2 December 2013
Lundbeck Investor & Analyst Event Company disclaimer
This presentation contains forward-looking statements that provide our expectations or forecasts of future events such as new product introductions, product approvals and financial performance.
Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Lundbeck's products, introduction of competing products, Lundbeck's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, changes in reimbursement rules and governmental laws and related interpretation thereof, and unexpected growth in costs and expenses.
Lundbeck undertakes no duty to update forward-looking statements.
Certain assumptions made by Lundbeck are required by Danish Securities Law for full disclosure of material corporate information. Some assumptions, including assumptions relating to sales associated with product that is prescribed for unapproved uses, are made taking into account past performances of other similar drugs for similar disease states or past performance of the same drug in other regions where the product is currently marketed. It is important to note that although physicians may, as part of their freedom to practice medicine in the US, prescribe approved drugs for any use they deem appropriate, including unapproved uses, at Lundbeck, promotion of unapproved uses is strictly prohibited.
NOT FOR PROMOTIONAL USE 2 Agenda
Time Min. Topic Speaker 1400-1430 - Coffee, registration - 1430-1450 20 Welcome and introduction + The Lundbeck journey Ulf Wiinberg 1450-1520 30 Lundbeck in psychiatry Andreas Eggert, Allan Wehnert 1520-1535 15 Break - 1535-1615 40 Brintellix – From idea to product, from product to brand Torsten Meldgaard Madsen, Andreas Eggert 1615-1630 15 Q&A Ulf Wiinberg moderator 1630-1645 15 Break - 1645-1705 20 Lu AE58054 – the next big product in Alzheimer’s? Allan Wehnert 1705-1730 25 Lundbeck in the U.S. Staffan Schuberg 1730-1755 25 Lundbeck in International Markets & Europe – focus on Brazil, Canada, China, and Japan Ole Chrintz, Herman Santoni Ramos 1755- - Final remarks and Q&A Ulf Wiinberg - Canapès and drinks
NOT FOR PROMOTIONAL USE 3 Presenters
Presenter Ulf Wiinberg President & CEO Ole Chrintz SVP, International Markets & Europe Andreas Eggert SVP, Global Product Strategy & Portfolio Development Torsten Meldgaard Divisional Director, Brintellix Science Team Madsen Herman Santoni Regional VP, Asia Ramos Staffan Schuberg President, Lundbeck Inc. (U.S.) Allan Wehnert VP, R&D Project Strategy & Portfolio Management
NOT FOR PROMOTIONAL USE 4 The Lundbeck Journey By Ulf Wiinberg, President & CEO Our vision, mission and values
OUR VISION OUR MISSION OUR VALUES
…is to become a world …is to improve the quality of Imaginative – Dare to be different leader in psychiatry and life of people suffering from Passionate – Never give up neurology psychiatric and neurological Responsible – Do the right thing disorders
NOT FOR PROMOTIONAL USE 6 Lundbeck – our strategy
1. R&D 2. LATE-STAGE STRATEGY PIPELINE Aggressive goal to rejuvenate our product portfolio 6. ORGANIZATIONAL EFFICIENCY AND 3. PRODUCT Stay focused on CNS HIGH PERFORMANCE DIVERSIFICATION CULTURE Be first or best in class High unmet need
5. PARTNERSHIPS 4. GEOGRAPHICAL AND BUSINESS EXPANSION DEVELOPMENT
NOT FOR PROMOTIONAL USE 7 The journey started in 2009
2009 2010 2011 2012 2013
Efficiency programs
Business Development Ovation Merck Xian- Cephalon Mochida Otsuka Janssen Product launches Xenazine Sabril Sycrest Lexapro - Onfi Treanda Abilify Selincro Japan Maintena (US) Phase III Brintellix Selincro Desmoteplase Onfi Zicronapine Abilify Maintena (EU) Brexpiprazole Health care reforms
NOT FOR PROMOTIONAL USE 8
Lundbeck core growth 2008-2013 (excluding Lexapro U.S.)
Revenue EBIT DKKm excl. Lexapro® excl. Lexapro® DKKm 16,000 2,000 15,000 * 1,800 14,000 1,600 * 1,400 13,000 1,200 12,000 1,000
11,000 800 600 10,000 400 200 0 0 2008 2009 2010 2011 2012 2013 -200 2008 2009 2010 2011 2012 2013
* Excl. restructuring costs of DKK 530m in 2012 and DKK 200m in 2013 NOT FOR PROMOTIONAL USE 9 Significant launch program ongoing
Product diversification
3 launches from 2003 to 2008
8 launches from 2009 to 2013
NOT FOR PROMOTIONAL USE 10 Non-European core revenue close to tripled
2008 revenue (excl. Lexapro) Geographical expansion 28% ROW Europe DKK 2.4bn sales outside EU in 2008*
9m 2013 revenue DKK 4.9bn sales outside EU in 9m 2013* ROW 53% Europe *Excl. Lexapro in U.S.
NOT FOR PROMOTIONAL USE 11 Lundbeck R&D achievements 2008-2013
5 FDA approvals in 5 years
2 EMA approvals and 1 positive CHMP opinion
1 PMDA approval
Positive phase III outcome in 4 out of 4 drugs vs. <50% success rate in CNS
NOT FOR PROMOTIONAL USE 12 Organizational structure in place for future growth
Reduced European commercial setup from 30 to 10 business units
Established a commercial Project Fit-for-the- infrastructure in the U.S. Future
Expanded presence in Asia/Latin America Project RECO
While… keeping costs in control Decisions Now
NOT FOR PROMOTIONAL USE 13 We free up resources from efficiency programs to invest in growth markets
2008: Q3 2013: 5,758 employees* 5,474 employees*
2%
10%
23% 37% 26% 35%
38% 29%
Headquarters Int. Markets EU excl. Headquarters US.
NOT FOR PROMOTIONAL USE * Incl. contracted sales force 14 Business development activity strengthen product offerings
Licensing partner of choice in CNS
Strong history and experience with all forms of licensing
Use of partnerships to ensure critical mass and innovation
Business development remains a priority
NOT FOR PROMOTIONAL USE 15 Mental disorders affect a wide range of patients in many ways
NOT FOR PROMOTIONAL USE 16 Mental disorders affect a wide range of patients in many ways
Risks & Harms Mortality & Morbidity i.e. crime, violence i.e. suicide, comorbidities
Social Family & Withdrawal Caregiver Burden i.e. i.e. emotional, unemployment physical and and deprivation financial support
NOT FOR PROMOTIONAL USE 17 Mental disorders cost EUR 113bn yearly – a quarter of the disease burden in EU
Mood disorders Dementia Psychotic disorders Anxiety Addiction Stroke Headache Mental retardation Sleep disorders TBI Personality disorders Child/Adolescent disorders Somatoform disorders Multiple sclerosis Epilepsy Direct healthcare costs Direct non-medical costs Parkinson's Neuromuscular disorders Indirect costs Brain tumor Eating disorders 0 20.000 40.000 60.000 80.000 100.000 120.000 = Lundbeck disease areas
NOT FOR PROMOTIONAL USE Gustavsson et al. 2011, EBC 2011, Eur Psychopharm 18 Huge disease burden provides need for new medicines
• CNS is the largest • USD 825bn WW in cost of • Dementia projected to therapeutic area (ref IMS depression nearly double every 20 2012) • By 2030 depression will be years • Over 1/3 of people in most the leading cause of • In 2013, Alzheimer's will countries report problems disease burden globally cost the U.S. USD 200bn with mental health (ref WHO) • >70 millions DALYs WW1) • This number is expected • USD >2,100bn WW in cost to rise to USD 1.2 trillion of illness by 20301) by 20502)
Mental Mood Alzheimer’s disorders disorders disease
1) Estimations calculated on World Eco Forum, 2011. 2) Alz.org (US Alzheimer’s Association) NOT FOR PROMOTIONAL USE 19 Factors influencing performance in the next few years
+ New product sales + Product launches + Underlying volume growth + Efficiency programs
- Generic exposures - Continued price pressure
NOT FOR PROMOTIONAL USE 20
Well placed for long-term growth
In 2018, we will have replaced Cipralex with Brintellix
In 2019, we will have more than doubled the importance of emerging markets Lundbeck to resume In 2020, we will have more than doubled our revenue base long-term growth
We have the sales potential to create 2-3 Lundbecks as we know it today
NOT FOR PROMOTIONAL USE 21 Agenda
Time Topic Speaker 1430-1450 Welcome and introduction + The Lundbeck journey Ulf Wiinberg 1450-1520 Lundbeck in psychiatry Allan Wehnert Andreas Eggert 1520-1535 Break - 1535-1615 Brintellix – From idea to product, from product to brand Torsten Meldgaard Madsen, Andreas Eggert 1615-1630 Q&A Ulf Wiinberg moderator 1630-1645 Break - 1645-1705 Lu AE58054 – the next big product in Alzheimer’s? Allan Wehnert 1705-1730 Lundbeck in the U.S. Staffan Schuberg 1730-1755 Lundbeck in International Markets & Europe – focus on Brazil, Canada, China, and Japan Ole Chrintz, Herman Santoni Ramos 1755- Newsflow, final remarks and Q&A Ulf Wiinberg Canapès and drinks
NOT FOR PROMOTIONAL USE 22 Lundbeck in psychiatry By Andreas Eggert & Allan Wehnert We are passionate about advancing the science and treatment of psychiatric brain diseases
Progress in Mind
Our heritage is psychiatry
Our passion and focus across functions is unique → Fully integrated from research to commercialization
We know and understand the science, the patients and their treating physicians
NOT FOR PROMOTIONAL USE 24 Progress in Mind In 2013 we received approvals for 3 new psychiatric therapies
Brexpiprazole
2012 2013 2014 2015+
NOT FOR PROMOTIONAL USE 25 Our passion is reflected in Lundbeck ranking first in a worldwide survey among 600 patient groups
Company 2012 Rank Lundbeck 1 Gilead 2 Novartis 3 Janssen 4 Pfizer 5 Abbott 6 Novo Nordisk 7 Roche 8 Lilly 9 GSK 10
NOT FOR PROMOTIONAL USE 26 We are tearing down internal silos to further strengthen our culture of close collaboration across R&D and Commercial
The Lundbeck Agora Building
NOT FOR PROMOTIONAL USE 27 We know the science High success rates in clinical trials and the development of new pre-clinical models underscore our scientific leadership in psychiatry
28 Over the last ten years, 90 percent of Lundbeck-conducted psychiatric phase III trials were positive
Positive phase III studies Lundbeck-conducted
Depression n = 22 95% 90% positive Psychosis n = 14 85%
n = 36 studies
Note: Lundbeck-conducted phase III studies (completed); not including extension studies, studies initiated NOTbefore FOR PROMOTIONAL 2000, studies USE completed before 2003, discontinued studies 29 The development of new schizophrenia treatments has been hampered by a lack of knowledge of the underlying disease biology
However, there is clearly a genetic link …
If you have a relative Your risk of getting with schizophrenia … schizophrenia is … Identical twin 46% Both parents 48% Sibling or parent 12% Aunt, nephew, grand parent 5% First cousin, great aunt 2% No relatives 1%
Source: Gottesman (1991)
NOT FOR PROMOTIONAL USE 30 Could Copy Number Variations (CNV) be the link to identifying better matches between groups of patients and medicines?
