Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (April 2022)
32 slides from Addex Therapeutics's investor presentation, Apr 25, 2022
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders April 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 3 Parkinson’s disease dyskinesia study – data in H1 2023 3 clinical programs underway • Phase 2 blepharospasm study – data in Q2 2022 • Phase 2 epilepsy study (J&J) – data in Q3 2022 • Validated & differentiated pharmacological approach Leading allosteric modulator • Proprieta
Slide 4: Addex Pipeline - 3 Clinical Programs Underway
Addex Pipeline - 3 Clinical Programs Underway Molecule / MoA Indication Partner Pre-clinical Phase 1 Phase 2 Phase 3 Milestone Data in PD-LID Dipraglurant H1 2023 (mGlu5 NAM) Data in Blepharospasm Q2 2022 ADX71149 Data in Epilepsy (mGlu2 PAM) Q3 2022 Substance use disorders GABAB PAM CMT1A mGlu7 NAM
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: Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease (PD-LID)
Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson’s Disease (PD-LID) 6
Slide 7: 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 8: 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 9: 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 10: 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 11: 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 12: 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 13: 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 14: 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 15: 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 16: Dipraglurant PD-LID Registration Program
Dipraglurant PD-LID Registration Program • Pivotal registration program ongoing • Study 301 started in June 2021 – Data read-out expected end of H1 2023 – Primary endpoint: UDysRS – Placebo mitigation is a priority • 12-month Open Label Study (302) on going – 6- and 12-month safety data • Second piv
Slide 17: Dipraglurant Pivotal PD-LID Study (301)
Dipraglurant Pivotal PD-LID Study (301) • Primary objective: Efficacy in reducing LID N = 70 Placebo ‒ UDysRS change from baseline at 3 months Moderate to • Secondary objectives severe PD-LID ‒ CGI-S N=140 N = 70 Dipraglurant (100mg) N = 70 Dipraglurant (100mg tid) ‒ MDS-UPDRS Part III change from b
Slide 18: UDysRS: An Improved and Validated Dyskinesia Rating Scale
UDysRS: An Improved and Validated Dyskinesia Rating Scale UDysRS mAIMS • Recommended by Movement Disorder Society • Suboptimal for detecting (MDS) treatment-related changes • FDA regulatory precedent (GOCOVRI® approval) • Limited to patient assessments • Contains anchored objective clinician evaluat
Slide 19: Dipraglurant PD-LID Studies – Management of Placebo Response
Dipraglurant PD-LID Studies – Management of Placebo Response • Use of UDysRS – More sensitive to changes in LID – Less prone to placebo response • Raters will be qualified by the MDS – Expert rater review to further ensure quality • Requirement for moderate to severe symptom scores at screening and
Slide 20: Dipraglurant for Dystonia – Blepharospasm
Dipraglurant for Dystonia – Blepharospasm 20
Slide 21: Blepharospasm (BSP)
Blepharospasm (BSP) • Type of dystonia affecting eyelid muscles – Results in sustained eyelid closure causing substantial visual disturbance or functional blindness – >50% of BSP patients symptoms spread to other cranio-facial muscles • At least 50,000 BSP patients in US, ~2000 new patients diagnose
Slide 22: Rationale for Targeting mGlu5 Inhibition in Dystonia & BSP
Rationale for Targeting mGlu5 Inhibition in Dystonia & BSP • Dystonias are neuro-functional rather than neuro-degenerative • Common features include alterations in neuronal connectivity/function and synaptic communication • BSP pathophysiology is linked to: A Reduction of dopamine input into striatu
Slide 23: Blepharospasm Phase 2 Feasibility Study
Blepharospasm Phase 2 Feasibility Study • Patients with benign essential BSP, who experience moderate/severe symptoms prior Baseline Post-Dose Pre-Dose to their regular dose of BoNT Post-Dose • Single center, randomized, double-blind, CMOR/Scales CMOR/Scales CMOR/Scales CMOR/Scales Patient Identific
Slide 24: ADX71149 (JNJ-40411813) for Epilepsy
ADX71149 (JNJ-40411813) for Epilepsy Partnered with Janssen Pharmaceuticals, Inc. 24
Slide 25: 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 26: ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model
ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model • Preclinical validation in pharmaco-resistant mouse epilepsy model: 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 ADX71149 +350mg LEV ~14 fold ~35
Slide 27: ADX 71149 Phase 2a Epilepsy Study
ADX 71149 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 ba
Slide 28: Financials
Financials 28
Slide 29: Financials and Stock
Financials and Stock • Cash runway through H1 2023 • 37.9M outstanding shares* – Cash at 31 December 2021: CHF20.5 million – New Enterprise Associates – 19.24% ($22.5 million) – Armistice Capital LLC – 35.04% – New Leaf Venture Partners – 6.89% • No debt – CAM Capital – 6.09% – Credit Suisse Asset M
Slide 30: Milestones
Milestones Milestone Timing Dipraglurant for PDLID Phase 2b/3 – study started June 2021 Phase 2b/3 - topline results H1 2023 Dipraglurant for Blepharospasm Phase 2a – study started Sept 2021 Phase 2a - topline results Q2 2022 ADX71149 for Epilepsy Phase 2a – study started June 2021 Phase 2a - toplin
Slide 31: Summary
Summary 3 clinical programs – data • Phase 3 Parkinson’s disease dyskinesia study – data in H1 2023 reading out from end Q2 • Phase 2 blepharospasm study – data in Q2 2022 2022 • Phase 2 epilepsy study (J&J) – data in Q3 2022 • Experienced team of drug developers Technology and • Pioneering alloster
Slide 32: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (April 2022) on 6ix