Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (August 2022)
37 slides from Addex Therapeutics's investor presentation, Aug 18, 2022
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders August 2022 Allosteric modulators for human health
Slide 2: Disclaimer
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 di
Slide 3: Addex Overview
Addex Overview • Phase 2 epilepsy study (J&J) – data in Q1 2023 Multiple high value programs • Dipraglurant – Phase 2 ready, under evaluation for multiple indications reaching significant • GABAB PAM for substance use disorder (Indivior) and other indications milestones • mGlu7 NAM for stress relate
Slide 4: Our Pipeline – Multiple Programs Underway
Our Pipeline – Multiple Programs Underway Molecule / MoA Indication Partner Pre-clinical Phase 1 Phase 2 Phase 3 Milestone ADX71149 Data in Epilepsy (mGlu2 PAM) Q1 2023 Dipraglurant PD-LID, SUD, NDD, pain, post-stroke/TBI Indication under (mGlu5 NAM) rehabilitation evaluation Substance use disorders
Slide 5: Experienced Team
Experienced Team Leadership Team Tim Dyer Dr Roger Mills Dr Robert Lutjens Dr Jean-Philippe Rocher Dr Mikhail Kalinichev CEO / CFO Chief Medical Officer Head of Discovery Biology Head of Discovery Chemistry Head of Translational Science Co-Founder of Addex Developed Nuplazid for PD Member of Addex f
Slide 6: ADX71149 (JNJ-40411813) for Epilepsy
ADX71149 (JNJ-40411813) for Epilepsy Partnered with Janssen Pharmaceuticals, Inc. 6
Slide 7: ADX71149 Opportunity in Epilepsy
ADX71149 Opportunity in Epilepsy • Market projected to reach $20 billion by 2026* – Keppra market leader with > 2M patients & €800M p.a.** Large market & unmet • High proportion of refractory patients (¼ of new patients***) - combination medical need treatments have limited therapeutic benefit • Lar
Slide 8: ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model
ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model • Preclinical validation in pharmaco-resistant mouse epilepsy model with high translational value: ED50 shift of Keppra by adding low dose of ADX71149 ED50 shift of ADX71149 by adding ED50 dose of LEV LEV alone ADX71149 alone LEV+10mg ADX71149 AD
Slide 9: ADX71149 Phase 2a Epilepsy Study
ADX71149 Phase 2a Epilepsy Study Placebo n=20 • Double blind placebo controlled • Establish 28-day seizure count (over 56-day baseline period) • Focal onset seizure with suboptimal response to • Primary endpoint: time to monthly baseline levetiracetam seizure count • 3-100 seizures/4weeks during bas
Slide 10: Dipraglurant (mGlu5 NAM) – Phase 2 Ready
Dipraglurant (mGlu5 NAM) – Phase 2 Ready Indications under evaluation: PD-LID, SUD, Post-stroke rehabilitation, pain and NDD 10
Slide 11: Dipraglurant Opportunity in Multiple Indications
Dipraglurant Opportunity in Multiple Indications • PD-LID: 200,000 patients in US, Orphan drug designation granted in US Significant target • SUD: 20 million patients in US and 2.2% of adult population worldwide patient population and • Pain: up to 10% of adult population are diagnosed with chronic
Slide 12: Compelling Rationale to Develop Dipraglurant for PD-LID
Compelling Rationale to Develop Dipraglurant for PD-LID • Large underserved patient population in need of improved treatment options • Significant commercial opportunity with limited competition – 1M Parkinson’s disease patients in US of which >170,000 have dyskinesia – Orphan drug designation grant
Slide 13: Disability and Impact of PD-LID
Disability and Impact of PD-LID • Dyskinesias caused by neurodegeneration Invariably associated with • Dopamine replacement lowers the triggering threshold for symptoms long-term L-dopa use • LID can become as disabling as the PD symptoms themselves • Uncontrollable muscle contractions, twisting and
Slide 14: MoA Rationale for Targeting mGlu5 Inhibition in PD-LID
