CBDMT – Market & Business Intelligence © 2010 www.cbdmt.com

Alzheimer’s Disease (AD) Report

Authors: Emilie Hilpert, Philippe Tramoy

Date: 01 June 2010

“Copyright 2010 CBDMT SARL. All rights reserved. Any unauthorized use or disclosure is prohibited. The information herein

was obtained from various sources; we do not guarantee its accuracy or completeness. This research report is prepared for

general circulation and is circulated for general information only. It does not have regard to specific investment objectives,

financial situation and the particular needs of any particular person who may receive this report. Investors should seek

financial advice regarding the appropriateness of investing in any securities or investment and trading strategies discussed

or recommended in this report and should understand that the statements regarding future prospects may not be realized.

Investors should note that income from such securities, if any, may fluctuate and that each security's price or value may rise

or fall. Accordingly, investors may receive back less than originally invested. Past performance is not necessarily a guide to

future performance. Neither the information nor any opinion expressed constitutes an offer to buy or sell any securities or

options or futures contracts. CBDMT SARL accepts no responsibility or liability whatsoever for any expense, loss or damages

arising out of or in any way connected with the use of all or any part of this report. CBDMT SARL does not have long or short

position in any securities or options of this issue(s)."

CBDMT – Market & Business Intelligence © 2010 www.cbdmt.com 2/70

Table of Contents

1 Global information .......................................................................................................................... 5

1.1 History ..................................................................................................................................... 5

1.2 Presentation of the disease ..................................................................................................... 5

1.3 Patients with Alzheimer’s disease forecast ............................................................................. 5

1.4 Prevalence ............................................................................................................................... 7

2 Alzheimer’s disease ......................................................................................................................... 7

2.1 Symptoms ................................................................................................................................ 7

2.2 Physiopathology ...................................................................................................................... 9

2.3 Risk factors ............................................................................................................................ 12

Age ................................................................................................................................................. 12

Sex ................................................................................................................................................. 12

Genetic affects ............................................................................................................................... 12

2.4 Alzheimer’s disease as a genetic disease .............................................................................. 13

2.5 Diagnosis ................................................................................................................................ 13

3 Market ........................................................................................................................................... 15

3.1 Overview ................................................................................................................................ 15

3.2 Treatments and products ...................................................................................................... 16

Acetylcholinesterase inhibitors ..................................................................................................... 21

NMDA receptor antagonist ........................................................................................................... 23

3.3 Market previsions .................................................................................................................. 23

4 Products in development .............................................................................................................. 25

4.1 Overview ................................................................................................................................ 25

4.2 Products in phase III .............................................................................................................. 26

Bapineuzumab ............................................................................................................................... 28

Dimebon ........................................................................................................................................ 30

EGb-761 ......................................................................................................................................... 35

Immune Globulin Intravenous....................................................................................................... 36

Leuprolide acetate implant ........................................................................................................... 37

CBDMT – Market & Business Intelligence © 2010 www.cbdmt.com 3/70

LY-450139 ...................................................................................................................................... 38

Neramexane .................................................................................................................................. 39

4.3 Products in phase II ............................................................................................................... 40

5 Pipeline of drugs for Alzheimer’s disease, Discovery to Phase II .................................................. 42

5.1 Drugs in phase II .................................................................................................................... 42

5.2 Drugs in phase I ..................................................................................................................... 45

5.3 Drugs in preclinical phase ...................................................................................................... 48

5.4 Drugs in discovery phase ....................................................................................................... 50

6 Company profiles .......................................................................................................................... 55

6.1 Baxter International Inc ......................................................................................................... 55

6.2 Bellus Health Inc .................................................................................................................... 57

6.3 Eisai Co Ltd ............................................................................................................................. 58

6.4 Elan Corp Plc .......................................................................................................................... 59

6.5 Eli Lilly and Co ........................................................................................................................ 61

6.6 Forest laboratories Inc ........................................................................................................... 63

6.7 Johnson & Johnson ................................................................................................................ 64

6.8 Merz pharmaceutical ............................................................................................................. 66

6.9 Novartis Ag ............................................................................................................................ 67

6.10 Pfizer Inc ................................................................................................................................ 69

List of Figures

Figure 1: Estimated evolution of people with Alzheimer’s disease 2010 to 2050 (in millions) by

geographical zones .................................................................................................................................. 6

Figure 2: Progression of Alzheimer's disease (black dots) ...................................................................... 9

Figure 3: Diagram of physiopathology mechanisms ............................................................................. 11

Figure 4: Sales repartition by types of drugs ......................................................................................... 15

Figure 5: Sales repartition by geographical zones ................................................................................. 15

Figure 6: Sales repartition by pharmaceutical companies .................................................................... 16

Figure 7: Therapeutic ways to treat Alzheimer's disease ...................................................................... 17

Figure 8: Sales of marketed drugs by therapeutic classes .................................................................... 19

