Addex Pharmaceuticals

Investor PresentationFebruary 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.

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•Goal: allosteric modulators for human health

•Focus: CNS, inflammation, metabolic disorders

•Proprietary allosteric modulator discovery platform

•15 proprietary products in the pipeline

• Pharma validation– Partners: J&J and Merck & Co. (2 programs)

– Investors: SR-One (GSK) and Roche Venture Fund

•138 staff / founded 2002 in Geneva, Switzerland

The Company

4

Financials• Cash for 2+ years of operations

guidance suggests ~CHF75m* (€62m/US$89m) at end 2009

• Market cap (5 Feb 10): CHF71.5m (€49m / US$67m)

• SIX Swiss Exchange: ADXN (ISIN:CH0029850754)

• 5,862,492 shares outstanding as of June 30, 2009

• Five 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      

*assuming mid-point of cash burn guidance for CHF43-47m was achieved

5

Platform Revenues

Partner Product Indication(s)Status

at signingUpfront Cash Milestones

Ortho-McNeil-Janssen

(a J&J company)ADX71149

mGluR2 PAMAnxiety &

schizophreniaHit-to-Lead

(Dec 2004)$4 million

not disclosed

Merck & Co., Inc. mGluR4 PAMParkinson’s

diseaseHit-to-Lead

(Dec 2007)$3 million

$167.5 million

Merck & Co., Inc.ADX63365

mGluR5 PAMSchizophrenia

Clinical Candidate

(Jan 2008)$22 million

$680

million

Proprietary Platform Cash Generation

• CHF43 ($40) million in partnering revenues received to date

• All three projects are fully funded by our partners

• Eligible for up to about $1 billion in milestones plus royalties

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Addex Pharmaceuticals~~~~~~~~

Pipeline & Selected Products in Development

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Inflammation

CNS

Metabolic Disorders

Mechanism PartnerAssay Dev &

ScreeningHit-to-Lead

Lead Optimization

Preclinical Phase I Phase II Milestone

mGluR5 NAM Start Ph II 4Q10

mGluR2 PAM J&J* not disclosed

mGluR5 PAM Merck & Co. not disclosed

GABAB PAM Start Ph I 4Q10

FSH NAM Start Ph I 1H11

mGluR2 NAM

mGluR4 PAM Merck & Co.

mGluR7 NAM

Orexin 2R NAM

GLP-1 PAM

GIPR PAM

TNF-R1 NAM

A2A PAM

IL-1R1 NAM

Type II diabetes

Type II diabetes

Rheumatoid Arthritis, Psoriasis, Alzheimer’s, Multiple Sclerosis

Pipeline

ADX71943 Pain / Urinary Incontinence / GERD

ADX68692 Endometriosis / Prostate Cancer

Alzheimer’s / Depression

Depression / Post Traumatic Stress Disorder

Psoriasis, Osteoarthritis

Gout, Type II diabetes

NAM = negative allosteric modulator (an inhibitor) *Ortho-McNeil-Janssen Pharmaceuticals Inc., a Johnson & Johnson companyPAM = positive allosteric modulator (an activator) ‡ undisclosed additional indications

ADX71149 Anxiety / Schizophreniafunded & developed by J&J

ADX63365 Schizophrenia‡funded & developed by Merck

ADX48621 Parkinson’s disease levodopa induced dyskinesia (PD-LID)

Parkinsons’s disease‡with Merck funding

Sleep disorders

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ADX48621

• mGluR5 NAM with NCE patents filed – Patents valid through 2025 in most territories

– Chemical series unrelated to other mGluR5 NAM

– Unique metabolic profile

– Unrelated backup series in clinical candidate selection

• Phase I completed– Three studies: SAD, MAD, gender & food effects

– 110 patients treated to date, including older volunteers

– Safety & tolerability justify further clinical study

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PD-LID & mGluR5• Strong rationale for mGluR5 in PD and PD-LID

– Inhibition of mGluR5 effective in humans* and in animal models of PD & PD-LID

– Loss of dopamine producing cells leads to excess glutamatergic stimulation

– Inhibition of mGluR5 has been shown to reduce glutamatergic stimulation

– Occurrence of LID is associated with a significant up-regulation of mGluR5 binding in the striatum and globus pallidus of Parkinsonian monkeys and humans

• Parkinson’s disease (PD) is growing with the aging population– 3.2 million PD patients in 2020 in EU, U.S. & Japan

160 million people over 65 in the 7 major markets by 2020, OECD estimates Incidence of PD is 2% in people over 65

