Addex Pharmaceuticals

Investor PresentationJune 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, metabolic disorders, inflammation

•Proprietary allosteric modulator discovery platform

•15 discovery/development programs

• Pharma validation– Partners: Johnson & Johnson and Merck & Co., Inc.

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

•138 staff / founded 2002 in Geneva, Switzerland

The Company

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Financials• Cash for operations through end of 2011

CHF76.6 million (€52m/US$71m) at end of 2009

• Market cap (25 May): CHF66.5m (€47m / US$57m)

• SIX Swiss Exchange: ADXN (ISIN:CH0029850754)

• 5,871,242 shares outstanding as of Dec 31, 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      

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

Start Ph I 4Q10

not disclosed

ADX71149mGluR2 PAM

Start Ph IIa2H10

Start Ph II 4Q10

Start Ph II 4Q10

Ortho-McNeil-JanssenStart Ph IIa

2H10

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

Start Ph I 1Q11

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

Dystonia

Schizophrenia

Anxiety

Osteoarthritic Pain

Schizophrenia ‡

Endometriosis / Benign Prostatic Hyperplasia

funded & developed by OMJPI*

funded & developed by OMJPI*

funded & developed by Merck

Partner Phase IIPreclinical Phase I MilestoneLead

OptimizationHit-to-Lead

Assay Development &

Screening

Molecule / Mechanism

DISCOVERY PROGRAMS

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,

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)

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Partnered Programs

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Agreement• With Ortho-McNeil-Janssen Pharmaceuticals, Inc. (OMJPI)

– Utilize Addex platform to identify & develop orally available mGluR2 PAM for schizophrenia, anxiety and undisclosed indications• OMJPI funds collaboration on discovery & lead optimization• OMJPI funds & performs preclinical and clinical development

– Addex sits on oversight committees

ADX71149

Terms

• €3 million upfront

• Research funding to Addex during discovery collaboration (2005-2007)

• €112 in potential milestones upon completion of clinical and regulatory milestones

• Low double-digit royalties

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Progress to Date

• Collaboration generated clinical candidates

– €4.2 million in R&D funding between 2005-2007

• Comprehensive Ph I program started in June 2009

– €1 million milestone paid upon initiation of Phase I

– More than 5 Phase I trials in healthy volunteers• SAD, MAD

• Food & gender

• Ketamine challenge (schizophrenia model)

• Anxiety challenge

• Phase II program scheduled to start in 2010

– schizophrenia

– anxiety

– potentially other indicationsNote

mGluR2 activation is clinically validated in anxiety & schizophrenia

ADX71149

* Nature Medicine 2007: http://bit.ly/bbnsyQ

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ADX63365

Agreement

• Merck & Co., Inc. licensed Addex mGluR5 PAMs in 2008

• mGluR5 PAM expected to be highly differentiated– Merck already had demonstrated mGluR5 PAM have efficacy in

animal models of schizophrenia

– Preclinical data show efficacy for cognitive deficit (& psychosis)

– Despite efficacy of marketed drugs many schizophrenia patients remain unable to learn new skills to support themselves

– FDA has recognized cognitive deficit as an unmet medical need in schizophrenia

• Merck is responsible for development of ADX63365 & backups

Terms

• $22 million upfront

• $680 million in milestones

• Undisclosed royalties

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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) with Merck & Co., Inc.

• 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

• $167.5 million in potential milestones

• Annual tech access fee $250,000

• Research funding 2009/2010

• Undisclosed royalties

• Option to co-promote in EU

mGluR4 PAM

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Platform Revenues

Partner Product Indication(s)Status

at signingStatus April

30, 2010Upfront

Cash

Milestones or R&D funding

received

Total Potential

Milestones

Ortho-McNeil-Janssen

Pharmaceuticals, Inc.mGluR2 PAM

ADX71149 Anxiety &

schizophreniaHit-to-Lead

(Dec 2004)Phase I €3 million €5.2 million €112 million

Merck & Co., Inc. mGluR4 PAMParkinson’s

diseaseHit-to-Lead

(Dec 2007)