22q11.21 1q21.1 15q13.3
22q11.21 1q21.1 15q11.2 15q13.3
NOT FOR PROMOTIONAL USE 31 Copy Number Variations (CNV) are chromosomal deletions and duplications containing several genes
Deletion Normal Duplication
Healthy Schizophrenia General population 100 1 22q11 100 30
NOT FOR PROMOTIONAL USE 32 From a biological point of view, the syndrome of schizophrenia is likely to include different diseases
Converging symptoms and diseases in different CNV deletion syndromes
NOT FOR PROMOTIONAL USE 33 Lundbeck identified a novel platform for developing new and more effective medicines for the treatment of schizophrenia
CNV mouse CNV carriers
There seems to be a biological link between phenotypes in both CNV animal models and humans
Schizophrenia patient
Novel targets may lead to new drug candidates in 4 to 5 years
NOT FOR PROMOTIONAL USE 34 Tackling alcohol dependence We believe that the concept of harm reduction removes a key barrier to treatment for people with alcohol dependence who cannot or do not want to completely stop drinking
35 Lundbeck paved the way towards the first and only medicine approved for the reduction of alcohol consumption
2006 EU Commission adopts strategy to support reduction of alcohol-related harm
2008 European Medicines Agency (EMA) confirms clinical development plan for nalmefene and endorses reduction treatment concept
2010 EMA issues new guideline for development of medicines for treatment of alcohol dependence
Guideline reflects outcome of Lundbeck EMA Scientific Advice
36
NOT FOR PROMOTIONAL USE Introducing Selincro
Acceptance among stakeholders of (1) alcohol dependence as disease, (2) burden of disease, (3) reduction concept, and (4) Selincro
Reimbursement & market access → Reimbursement is key success factor → Cost-effectiveness confirmed by SMC in first completed HTA* → First markets with full reimbursement: Netherlands, Scotland
2014 key launches include France, Germany and UK**
* SMC = Scottish Medicines Consortium; HTA = Health Technology Appraisal ** Full commercial launch after NICE assessment NOT FOR PROMOTIONAL USE 37 Due to the exponentially increasing risk of alcohol consumption, reduction of high drinking levels reduces significant harm
Typical risk curve for alcohol consumption (e.g., liver cirrhosis mortality)
60
50
40 For many patients, abstinence is 30 an unrealistic or unacceptable
20 treatment goal
Relative Relative mortality risk 10
0 0 5 10 15 20 Number of drinks per day
NOT FOR PROMOTIONAL USE Source: Adapted from Rehm et al (2011) 38 In clinical trials, Selincro demonstrated a significant reduction in alcohol consumption
NOT FOR PROMOTIONAL USE Source: Lundbeck analysis; data on file 39 Selincro has been launched into an underdeveloped market with one of the lowest treatment rates in psychiatry
Alcohol Dependence in Europe EUROPE
5% treatment rate with Selincro
DKK 2.0 billion in annual sales* Source: Lundbeck analysis
* ~120 tablets per patient/year; EUR 3-4 per tablet
NOT FOR PROMOTIONAL USE 40 Schizophrenia We believe that non-adherence to therapy is one of the biggest tragedies in schizophrenia
41 In patients with schizophrenia, relapses result in functional decline and substantial, lasting neurological damage
Clinical and pathophysiological course of schizophrenia
NOT FOR PROMOTIONAL USE Source: Lieberman et al (2006) 42 Poor treatment adherence is a major driver of relapse, resulting in increased morbidity and healthcare resource utilization
Time to relapse in adherent and Impact of increased medication gaps
non-adherent patients on hospitalisation rates
rate in % ratein
Rehospitalization
Months Maximum number of days without medication
Source: Caseiro 2012 Source: Weiden 2004
NOT FOR PROMOTIONAL USE 43 Only 15 years ago, long-acting therapies (LAT) were considered “standard of care” in several key markets Typical LAT usage Atypical LAT usage [% of N5A antipsychotic treatment days] [% of N5A antipsychotic treatment days]
UK
France
Italy
Germany Spain
Spain USA
With only limited product options the atypical LAT market remains underdeveloped
LAT = long acting therapies NOT FOR PROMOTIONAL USE Source: IMS 44 In the U.S. early physician feedback about Abilify Maintena has been very positive Abilify Maintena Perceived Performance vs. Competition [% Top 2 Box; current prescribers of each brand]
NOT FOR PROMOTIONAL USE 45 Abilify Maintena is launched into a growing market that is quickly approaching USD 3 billion in sales
Global market for atypical antipsychotic long-acting therapies [USD millions] ~10% annual market growth
x
20% volume share
DKK 2.5 billion in annual sales*
* Lundbeck revenue
NOT FOR PROMOTIONAL USE 46 Depression and behavioral disorders We believe that the complexity of major depression and behavioral disorders requires an evolutionary* approach to new and better treatments
* As opposed to revolutionary 47 The goal is to identify the “sweet spot” to normalize both hyper- and hypo-dopaminergic states
Acute Strong Stressor Chronic stressor Clinical relevance Clinical relevance • Possible role in depression & psychosis • Precipitation of depression & anxiety • Exacerbation of psychosis mPFC mPFC • DA release ↑/(↓) • DA release ↓
NAc: NAc: • DA release ↑ • DA release ↓ (basal) • pCREB ↑ • DAT ↓ • iKk-beta ↑ • D1 ↓
VTA VTA • DA firing ↑ • DA firing ↓ • DA burst activity ↑ • %spikes in burst ↑ • AMPA/NMDAR ↑
Hyper-dopaminergic Hypo-dopaminergic Brexpiprazole may normalize both state state hyper- and hypo-dopaminergic states
NOT FOR PROMOTIONAL USE 48 Brexpiprazole has a unique and distinct pharmacology with high affinity to multiple serotonin, dopamine and norepinephrine receptors
Designed to address unresolved Designed for improved symptoms of psychiatric disorders safety and tolerability
Equally high affinity for 3 key efficacy Lower intrinsic activity at D2 receptor receptors than aripiprazole
Highest affinity in class for 5-HT1A as partial agonist Much lower affinity for H1 receptor vs. key efficacy receptors Partial agonist at D2 receptor Relatively low affinity for 5-HT2C receptor Highly potent 5-HT2A antagonist Lack of affinity for muscarinic receptors
Higher affinity blockade of α1 receptor vs. aripiprazole
NOT FOR PROMOTIONAL USE 49 We see opportunities for brexpiprazole beyond depression and schizophrenia
Brexpiprazole promise and rationale
• Broad efficacy Schizophrenia • Potential effect on cognitive symptoms • Favorable safety/tolerability profile vs other antipsychotics
• Strong pre-clinical support Major depression • Favorable safety/tolerability profile vs other antipsychotics • Synergistic effects with SSRIs/SNRIs
• Supported by pre-clinical impulsivity models Agitation in • Favorable safety/tolerability profile (elderly) Alzheimer’s disease • Clinical proof of concept obtained with other antipsychotics (contraindicated due to safety concerns)
Post-traumatic stress • Supported by pharmacology and pre-clinical data • ”Novel concept” for treating cognitive aspects of PTSD disorder (PTSD)
NOT FOR PROMOTIONAL USE 50 Pre-clinical models confirm a differentiated profile of brexpiprazole
Novel Object Recognition CogState Composite Score Brexpiprazole vs. aripiprazole Pre-Clinical Model of Wisconsin Card Sorting Test Brexpiprazole vs. aripiprazole Brexpiprazole vs. aripiprazole
D2: 17% D2: 56% 5HT2A: 15% 5HT2A: 39% 0,8 Brexpiprazole *** ** 0,6 Placebo 0.25 brexpiprazole 1.0 brexpiprazole 0,4 2.5 brexpiprazole 5 brexpiprazole D2: 74%
Discrimination index Discrimination 5HT2A: 3% 15 aripiprazole 0,2 # baseline from change Mean
Aripiprazole Week 3 Week 6 0,0
Gr 1 Veh+Veh Gr 2 PCP +Veh
Gr 4 PCP +1mg/kgGr 5AF41156 PCP +3mg/kg AF41156 Gr 3 PCP +0.3mg/kg AF41156 Gr 6 PCP +10mg/kg AF41155
Data on file
NOT FOR PROMOTIONAL USE 51 Pre-clinical models confirm a differentiated profile of brexpiprazole
Pre-Clinical Model of Wisconsin Card Sorting Test Brexpiprazole vs. aripiprazole Novel Object Recognition CogState Composite Score Brexpiprazole vs. aripiprazole Pre-Clinical Model of Wisconsin Card Sorting Test Brexpiprazole vs. aripiprazole Brexpiprazole vs. aripiprazole
D2: 17% D2: 56% 5HT2A: 15% 5HT2A: 39% 0,8 Brexpiprazole *** ** 0,6 Placebo 0.25 brexpiprazole 1.0 brexpiprazole 0,4 2.5 brexpiprazole 5 brexpiprazole D2: 74%
Discrimination index Discrimination 5HT2A: 3% 15 aripiprazole 0,2 # baseline from change Mean
Aripiprazole Week 3 Week 6 0,0
Gr 1 Veh+Veh Gr 2 PCP +Veh
Gr 4 PCP +1mg/kgGr 5AF41156 PCP +3mg/kg AF41156 Gr 3 PCP +0.3mg/kg AF41156 Gr 6 PCP +10mg/kg AF41155
Data on file
NOT FOR PROMOTIONAL USE 52 Pre-clinical models confirm a differentiated profile of brexpiprazole
CogState Composite Score Brexpiprazole vs. aripiprazole