• Levodopa induced dyskinesia (LID) is an unmet medical need – 40% of Parkinson’s disease (PD) develop LID

– Unmet medical need

– Faster path to market than PD

– Pricing advantage

* Novartis AFQ06 Ph II PD-LID data from Nov. 2008 R&D Day: http://bit.ly/16dyM5 & http://bit.ly/g9enD

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0

10

20

30

40

50

60

70

80

90

Vehicle ADX48621, 1mg/kg

ADX48621, 3mg/kg

ADX48621, 10mg/kg

ADX48621, 30mg/kg

MTEP, 30mg/kg

Lat

ency

(se

c)

1st experiment2nd experiment3rd experiment

***

*********

****

***

**

***

+ 1 mg/kg haloperidol

ADX48621 efficacy in HIC model

• Haloperidol induced catalepsy (HIC) is a model of PDADX48621 dose-dependently reversed HIC in 3 independent experimentsThis effect was comparable to MTEP (well-known to work in these models)

• ADX48621 effects in HIC suggest that itshould be tested further as a potential drug for PD has potential to be a dopamine sparing agent

**p<0.01, ***p<0.001 versus vehicle group

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ADX48621 non-human primate data

• Macaque monkeys rendered Parkinsonian by repeated daily injections of MPTP • Animals received levodopa until the development of dyskinesia

– Levodopa administered twice daily– Dyskinesia severity comparable to humans (score of 10 = completely disabled)

• Animals were treated 30 min prior to levodopa– ADX48621 (3, 10 or 30 mg/kg in water) – Vehicle

• Behavioral assessment began at levodopa administration (first 10 min every 30 min)– trained observers– video review

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

*

dys

kin

esia

(0-

2 h

r) Dose dependent improvement

0 60 120 180 240

vehicle

none

mild

moderate

marked

severe

+ L-DOPA

ADX48621 (30 mg/kg)

ADX48621 (3 mg/kg)ADX48621 (10 mg/kg)

time (mins)

dis

abil

ity

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ADX48621 unique anti-dyskinetic effect

ADX48621 is the first compound shown to have such an effect on dystonia

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

*

dys

ton

ia (

0-2

hr)

Dystonia

Dystonia = sustained muscle contractions

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

**

chor

ea (

0-2

hr)

Chorea

Chorea = involuntary movements

ADX48621 dose dependently reduced levodopa-induced chorea and dystonia.

The highest dose virtually abolished both chorea and dystonia in the majority of the animals.

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Developing ADX48621for PD-LID

• ADX48621 to start in 4Q10 Phase IIb dose-range finding study– 150-200 patients / 12 weeks dosing

– Multiple instruments for measuring LID (in consultation with KOLs)

– Data late 2011/early 2012

• NDA / MAA filing as early as 2016

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Marketing ADX48621for PD-LID

• PD marketing – Specialty neurology sales force (120 reps in US)– 1st-line symptomatic treatment is competitive

• manly marketed dopaminergic drugs• non-dopaminergic drugs will have an advantage

– Growth sustained by ageing population (+2%/year)

• PD-LID is the short-term opportunity for growth in PD– Immature market, awareness has to be raised in patients

• Physicians (but not patients) are educated about the cause of the disorder• Poorly addressed - no approved drugs for dyskinesia• Limited number of investigational drugs likely to capture big market share

– Fast uptake likely • debilitating symptoms• high unmet need• no therapy switch

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ADX71943

• ADX71943 is a GABAB PAM in preclinical development– Allosteric mechanism may avoid dose dependent

CNS side effects (somnolence/dizziness) seen with orthosteric agonists of GABAB

– Allosteric mechanism may avoid desensitization and open the possibility of oral chronic use thus allowing potential to treat pain (i.e. osteoarthritis)

• ADX71943 is available for partnering

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ADX71943 for chronic pain

• Main focus on chronic pain– Osteoarthritis pain

– Other types of chronic nociceptive pain

• Osteoarthritis is a widespread condition affecting ~90 million patients – mostly the elderly population

– debilitating symptom is chronic pain

• Current chronic treatments (NSAID, opioids) are unsatisfactory– Limited efficacy of both drug classes

– NSAIDs increase risk of serious thrombotic and GI events

– Opioids are associated with GI disturbances, sedation and addiction

– Apart from injectable NGF antagonists, no new drug class has emerged from clinical trials

• A major opportunity for ADX71943– Product profile fits with market needs (orally available, once daily dosing)