preclinical efficacy in PD model

$3 million $2.5 million $167.5 million

Merck & Co., Inc.mGluR5 PAM

ADX63365 schizophrenia

Clinical Candidate

(Jan 2008)

not disclosed

$22 million n.a. $680 million

Proprietary Platform Revenues

• Addex has received partnering revenue every year since 2004

• Cash inflows generated to date: CHF43 million

• All three partnerships are fully funded by our partners

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

* and undisclosed indications

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Wholly Owned Programs

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ADX48621 Overview

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

– 110 patients treated to date, including older volunteers

– Safety & tolerability justify further clinical study

• Differentiated– Only product shown to reduce dystonia in MPTP model

– Chemical series unrelated to other mGluR5 NAMUnique metabolic profile

– NCE patents valid through 2025 in most territories

– Unrelated series of backup molecules in clinical candidate selection

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•ADX48621 effects in HIC model suggestIt should be tested further as a potential drug for PD It has potential to be a dopamine sparing agent

ADX48621 efficacy in HIC model• Haloperidol induced catalepsy (HIC) is a preclinical model of PD

ADX48621 dose-dependently reversed HIC in 3 independent experimentsMTEP mGluR5 antagonist is well documented to work in the HIC model

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

Late

ncy

(sec)

1st experiment2nd experiment3rd experiment

***

*********

****

***

**

***

+ 1 mg/kg haloperidol

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

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MPTP model of PD-LID

What is the MPTP Model?

• MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

– Neurotoxin destroys dopaminergic neurons

– Symptoms similar to PD, treatable with levodopa

• MPTP monkeys develop levodopa induced dyskinesia (LID), including both chorea (trembling) and dystonia (cramping) seen in humans

• MPTP PD-LID model is predictive of efficacy in humans

– KOLs consider it among the most translational models in the CNS space

– AFQ056 (mGluR5/Novartis) showed efficacy in MPTP PD-LID model

– AFQ056 showed efficacy in Phase IIa PD-LID trial

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• ADX48621 or vehicle 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 2hrs)

lower scores (left axis) indicate fewer symptoms/disabilitydyskinesia symptoms are side effects from levodopadisability is a measure of Parkinson’s disease severity

ADX48621 MPTP Study Design

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ADX48621 reduced dyskinesia without compromising levodopa efficacy

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

*

dysk

ines

ia (

0-2

hr)

ADX48621 dose-dependently reduced dyskinesia

(chorea + dystonia)

Dyskinesia

ADX48621 efficacy in MPTP model

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

ab

ilit

y

ADX48621 does not reduce levodopa efficacy

Disability

+ levodopa

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ADX48621 is the first drug-candidate known 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

Dystonia = sustained muscle contractions (e.g. cramps)

0

5

10

15

L-DOPA (100%)

vehicle

ADX48621 (mg/kg)

3 10 30

**

chor

ea (

0-2

hr)

Chorea

Chorea = involuntary

movements (e.g. trembling)

ADX48621 efficacy in MPTP model

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ADX48621development plan

• PD-LID: Study ADX48621-201– U.S. & EU Phase II trial in about 140 PD-LID patients – Double-blind, placebo-controlled, two doses of ADX48621– 6 weeks treatment– Endpoints: multiple instruments (in consultation with KOLs)– Start 4Q2010– Report data end 2011 or early 2012

• Dystonia: Study ADX48621-202– EU Phase IIa trial in about 32 dystonia patients– Double-blind, placebo-controlled, two-way crossover (two dose groups)– 2 week treatment period– Endpoints: multiple instruments (in consultation with KOLs)– Start 4Q2010 – Report data end 2011 or early 2012

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ADX48621Commercial Potential

• Levodopa induced dyskinesia (LID) and dystonia are an unmet medical needs– Most Parkinson’s disease (PD) patients develop LID

– no drugs specifically approved for PD-LID – growing unmet medical need– PD-LID/dystonia is a faster path to market than PD