Novel Object Recognition CogState Composite Score Brexpiprazole vs. aripiprazole Pre-Clinical Model of Wisconsin Card Sorting Test Brexpiprazole vs. aripiprazole Brexpiprazole vs. aripiprazole
D2: 17% D2: 56% 5HT2A: 15% 5HT2A: 39% 0,8 Brexpiprazole *** ** Placebo 0,6 Placebo 0.25 brexpiprazole0.25 brexpiprazole 1.0 brexpiprazole1.0 brexpiprazole 0,4 2.5 brexpiprazole 2.5 brexpiprazole5 brexpiprazole D2: 74%
Discrimination index Discrimination 5HT2A: 3% 15 aripiprazole 0,2 # baseline from change Mean 5 brexpiprazole 15 aripiprazole
Aripiprazole baseline Mean from change Week 3 Week 6 0,0
Gr 1 Veh+Veh Gr 2 PCP +Veh Week 3 Week 6
Gr 4 PCP +1mg/kgGr 5AF41156 PCP +3mg/kg AF41156 Gr 3 PCP +0.3mg/kg AF41156 Gr 6 PCP +10mg/kg AF41155
Data on file
NOT FOR PROMOTIONAL USE 53 The development plan includes programs in patients with Alzheimer’s disease and post-traumatic stress disorder
Post-traumatic stress
disorder (PTSD)* equity Agitation in Alzheimer’s disease
Comprehensive phase III program Brand - 16 ongoing studies Schizophrenia - 6,000+ patients
Major depression*
Time *NOT adjunct FOR PROMOTIONAL USE 54 Progress in Mind: Lundbeck in Psychiatry
Focus on science, passion for patients
Product assets to address medically relevant unmet needs Selincro: Empowering patients with alcohol dependence Abilify Maintena: Towards a paradigm shift in the treatment of schizophrenia Brexpiprazole: Opening new doors for multiple psychiatric diseases
… and Brintellix: Advancing the science and treatment of depression
NOT FOR PROMOTIONAL USE Break 15 minutes
NOT FOR PROMOTIONAL USE Brintellix – From idea to product, from product to brand (part I) By Torsten Meldgaard Madsen
NOT FOR PROMOTIONAL USE The Brintellix regulatory process is well on track
U.S.: Approved by FDA on 30 September 2013; SBA public 1 November 2013 EU: positive opinion (by consensus) issued by CHMP on 25 October 2013
Ongoing review Canada Mexico South Africa Australia Turkey Brazil
SBA=Summary for Basis of Approval
NOT FOR PROMOTIONAL USE 58 Unique pharmacology supports unique clinical profile
Label includes all targets in mechanism Label includes all targets, and of action or pharmacodynamics multimodal action
WHO: NO6AX26, ”other” class Multimodality terminology proposed by the scientific field
NOT FOR PROMOTIONAL USE 59 Brintellix labels: Efficacy
6/9 positive studies support efficacy, 9/12 studies positive, supporting efficacy, including one elderly study including one elderly study
Maintenance of effect in a relapse Maintenance of effect in a relapse prevention study prevention study Superiority to agomelatine 5-20 mg, dose response, increase dose as tolerated for all patients 5-20 mg, dose response, caution on >10mg in elderly
Effect on a broad range of symptoms
NOT FOR PROMOTIONAL USE 60 Approval is based on an extensive clinical programme
NOT FOR PROMOTIONAL USE 61 Relapse prevention in depression: Brintellix provides longer time to recurrence
Placebo: Cox p-value = 0.0035 N=192; Relapses: 50 (26%)
Brintellix (5 and 10 mg/day): N=204; Relapses: 27 (13%)
Hazard ratio: 2.01
NOT FOR PROMOTIONAL USE Source: U.S. label 62 REVIVE: study in previously treated SSRI/SNRI patients
Inclusion Male or female aged ≥18 and ≤75 years DSM-IV-TR diagnosis of single or recurrent episode of MDD Depressive symptoms considered as non or partially responsive to No more than one adequate course of SSRI/SNRI mono-therapy Is candidate for a switch in the investigator’s opinion Patient wants to stop current SSRI/SNRI due to inadequate response Poster from NCDEU May 2013 MADRS total score ≥22 MADRS item 1 (apparent mood) ≥3
NOT FOR PROMOTIONAL USE 63 Population in REVIVE study represents clinical practice
Physicians often see patients with inadequate response to the previous treatment
Few drugs on the market offer treatment alternative to SSRI/SNRI
Treatment choices limited to within class treatment changes
Brintellix and agomelatine both offer new pharmacological actions
Poster from EPA, March 2013
NOT FOR PROMOTIONAL USE 64 Change from baseline in MADRS total score 0 2 4 6 8 10 12 0 -5 * p< 0.05, ***p<0.001 -10 * MADRS total scoretotal MADRS -15 ***
Mean change from Baseline in in Baseline Mean from change Vortioxetine (n=252) *** -20 *** Agomelatine (n=241)
NOT FOR PROMOTIONAL USE Source: Own data presented at EPA 2013 65 Remission week 8 & 12
Vortioxetine 100 80 60 *** ** ** * 40 20
remission rate (%) rate remission 0 MADRS ≤ 10 CGI-S ≤ 2
Week 8 Week 12 Week 8 Week 12
p – value: *<0.05, **<0.01, ***<0.001
NOT FOR PROMOTIONAL USE Source: Own data presented at EPA 2013 66 Brintellix labels: Tolerability
Lack of weight increase (incl. long Lack of weight increase term) No effect on lab or vital signs No effect on lab or vital signs Abrupt discontinuation Abrupt discontinuation Low level of treatment emergent sexual Lack of sleep disturbances dysfunction Low level of treatment emergent sexual dysfunction
NOT FOR PROMOTIONAL USE 67 Brintellix has a favorable tolerability profile
Studies included in the MDD short-term pool: 303, 304, 305, 11492A, 11984A, 13267A, 316, 315 and 12541A (elderly) NOT FOR PROMOTIONAL USE TEAE’s in the core treatment period. Dashes (-) indicate no AE reported. Sorted by Lu AA21004 20 mg/day. 68 DSST and RAVLT were used to evaluate cognitive performance in the elderly study
DSST3 RAVLT4,5
• Measure of executive function, working memory, • Test of verbal learning, including recall and processing speed and visuospatial attention recognition
Delayed recall Acquisition – Learning (20–30 min) - Memory
1. Olsen C et al. Poster NR8-42 presented APA 2012. 4. Wechsler D. Wechsler Adult Intelligence Scale. 3rd ed. 1997. DSST: Digit-Symbol Substitution Test 2. Katona C et al. Int Clin Psychopharmacol.2012;27:215–223. 5. Rey A. L’Examen Clinique en Psychologie. 1964. RAVLT: Rey Auditory Verbal Learning Test NOT FOR PROMOTIONAL USE 3. Lezak MD. Neuropsychological Assessment. 2nd ed. 1983. 69 Brintellix - cognition data in elderly patients with major depression
Significant improvement in cognitive functioning vs. placebo on DSST scale
Significant improvement in cognitive functioning vs. placebo on RAVLT scale1
Path analysis: 83% of effect on DSST was direct1
1) Efficacy and Safety of Lu AA21004 in a Randomised, Double-Blind, Placebo-controlled, Active-referenced, Fixed-dose Study in Elderly Depressed Patients, Christina K Olsen, PhD et al., APA 2012, poster 8-42 DSST= Digital Symbol Substitution Test, RAVLT = Rey Auditory Verbal Learning Test NOT FOR PROMOTIONAL USE 70 Further investigating cognitive domains known to be affected in depression
NOT FOR PROMOTIONAL USE 71 FOCUS study to be presented at ACNP on 10 December 2013
Both doses of Brintellix were significantly better FOCUS study than placebo Doses: Brintellix (10 and 20mg) and placebo Mean treatment differences versus placebo of (1:1:1) 0.36 (10mg, p<0.0001) and… 0.33 (20mg, p<0.0001) on the composite Duration: 8 weeks cognition score Number of patients: ~600 The effects were largely independent of Brintellix’ effect on improving depressive symptoms Primary end-points: DSST and RAVLT
Effect on cognitive function supported by: Study conducted in Australia, Europe, Mexico, Statistically significant improvements in North America and South Africa performance on all objective neuropsychological tests Subjective patient-reported cognitive function
NOT FOR PROMOTIONAL USE Source: Roger S. McIntyre: “A Randomized, Double-blind, Placebo-controlled Study of Vortioxetine on Cognitive Function in Depressed Adults”; abstract from ACNP 2013 72 Data support Brintellix for cognitive dysfunction in major depression
Robust preclinical research indicates differentiated profile for Brintellix on measures of cognitive functioning
Data from two clinical studies support a role for Brintellix in cognitive function associated with major depression
Further studies ongoing
NOT FOR PROMOTIONAL USE 73 Brintellix: Meaningful differentiation
Different MoA recognised in label
Efficacy and tolerability, short and long-term
Efficacy in previously treated SSRI/SNRI population
Preclinical and clinical evidence show efficacy in cognitive functioning in MDD patients
Several studies underway for further differentiation
NOT FOR PROMOTIONAL USE 74 Brintellix – From idea to product, from product to brand (part II) By Andreas Eggert BRINTELLIX BRAND VISION To transform the future treatment of depression by enabling patients to not only feel better but to think and do better
NOT FOR PROMOTIONAL USE The antidepressant market Despite the availability of multiple and already genericized antidepressants, the treatment of depression remains vastly underserved