Figure 9: Sales distribution of Aricept in 2009 ...................................................................................... 22

Figure 10: Estimated evolution of sales for Alzheimer's disease drugs for 2009 to 2020 .................... 23

Figure 11: Repartion of Alzheimer's drugs turnover for 2009 to 2020 ................................................. 24

CBDMT – Market & Business Intelligence © 2010 www.cbdmt.com 4/70

Figure 12: Pipeline drugs in development in 2010 ................................................................................ 25

Figure 13: Clinical trials by development phases .................................................................................. 26

Figure 14: Drugs in phase III by therapeutic classes.............................................................................. 26

Figure 15: Drugs in phase II by therapeutic classes............................................................................... 40

Figure 16: Repartition of symptomatic treatments by mechanisms of action ..................................... 41

Figure 17: Repartition of curative treatments by mechanisms of action ............................................. 41

List of Tables

Table 1: Total population over 65, estimated number of people with Alzheimer’s disease from 2010

to 2020 (in millions) by geographical zones ............................................................................................ 6

Table 2: Incidence and prevalence on population aged 65 and over in 2010, 2015 and 2020 by

geographical zones .................................................................................................................................. 7

Table 3: Main warning signs of Alzheimer's disease ............................................................................... 7

Table 4: Common clinical features in Alzheimer’s disease ..................................................................... 8

Table 5: Potential risks and protective factors for Alzheimer’s disease ............................................... 12

Table 6: Differences between genetic disease and genetic susceptibility4 ........................................... 13

Table 7: Main brand-name drugs sold in the world .............................................................................. 18

Table 8: Alzheimer's degree of severity treated by marketed drugs .................................................... 19

Table 9: Current drug treatments for Alzheimer's disease ................................................................... 20

Table 10: Sales and forecast of main acetylcholinesterase inhibitor drugs .......................................... 21

Table 11: Sales and forecast of main NMDA receptor antagonist drugs .............................................. 23

Table 12: Drugs in phase III ................................................................................................................... 26

Table 13: Alzheimer's degree of severity treated by drugs in phase III ................................................ 27

Table 14: Clinical trials of Bapineuzumab ............................................................................................. 29

Table 15: Clinical trials of Dimebon ....................................................................................................... 32

Table 16: Clinical trials of EGb-761 ........................................................................................................ 35

Table 17: Clinical trials of Gammagard (Immune Globulin Intravenous) .............................................. 36

Table 18: Clinical trials of Memryte (leuprolide acetate implant) ........................................................ 37

Table 19: Clinical trials of LY-450139 ..................................................................................................... 38

Table 20: Clinical trials of Neramexane ................................................................................................. 40

CBDMT – Market & Business Intelligence © 2010 www.cbdmt.com 5/70

1 Global information

Alzheimer’s disease is a neurological disorder affecting the central nervous system (CNS) that leads to

a progressive loss of memory, language, and the ability to recognize friends and family. The average

course of the disease, from early symptoms to complete loss of cognitive ability, is 10 years.

1.1 History

In 1906, at a psychiatry meeting, the German psychiatrist Alois Alzheimer (1864-1915) presented the

Auguste’s case, a patient whom he examined a few years before. Auguste D. was a 51-year-old

woman, who was suffering from disorientation, aphasia, auditory hallucinations, paranoia,

unpredictable behavior and pronounced psycho-social impairment. Alois Alzheimer described

organic changes in her brain, like plaques, tangles and arteriosclerosis. This finding formed his

hypothesis of her dementia having an organic cause. Even if History has retained Alzheimer’s name

for talking about this kind of dementia, his description was not a new discovery. The association

between plaques and dementia had been reported in 1887 for the first time by S. Beljahow.

1.2 Presentation of the disease

Alzheimer’s disease (AD) is by far the most common cause of dementia1 associated with aging; it

accounts for more than 60% of all dementia. Alzheimer’s disease is characterized by an insidious

onset and slow deterioration in cognition, functional ability (e.g., activities of daily living), behavior,

and mood. In USA, AD is the 7th leading cause of mortality.

In 2010, more of 21 million people will be affected by this disease in the world. As the world

population ages, this number will increase.

1.3 Patients with Alzheimer’s disease forecast

Today, more than 20.8 million people are affected by Alzheimer’s disease around the world. The

Alzheimer’s disease patient population will grow over the next 10 years. As the ‘baby boomer’

generation ages in developed countries, the percentage of the population aged 65 and over will

increase to reach 716.4 million by 2020. The Alzheimer’s disease patient population is forecast to be

up to 31.3 million by 2020. Estimations predict nearly a doubling of patients every 20 years.

The Alzheimer’s disease population in Asia is projected to grow at the highest rate to reach 15 million

accounting for nearly half of AD patients by 2020.

1 Dementia is a syndrome due to disease of the brain, usually chronic, characterized by a progressive, global deterioration in intellect including memory, learning, orientation, language, comprehension and judgment.