• Addex can retain co-promotion rights– treated by specialists– geographic split possible– mGluR4 PAM & mGluR2 NAM represent potential additions to future

neurodegenerative disease franchise

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ADX71943

• ADX71943 is a gamma-aminobutyric acid subtype B (GABAB)receptor PAM

–Clinically/commercially validated mechanismgeneric GABAB agonist, baclofen, is marketed

other orthosteric GABAB agonists are clinically validated

–ADX71943 is differentiatedADX71943 is the only allosteric modulator of GABAB in development

Demonstrated analgesic effects in three preclinical pain models Potential for chronic pain (e.g. osteoarthritis) and other indications

• Phase I to start 4Q10

• ADX71943 is available for partnering

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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

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

Status

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

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

• In late preclinical development

• ADX68692 is available for partneringPreclinical Data & Potential Indications

• Statistically significant reduction in testosterone & prostate weight Benign prostatic hyperplasia (BPH)

• Statistically significant reduction in estradiol Endometriosis

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Allosteric ModulatorDiscovery & Optimization

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Allosteric Modulation

Because they bind a different site on the receptor, allosteric modulators do not turn receptors on or off the way the body’s natural activators and most drugs do. Instead, they act more like a dimmer switch, offering control over the ease & intensity of (de-)activation while allowing the body to retain its natural control over initiating receptor activation via the active site (e.g. the on/off switch).

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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. GLP-1

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

•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

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Serendipity has yielded some marketed allosteric modulators. Most recent examples include:

• Sensipar/Mimpra cinacalcet (Amgen) – Positive allosteric modulator (PAM) of calcium sensing receptor– Approved 2004– treats secondary hyperparathyroidism

• Selzentry/Celsentri maraviroc (Pfizer) – Negative allosteric modulator (NAM) of CCR5– Approved 2007– Treats CCR5-tropic HIV-1

Allosteric Modulators 101

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• Allosteric modulators are hard to find– Industrial tools for orthosteric drugs are not appropriate – Pharma has been focused on tools for finding orthosteric drugs– Why didn’t pharma industrialize allosteric drug discovery?

• Upfront investment to build allosteric drug discovery platform was high

• Time to value creation was long & uncertain

• Addex is industrializing allosteric modulation discovery– Proprietary assays

• High throughput screening & optimization tools (384 well plates & robotics)

• Direct detection systems – proximal to target – continuous real-time observation– works for molecules (i.e. allosteric modulators) that do not activate target receptor

– Allostery biased library of over 70,000 compounds

The Addex raison d'être

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Proprietary Screening AssaysG-Protein Coupled Receptors

• Phoenyx– a cAMP dynamic non stop assay

• FBBA (GLP1R, mGluR7)– Fluorescence-Based Binding Assay – Measures bi-molecular interactions

• Proxylite (GLP1R, GIP)– Proximal & dynamic assays for functional measurements of

all types of GPCRs

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• APRA (TNFR1)–Accessory Protein Relocalization Assays

• ADX-tags series 1 (IL1R) –Proximal & dynamic assays for functional measurements –Measures activation-dependent association or dissociation of

binding partners

• ADX-tags series 2 (TNFR1, IL1R)–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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Allostery Biased 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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Platform Validation

• Addex identified selective orally available small molecules for– Challenging GPCRs (mGluRs, GABA-B & A2A)– Peptide receptors (GLP1R, GIPR)– Cytokine receptors (TNFR1 & IL1R1)

• The proof is in the pudding – Merck & Co., Inc. licensed mGluR4 PAM & mGluR5 PAM– Johnson & Johnson licensed mGluR2 PAM

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Summary

• 15 Programs for High Value Targets/Indications–Highly differentiated allosteric mechanism

–Low target related risk (i.e. mostly clinically validated targets)

• Allosteric Modulator Platform–Proprietary tools + tailored library

–Platform + multi-disciplinary approach are scalable

• 3 Validating Partnerships (MRK/J&J)

• Top Tier Investors

• Cash to end of 2011

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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

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www.addexpharma.com

allosteric modulators for human health