Addex Pharmaceuticals

Investor PresentationOctober 2010

Disclaimer

These materials do not constitute or form part, or all, of any offer or invitation to sell or issue, neither in the United States of America nor elsewhere, or any solicitation of any offer to purchase or subscribe for, any securities, nor shall part, or all, of these materials or their distribution form the basis of, or be relied on in connection with, any contract or investment decision in relation to any securities.

These materials contain forward-looking statements based on the currently held beliefs and assumptions of the management of Addex Pharmaceuticals Ltd, which are expressed in good faith and, in their opinion, reasonable. Forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause the actual results, financial condition, performance, or achievements of Addex Pharmaceuticals Ltd, or industry results, to differ materially from the results, financial condition, performance or achievements expressed or implied by such forward-looking statements. Given these risks, uncertainties and other factors, recipients of this document are cautioned not to place undue reliance on these forward-looking statements. Addex Pharmaceuticals Ltd disclaims any obligation to update these forward-looking statements to reflect future events or developments.

These materials are strictly confidential and must not be disclosed or distributed to third parties.

3

Vision

Goal: allosteric modulators for human health

How: proprietary discovery platform

Focus: CNS, metabolic disorders & inflammation

4

Resources

Addex can fund operations through 1Q 2013

CHF 20 million raised from BVF on Sep 14, 2010

$900k from The Michael J. Fox Foundation

for Phase II testing of lead product

Merck and J&J are funding 3 of our 14 programs

5

• Allosteric modulators are hard to find– Industrial tools for orthosteric drugs are not

appropriate – Why didn’t pharma industrialize allosteric drug

discovery?• Big upfront investment • Time to value creation long & uncertain

• Addex is industrializing allosteric drug discovery

raison d'être

6

Allosteric Modulation

Orthosteric

agonist/antagonist

7

Allosteric Advantages

• Exquisite specificity/selectivity– e.g. mGluRs

• Can target receptors considered “intractable” or only tractable by biologics, peptides or proteins

– e.g. GLP-1

• Non-competitive mechanism– Un-exploited intellectual property

•Acts like a dimmer not “on/off” switch– Body maintains control of receptor activation cycle

Natural ligand

Time

PAM + natural ligand

NAM + natural ligand

Bio

log

ical

res

po

nse

Allostery preserves natural rhythm

Time

Natural ligand

Agonist

Antagonist

Bio

log

ical

res

po

nse

Orthosterics are steady state

8

Platform

Patented high throughput screening/optimization systems

70,000 compound allostery-biased library

People: competence & multi-disciplinary approach

9

Platform Performance

Partner Product Indication(s)Status

at signingUpfront

CashRevenues

to date

Total Potential

Milestones

Ortho-McNeil-Janssen

mGluR2 PAM ADX71149

Anxiety & schizophrenia*

Hit-to-Lead

(Dec 2004)€3

million€5.2 million €112 million

Merck & Co., Inc.

mGluR4 PAMParkinson’s

disease*Hit-to-Lead

(Dec 2007)$3

million$2.5 million $167.5 million

Merck & Co., Inc.

mGluR5 PAM ADX63365

Schizophrenia*Clinical

Candidate

(Jan 2008)

$22 million

n.a. $680 million

• Addex has received partnering revenue every year since 2004

• Cash inflows generated to date: CHF43 (US$42) million

• All three partnerships are fully funded by our partners

• Addex is now eligible for up to about $1 billion in milestones plus royalties

* and undisclosed indications

Partner Phase IIPreclinical Phase I MilestoneLead

OptimizationHit-to-Lead

Assay Development &

Screening

Molecule / Mechanism

PIPELINE

Merck & Co., Inc.

Ortho-McNeil-Janssen

ADX68692FSHR NAM

ADX63365mGluR5 PAM

ADX71943GABA-B PAM

ADX71149mGluR2 PAM

Start Ph IIa1Q11

Start Ph II 4Q10

Start Ph IIa 2011

Ortho-McNeil-Janssen

ADX48621mGluR5 NAM

NAM = negative allosteric modulator (an inhibitor) ‡ and undisclosed additional indications PAM = positive allosteric modulator (an activator) *

Ortho-McNeil-Janssen Pharmaceuticals, Inc., a Johnson & Johnson subsidiary

Parkinson’s Disease Levodopa Induced Dyskinesia (PD-LID)

Dystonia

Schizophrenia

Anxiety

Osteoarthritic Pain

Schizophrenia ‡

Endometriosis

funded & developed by OMJPI*

funded & developed by OMJPI*

funded & developed by Merck

partially funded by The Michael J. Fox Foundation

Partner Phase IIPhase I MilestoneLead

OptimizationHit-to-Lead

Assay Development &

Screening

Molecule / Mechanism

DISCOVERY

NAM = negative allosteric modulator (an inhibitor) ‡ and undisclosed additional indications PAM = positive allosteric modulator (an activator)

Inflammation

CNS

Metabolic Disorders

Merck & Co., Inc.