77 Do we narrow major depression to what we measure?
Behind every rating scale score is an individual patient. Montgomery-Åsberg Depression Rating Scale (MADRS): Measured items 1 - APPARENT SADNESS 2 - REPORTED SADNESS 3 - INNER TENSION 4 - REDUCED SLEEP 5 - REDUCED APPETITE 6 - CONCENTRATION DIFFICULTIES 7 - LASSITUDE 8 - INABILITY TO FEEL 9 - PESSIMISTIC THOUGHTS 10 - SUICIDAL THOUGHTS
Standard rating scales were developed primarily for regulatory purposes and do not sufficiently reflect the heterogeneity of depression
NOT FOR PROMOTIONAL USE 78 Only a minority of patients achieve “remission” per line of antidepressant treatment
STAR*D: Remission Rate by Treatment Step 1
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Step 1
Step 2 A third of patients fail to achieve full resolution of depressive symptoms after Step 3 four established treatments1
Step 4
NOT FOR PROMOTIONAL USE 1 Rush et al; Am J Psych 2006; 163: 1905-1917 79 As a result, the antidepressant market is characterized by significant patient “churn”
Patient flow in U.S. antidepressant market
Brintellix opportunity
In contrast to many other markets, even a 3rd or 4th line antidepressant position is commercially attractive
*First Psych Rx Intervention (Switch, Continuing, Add-on, Continuing Add). SourceNOT FOR: PROMOTIONAL Lundbeck & USE Vanguard analysis 80 Despite the significant unmet medical need, the depression pipeline includes only few late-stage development projects
2013 2014 2015 2016 2017
USA
USA
Phase III Development Programs
Edivoxetine Adjunct therapy in major depression (NRI; Lilly) Vyvanse Adjunct therapy in major depression; controlled substance (lisdexamfetamine; Shire) Brexpiprazole Adjunct therapy in major depression (Otsuka/Lundbeck)
NOT FOR PROMOTIONAL USE Source: Lundbeck analysis 81 Cognitive dysfunction In patients with depression, cognitive dysfunction severely affects their ability to re-engage with life Cognitive dysfunction is frequent and often remains unresolved even after “remission” of depressive symptoms
Percentage of time patients met DSM-IV criteria per symptom cluster 1
100 During major depressive episode 90 During remission
80
70 60
50 Time (%) Time 40 30 20 10 0
1. Conradi HJ et al. Psychol Med 2011;41:1165-1174; 83 NOT FOR PROMOTIONAL USE DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Cognitive dysfunction correlates with negative impact on functioning in patients with major depression
Absenteeism1 1 Presenteeism Length of sick-leave1 (% time impaired) (% time impaired) Mild cognitive (days) dysfunction 70 50 48 PDQ-5 score [0-8] 70 64 Severe cognitive 60 60 40 dysfunction PDQ-5 score [15-20] 50 44 50
37 30 Perceived Deficit Questionnaire 5-item 40 40 (PDQ-5) measures the frequency of subjective cognitive symptoms 30 19 (memory, concentration, executive 25 30 20 function) 20 20 10 10 10
0 0 0 Mild Severe Mild Severe Mild Severe Cognitive dysfunction Cognitive dysfunction Cognitive dysfunction
Cognitive dysfunction can significantly contribute to impairment at work, particularly with respect to presenteeism or impaired performance during active workdays2
1 Saragoussi et al, Preliminary Findings from the PERFORM Study presented at ISPOR congress in 2013 NOT FOR PROMOTIONAL USE 2 Greer TL et al (2010) 84 Patients with depression frequently report cognitive dysfunction as difficulty concentrating, forgetfulness and inability to make decisions
Rebecca DiFilippo Patient with major depression
NOT FOR PROMOTIONAL USE 85 Physicians confirm the need for the treatment of cognitive dysfunction in patients with major depression
Professor David Nutt DM, FRCP, FRCPsych, FSB, FMedSci Imperial College, London, UK
Dr Nutt is a consultant and speaker for Lundbeck NOT FOR PROMOTIONAL USE 86 Introducing Brintellix Brintellix addresses a medical need that is clinically meaningful and commercially attractive
87 With new clinical data we will build and strengthen the Brintellix brand over time
BRAND VISION
New clinical studies
equity CONNECT data
FOCUS data Brand
EU Public Assessment Report
Label
Time NOT FOR PROMOTIONAL USE 88 A key launch objective is to establish the broad antidepressant efficacy, safety and tolerability profile of Brintellix
DRAFT promotional materials; notNOT for FOR use PROMOTIONAL in promotion. USE 89 In Europe, the REVIVE and FOCUS data will further differentiate Brintellix from competition
…
Improvement of cognitive performance as measured by DSST
Improvement in patient-reported cognitive function outcomes
Efficacy in patients with suboptimal response to SSRI or SNRI treatment In patients with major depression, Brintellix takes care of more than mood
DRAFT promotional materials; notNOT for FOR use PROMOTIONAL in promotion. USE 90 Assuming a price similar to Cymbalta, an average market share of 2% would result in Lundbeck revenue of more than DKK 5 billion/year
Cymbalta (duloxetine) Market 2012 - all indications Brintellix
% volume Average $ per % volume Lundbeck $ revenue share 60 mg dose share revenue share
USA 5.7% $ 6.48 $ 4,560m approx. 33%
Europe 4.0% $ 1.69 $ 653m 100%
Japan 9.8% $ 3.46* $ 243m approx. 33%**
~1.6 – 3.2% 100% China 2.5% $ 1.84 $ 18m (average)
Brazil 2.0% $ 3.33 $ 64m 100%
Canada 3.6% $ 3.79 $ 166m 100%
Other 2.1% $ 1.42 $ 135m 100%
Source: IMS 2012, Lundbeck analysis; volume shares based on treatment days; $ 5,838m DKK 10-20bn DKK 5-10bn does not take into account differences in gross vs. net prices. DKK 33bn molecule revenue Lundbeck revenue * Usual recommended dose of 40 mg **NOT Assumes FOR PROMOTIONAL Takeda/Lundbeck USE co-promotion in Japan 91 Unlocking depression
Advancing understanding and treatment of depression represents major commercial opportunity
→ High patient churn in one of the largest pharmaceutical markets
Cognitive dysfunction in depression → Opportunity to raise awareness among patients, physicians and payers
Unique pharmacology supports unique clinical profile
92
NOT FOR PROMOTIONAL USE Q&A Moderator: Ulf Wiinberg, President & CEO Break 15 min Lu AE58054 – The next big product in Alzheimer’s? By Allan Wehnert Lundbeck in Alzheimer’s disease (AD)
Lundbeck launched Ebixa in 2002 Net sales (EURm) At peak Ebixa had 27% of the European market 400 Revenue of DKK 2.8bn in 2012 350 Expected to decline 25-30% in 2013 following generic erosion 300
250 Lu AE58054 is one of the most advanced novel AD compounds in clinical development (phase III) 200
150 Brexpiprazole in agitation associated with AD (phase III) 100
50 Therapeutic vaccine against beta-amyloid, Lu AF20513 (phase I in 2014) 0
NOT FOR PROMOTIONAL USE 96 Alzheimer’s disease is increasingly a burden to society
Alzheimer's disease (AD) is the most common type of dementia
The total number of people with dementia worldwide in 2010 is estimated at 35.6m Projected to nearly double every 20 years, to 65.7m in 2030 and 115.4m in 2050
AD is an increasing problem for patients, caregivers, and society
Global society costs estimated to exceed USD 600bn annually or 1% of world GDP
NOT FOR PROMOTIONAL USE 97 The Alzheimer’s brain
Neurodegeneration
Neurotransmission Activity Cognition
NOT FOR PROMOTIONAL USE 98 How is Alzheimer’s treated today?