– Unmet needs for such a mature market are strong enough to allow a fast uptake of innovative drug, as underlined by the success of Celebrex which hit $3.3bn sales 5 years after launch

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ADX71943 analgesic-like effects in preclinical models

Analgesic-like effect of ADX71943 in the CFA* model in rats after oral administration

ADX71943 caused a dose-dependent increase in the withdrawal threshold in the CFA induced mechanical hypersensitivity test in rats, with a minimum effective dose of 10 mg/kg p.o.

non-CFA CFA 1 hr 2 hr0

5

10

15

20

25

*****

Time post-dose (hr)

Wit

hd

raw

al T

hre

sho

ld

Vehicle

1 mg/kg ADX-71943

3 mg/kg ADX-71943

10 mg/kg ADX-71943

30 mg/kg ADX-71943

30 mg/kg Naproxen

Analgesic-like effect in the writhing test of oral ADX71943 in mice

ADX71943 caused a dose-dependent reduction of acetic acid-induced writhing in mice with a minimum effective dose between 3 and 10 mg/kg p.o.

*p<0.05, **p<0.01, ***p<0.001 vs. JQ-02 vehicle; +++p<0.001 vs. 1%CMC vehicle

Experiment 1Experiment 2Experiment 3Experiment 4

vehicle

Nu

mb

er

of

wri

the

s

0

24

6

810

1214

16

1820

22

0.3 1 3 10 30 100 3

+++****** ***

***

*

** ***

*

mg/kgmg/kg

AD

X71

943

Bac

lofe

n

ADX71943 Baclofen

*CFA = Complete Freund's Adjuvant

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ADX68692• ADX68692 is an FSH NAM in preclinical development• Potential indications

– Benign prostatic hyperplasia (BPH)– Endometriosis

• ADX68692 is available for partnering

Roles of FSH/LH

Females

• FSH involved in folliculogenesis– maturation of follicles– estrogen production

• LH triggers ovulation, progesterone

Males

• FSH supports spermatogenesis

• LH stimulates testosterone production

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ADX68692 for BPH

• ADX68692 oral administration of in male rats for 4 weeks

• Statistically significant reduction in testosterone

• Statistically significant reduction in prostate weight

BPH patient population is expected to grow:

• 15+ million men suffer from symptomatic BPH across the 7 major markets

• Market grew 17.5% to $3.7 billion from 2007 to 2008 in the 7 major markets

• Projections indicate 12.9% increase in # of BPH sufferers from 2009 to 2025

0.0

5.0

10.0

15.0

20.0

25.0

After 3-week treatment with ADX68692

Tes

tost

ero

ne

(nn

mo

l/L)

******

Group 1 (0 mg/kg/day) Group 2 (2 x 10 mg/kg/day)

Group 3 (2 x 30 mg/kg/day) Group 4 (2 x 100 mg/kg/day)

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Control group

02468

1012141618

-14 -11 -8 -5 -2 2 5 8 11 14 17 20 23 26 29

Day of treatment

ADX68692: 20 mg/kg/day

02468

1012141618

-14 -11 -8 -5 -2 2 5 8 11 14 17 20 23 26 29

Day of treatment

ADX68692 for endometriosis

• Oral ADX68692 for 4 weeks was well tolerated in female rats

• It reduced the number of rats in the estrus/proestrus phase (ovulatory phase)

• It increased the number of female rats in the diestrus phase

• Eventually animals were found in persistent diestrus phase

• Estradiol levels were lowered, even in the proestrus phase

• Reduction in estradiol suggests ADX68692 has potential for treatment of endometriosis

• Endometriosis is estrogen dependent

SynchronisationTreatment start

To

tal n

um

ber

of

anim

als

in P

roes

tru

s/E

stru

s st

age

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Partnered Programs

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mGluR2 PAM and J&J

• mGluR2 PAM program partnered with Ortho-McNeil-Janssen, a Johnson & Johnson company, in 2005

• Comprehensive Phase I program started June 2009– J&J responsible development– Industry average for Phase I is 9-10 months– Phase II could start in mid-2010

• mGluR2 activation is clinically validated by Eli Lilly with their mGluR2/3 agonist– Positive Phase II POC in anxiety– Positive Phase II POC in schizophrenia

• Schizophrenia is important for J&J (Risperdal)