Alzheimer’s / Depression

Parkinson’s Disease ‡

DepressionPost Traumatic Stress Disorder

Sleep Disorders

Type II Diabetes

Type II Diabetes

Rheumatoid Arthritis, Psoriasis, Inflammatory Bowel Disease

Alzheimer’s, Multiple Sclerosis

Psoriasis, Osteoarthritis

Gout, Type II Diabetes

funded by MerckmGluR4 PAM

GIPR PAM

TNFR1 NAM (CD120a)

GLP1 PAM

Orexin 2R NAM

mGluR7 NAM

mGluR2 NAM

A2A PAM

IL1R1 NAM (CD121a)

Preclinical

12

Milestones

Product Indication(s) Milestone When

mGluR2 PAM

ADX71149 schizophrenia, anxiety*

Ph I complete

Ph II “go” decisionAug, 2010

mGluR5 NAM

ADX48621PD-LID

MJFF Grant

$900,000Sep 8, 2010

mGluR5 NAM

ADX48621PD-LID Ph IIa start 4Q10

mGluR4 PAM Parkinson’s disease*completion of collaboration

4Q10

mGluR5 NAM

ADX48621Dystonia

formulation

development completed 4Q10

mGluR2 PAM

ADX71149 schizophrenia Ph IIa start 1Q11

2010/2011

BD activities

PD-LID, osteoarthritis, endometriosis, Alzheimer’s

disease, other

out-licensing /

strategic collaboration?

* and undisclosed indications

13

Partnering Priorities

• mGluR5 NAM (ADX48621 & backups) – PD-LID / Dystonia– Fragile X / Autism– other indications

• GABA-B receptor PAM (ADX71943)– Chronic pain– GERD– Urinary incontinence

• FSH receptor NAM (ADX68692)– endometriosis

• mGluR2 NAM– Alzheimer’s disease– Depression

14

ADX48621 Overview

• Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator– Glutamate is a major neurotransmitter, like dopamine & serotonin– mGluR5 inhibition is clinically validated in multiple indications including

• Parkinson’s disease levodopa-induced dyskinesia (PD-LID)• Gastroesophageal reflux disease (GERD)• Generalized anxiety disorder (GAD)

• Initial Phase I program completed sucessfully– Three studies: SAD, MAD, gender & food effects – 132 subjects studied to date, including 30 older subjects– Safety & tolerability support further clinical study

• Exceptional preclinical data in PD-LID model

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Why PD-LID & Dystonia?

• PD-LID– Clinically validated by another mGluR5 NAM (AFQ056 from Novartis*)– Attractive specialty pharma commercial opportunity

• Dystonia (abnormal sustained muscle contractions)– Third most common movement disorder (following PD and essential

tremor)– ADX48621 is the first drug-candidate to report efficacy for dystonia in LID

models

• The Michael J. Fox Foundation grant– MJFF advisors, PD key opinion leaders (KOLs), reviewed the ADX48621

preclinical data and Ph IIa trial design– Publicity & KOL familiarity (via grant review) with ADX48621 could

facilitate enrollment

*for data: http://bit.ly/dgEVbH

16

• Parkinsonian macaques with levodopa induced dyskinesia (LID)– Received ADX48621 or vehicle

– One dose administered 30 min prior to levodopa

• Behavioral assessment began upon levodopa administration – trained observers performed video review

– dyskinesia & PD disability scoring (10 min every 30 min for 4hrs) lower scores (left axis) indicate fewer symptoms/disability dyskinesia symptoms are side effects from levodopa disability is a measure of Parkinson’s disease severity

• Efficacy in the MPTP model also shown with AFQ056, which later achieved clinical Phase IIa proof of concept in PD-LID patients

ADX48621 in the MPTP Model

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first drug-candidate / mechanism reported to have efficacy on dystonia

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

*

dys

ton

ia (

0-2

hr)

Dystonia (sustained muscle contractions)

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

**

chor

ea (

0-2

hr)

Chorea (rapid uncontrolled movements)

