara, neighbour Change To have high goals and establish a creative forum. To combine experience and vision. To coup Report 2000 Changes in accounting policies The years important events In February, Lundbecks UK sub Net profit for the year (DKKm) 1.000 900 800 700 600 500 400 300 200 100 0 1996 Net profit ratio Net Revenue worldwide 11% Revenue by product 18% 21% 20% 62% 68% Europe USA Rest of world Cipramil® Income from Celexa® (DKKm) 1.400 1.200 20% 1.000 800 600 400 5% 200 0 1996 1997 1998 1999 2000 0 15% Number of employees at year-end 3.500 3.000 2.500 2.000 1.500 1.000 500 0 1996 1997 1998 1999 2000 2 Research and development costs (DKKm) 1.600 1.400 1.200 1.000 800 600 400 200 0 1996 1997 1998 1999 Generic competition The production of citalopram is protected by a large number of strong process pa Expectations for 2001 Lundbeck expects sales of citalopram to continue rising in 2001, mainly in the Memories of a Pscyhopharmacologist Changing Minds, Changing Lives By Arvid Carlsson Winning the Nob Carrara is not just marble. Other reasons why thousands of sculptors go to the region is that it imp Changing the World From Sweden So, I struck out on my own and went back to Lund to work with Hillarp It takes knowledge and experience to read the stones reactions when the rough cutting is done with d mine, the other root molecule identified by us in the early series of amine uptake inhibiting agents I am afraid that the very nature of depression will limit the possibility of success in these areas. Look at the long term effects of blocking receptors with neuroleptics. The brain doesnt like it at a The rough shaping is done by removing large and small chunks with modern, special tools. 21 Conjuring the precise, planned shape out of the recalcitrant block of granite is physically hard wor Lundbeck has 735 employees in Research and Development, including about 250 in Drug Discovery. Drug In the summer of 2000, the sequence of the human genome was published. This opened the way for findi A research process Target identification & validation Disease ­ unmet need Assay development H Development Lundbeck aims to be a world leader within the development of pharmaceuticals for the tr Here, the bottom face is adjusted. This is the base from which the sculptor calculates the precise m Lundbeck has also entered into a research and development agreement with the Danish biotechnology co Development pipeline per 31.12.2000 Compound Almotriptan Escitalopram Memantine Etilevodopa Rasagili Escitalopram is the first of the new SSRI* generation Lundbecks new antidepressant, escitalopram, i Escitalopram developed in a short space of time In the summer of 1997, H. Lundbeck A/S and Forest La The clinical development programme The clinical effect of escitalopram has been documented in a numb Here, the block of granite is seen lying down, with the base of the sculpture on the left. Red lines Lundbecks products Antidepressants Cipramil®/Seropram®/Cipram®/Celexa® (citalopram) Indication: dep On the face of it, the preliminary phases of the sculptors work may look rather random, but everythi The modern sculptor naturally makes use of cranes, technical aids and modern tools, but it is still Growth in a good environment It is Lundbecks mission to improve the quality of life of those suffer Raw materials consumption (tonnes) 10,000 Environmental performance Lundbecks environmental initiat Water consumption ( 1,000 m3) 250 Wastewater (1,000 m3) 250 200 200 150 150 100 100 50 50 Energy consumption (MWh) 100,000 Waste (tonnes) 16,000 14,000 80,000 12,000 10,000 8,000 60,000 Statement from Deloitte & Touche We agreed with the Companys management to perform a review of Shareholder information H. Lundbeck A/Ss shares are listed on the Copenhagen Stock Exchange and wer Shares traded and stock performance, 2000 700,000 800 600,000 700 500,000 600 400,000 500 300 Share ratios Ratios per share, DKK Earnings (EPS) Cash flow Net asset value Dividend Dividend as a p Change takes shape 45 Composition of the shareholder group 6% 7% Composition of the shareholder group (excl. LFI A/S) 4% Announcements to the Copenhagen Stock Exchange from H. Lundbeck A/S in 2000 No. 37 36 35 34 33 32 31 The 5-tonne block of granite has been transformed into an exciting sculpture. Its weight is now down Financial calendar 2001 Tentative dates 6 27 15 14 6 March 2001 March 2001 May 2001 August 2001 Nove It is not without reason that artists seek inspiration in the Tuscan landscape around Carrara. In th Summary for the Group 1993-2000 The comparative figures have been adjusted for changes in accounting Ratios Net profit ratio (%) Return on assets (%) Return on equity (%) R&D costs as a percentage Financial review Changes in accounting policies