Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (July 2020)
33 slides from Addex Therapeutics's investor presentation, July 2020
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders July 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 ready to start but suspended due to Covid-19 Dipraglurant for dyskinesia in pandemic, expect to dose first patient in H2 2020* Parkinson’s disease ➢ US PD-LID market estimated at $4.2B ➢ FDA Orphan Drug Designation granted in PD-LID ➢ Indivior partnershi
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 Expect topline PD-LID (mGlu5 NAM) results in Q2 2022 Dipraglurant-ER Dystonia (mGlu5 NAM) ADX71149 Epilepsy (mGlu2 PAM) Addiction GABAB PAM CMT1A Post-traumatic stress mGlu7
Slide 6: Dipraglurant for Parkinson's Disease
Dipraglurant for Parkinson’s Disease 6
Slide 7: The Dipraglurant Opportunity in Dyskinesia associated with PD
The Dipraglurant Opportunity in Dyskinesia associated with PD ➢ Pivotal study ready to dose patients but suspended due to Covid-19 pandemic, Clear development & expect to dose first patient in H2 2020* regulatory path ➢Precedented FDA regulatory path Unmet need and significant ➢>1M Parkinson’s disea
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 ➢Dyskinesias result from the neurodegenerative process that underlies PD ➢Dopamine replacement does not lead to dyskinesia per se, but lowers the invariably associated with the triggering threshold for symptoms 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) with L-Dopa are at the basis of LID development STRIATUM L-DOPA L-dopa (drug) • In the striatu
Slide 10: 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 1800 L-dopa* in Humans to peak levels of L-dopa 1600 Dipraglurant (100 mg) • PK profile of dipraglurant mirrors that DYSKINESIA 1400 Plasma conc (ng/ml) 1200 l-dopa ca
Slide 11: 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: 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: Dipraglurant PD-LID Registration Program Started
Dipraglurant PD-LID Registration Program Started • First pivotal registration study (301) is ready to start dosing patients, but suspended due to Covid-19 pandemic – Study is expected to read out 18 months from first patient dosing • 12 month Open Label Study (302) starting in parallel to study 301
Slide 18: Dipraglurant 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: Dipraglurant 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 LID has a large unmet ➢> 170K LID patients in US need and market ➢~ $1B US peak sales potential for dipraglurant opportunity Limited competition – ➢Gocovri (reformulation of generic amantadine) approved in August 2017, safety profile similar to generic only one FDA appro
Slide 21: ADX71149 for Epilepsy Partnered with Janssen (JNJ)
ADX71149 for Epilepsy Partnered with Janssen (JNJ) 21
Slide 22: JPI Partnership mGlu2 PAM (ADX71149/JNJ-40411813)
JPI Partnership mGlu2 PAM (ADX71149/JNJ-40411813) • Status of ADX71149 development: – Phase I complete (more than 8 studies conducted) – Phase II study in schizophrenia as adjunctive therapy reported positive data in negative symptoms of schizophrenia – reported 2012 – Phase II study as adjunctive t
Slide 23: JPI Partnership (ADX71149/JNJ-40411813) – Epilepsy POC
JPI Partnership (ADX71149/JNJ-40411813) – Epilepsy POC • Preclinical validation in 6Hz (44 mA) pharmacoresistant mouse Epilepsy model: ED50 shift of LEV by adding inactive dose of JNJ-813 ED50 shift of JNJ-813 by adding ED50 dose of LEV ~14 fold ~35 fold • Observed increased potency of LEV (levetira
Slide 24: GABA B PAM for Addiction & CMT 1A Neuropathy
GABA B PAM for Addiction & CMT 1A Neuropathy Collaboration with Indivior for Addiction 24
Slide 25: GABAB PAM Program for Addiction and CMT1A
GABAB PAM Program for Addiction and CMT1A • GABAB is the metabotropic receptor for GABA, main inhibitory neurotransmitter – Activation of GABAB is clinically validated through the use of baclofen in alcoholism and CMT1A – PAM is a differentiated approach, resulting in potential safety and efficacy a
Slide 26: mGlu7 NAM for Post Traumatic Stress Disorder
mGlu7 NAM for Post Traumatic Stress Disorder Eurostar Funded Consortium Collaboration 26
Slide 27: mGlu7 NAM Program for Post-Traumatic Stress Disorder
mGlu7 NAM Program for Post-Traumatic Stress Disorder • mGlu7 appears to play a central role in fear and anxiety – Expression studies, genetic and pharmacological manipulations, have revealed the important role of mGIu7 receptors in anxiety disorders – Preclinical proof-of-concept studies in PTSD mod
Slide 28: Addex Allosteric Modulation Technology Platform
Addex Allosteric Modulation Technology Platform Becoming an Exciting Space 28
Slide 29: 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 29
Slide 30: 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 compared to orthosteric ligands Affinity Modulation • Bind to non-competitive sites and theref
Slide 31: Financials
Financials 31
Slide 32: Financials and Stock
Financials and Stock • Cash runway through 2021 • 32,848,635 shares outstanding 44.6M – Cash of CHF 27.1M at 31 March 2020 (fully diluted) – New Enterprise Associated - 13.91% – New Leaf Venture Partners - 4.86% • Market capitalization: approx. CHF 45M – CAM Capital – 4.86% – Credit Suisse Asset Man
Slide 33: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH WWW.ADDEXTHERAPEUTICS.COM 33
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