ADX48621 in the MPTP model

LID has two components: chorea & dystonia

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Perspectives

• ADX48621 has the potential to be a best-in-class for PD-LID– Key opinion leaders say mGluR5 inhibition is the most attractive mechanism

of action to tackle LID

– MJFF has been funding research on mGluR5 for 5 years

• mGluR5 inhibition may help more than just LID– reverses preclinical Parkinsonian symptoms and deficits

– may treat comorbid anxiety/depression (common in PD)

– may reduce cognitive deficits induced by dopamine depletion

– mGluR5 inhibitor effects on intestinal motility might be of benefit (gastrointestinal dysfunction is a frequent and occasionally dominating symptom of PD)

19

ADX48621 PD-LID TrialStudy ADX48621-201 (n=90)

– Phase IIa trial in the EU and US• Randomised, double-blind, placebo-controlled, muliticenter• Patients with moderate to severe LID• Treatment duration 4 weeks

– Placebo or ADX48621 • Taken with 3 of the patients’ daily levodopa doses• Dose titration for 50mg o.d. to 100mg t.d.s over the 4 weeks

– Primary objective: safety & tolerability– Secondary objective: exploratory efficacy

• Objective evaluation in the clinic – Before starting treatment and at weeks 2 and 4– Trained observer scores LID severity– Abnormal Involuntary Movement Score (AIMS)

• Patient diaries – PD rating scales (including dystonia) – Evaluation of mood

20

GABA-B Receptor PAM

– Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor is clinically/commercially validatedgeneric GABA-B receptor agonist, baclofen, is marketed for spasticity &

some spinal chord injuries

other orthosteric GABA-B agonists are in development and clinically

validated in gastroesophageal reflux disease (GERD)

–GABA-B receptor PAM are differentiated from baclofenAllostery may reduce/eliminate development of tolerance & dependenceAllostery may reduce other tolerability issues, like somnolence ADX71943 demonstrated potential for chronic pain (e.g. osteoarthritis)Has potential for GERD and urinary incontinence

21

ADX71943 demonstrated antihyperalgesic effects in a model of osteoarthritis

Days post-monosodium iodocate (MIA)

0

50

100

150

200

250

300

350

Pre-MIA Post-MIA Day 1 Day 8

With

draw

al th

resh

old

(g)

Max

imum

resp

onse

bew

teen

1 a

nd 2

hr

Vehicle 1 mg/kg ADX71943 3 mg/kg ADX7194310 mg/kg ADX71943 30 mg/kg ADX71943 Celecoxib (30 mg/kg)

* ***

***

*****

Pre-treatment Treatment

-1 14 14 21

###p<0.001 vs. Pre-MIA baseline; paired t-test, n=10 rats per group. *p<0.05, **p<0.01, ***p<0.001 vs. vehicle;one-way ANOVA with Dunn's multiple comparison n=10 per group.

###

22

FSHR NAM

GnRH, FSH & Endometriosis

• FSH NAM offer a more specific approach to estradiol control compared to GnRH antagonists

• Endometriosis is linked to excess estradiol

• GnRH antagonists have been shown to reduce estradiol & endometriosis symptoms

• FSH is downstream from GnRh and is more directly responsible for production of estrogen/estradiol

Status

• ADX68692 is a follicle stimulating hormone receptor (FSHR) NAM

• Orally available non-steroid molecule with drug-like characteristics

• In late preclinical development

• ADX68692 is available for partnering

GnRH

23

ADX68692 efficacy in rats 4 week treatment

Effect on Oestrus cycle duration

0

2

4

6

8

10

12

14

16

18

20

Number of Estrous cycles during treatment duration Mean duration of Estrous cycle (days)

0 mg/kg/day 2x10 mg/kg/day 2x30 mg/kg/day 2x100 mg/kg/day 2x300 mg/kg/day

***

***

***

***

POC that ADX68692 disrupts the oestrus cycle and increases its mean duration, eventually leading to complete blockade at high dose.

