Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (October 2019)
26 slides from Addex Therapeutics's investor presentation, October 2019
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders October 2019 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 ➢ Pivotal registration program on track to dose patients in Q1 2020 Dipraglurant for dyskinesia in ➢ US PD-LID market estimated at $4.2B Parkinson’s disease ➢ FDA Orphan Drug Designation granted in PD-LID ➢ Indivior partnership - $330m in milestones, tiered royalties up to double Vali
Slide 4: Experienced Leadership Team and Board of Directors
Experienced Leadership Team Tim Dyer Dr Roger Mills Dr Robert Lutjens Dr Jean-Philippe CEO / CFO Chief Medical Officer Head of Discovery Rocher Biology Head of Discovery Co-Founder of Addex Developed Nuplazid in Formerly with PwC PD Pyschosis Member of Addex Chemistry UK Chartered 30 years in Pharma
Slide 5: Extensive Pipeline Driving Long-Term Growth
Extensive Pipeline Driving Long-Term Growth Pre- Molecule / MoA Indication Partner Phase 1 Phase 2 Phase 3 Milestone clinical Dipraglurant-IR Top line data PD-LID Q3 2021 (mGlu5 NAM) Dipraglurant-ER Dystonia (mGlu5NAM) ADX71149 Epilepsy (mGlu2 PAM) Addiction GABAB PAM CMT1A Post-traumatic stress mGl
Slide 6: What are Allosteric Modulators?
What are Allosteric Modulators? Endogenous Ligand Active Site Active Site Outside Cell Negative Positive Cell Allosteric Allosteric Membrane Modulator Modulator Inside Cell NAM PAM Reduces signal Increases signal Addex is based on a world leading technology platform 6
Slide 7: Potential benefits of Allosteric Modulation Approach
Potential benefits of Allosteric Modulation Approach • Novel, orally available drug class • Superior receptor sub-type selectivity • Potentially more GPCR targets – address intractable targets • Re-address well characterized and clinically validated GPCR targets • Potentially improved safety • Clini
Slide 8: Dipraglurant in Parkinson's Disease
Dipraglurant in Parkinson’s Disease 8
Slide 9: The Dipraglurant Opportunity in Dyskinesia associated with PD
The Dipraglurant Opportunity in Dyskinesia associated with PD ➢Pivotal studies on track to dose patients in Q1 2020 Clear Development & ➢Manufacturing and planning ongoing Regulatory Path ➢Precedented FDA regulatory path Unmet Need and Significant ➢>1M Parkinson’s disease patients in US of which >17
Slide 10: Levodopa-Induced Dyskinesia in Parkinson's Disease (PD-LID)
Levodopa-Induced Dyskinesia in Parkinson’s Disease (PD-LID) Long-term L-dopa use is ➢ Dopamine replacement does not lead to dyskinesia per se, but lowers the triggering threshold for symptoms invariably associated with the ➢ Dyskinesias result from the neurodegenerative process that underlies PD dev
Slide 11: Dipraglurant - Overview and Mechanism of Action
Dipraglurant - Overview and Mechanism of Action Severe PD • Loss of substantia nigra neurons combined with the (advanced neuron degeneration) non-physiological, pulsatile stimulation of dopamine STRIATUM L-DOPA receptors are at the basis of LID development L-dopa (drug) • In the striatum, LID is the
Slide 12: Dipraglurant PK is a Key Advantage for Treating LID
Dipraglurant PK is a Key Advantage for Treating LID Pharmacokinetic profile of Dipraglurant and • Dyskinesia symptoms are correlated to 1800 L-Dopa* in Humans Dipraglurant (100 mg) peak levels of levodopa therapy 1600 l-dopa carbidopa 100/25 DYSKINESIA 1400 • PK profile of dipraglurant mirrors that
Slide 13: Dipraglurant EU and US Phase 2a Study in LID
Dipraglurant EU and US Phase 2a Study in LID • Primary objective: Multicentre study in 25 centres across US and Europe safety & tolerability N= 24: Placebo • Secondary objective: N=76 R exploratory efficacy: ‒ Modified Abnormal Involuntary Movement N=52: Dipraglurant Scale (mAIMS) on Day 1, 14 and 2
Slide 14: Dipraglurant Reduces LID Severity by 30%