There is no cure for Alzheimer's disease
Attempts to modify the disease by removing beta-amyloid from the brain have until now been unsuccessful
Available medications may relieve symptoms: Cholinesterase inhibitors (for mild-moderate AD) Donepezil = Aricept® Rivastigmine = Exelon® Galantamine = Reminyl®
Glutamate receptor antagonist (for moderate-severe AD) Memantine = Ebixa®
NOT FOR PROMOTIONAL USE 99 Lu AE58054 has the potential to be the first new Alzheimer's treatment in nearly 20 years
failed
failed Failed first time failed
failed
NOT FOR PROMOTIONAL USE 100 Lu AE58054 offers a new pharmacological approach to the treatment of Alzheimer’s
Lu AE58054 is a selective and high affinity antagonist of the 5-HT6 receptor
5-HT6 receptor function
NOT FOR PROMOTIONAL USE Source: Arnt et. al., Int. J. Neuropsychopharmacol,, 2010 101 5-HT6 receptor expression in the brain
Rat brain Human brain (PET ligand)
The 5-HT6 receptor is expressed almost exclusively in the brain – in regions affected by Alzheimer’s disease
Due to its expression in cortical and limbic regions, the 5-HT6 receptor plays a role in cognition, memory and emotionality
NOT FOR PROMOTIONAL USE Sources: Parker et. al., J. Nuclear Medicine, 2012; East et al., Synapse, 2002 102 Lu AE58054 – Potentiating multiple transmitter systems
Lu AE58054 Hypothesis for MoA
Restores activity by reducing the ‘natural break’ in the system (GABA) GABA Impacts multiple neurotransmitters by reducing inhibition
Neurotransmission ACh, Glu, DA, 5-HT Complimentary to current treatment with potential for added benefit (e.g. donepezil)
Cognition Improves cognition in AD and possibly other disorders
NOT FOR PROMOTIONAL USE 103
Synergistic efficacy when adding to donepezil
180
160 Vehicle (n = 4) 140 Lu AE58054 (n = 5) A dramatic increase in 120 100 Theta power is observed 80 when given together with 60
40 donepezil
20 Theta power (%of baseline)Theta power 0 0 -300 300 600 900 1200 1500 1800 2100 2400 2700 3000 3300 3600 Two-way ANOVA: P < 0.0001 vehicle + vehicle vs. vehicle + donepezil Time (s) injection P < 0.0001 vehicle + donepezil vs. Lu AE58054 + donepezil 400 Vehicle + Vehicle (n = 5) Vehicle + donepezil (n = 3) 300 Lu AE58054 + donepezil (n = 3) 11000 * 10000 200 9000 8000 7000 6000 5000 100 4000 3000
Theta power (AUC)Theta power 2000
Theta power (% baseline)of Theta power 1000 0 0 Vehicle + Lu AE58054 + 0 donepezil donepezil -300 300 600 900 1200 1500 1800 2100 2400 2700 3000 3300 3600 Time (s) Injection
NOT FOR PROMOTIONAL USE JFB SfN poster 2011 104 Why could Lu AE58054 be a new valuable Alzheimer’s treatment?
Lu AE58054 has a different mode of action compared to existing
symptomatic treatments (blockade of 5-HT6 receptors)
Blocking this particular kind of serotonin receptors (5-HT6 receptors) has beneficial effects on several neurotransmitter systems in the brain
Lu AE58054 has demonstrated beneficial effects on cognition: In animal models In AD patients on stable donepezil treatment
NOT FOR PROMOTIONAL USE 105 Lu AE58054 phase II study design
Clinical phase II 24 weeks study of Lu AE58054 in combination The primary objective is to explore the effect therapy with donepezil in Alzheimer’s disease on cognitive performance (ADAS-cog) Lu AE58054 TID + donepezil (n=135) Initiated in November 2009 donepezil donepezil 278 patients with moderate Alzheimer’s placebo TID + donepezil (n=135) Add-on to donepezil
2 weeks 24 weeks 4 weeks Treatment period of 24 weeks Screening baseline completion Safety follow-up Study conducted in Europe, Canada and Australia
NOT FOR PROMOTIONAL USE 106 Statistically significant improvement for Lu AE58054 as add-on to donepezil, versus donepezil alone
ADAS-Cog (COGNITION)
-2 Lu AE58054 Placebo
p=0.013
-1 p=0.004
0
1 Adjusted Adjusted mean change frombaseline
2 0 4 8 12 16 20 24 Week
NOT FOR PROMOTIONAL USE 107
Secondary efficacy endpoints support superiority
ADCS-ADL23 ADCS-CGIC (FUNCTION) (GLOBAL IMPRESSION)
2 3,8
1 p=0.020 Lu AE58054 4,0 0 Placebo Lu AE58054 Placebo p=0.243
-1
baseline baseline scores - 4,2 p=0.116 p=0.124 -2
-3 Adjusted Adjusted post 4,4
Adjusted Adjusted mean change frombaseline -4
-5 4,6 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Week Week
NOT FOR PROMOTIONAL USE 108 Lu AE58054 phase II outcome: effective in AD patients
Lu AE58054 demonstrated significant improvements in cognitive function compared to donezepil monotherapy as assessed by the cognition scale ADAS-cog
Secondary endpoints, including measures of global status and activities of daily living also showed positive trends with Lu AE58054, compared with patients who only received donepezil
Lu AE58054 was considered overall to be well tolerated
NOT FOR PROMOTIONAL USE 109 Positive FDA and EMA feedback and strong support for the overall development program
The planned program with donepezil base treatment will support an indication for: Treatment of mild to moderate dementia of Alzheimer’s type as adjunctive therapy to donepezil
Inclusion of patients on other AChEIs may support indication for use as adjunctive treatment in combination with all AChEIs, if supported by descriptive analyses of data from these patients (FDA only)
Effect on ADAS-Cog and at least one of ADCS-ADL or ADCS-CGIC is acceptable demonstration of symptomatic efficacy in mild-to-moderate AD
NOT FOR PROMOTIONAL USE 110
The planned clinical phase III program – data read-out in 2016
Primary Treatment Lu AE58054 Donepezil Endpoint Study Duration Design (mg/day) (mg/day) Scale No. of patients Currently planned phase III studies Study 1 24 weeks 30 and 60 10 ADAS-cog ~930 Randomised, DB, PBO, parallel- Study 2 24 weeks group, fixed-dose 10 and 30 10 ADAS-cog ~850 adjunctive Study 3 24 weeks treatment to 60 10 ADAS-cog ~550 donepezil
Study 4 24 weeks AChEIs 60 - ADAS-cog ~750
DB: double-blind; PBO: placebo-controlled
NOT FOR PROMOTIONAL USE 111 Beyond symptomatic treatment
The next breakthrough in treating the underlying cause of Alzheimer’s disease
Beyond symptomatic treatment
NOT FOR PROMOTIONAL USE 112 The amyloid cascade hypothesis in Alzheimer’s
NOT FOR PROMOTIONAL USE 113 Strong belief in potential for anti-Aβ immunotherapy in treatment of AD Active vaccines
Compound Sponsor Dev. stage V950 Aβ1-7 associated with carrier protein Merck Phase I study completed Jan 2012 UB311 Aβ1-14 fused with undisclosed T helper epitope United Biomedical UB initiating phase II study
CAD106 Aβ1-6 attached to Qb virus like particles Novartis Phase IIa + b (dose finding) in mild AD completed Dec 2012 ACC-001 Aβ1-6 associated with carrier protein Pfizer/Wyeth Six Phase II (IIa/IIb) ongoing/completed
Affitope AD02 Synthetic peptide mimotope N-terminal Aβ1-6 with carrier Affiris/GSK Phase II ongoing Affitope AD03 Affiris/GSK Phase I Passive vaccines Compound Sponsor Dev. stage Solenezumab Aβ mAb Eli Lilly Phase III
Phase III completed with negative results. Continuing Bapineuzumab Aβ mAb, IV formulation Elan development of subcutaneous formulation Gantenerumab Aβ mAb MorphoSys Phase II