Comparative figures and financial highlights and r Tax on the policy changes increases net profit for the year by DKK 167 million and reduces deferred Lundbecks sales of other antidepressants and antipsychotics were DKK 798 million in 2000, a decline Net exchange gain relating to finance income was DKK 39 million in 2000 compared to DKK 41 million i In 2000, Lundbecks interest-bearing net cash (the companys holding of cash and cash equivalents less million. Capital and reserves exclusive of the proposed dividend will amount to DKK 3,560 million af The options are earned by one-third a year over a three-year period. The first portion could be exer Effect of incentive plans Treasury shares/current assets DKKm Obligation/ provisions DKKm Staff cost Employees In 2000, the average number of full-time employees totalled 3,002, an increase of 349 comp 1999 Currencies of the cash inflows of H. Lundbeck A/S and its Danish subsidiaries in 1999 og 2000 Accounting Policies General The parent financial statements and the consolidated financial statemen Forward contracts and other derivative financial instruments are stated at market value. Both realis Other operating income and expenses Other operating income and expenses comprise, among other things Gains and losses are included in the income statement under the same items as the associated depreci Obligations relating to employees of foreign companies under the share price based plan are included Income statement for the year ended 31 December 2000 PARENT 1999 DKKm 2,712.7 759.4 420.5 328.9 1,20 Balance sheet at 31 December 2000 Assets PARENT 1999 DKKm 8.2 55.0 63.2 644.7 228.8 144.4 133.5 1,15 Balance sheet at 31 December 2000 Liabilities PARENT 1999 DKKm 1,165.5 448.2 269.9 202.8 695.2 129.6 Cash flow statement for the year ended at 31 December 2000 KONCERN 2000 DKKm 1,004.0 189.7 455.4 1,6 Signatures Copenhagen, 6 March 2001 The Supervisory Board and the Board of Management have today co Notes 1. Revenue PARENT 1999 DKKm 308.8 1,750.1 533.7 120.1 2,712.7 23.0 141.5 2000 DKKm 295.6 2,30 2. Staff costs ­ continued Incentive plans: In 1999, the company introduced a share option plan for Notes 3. Depreciation and amortisation PARENT 1999 DKKm 2000 DKKm Depreciation and amortisation in 6. Income tax expense PARENT 1999 DKKm 154.0 1.4 2000 DKKm 498.7 (0.5) Current tax Prior year adjust Notes 7. Intangible and tangible assets GROUP Goodwill Product rights DKKm 40.1 18.4 58.5 31.9 7.2 GROUP Land and buildings DKKm 878.2 22.2 261.8 30.5 4.7 1,188.0 211.5 9.8 10.4 46.1 2.0 275.8 912.2 Notes 8. Investments in subsidiaries Total DKKm Carrying amount at 1.1.2000 Capital contribution Di 8. Investments in subsidiaries ­ continued Currency Nominel capital `000 200 1,000 200 400 5 60 500 Notes 9. Other investments and other receivables PARENT Other investments DKKm 103.2 Receivables fr 12. Capital and reserves GROUP Share capital DKKm 1999 Capital and reserves at 1.1.1999 Adjustment d Notes 12. Capital and reserves ­ continued PARENT Share capital Share premium Reserve for net reval 13. Retirement benefit obligations GROUP The majority of the employees of the Group are covered by r Notes 14. Deferred tax liabilities GROUP Temporary differences between assets and liabilities as st 14. Deferred tax liabilities ­ continued PARENT Temporary differences between assets and liabilities Notes 15. Other provisions GROUP Share options for Group management and key employees DKKm Provisio 16. Non-current liabilities PARENT 1999 DKKm 15.9 2000 DKKm 14.2 Mortgage debt due after 5 years 200 Notes 17. Contractural obligations Rental and leasing obligations Lundbeck has obligations amountin 18. Contingent liabilities Letters of intent The parent has issued letters of intent to subsidiaries Notes 19. Financial instruments ­ continued Credit risks The primary financial instruments shown in 20. Related parties Lundbeck defines related parties as: ­ the companys principal shareholder, LFI A Notes 22. Earnings per share (EPS) Earnings per share (EPS) are calculated as: (profit after tax an 25. Acquisition of companies In 2000, Lundbeck acquired 78.29% of the share capital of VIS Farmaceut Summary for 1999-2000 by quarter The tables show financial highlights by quarter according to the ne New accounting policies (DKKm) Financial highlights by quarter: Q1 - 1999 Revenue Profit from operat Lundbeck Worldwide For further information please see our homepage: www.lundbeck.com Parent Company On its way to its final position between Lundbecks coming canteen and the new head office, which are Photos Thomas Grøndahl, Steen Vedel Design og production Creavision A/S Reproduction Highlight Grafi Annual Report 2000 H. Lundbeck A/S 9 Ottiliavej DK-2500 Copenhagen ­ Valby Denmark Tel.: +45 3630