Dipraglurant Reduces LID Severity by 30% MMRM analysis of the effect of dipraglurant on the Change from Baseline in Peak mAIMS at peak mAIMS score reported as reduction from baseline 1 Dipraglurant Placebo • Dipraglurant had a statistically significant 90min (LS means +/- SE) 0 effect on the first d
Slide 15: Responder Analysis Demonstrates Dipraglurant Significant Benefit
Responder Analysis Demonstrates Dipraglurant Significant Benefit Dipraglurant cumulative % of PD-LID patients showing ≥ 30% change of peak mAIMS from baseline Dipraglurant 60 p = 0.0132 p= 0.0474 Placebo 50 Cumulative % of Responders 40 30 • A 30% reduction in mAIMS is p = 0.2377 20 clinically meani
Slide 16: Clinician Rated Global Impression of Change - Dyskinesia
Clinician Rated Global Impression of Change - Dyskinesia Clinician rated global impression of change in LID patients after administration of dipraglurant and 50% placebo Dipraglurant • Relatively simple scale that reflects 45% 40% Placebo everyday clinical practice 35% • Assessment by treating physi
Slide 17: Patient Diaries – Improvement Throughout the Waking Day
Patient Diaries – Improvement Throughout the Waking Day Pattern of motor complications of dipraglurant patients over the course of a day, as reported in patients’ diaries Baseline (n=42) Week 4 (n=42) on w/o dyskinesia on w/o dyskinesia 100% 100% on with dyskinesia on with dyskinesia 90% Asleep 90%
Slide 18: Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients
Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients • Adverse events were common in both treatment groups (dipraglurant 88.5%, pbo 75%) • The majority of patients completed the dose escalation regimen • Most common AEs: Dipraglurant Placebo Worsening 21% 12.5% ⃰ 3 of the 11 patient
Slide 19: Phase 3 Trial On-Track to Start Dosing in Q1 2020
Phase 3 Trial On-Track to Start Dosing in Q1 2020 • The Phase 3 trial is fully funded and expected to report out in Q3 2021 • Considering Fast-Track and/or Breakthrough Therapy applications after first pivotal study readout • Primary endpoint: UDysRS – more sensitive to treatment effect than mAIMS (
Slide 20: Dipraglurant First Pivotal PD-LID Study (301)
Dipraglurant First Pivotal PD-LID Study (301) Study Design • Primary objective is efficacy Moderate to N = 70 Placebo in reducing LID severe PD-LID ‒ Change over time in UDysRS at 3 N=140 R months N = 70 Dipraglurant (100mg) • Secondary objectives Fixed dose ‒ Change over time in MDS- Double-blind t
Slide 21: Dipraglurant Confirmatory Phase 3 PD-LID Study (303)
Dipraglurant Confirmatory Phase 3 PD-LID Study (303) • Primary objective efficacy in Study Design reducing LID ‒ Change over time in UDysRS at 3 N = 70 Placebo Moderate to months severe PD-LID • Secondary objectives N=140 R ‒ Change over time in UDysRS at 6 N = 70 Dipraglurant (100mg) months Fixed d
Slide 22: Dipraglurant LID Opportunity
Dipraglurant LID Opportunity ➢> 170K LID patients in US LID has a large unmet need ➢~$1.4bn US market opportunity for dipraglurant and market opportunity ➢ >Gocovri (reformulation of generic amantadine): Approved on 24th August 17, Limited competition – only safety profile similar to generic one FDA
Slide 23: Financials
Financials Therapeuties
Slide 24: Financials and Stock
Financials and Stock • Cash runway through 2021 – Cash of CHF36.7M at 30 June 2019 – Fully funded through dipraglurant study 301 readout • Traded on SIX Swiss Exchange: ADXN (ISIN:CH0029850754) • 32,848,635 shares outstanding 44.6M (fully diluted) – New Enterprise Associated - 13.91% – New Leaf Vent
Slide 25: Upcoming Major Development Milestones
Upcoming Major Development Milestones Milestone Timing Dipraglurant – LID Phase 3 Registration Program Complete manufacturing of Drug Product Q4 2019 Study 301 – Start dosing Q1 2020 Study 301 – Top line data Q3 2021 25
Slide 26: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH WWW.ADDEXTHERAPEUTICS.COM 26
Addex Therapeutics — Investor Presentation (October 2019) on 6ix