MoA Rationale for Targeting mGlu5 Inhibition in PD-LID • Loss of substantia nigra neurons combined with the non-physiological, pulsatile stimulation of dopamine receptors with L-dopa are at the basis of LID development • In the striatum, LID is the result of: A D1 receptor priming B Excess glutamate
Slide 15: Dipraglurant PK is a Key Advantage for Treating LID
Dipraglurant PK is a Key Advantage for Treating LID 3 Dipraglurant and L-Dopa plasma concentration 2,5 • Dyskinesia symptoms are correlated to peak levels of L-dopa 2 Dyskinesia • PK of dipraglurant allows control of (µg/ml) 1,5 glutamatergic tone ahead of L-dopa Cmax 1 Dipraglurant normalizes abnor
Slide 16: Dipraglurant Phase 2a Study in LID (in US and Europe)
Dipraglurant Phase 2a Study in LID (in US and Europe) • Primary objective: N=24: Placebo safety & tolerability N=76 • Secondary objective: exploratory efficacy: ‒ Modified Abnormal N=52: Dipraglurant Involuntary Movement Scale (mAIMS) on days 1, 14 and 28 50 mg 100 mg 100 mg ‒ Clinician Global Impre
Slide 17: Dipraglurant Improves LID by 30%
Dipraglurant Improves LID by 30% Change from Baseline in Peak mAIMS at 90min 1 • Statistically significant effects: 0 Day 1 (50mg) and Day 14 (100mg) • Improvement maintained through (LS means +/- SE) -1 Day 28 p=0.041 • Increasing placebo response caused -2 significance to be lost at Day 28 -3 p=0.
Slide 18: Responder Analysis Demonstrates Dipraglurant Significant Benefit
Responder Analysis Demonstrates Dipraglurant Significant Benefit Percent of patients with ≥ 30% improvement on mAIMS 60 p = 0.0132 p= 0.0474 50 Responder analysis Cumulative % of Responders (≥30% change of mAIMS from baseline) 40 Midday dose Dipraglurant Placebo 30 Day 1 (50 mg) n=13 26.0% n=3 12.5%
Slide 19: Significant Improvement on CGI-C
Significant Improvement on CGI-C 50% Dipraglurant Placebo 45% Improved 40% 71.2% 49.9% (p<0.05) 35% No 17.3% 45.8% change % of Patients 30% 25% • Simple scale reflecting clinical assessment 20% by treating physician 15% 10% • More objective than mAIMS 5% • Assessed at end of study compared to 0% bas
Slide 20: Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients
Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients • Adverse events common in both treatment groups (dipraglurant 88.5%, placebo 75%) • Most common AEs: Dipraglurant Placebo Worsening 21% 12.5% * 3 of 11 AEs of “worsening dyskinesia” occurred in the follow up period Dyskinesia (15
Slide 21: Dipraglurant PD-LID – Status of Development
Dipraglurant PD-LID – Status of Development • Pivotal registration program –Study 301 & 12-month Open Label Study (302) terminated in June 2022 due to slow recruitment rate attributed to COVID related constraints • Future development under evaluation, including: –PD-LID –Substance use disorder –Neur
Slide 22: Compelling Rational to Develop Dipraglurant for SUD including CUD
Compelling Rational to Develop Dipraglurant for SUD including CUD • SUD: 20 million patients in US and 2.2% of adult population worldwide Unmet medical need - • CUD: 5.2 million people (1.9% of population) reported using cocaine in the target patient population past 12 month and commercial • The cur
Slide 23: Compelling Rational to Develop Dipraglurant for Pain
Compelling Rational to Develop Dipraglurant for Pain in Migraine, Trigeminal Neuralgia, and Other Conditions • Pain: 20 million patients in US and up to 10% of adult population are Unmet medical need - diagnosed with chronic pain every year target patient population • Migraine: 12-18% of adult popul
Slide 24: Compelling Rational to Develop Dipraglurant for ASD & NDD incl. Fragile X
Compelling Rational to Develop Dipraglurant for ASD & NDD incl. Fragile X • NDD (Fragile X) – 50K Fragile X patients in US, affecting 1 in 4,000 males Unmet medical need - and 1 in 8,000 females target patient population • No curative treatment, disease management through behavioural therapies & com