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mGluR2 NAM

• Data from Addex and others show that mGluR2 inhibition can reverse cognitive deficit – in models of cognitive deficit– in physiologically relevant models of AD– mechanism may be complementary to marketed drugs

• Published data suggest that mGluR2 inhibition may reduce generation of beta-amyloid*– mGluR2 NAM may also be disease modifying

*The Journal of Neuroscience, March 17, 2010; 30(11):3870-3875

25

Familiar object

Novel object

ADX92639 reverses cognitive impairment induced by intracebroventricular (icv)

β-amyloid in the rat NOR test after oral administration:

– Full and donepezil-like reversal of the memory deficit at 30 mg/kg

– No effect on locomotor activity observed during the test

ADX92639 effective inicv β amyloid-induced deficit in rat NOR

ADX92639 (mg/kg, p.o.)

veh 10 30 Donepezil

18

0

3

6

9

12

15 *** *** ***

Exploration of novel vs familiar objects

veh veh veh veh 0

3

6

9

12

15

18

Exp

lora

tio

n t

ime

(se

c)

***

sham β-Amyloid*

*Single administration into the lateral ventricle of 8 μl solutionFinal concentration of amyloid = 2 mg/ml

(1 mg/kg, ip)

120

sham β- Amyloid*

0

30

60

90

t1 t2 t1 t2 t1 t2 t1 t2

Veh 10 30 Donepezil

ADX92639 (mg/kg, p.o.)

Lin

e c

ros

se

s

Locomotor activity during the test

(1 mg/kg, ip)

26

Oral GLP1R PAM in db/db mouse model

• Leptin receptor–deficient db/db knockout mice – develop human Type II diabetes mellitus – develop hypertension and obesity – have disrupted circadian blood pressure (BP) rhythm

• We orally administered to 3 groups of db/db mice– ADX91886 GLP1R PAM – sitagliptin (Januvia) DPP IV inhibitor– or vehicle

• 15 min later 2 g/kg glucose was given orally• Blood glucose + insulin levels were measured 10 ;

20 ; 30 ; 60 ; 90 min after glucose administration

27

Plasma glucose

15 30 45 60 75 90

0

10

20

30

40

50

C: Sitagliptin 10 mg/kg poB: ADX91886 (220 mg/kg po)

A: Vehicle po

B

*****

******

***

**

**

Time (min)

Pla

sma

glu

cose

(mM

)

Plasma insulin

15 30 45 60 75 90

0

5

10

15

20

25

30

C: Sitagliptin 10 mg/kg po

B: ADX91886 (220 mg/kg po)

A: Vehicle po

B

** ** **

***

***

*** ***

Time (min)

Pla

sma

insu

lin(n

g/m

l)

GPL1R PAM vs sitagliptin in db/db mice

Glucose AUCB (0-90 min)

A B C0

5

10

15

20

25

30

A: Vehicle po

B: ADX91886 (220 mg/kg po)

C: Sitagliptin 10 mg/kg po

***

*

Glu

cose

AU

CB

(mM

.hr)

28

29

Management & Financial

30

Management & Boards

Vincent Mutel, Chief Executive Officer Tim Dyer, Chief Financial Officer Charlotte Keywood, Chief Medical Officer Sonia Poli, Head of Non-Clinical Development Laurent Galibert, Head of Inflammation & Metabolic Disorders

Board of Directors

André J. Mueller, Chairman

Vincent Mutel, Vice Chairman & CEO of Addex

Andrew Galazka, SVP Scientific Affairs, Merck-Serono

Ray Hill, former Head of EU Licensing, Merck & Co., Inc.

Vincent Lawton, former MD of Merck Sharp & Dohme U.K.

Beat E. Lüthi, CEO of CTC Analytics

Antoine Papiernik, Sofinnova Partners

Scientific Advisory Board

George F. Koob, Ph.D., Chairman

Bernhard Bettler, Ph.D.

Arthur Christopoulos, Ph.D.

Patrick M. Sexton, Ph.D.

Mark A. Geyer, Ph.D.

Barbara J. Mason, Ph.D.

Jean-Philippe Rocher, Head of Core Chemistry Robert Lütjens, Head of Core Biology Tatiana Carteret, Head of Human Resources

Chris Maggos, Investor Relations & Communications

Executive Management

31

Financials & Stock• Cash through early 2013

CHF56.7 (US$54/€42) million in cash as of June 30 CHF20 ($20) million raised on Sep 14 $900,000 grant from The Michael J. Fox Foundation on Sep 8

• Market cap (15 Sep): CHF77 (€59 / US$76) million

• Symbol on SIX Swiss Exchange: ADXN (ISIN:CH0029850754)

• 7,835,878 shares outstanding (fully diluted)

• Six analysts covering:

Piper Jaffray Sam Fazeli & Michael AitkenheadJefferies Peter Welford & Philippa GardnerHelvea Olav Zilian Bank Vontobel Andrew C. Weiss  & Silvia SchanzBank am Bellevue Bob Pooler       Edison Robin Davison

32

www.addexpharma.com

allosteric modulators for human health