Crenezumab Aβ mAb AC Immune (Roche) PhaseII
GSK-933776 Aβ mAb GlaxoSmithKline Phase I AAB-003 Aβ mAb Elan (Pfizer, J&J) Phase I BAN2401 Aβ mAb BioArctic Neuroscience (Eisai) Phase I BIIB037 Aβ mAb Neurimmune Therapeutics (Biogen Idec) Phase I
NOT FOR PROMOTIONAL USE 114 Strong potential for active anti-Aβ immunotherapy in treatment of AD
Antibodies mediate effective and highly specific immune clearance of toxic antigens and neutralise toxicity
Polyclonal antibody response is anticipated to be effective for neutralisation and clearance of heterogenous proteins such as Aβ in AD
Antibodies are natural physiologic response proteins to aberrant antigens and under tight control of immune regulatory mechanism
Active vaccines are simple treatments that can be applied everywhere (caregiver controlled)
NOT FOR PROMOTIONAL USE 115 Lu AF20513 - Anti-Aβ active vaccine concept
AutoVac – a unique and properitary concept
Wanted from AF20513 FIH study Not wanted Safe and tolerable: Aβ specific T-cells Low level of ARIA-E and ARIA-H High IgM over IgG ratio No meningo-encephalitis Very low responder rate High antibody responder rate
Fast antibody response (< 6 months) High affinity Aβ specific antibodies (for CNS clearance) Clinical study in AD patients to start mid 2014
NOT FOR PROMOTIONAL USE 116 Our Alzheimer's R&D pipeline is unique
Lu AE58054 demonstrated positive phase II results as add-on to donepezil in moderate AD Phase III commenced in October 2013
Brexpiprazole in patients with agitation associated with dementia of the Alzheimer's type Phase III commenced in July 2013
Lu AF20513 to be the next generation active vaccination with potential to modify disease progression Phase I to commence in 2014
NOT FOR PROMOTIONAL USE 117 Lundbeck in the U.S. By Staffan Schuberg, President, Lundbeck U.S. Strategy and Understanding of Market Dynamics Crowns Share of Voice The U.S. story
• Cross Atlantic Integration • Multiple product launches in Neurology • Built local partnership with Takeda and Otsuka • Divested all non-strategic products
• Acquisition of Ovation Pharmaceuticals as Lundbeck’s U.S. Platform for Commercialization and Drug Development
• Lundbeck’s only US presence was Paramus Research facility (NJ) • All commercialization done by partner (Forest Labs)
2008 2009 2010 2011 2012 2013
NOT FOR PROMOTIONAL USE 120 Lundbeck U.S. today
CNS growth company integrated into Lundbeck’s global vision and mission
Fully integrated U.S. organization including Research, Drug Development, Commercial and Business Development with shared supporting functions
Strong commercial platform with four successful launches in CNS
Development organization with local excellence and global competence
Lundbeck global neuro-inflammation research center of excellence
Successful business unit build-out ahead of psychiatry product launches
2013 expected U.S. net sales of USD ~550m
~800 Lundbeck U.S. employees by end of 2013
NOT FOR PROMOTIONAL USE 121 Lundbeck U.S. executes well according to growth agenda
NOT FOR PROMOTIONAL USE 122 A robust neurology portfolio
Xenazine® (tetrabenazine) Launched 24 November 2008 • Chorea associated with Huntington’s disease • Partner with Valeant
Sabril® (vigabatrin) Launched 21 September 2009 • Infantile spasms • Add-on therapy for adults with refractory complex partial seizures
ONFI® (clobazam) Launched 2 January 2012 • Adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in patients two years and older
NOT FOR PROMOTIONAL USE 123 • First 9m 2013 net sales of DKK 1,033m • Compound Annual Growth Rate of 40% from 2010 – 2013 • Continue to uncover HD patients with high unmet need where Xenazine can help • Expected peak sales exceeding DKK 1.5bn
NOT FOR PROMOTIONAL USE 124 • 9m 2013 net sales DKK 396m • Compound Annual Growth Rate of 45% from 2010 – 2013 • Standard of care for infantile spasms patients with Tuberous Sclerosis • Pediatric exclusivity granted by FDA 26th October 2013 • Approximately DKK 1bn expected peak sales
NOT FOR PROMOTIONAL USE 125 • 9m 2013 net sales DKK 367m • High acceptance and usage by epileptologists • Compound Annual Growth Rate of 33% from 2012 – 2013 • New formulations, liquid and scored tablets launched Aug. 2013 • DKK 1-1.5 bn expected peak sales • Development work started in Dravet’s syndrome (PED)
NOT FOR PROMOTIONAL USE 126 Deep Insight and Knowledge of Your Market: Today’s Way to Win Competitive comparison – Onfi v. Banzel™ 3.000 “At Launch” Comparison Banzel: 2.500 For adjunctive treatment of 2.000 seizures associated with LGS in 1.500 children 4 years and older and 1.000 adults Onfi: 500 Banzel (since Launch) Onfi For seizures associated with
0
3 5 7 9
1 Lennox-Gastaut syndrome in
21 23 43 45 11 13 15 17 19 25 27 29 31 33 35 37 39 41 47 49 51 people 2 years of age or older Current Comparison 25000 20000 15000 Banzel 10000 Onfi 5000
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
NOT FOR PROMOTIONAL USE 128 Capitalizing on partnership to gain strength and presence in U.S. psychiatry market
1998-2009 2013 2014 2015 2016-2017 TBD
No Comm Org
Significant Comm Org.
Brexpiprazole LuAE58054
Lundbeck Share of Revenue 20% 20% 20% ~33%+ ~50/50% ~50/50%
Strategic and R&D input
Strategic and R&D input and Commercial effort
NOT FOR PROMOTIONAL USE 129 Growing psychiatry portfolio
Abilify Maintena Launched April 2013 • Maintenance treatment of schizophrenia • Partner with Otsuka
Brintellix Commercial launch by end January 2014 • Treatment of depression • Partner with Takeda
Brexpiprazole Expected launch 2015 brexpiprazole • Studies in treatment of schizophrenia and as adjunct in MDD • Partnered with Otsuka
NOT FOR PROMOTIONAL USE 130 • Approved by FDA end of February 2013 • Approximately 5% of LAI market • More than 4,000 patients in receipt of samples • Early physician feedback about Abilify Maintena has been very positive • New HCP friendly dual-chamber syringe expected approval Q4 2014 • Deltoid injection expected approval Q4 2015 • Registrational trial for bipolar indication is ongoing • Approximately DKK 2.5bn expected global peak income
NOT FOR PROMOTIONAL USE 131 “Lundbeck, Takeda win U.S. Approval for Depression Therapy” “FDA Approves New Drug to Treat Major Depressive Disorder” “FDA Approves a new antidepressant” “All about Brintellix, the new FDA-approved antidepressant” “…Brintellix is expected to do well in the market thanks to its potential for positive effects on cognition and benign side effect profile.”
“Brintellix Label Gives Lundbeck Ground For Tolerability Claims” “FDA Approves a new antidepressant: Brintellix”
NOT FOR PROMOTIONAL USE 132 The impact of major depression
14
MILLION Evidence suggests that MDD may be associated MDD affects with the increased nearly 14 morbidity and mortality million Largest from such illnesses as Americans contributor of diabetes and heart disability in the disease U.S.