Slide 25: Compelling Rational to Develop Dipraglurant for Post-stroke Rehabilitation
Compelling Rational to Develop Dipraglurant for Post-stroke Rehabilitation Unmet medical need - • Globally >77 million people have survived an ischemic stroke (nearly 2/3 of these target patient population & are <70 yrs old) + 4.3 million/year *(800k strokes in US in 2016**) • No drugs to support re
Slide 26: Key Preclinical Programs
Key Preclinical Programs 26
Slide 27: GABAB PAM for Substance Use Disorder
GABAB PAM for Substance Use Disorder • High prevalence;1.8% of US population* Large market & unmet • Current treatments have undesirable side-effects and prone to relapse medical need • Burden to society in US is >$600B annually** • Baclofen (GABAB agonist) used off label for alcohol use disorder •
Slide 28: Addex GABAB PAM for Chronic Cough
Addex GABAB PAM for Chronic Cough • Widespread prevalence – Up to 10% of adult population worldwide* Large market & unmet – More prevalent (10-20%) in Europe, America and Australia than in Asia (5%)* medical need • Opioid drugs (codeine) offer suboptimal relief and are linked to undesirable side eff
Slide 29: Addex GABAB PAM for Chronic Pain
Addex GABAB PAM for Chronic Pain • Widespread prevalence – Cancer pain - >50% of patients experience pain during cancer treatment* Large market & unmet – Trigeminal neuralgia - estimated at 4 to 13 people per 100,000/year** – Pelvic / bladder pain - 6.5% of US women show bladder pain symptoms*** med
Slide 30: Addex GABAB PAM for CMT1a
Addex GABAB PAM for CMT1a Large market & unmet • Prevalence and treatment – CMT1a prevalence is 6.9/100000* medical need – No approved drugs and limited R&D pipeline • PXT3003 (fixed-dose combination of three FDA-approved drugs: naltrexone, baclofen, sorbitol) currently in Phase 3 clinical study for
Slide 31: Addex mGlu7 NAM for Stress Related Disorders (including PTSD)
Addex mGlu7 NAM for Stress Related Disorders (including PTSD) • PTSD affects approximately 3.5% of U.S. adults Large market & unmet • Current treatments are primarily based on psychotherapy, medication is medical need nonspecific (off-label use of anxiolytics and antidepressants) and usually ineffec
Slide 32: Addex mGlu2 NAM for mNCD and Depression
Addex mGlu2 NAM for mNCD and Depression • Prevalence in 65–69 year olds is 6.7% and 25% in 80–84 year olds* Large market & unmet • Donepezil approved for mNCD, but does not work in all patients and has medical need suboptimal tolerability profile • Preclinical and post-mortem evidence - blockade of
Slide 33: Addex Financials, Stock and Milestones
Addex Financials, Stock and Milestones 33
Slide 34: Financials and Stock
Financials and Stock • Cash at 30 June 2022: CHF 8.8 million • 37.9M outstanding shares* ($9.1 million) – Armistice Capital LLC – 35.04% – CHF 4.6 million raised 22 July 2022 – New Enterprise Associates – 19.24% – New Leaf Venture Partners – 6.89% • No debt – CAM Capital – 6.09% – Credit Suisse Asse
Slide 35: Milestones
Milestones Milestone Timing ADX71149 for epilepsy Phase 2a – study started June 2021 Phase 2a - topline results Q1 2023 GABAB PAM for substance use disorders Start IND enabling studies H1 2023 mGlu7 NAM for stress-related disorders - PTSD Start IND enabling studies H1 2023 35
Slide 36: Summary
Summary • Phase 2 epilepsy study (J&J) – data in Q1 2023 Multiple high value • Dipraglurant Phase 2 ready with interest in multiple indications programs reaching • GABAB PAM for substance use disorder (Indivior) and other indications significant milestones • mGlu7 NAM for stress related disorders (P
Slide 37: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (August 2022) on 6ix