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Addex Pharmaceuticals Investor Presentation October 2010 PowerPoint Presentation
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Addex Pharmaceuticals Investor Presentation October 2010

Addex Pharmaceuticals Investor Presentation October 2010

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Addex Pharmaceuticals Investor Presentation October 2010

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  1. Addex PharmaceuticalsInvestor PresentationOctober 2010

  2. 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. raison d'être • 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

  6. Allosteric Modulation Orthosteric agonist/antagonist

  7. Orthosterics are steady state Biological response Natural ligand PAM + natural ligand Agonist Time NAM + natural ligand Antagonist Allostery preserves natural rhythm Natural ligand Biological response Time 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

  8. Platform Patented high throughput screening/optimization systems 70,000 compound allostery-biased library People: competence & multi-disciplinary approach

  9. Platform Performance • 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

  10. PIPELINE Molecule / Mechanism Partner Assay Development & Screening Hit-to-Lead Lead Optimization Preclinical Phase I Phase II Milestone ADX48621mGluR5 NAM Parkinson’s Disease Levodopa Induced Dyskinesia (PD-LID) Start Ph II 4Q10 partially funded by The Michael J. Fox Foundation Dystonia Start Ph IIa 2011 Ortho-McNeil-Janssen Schizophrenia ADX71149mGluR2 PAM Start Ph IIa1Q11 funded & developed by OMJPI* Ortho-McNeil-Janssen Anxiety funded & developed by OMJPI* Osteoarthritic Pain ADX71943GABA-B PAM ADX63365mGluR5 PAM Merck & Co., Inc. Schizophrenia ‡ funded & developed by Merck Endometriosis ADX68692FSHR 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

  11. DISCOVERY Molecule / Mechanism Partner Assay Development & Screening Hit-to-Lead Lead Optimization Preclinical Phase I Phase II Milestone CNS Alzheimer’s / Depression mGluR2 NAM Merck & Co., Inc. Parkinson’s Disease ‡ mGluR4 PAM funded by Merck DepressionPost Traumatic Stress Disorder mGluR7 NAM Sleep Disorders Orexin 2R NAM Metabolic Disorders Type II Diabetes GLP1 PAM Type II Diabetes GIPR PAM Inflammation Rheumatoid Arthritis, Psoriasis, Inflammatory Bowel Disease Alzheimer’s, Multiple Sclerosis TNFR1 NAM (CD120a) Psoriasis, Osteoarthritis A2A PAM Gout, Type II Diabetes IL1R1 NAM (CD121a) NAM = negative allosteric modulator (an inhibitor) ‡ and undisclosed additional indications PAM = positive allosteric modulator (an activator)

  12. Milestones * 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) • InitialPhase 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

  15. 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. ADX48621 in the MPTP Model • 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

  17. Chorea (rapid uncontrolled movements) Dystonia (sustained muscle contractions) ADX48621 in the MPTP model LID has two components: chorea & dystonia first drug-candidate / mechanism reported to have efficacy on dystonia

  18. 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 Trial Study 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 validated • generic 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 baclofen • Allostery may reduce/eliminate development of tolerance & dependence • Allostery may reduce other tolerability issues, like somnolence • ADX71943 demonstrated potential for chronic pain (e.g. osteoarthritis) • Has potential for GERD and urinary incontinence

  21. Pre-treatment Treatment 350 *** 300 ** * * 250 *** 200 ### ** Withdrawal threshold (g) Maximum response bewteen 1 and 2 hr 150 100 50 0 Pre-MIA Post-MIA Day 1 Day 8 -1 14 14 21 Vehicle 1 mg/kg ADX71943 3 mg/kg ADX71943 10 mg/kg ADX71943 30 mg/kg ADX71943 Celecoxib (30 mg/kg) ###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. ADX71943 demonstrated antihyperalgesic effects in a model of osteoarthritis Days post-monosodium iodocate (MIA)

  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 GnRH 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

  23. ADX68692 efficacy in rats 4 week treatment Effect on Oestrus cycle duration‏ POC that ADX68692 disrupts the oestrus cycle and increases its mean duration, eventually leading to complete blockade at high dose.

  24. 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 Locomotor activity during the test Exploration of novel vs familiar objects sham β-Amyloid* 18 β- Amyloid* 120 sham 15 *** 12 9 90 6 3 Line crosses 0 Exploration time (sec) veh veh veh veh 60 18 *** *** 15 30 *** 12 9 6 0 t1 t2 t1 t2 t1 t2 t1 t2 3 veh 10 30 Donepezil Veh 10 30 Donepezil 0 (1 mg/kg, ip) (1 mg/kg, ip) ADX92639(mg/kg, p.o.) ADX92639 (mg/kg, p.o.) *Single administration into the lateral ventricle of 8 μl solution Final concentration of b amyloid = 2 mg/ml ADX92639 effective in icv β amyloid-induced deficit in rat NOR • 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

  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. 30 * 25 20 Glucose AUCB (mM.hr) 15 10 *** 5 Glucose AUCB (0-90 min) 0 A: Vehicle po B: ADX91886 (220 mg/kg po) C: Sitagliptin 10 mg/kg po A B C GPL1R PAM vs sitagliptin in db/db mice

  28. Management & Financial

  29. Management & Boards Executive Management Jean-Philippe Rocher, Head of Core Chemistry Robert Lütjens, Head of Core Biology Tatiana Carteret, Head of Human Resources Chris Maggos, Investor Relations & Communications 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.

  30. 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:

  31. allosteric modulators for human health www.addexpharma.com