* Kessler, R., Berglund, P., et al (2003). The Epidemiology of Major Depressive Disorder: Results From the National Comorbidity Survey Replication. Journal of the American Medical Association, 289 (23):3095-3105. ** World Health Organization Website: Depression Fact Sheet. http://www.who.int/mediacentre/factsheets/fs369/en/index.html. Last accessed: 11/1/12. NOT FOR PROMOTIONAL USE *** Katon WJ. Clinical and health services relationships between major depression, depressive symptoms and general medical illness. Biol Psychiatry 54:216–26. 2003 133
Cost of major depression
$83 $44 BILLION Total cost of BILLION depression each Annual cost for year in medical employers in expenses and lost productivity indirect costs in 2002
* Stewart WF et al. (2003): Cost of Lost Productive Work Time Among U.S. Workers with Depression. JAMA, 3135-3144. ** Greenberg, PE, Kessler, RC, Birnbaum, HG, Leong, SA, Lowe, SW, Berglund, PA, et al. (2003). The economic burden of depression in the United 134 NOT FOR PROMOTIONAL USE States: How did it change between 1990 and 2000? Journal of Clinical Psychiatry, 64 (1465-1475). U.S. antidepressant market overview
Depression affects 6.5% or Payer pressures will continue to 14 million U.S. adults increase
Providers and patients recognize a No antidepressant has a dominant need for new treatment options with share of the market novel MoA, better efficacy and
tolerability Private payers account for 70% of Rxs
and are influenced by providing Highly heterogenious disorders competitive formulary
NOT FOR PROMOTIONAL USE 135 Genuine interest among U.S. physicians
Interest level in Brintellix: After detailed discussion Rating of interest level
1 2 3 4 5 6 7 8 9 10
Not at all Extremely interested Avg. rating after detailed interested review of draft sales aid
NOT FOR PROMOTIONAL USE Source: Lundbeck/Takeda Market Research 2013 136 Brintellix: Strong and Meaningful Label
This chart provides label information only and is not intended to reflect comparative trial or to imply superiority. NOT FOR PROMOTIONAL USE 137 U.S. antidepressant market overview
Depression affects 6.5% or Payer pressures will continue to 14 million U.S. adults increase
Providers and patients recognize a No antidepressant has a dominant need for new treatment options with share of the market novel MoA, better efficacy and tolerability Private payers account for 70% of Rxs and are influenced by providing Highly heterogenious disorders competitive formulary
NOT FOR PROMOTIONAL USE 138 Brintellix Meets Many Unmet Needs in the Marketplace
No Short or Long-term Low Sexual Novel Mechanism Efficacy Weight Gain Adverse Events
139 Antidepressants are a Center for Medicare & Medicaid Services (CMS) Protected Class
140 Brintellix’s multiple pharmacological effects have resulted in its classification by U.S. drug • First Data Bank price • MediSpan • Gold Standard reference groups* • Redbook as being different • USP than SSRIs and SNRIs
141 2/3 of patients do not achieve remission with their first antidepressant
Source: Trivedi MH, Rush AJ, Wisniewski SR, et al. (2006). Evaluation of outcomes with citalopram for depression using measurement- based care in STAR*D: implications for clinical practice. Am J Psychiatry, 163 (1):28-40 142 Treatment algorithm and guidelines
Start: SSRI or SNRI
Increase dose or Switch APA Practice Guidelines
“For patients who do not show a Refer response to an initial antidepressant, (Specialist, Tertiary Diagnosis, Duration, Dosing consider changing to a different Center) antidepressant in the same class, or in a different class. “
Switch, Augment, Combine
Non-pharmaceutical treatments
NOT FOR PROMOTIONAL USE 143 Pristiq and Viibryd commercial health plans
Pristiq Status Viibryd Status 7,9% 11,1% 6,6% 6,5%
85,5% 81,4%
NOT FOR PROMOTIONAL USE 144 Impact of payer restrictions
2,5
2
1,5
1
0,5 Percentage of Usage ofPercentage
0 Pristiq Viibryd All Commercial Payers: No Restrictions All Payers: Step Therapy
NOT FOR PROMOTIONAL USE *Source data: Q1 2013 Wolters Kluwer claims using Lundbeck U.S. MDD market basket 145 Commercial co-pay sensitivity new start abandonment
SNRI Commercial Abandonment 2011 New Starts Prior Therapy Naïve (n = 46,374) (n = 54,968)
60% 50% 50% 40% 31% 29% 30% 25% 24% 23% 21% 19% 20% 17% 17% 12% 13% 9% 10% 9% 8% 8% 6% 6% 10% 4% 4% 5% 5% 6% 4% 2% 2% 2% 3% 3% 3% 4%
New Start Abandonment Abandonment New Start Rate 0% <$5 $5 - $10 - $15 - $20 - $25 - $30 - $35 - $40 - $45 - $50 - $55 - $60 - $65 - $70 - $75+ $9 $14 $19 $24 $29 $34 $39 $44 $49 $54 $59 $64 $69 $74
Avg. Tier 2 Co-pay Avg. Tier 3 Co-pay
NOT FOR PROMOTIONAL USE Source: Wolters Kluwer PTD Dataset (2008-2011); Amundsen Group analysis 146 Commercial co-pay sensitivity new start adherence
SNRI Commercial Adherence 2010 New Starts Prior Therapy Naïve (n = 66,341) (n = 77,574) 250
195 197 189 190 186 185 200 179 178 177 168 170 174 174 170 161 161 162 164 161161 159 164 151 155 155 151 150 152 150 145 145 118119 100
50
0
<$5 $5 - $10 - $15 - $20 - $25 - $30 - $35 - $40 - $45 - $50 - $55 - $60 - $65 - $70 - $75+ (DOT) Average Annual Days of Therapy Average $9 $14 $19 $24 $29 $34 $39 $44 $49 $54 $59 $64 $69 $74
NOT FOR PROMOTIONAL USE Source: Wolters Kluwer PTD Dataset (2008-2011); Amundsen Group analysis 147 WAC price per tab for branded MDD products
$8,00 $7,27 $7,27 $7,00 $6,75 $6,48 $5,89 $6,00
$5,00
$5,00
$4,00
$3,00
WAC Tab WAC PerPrice $2,00
$1,00
$0,00 Brintellix Cymbalta (30mg and 60mg) Cymbalta (20mg) Fetzima Pristiq Viibryd
NOT FOR PROMOTIONAL USE 148 Access team is already actively engaged with payers to achieve goal of 80-85% access within the first year of launch
Approximately 1,000 patients will have initial access to Brintellix through the early experience program
Brintellix is now available for patients through the Patient Assistance Program
Approximately 325 physicians trained as Brintellix speakers
A competitive and experienced Lundbeck and Takeda sales force has been trained and are executing targeting activities
Launch Meeting and initiate representative promotion end of January 2014 Expected peak sales in the U.S.: USD 1-2bn
NOT FOR PROMOTIONAL USE 149 Heterogeneous Population
Protected Class
Step Therapy: Patients Have No Impact Low Cost Sensitivity
150 Lundbeck US Summary Fully integrated U.S. Operations With Strong Growth and Track Record from 2009 – 2013
Our Strategy and True Understanding of Market Dynamics Will Continue to Advance our Business
We are Prepared for Opportunities on the Horizon, Notably Brintellix Lundbeck in Europe and International Markets - Focus on Brazil and Canada By Ole Chrintz
NOT FOR PROMOTIONAL USE
Global pharma market Rank 2007 Rank 2012 Rank 2017 1 United States 1 United States 1 United States 2 Japan 2 Japan 2 China 3 France 3 China 3 Japan 4 Germany 4 Germany 4 Brazil 5 China 5 France 5 Germany 6 Italy 6 Brazil 6 France 7 UK 7 Italy 7 Italy 8 Spain 8 Canada 8 Russia 9 Canada 9 UK 9 India 10 Brazil 10 Spain 10 Canada 11 Mexico 11 Russia 11 UK 12 South Korea 12 Australia 12 Spain 13 Turkey 13 India 13 Australia 14 Russia 14 Mexico 14 Argentina 15 India 15 South Korea 15 South Korea 16 Australia 16 Turkey 16 Mexico 17 Netherlands 17 Venezuela 17 Turkey 18 Poland 18 Poland 18 Indonesia 19 Greece 19 Argentina 19 Venezuela 20 Belgium 20 Belgium 20 Poland
NOT FOR PROMOTIONAL USE Source: IMS Market Prognosis, March 2013; Market size ranking in USD for 2007 and 2012; For 2017 in constant USD. Contains Audited + Unaudited data. 154 High growth in Emerging Markets
Lundbeck Revenue, DKK Emerging Markets* ~5 billion
15% CAGR DKK 2½ billion
2014 2019
NOT FOR PROMOTIONAL USE * Emerging Markets: Asia (excl. Japan), Latin America & Africa, Middle East and Russia 155 New regional focus in Int. Markets and Europe
Latin Middle East Europe Asia America Canada & Global & Africa Distribution
NOT FOR PROMOTIONAL USE 156 Europe – major restructure
Sales structure
Sales force restructure – 2012 GP sales force reduction Rented sales force
New affiliate structure – 2013 Specialist From 30+ to 10 strong Affiliate sales force Units
Local partners if needed
NOT FOR PROMOTIONAL USE 157 European sales development – no impact from restructure
% Lundbeck Annual Revenue Growth Rates (excl. Ebixa) 6
5
4 Restructure announced 3 June 2012 2
1
0 Q2 '12 Q3 '12 Q4 '12 Q1 '13 Q2 '13 Q3 '13 -1
-2
-3
-4
NOT FOR PROMOTIONAL USE 158 Benefits of new European organization
Operating at significant lower cost levels
Flexible cost structure with market access based investments
Increased competencies particularly for market access
Increased ability to coordinate efficiently
Higher likelihood of succeeding with new products
NOT FOR PROMOTIONAL USE 159 Significant growth in International Markets
DKKm