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mGluR5 PAM & Merck

• Merck & Co., Inc. licensed ADX63365 and mGluR5 PAM backups in 2008

• mGluR5 PAM have demonstrated efficacy in animal models of schizophrenia

• mGluR5 PAM will be highly differentiated if they address cognitive deficit in schizophrenia clinical testing– Many schizophrenia patients are unable to learn skills or support

themselves– Marketed drugs and most drugs in development can reduce psychosis

BUT have not been shown to improve cognitive function – FDA has recognized that cognitive deficit is an unmet medical need in

schizophrenia

• Merck is responsible for development of ADX63365/backups

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Progress

• Deal signed (Dec 07)

• 1st Preclinical milestone (Feb 08)– $250,000

• 2nd preclinical milestone (Jul 09)– $500,000

– Orally available mGluR4 PAM showed efficacy in model of PD

• Collaboration extended (Dec 09)– Merck commits $1.8 million in research funding

– Going forward all costs transferred to Merck

Agreement

• Discover and develop metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAM)

• The deal includes mGluR4 PAM leads already discovered by Addex

• Merck is responsible for preclinical and clinical development

• Addex will sit on oversight committees Terms

• $3 million upfront

• $106.5 million in milestones

– 1st product in multiple indications

• Additional $61 million milestones

– For a 2nd and 3rd product

• Undisclosed royalties

• Option to co-promote in certain EU countries

mGluR4 PAM & Merck

Clinical Candidate

(late 2010)

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Addex Pharmaceuticals~~~~~~~~

Allosteric Discovery & Optimization Platform

26

Unlike orthosteric drugs, allosteric modulators are non-competitive. Therefore, their effects on signal transduction are observed

primarily when endogenous ligands bind the active site.

Allosteric Modulation Explained

NB: Most marketed

drugs are orthosteric.

Endogenous ligands

are natural activators

in the body.orthosteric drugs compete

with endogenous ligands for

the active site on a receptor

allosteric drugs

bind another site

on same receptor

NB: Most marketed

drugs are orthosteric.

Endogenous ligands

are natural activators

in the body.orthosteric drugs compete

with endogenous ligands for

the active site on a receptor

allosteric drugs

bind another site

on same receptor

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Allosteric Advantages

• Greater specificity than orthosteric molecules – e.g.: mGluRs

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

– e.g.: GLP1

• Non-competitive mechanism– Un-exploited intellectual property– Less dose related toxicity

•Acts like a dimmer not “on/off” switch

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

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Unique Library in-silico analysis

Addex library and marketed drugs share the same physicochemical property space BUT Addex library occupies a unique structural space

Addex library and marketed drugs share the same physicochemical property space BUT Addex library occupies a unique structural space

Physicochemical Comparison Structural Comparison

Addex CompoundsMarketed Drugs

Addex CompoundsMarketed Drugs

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Proprietary Screening AssaysG-Protein Coupled Receptors

• Phoenyx– a cAMP dynamic non stop assay

• FBBA (GLP1, mGluR7)– Fluorescence-Based Binding Assay – Measures bi-molecular interactions

• Proxylite (GLP1, GIP)– Proximal & dynamic assays for functional measurements of

all types of GPCRs

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• APRA (TNF R1)–Accessory Protein Relocalization Assays

• ADX-tags series 1 (IL-1R) –Proximal & dynamic assays for functional measurements –Measures activation-dependent association or dissociation of

binding partners

• ADX-tags series 2 (TNF R1, IL-1R, BMP2)–measures conformational changes that lead to activation signal–measures multimerization changes that lead to activation signal

Proprietary Screening Assaystype 1 single-pass transmembrane proteins

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Addex Platform

d i s c o v e r y

assay

development6 months

screening

hit validation4-6 months

lead

optimization24 months

p r e c l i n i c a l

clinical candidate

selection6-12 months

phase 012 months

IND

32

The Addex Platform

Inflammation CNSMetabolicDisorders

Core Chemistry

Non-Clinical Development

Clinical Development

Core Biology

33

Summary

• Allosteric Modulator Platform– Proprietary tools + unique library

– Unique multi-disciplinary approach

• 15 Products for High Value Targets/Indications– Low target related risk

– Highly differentiated mechanism

• 3 Partnerships (MRK/J&J)

• Top Tier Investors

• 2+ Years of Cash

34

Management & Boards

Vincent Mutel, Chief Executive Officer Tim Dyer, Chief Financial Officer Charlotte Keywood, Chief Medical Officer Sonia Poli, Head of Non-Clinical Development Emmanuel Le Poul, Head of CNS

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.

Laurent Galibert, Head of Inflammation

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