Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (January 2020)
27 slides from Addex Therapeutics's investor presentation, January 2020
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders January 2020 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 digi
Slide 4: Leadership Team and Board of Directors
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 founding te
Slide 5: In House Discovered Pipeline
In House Discovered Pipeline 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 mGlu7 NAM disorder
Slide 6: Dipraglurant in Parkinson's Disease
Dipraglurant in Parkinson’s Disease 6
Slide 7: 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 8: 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 devel
Slide 9: Dipraglurant - Overview and Mechanism of Action
Dipraglurant - Overview and Mechanism of Action • Loss of substantia nigra neurons combined with the non- Severe PD physiological, pulsatile stimulation of dopamine receptors (advanced neuron degeneration) are at the basis of LID development STRIATUM L-DOPA L-dopa (drug) • In the striatum, LID is th
Slide 10: 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 1800 L-Dopa* in Humans to peak levels of levodopa therapy 1600 Dipraglurant (100 mg) • PK profile of dipraglurant mirrors that DYSKINESIA 1400 Plasma conc (ng/ml) 1200
Slide 11: 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: exploratory efficacy: N=76 R ‒ Modified Abnormal Involuntary Movement Scale (mAIMS) on Day 1, 14 and 28 N=52: Dipragluran
Slide 12: Dipraglurant Reduces LID Severity by 30%
Dipraglurant Reduces LID Severity by 30% MMRM analysis of the effect of dipraglurant on • Dipraglurant had a statistically significant mAIMS at 90min (LS means +/- SE) the peak mAIMS score reported as reduction effect on the first day Change from Baseline in Peak 1 from baseline • Dipraglurant reduc
Slide 13: 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 60 p = 0.0132 p= 0.0474 Dipraglurant 50 • A 30% reduction in mAIMS Cumulative % of Responders Placebo 40 – One patient was able to hold & rea
Slide 14: 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 • Relatively simple scale that reflects 45% Dipraglurant everyday clinical practice 40% Placebo 35% • Assessment by treating physi
Slide 15: 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 % of Subjects i
Slide 16: 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%, placebo 75%) • The majority of patients completed the dose escalation regimen • Most common AEs: Dipraglurant Placebo ⃰ 3 of the 11 patients who reported “
Slide 17: PD-LID Registration Program Started
Dipraglurant PD-LID Registration Program Started • Manufacturing of drug product completed • First pivotal registration trial on track to start dosing patients in Q1 2020 – Fully funded and expected to report out in Q3 2021 • Primary endpoint: UDysRS – more sensitive to treatment effect than mAIMS (
Slide 18: First Pivotal PD-LID Study (301)
Dipraglurant First Pivotal PD-LID Study (301) Study Design • Primary objective is efficacy in reducing LID N = 70 Placebo ‒ Change over time in UDysRS at 3 Moderate to severe PD-LID months R • Secondary objectives N=140 ‒ Change over time in MDS- UPDRS Part III N = 70 Dipraglurant (100mg) ‒ Patient
Slide 19: Confirmatory Phase 3 PD-LID Study (303)
Dipraglurant Confirmatory Phase 3 PD-LID Study (303) Study Design • Primary objective efficacy in reducing LID ‒ Change over time in UDysRS at 3 months N = 70 Placebo Moderate to • Secondary objectives severe PD-LID ‒ Change over time in UDysRS at 6 N=140 R months ‒ Change over time in MDS- UPDRS Pa
Slide 20: Dipraglurant LID Opportunity
Dipraglurant LID Opportunity Limited competition – ➢> 170K LID patients in US only one FDA approved ➢~$1.4bn US market opportunity for dipraglurant medicine LID has a large unmet ➢ >Gocovri (reformulation of generic amantadine) ➢ Approved on 24th August 17, safety profile similar to generic need and
Slide 21: Addex Allosteric Modulation Technology Platform
Addex Allosteric Modulation Technology Platform Becoming an Exciting Space 21
Slide 22: 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 leading technology platform 22
Slide 23: Using Allosteric Modulation to Discover Novel CNS Drug Candidates
Using Allosteric Modulation to Discover Novel CNS Drug Candidates Orthosteric Allosteric (primary) Site Site Potential benefits • Novel, orally available drug class • Superior receptor sub-type selectivity Affinity • Bind to non-competitive sites and therefore potential to address Modulation intract
Slide 24: Addex Platform Already Validated – Indivior Partnership Case Study
Addex Platform Already Validated – Indivior Partnership Case Study The alliance with Indivior focusing on discovery of GABAB Positive Allosteric Modulators (PAMs) for addiction • Positive Allosteric Modulator (PAM) is a differentiated pharmacological approach – Potential safety and efficacy advantag
Slide 25: Financials
Financials Therapeutics
Slide 26: Financials and Stock
Financials and Stock • Cash runway through 2021 • 32,848,635 shares outstanding 44.6M – Cash of CHF31.5M at 31 December 2019 (fully diluted) – Fully funded through dipraglurant study 301 – New Enterprise Associated - 13.91% readout – New Leaf Venture Partners - 4.86% – CAM Capital – 4.86% • Market c
Slide 27: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH WWW.ADDEXTHERAPEUTICS.COM 27
Addex Therapeutics — Investor Presentation (January 2020) on 6ix