4.000 Future launches 11% CAGR Brintellix – 2014/2015 3.000 Azilect – 2014/2015 (Korea & China) 2.000 Abilify Maintena – 2015
Selincro – 2015 1.000
0 2008 2009 2010 2011 2012 2013
NOT FOR PROMOTIONAL USE 160 Cipralex – the leading product in International Markets
Market Value Market Share Share (%) July 2013 20 18 16
14 Generics
12
10 Brand 8 6
4 Cipralex 2
0
Sertraline
Bupropion
Fluoxetine
Duloxetine
Paroxetine
Citalopram
Venlafaxine
Agomelatine
Escitalopram Desvenlafaxine
NOT FOR PROMOTIONAL USE Source: IMS Health August-2013, retail only 161 Cipralex DKK >1bn in sales in Canada
Cipralex® in Canada Market share CADm value 200 30%
Revenue Market share 25% 150 20%
100 15%
10% 50 5%
0 0% 2008 2009 2010 2011 2012 2013
NOT FOR PROMOTIONAL USE 162 Brintellix in Canada – A substantial opportunity
Market for anti-depressants: CAD ~900m
70% of depressed patients in a job situation
High awareness on functionality issues for depressed patients at the workplace
Brintellix cognitive benefit profile: - meets unmet needs for working patients and other patient groups
NOT FOR PROMOTIONAL USE 163 High growth in Emerging Markets
Lundbeck Revenue, Emerging Markets* DKK ~5 billion
15% CAGR DKK 2½ billion
2014 2019
NOT FOR PROMOTIONAL USE * Emerging Markets: Asia (excl. Japan), Latin America & Africa, Middle East and Russia 164 Lundbeck – full coverage of Latin America
Lundbeck affiliates Brazil Mexico Argentina Chile Colombia Venezuela Central America
NOT FOR PROMOTIONAL USE 165 Brazilian antidepressants market – explosive growth
USDm Market for anti-depressants 1.000 Brazil
500
0 2009 2010 2011 2012 2013
NOT FOR PROMOTIONAL USE Source: PMB IMS Sep/2013. Note: all years are MAT September. Ex-rate: 1USD = 2,21875R$ 166 Brintellix – a key driver in Latin American sales outlook
DKKm 2.000 Lundbeck revenue Latin America
1.500
1.000
500
0 2014 2019
NOT FOR PROMOTIONAL USE 167 Strong progress in Asia
Regions share of Lundbeck sales and world CNS markets
Share of total Share of world Lundbeck sales (%) CNS market (%)
Asia* 9½ 15½ Asia excl. Japan 7½ 7 Latin America 5½ 5½ Middle East 2 1-2
* Japan, China, Korea, India, South East Asia and Turkey
NOT FOR PROMOTIONAL USE 168 Lundbeck in International Markets - Focus on Asia By Herman Santoni Ramos Long-term trends contributing to pharmaceutical growth in China
New Mental Health Law
Strong Growth in GDP Strong Growth in HealthCare New Mental Health Law China is forecasted to increase China is forecasted to triple The new Mental Health law was GDP >4 times in next decade, to health expenditure in this decade implemented on May 1st 2013. become largest world economy Gives doctors and hospitals a mandate to treat CNS patients
Source: China Stats, MoH, Mckinsey and Standard Charted Forecast, NOT FOR PROMOTIONAL USE 170 Lundbeck is increasing its footprint in China
Beijing WFOE1) established in 2007
Products include Lexapro, Ebixa, Cipramil, Deanxit. Partnerships as co-promotion, exclusive distribution and importation
Rich pipeline with CTA / clinical trials ongoing for 3 promising CNS products in China
Commercial Operations in Beijing, research center in Shanghai and production site in Tianjin
1) The Wholly Foreign Owned Enterprise (WFOE or WOFE) is a Limited liability company wholly owned by the foreign investor(s)
NOT FOR PROMOTIONAL USE Lundbeck – now a leading CNS player in China Performance of Top 10 Corporations in CNS Market, MAT 2Q’13 Sales Ranking Market Share Growth Corporation MAT 2Q’13 MAT Q2’13 MAT 2Q’13 1 Eli Lilly Group 8.1% 14.6% 2 Jiangsu Hansoh 7.6% 28.0% 3 Lundbeck products 7.1% 26.0% 4 Glaxo Smith Kl Group 6.0.% 26.6% 5 J&J Group 5.3% 10.2% 6 Pfizer Group 4.9% 24.6% 7 Sc. Cd. Tiantaishan 3.9% 9.8% 8 Sanofi Group 3.7% 13.6% 9 Cd. Kanghong Group 2.8% 18.4% 10 Eisai Group 2.5% 20.8%
NOT FOR PROMOTIONAL USE Source: IMS Hospital Audit(>=100 beds), 2Q 2013. Lundbeck products = in-market sales 172 Cipralex market shares growing in China despite generic competition
Value market share
9,0% Depression market in 2013 is RMB 2.7bn – up 25% vs. 2012 8,0%
7,0% Cipralex is marketed in co-promotion with XJP
6,0% Cipralex was launched in China in 2005 5,0% Cipralex is outgrowing the market by almost 2x 4,0% 1st qrt. 2nd qrt. 3rd qrt. 4th qrt. 1st qrt. 2nd qrt. 3rd qrt. 4th qrt. 1st qrt. 2nd qrt. 2011 2011 2011 2011 2012 2012 2012 2012 2013 2013
NOT FOR PROMOTIONAL USE Source: IMS 173 Mood Disorders Educational Projects: WPA / Lundbeck Institute
Reported from CCTV:
NOT FOR PROMOTIONAL USE Ebixa market shares growing in China
Value market share
32,0% Alzheimer's market in 2013 is RMB 368m – up
30,0% 24% vs. 2012
28,0% Ebixa was launched in China in 2006 and 26,0% marketed by Lundbeck only 24,0% 22,0% Ebixa is also outgrowing the market by almost 2x 20,0% 18,0% 1st qrt. 2nd qrt. 3rd qrt. 4th qrt. 1st qrt. 2nd qrt. 3rd qrt. 4th qrt. 1st qrt. 2nd qrt. 2011 2011 2011 2011 2012 2012 2012 2012 2013 2013
NOT FOR PROMOTIONAL USE Source: IMS 175 National awareness campaigns CCTV broadcast on “Alzheimer’s Disease” Sep.-Oct. 2012
NOT FOR PROMOTIONAL USE http://news.cntv.cn/special/special/fqmq/ 176 Future product opportunities in China
Compound Indication Status
Azilect Parkinson NDA submission Dec 2013
Brintellix Mood disorders Late phase III
Nalmefene Alcohol dependency Ongoing development
NOT FOR PROMOTIONAL USE 177 Total pharmaceutical market in Japan
Japanese USDm 120.000 total pharma market nd 27% 27% 2 largest pharma market in the world 100.000
26% CNS market is relatively underdeveloped 12% 80.000 compared to the total market
60.000 CNS market is ~11% of total sales in Japan vs. ~20% in North America
40.000
20.000
0 2008 2009 2010 2011 2012
NOT FOR PROMOTIONAL USE Source: IMS health 178 Significant potential in the antidepressant market for Lundbeck in Japan
Japanese Total anti-depressant market Depression: USD 1.4bn market and still growing USDm 1.400 >1 million patients diagnosed with depression
1.200 Public awareness of depression has grown in 1.000 recent years 800 600 Current market leaders (value):
400 Paroxetine (23%), duloxetine (21%), sertraline (18%) and mirtazapine (17%), escitalopram 200 (11%) 0 '00 '02 '04 '06 '08 '10 '12
NOT FOR PROMOTIONAL USE Source: IMS health 179 Uptake of Cipralex in Japan
Cipralex MAT Launched in August 2011 14% value market share
12% Market share of ~11% (September 2013)
10%
8% Peak market share expectation ~ 25%
6%
4%
2%
0% Sept. Dec. Mar. Jun. Sept. Dec. Mar. Jun. Sept. 2011 2011 2012 2012 2012 2012 2013 2013 2013
NOT FOR PROMOTIONAL USE 180 Future product opportunities in Japan
Compound Indication Status
Lexapro® Mood disorders Commercialised (escitalopram) Brintellix Mood disorders Late phase III
Nalmefene Alcohol dependency Ongoing development with partner
Desmoteplase Stroke Late phase III Other pipeline Alzheimer’s, Schizophrenia, etc. Under development products
NOT FOR PROMOTIONAL USE 181 Substantial growth in the Asian markets
Lundbeck revenue from the Asian markets DKK ~4 billion
DKK ~1,5 billion
2013 2019
NOT FOR PROMOTIONAL USE 182 Final remarks and Q&A By Ulf Wiinberg, President & CEO More opportunities than ever and in several therapeutic categories
Peak estimate Product Partners Comments (Lundbeck sales) Brintellix DKK 5-10bn Takeda Mood disorders Cipralex DKK >5.5bn - Mood disorders Selincro, - DKK 2-2.5bn each Alcohol dependency, schizophrenia Abilify Maintena Abilify - Otsuka Azilect, Xenazine DKK >1.5bn each - Parkinson’s, Huntington’s Onfi ▲ DKK 1-1.5bn - Epilepsy Mitsubishi Tanabe & Lexapro Japan ▼1) DKK 0.5-1bn (royalty) Mood disorders Mochida Sabril ▲ DKK ~1bn - Epilepsy Treanda, Oncology, DKK ~0.5bn - Saphris/Sycrest Schizophrenia and Bipolar Brexpiprazole DKK >5bn Otsuka MDD + Schizophrenia Lu AE58054 DKK >2.5bn Otsuka Alzheimer’s Desmoteplase DKK >5bn - Ischaemic stroke Other late stage projects: Zicronapine (psychosis), tedatioxetine (MDD)
NOT FOR PROMOTIONAL USE 1) Strong negative currency impact from JPY 184 2014 news flow is significant
H1 2014
• Launch Brintellix in the U.S. and Europe • Launch Abilify Maintena in Europe • 2014 financial guidance • Desmoteplase (DIAS 3) headline conclusions • Brexpiprazole headline conclusions • CONNECT data on Brintellix
H2 2014
• HTA assessment on Selincro in selected major markets • Brexpiprazole FDA submission (pending data) • Phase I start on Lu AF20513 in Alzheimer’s • Decision on zicronapine
NOT FOR PROMOTIONAL USE 185 Well positioned for long-term growth
In 2018 we will have replaced Cipralex with Brintellix
In 2020 we will have more than doubled our revenue base Lundbeck to resume We will have more than doubled the importance of emerging markets long-term growth
We have the sales potential to create 2-3 Lundbecks as we know it today
NOT FOR PROMOTIONAL USE 186 NOT FOR PROMOTIONAL USE 187