Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (April 2018)
28 slides from Addex Therapeutics's investor presentation, April 2018
Slide 1: Addex Corporate Presentation
Addex Corporate Presentation April 2018 Innovative Treatments for Central Nervous System Disorders SIX: ADXN 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
Slide 3: Our Story on a Page
Our Story on a Page >1M PD patients in US of which > 170,000 have Levodopa-Induced-Dyskinesia Important z Unmet (LID); 90% experience LID after 9-15 years of L-dopa exposure Need in PD-LID Adamas’ Gocovri (reformulated generic amantadine): Approved Aug 2017 – safety profile similar to generic Di
Slide 4: Experienced Team
Experienced Team • Executive Management: • Clinical Advisors: – Tim Dyer, CEO / CFO – PD-LID • Co-founder of Addex, formerly with PwC • Michael J. Fox Foundation for Parkinson’s – Roger Mills, CMO Research • Formerly with Acadia Pharmaceuticals • Dr. Erwan Bézard • Prof. Chris Goetz – Robert Lutjens
Slide 5: Clinical Stage Pipeline with Registration Trial-Ready Program
Clinical Stage Pipeline with Registration Trial-Ready Program Multiple Orphan Drug Opportunities Molecule / MoA Preclinical Phase 1 Phase 2 Phase 3 Pivotal Dipraglurant-IR (mGluR5 NAM) Parkinson’s disease levodopa-induced dyskinesia Dipraglurant-ER Focal cervical dystonia (mGluR5 NAM) ADX71441 (GABA
Slide 6: Extensive Preclinical Stage Pipeline for Long-Term Growth
Extensive Preclinical Stage Pipeline for Long-Term Growth Molecule / Lead Clinical Hit to Lead Collaboration Partners MoA Optimization Candidate Parkinson’s disease, addiction, mGluR4 PAM autoimmune disease mGluR2 NAM Depression, stroke Endometriosis, uterine FSH / LH NAM fibrosis, polycystic ovaria
Slide 7: Upcoming Development Milestones
Upcoming Development Milestones Milestone Timing Dipraglurant – LID Phase 3 Registration Program Study 301 – start dosing H2 2018 Study 301 – results H1 2020 Study 302 – start dosing H1 2020 Study 302 – results H2 2021 Dipraglurant – Focal Cervical Dystonia Phase 2 POC Study 202 – start dosing H1 20
Slide 8: Dipraglurant in PD-LID: What Has Changed Since 2012?
Dipraglurant in PD-LID: What Has Changed Since 2012? 2012 2018 • 170K PD-LID patients in US • Patient numbers unclear PD-LID US • Pricing expected in range of $20K-$30K pa based on • Pricing in range of $3K-$4K pa Market Size recent pricing of Nuplazid, Ingrezza and Gocovri • Less than $400mm • $4.2
Slide 9: Dipraglurant in Parkinson's Disease
Dipraglurant in Parkinson’s Disease 9
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 invariably associated with the development of dyskinesias - as disabling as the PD symptoms themselves • Prevalence of LID is related to disease duration – Within 4-6 years of L-dopa treatment, LID is experienced b
Slide 11: Dipraglurant - Overview & Mechanism of Action
Dipraglurant - Overview & Mechanism of Action Severe PD (advanced neuron degeneration) • Loss of substantia nigra neurons combined with the 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 r
Slide 12: Dipraglurant PK is a Key Advantage for Treating LID
Dipraglurant PK is a Key Advantage for Treating LID • Dyskinesia symptoms are correlated to peak levels of levodopa therapy • PK profile of dipraglurant mirrors that of levodopa • Dipraglurant inhibits abnormal glutamate stimulation during peak levodopa dose but releases the receptor during normal g
Slide 13: EU and US Phase 2a Study in LID
Dipraglurant EU and US Phase 2a Study in LID Multicentre study in 25 centres across US and Europe N= 24: Placebo Primary objective: safety & tolerability Secondary objective: N=76 R exploratory efficacy: Modified Abnormal Involuntary Movement Scale (mAIMS) on Day 1, N=52: Dipraglurant 14 and 2
Slide 14: Dipraglurant Reduces LID Severity by 30%
Dipraglurant Reduces LID Severity by 30% Change from baseline in peak mAIMS at 90 min MMRM model, changes over time, ITT population (Dipraglurant) • Dipraglurant had a statistically significant effect on the first day • Dipraglurant reduced dyskinesia compared to placebo at all visits over the 28 da
Slide 15: Responder Analysis Demonstrates Dipraglurant Significant Benefit
Responder Analysis Demonstrates Dipraglurant Significant Benefit Cumulative % of Patients Showing ≥ 30% Change of Peak mAIMS from Baseline Responder analysis • A 30% reduction in mAIMS is clinically (≥30% change of peak mAIMS from baseline) meaningful Midday dose Dipraglurant Placebo p-value ‒ One p
Slide 16: Clinician Rated Global Impression of Change - Dyskinesia
Clinician Rated Global Impression of Change - Dyskinesia • Relatively simple scale that reflects everyday DIP clinical practice • Assessment by treating physician and thus is a more objective assessment than the more subjective mAIMS • Assessment performed at end of study compared to baseline • Grea
Slide 17: Patient Diaries – Improvement Throughout the Waking Day
Patient Diaries – Improvement Throughout the Waking Day Dipraglurant Arm – Baseline (N=42) Dipraglurant Arm – Week 4 (N=42) After 4-week treatment with dipraglurant: • ON time with dyskinesia reduced during the day • ON time without dyskinesia increased and maintained during the day 17
Slide 18: Dipraglurant Demonstrated Safety and Satisfactory Tolerability in PD Patients
Dipraglurant 50 and 100 mg Doses Demonstrated Safety and Satisfactory 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 • 3 of the 11
Slide 19: Summary of Efficacy Data
Summary of Efficacy Data • Dipraglurant showed a clinical meaningful improvement of dyskinesia – Significant improvement of mAIMS on Days 1 and 14 – Trial design exacerbated placebo response – confounding significance at Day 28 – Responder analysis (≥30% improvement) demonstrates clinically meaningf
Slide 20: Clinical Development Plan
Clinical Development Plan • Pivotal trials: – Two studies required for registration • Primary endpoint: UDysRS - more sensitive to treatment effect than mAIMS and less prone to placebo response (Goetz 2013) • Pivotal Study 1 (301) – 13 weeks – data H1 2020 • Pivotal Study 2 (302) – 26 weeks (primary
Slide 21: Management of Placebo Response
Management of Placebo Response Objective Strategy • Minimize rater variability • Use independent (centralized) raters (across and within sites) • Raters blinded to visit and do not rate the same • Reduce expectancy bias patient at baseline and study endpoint • Exclude patients with • Ensure that sym
Slide 22: Dyskinesia Rating Scales: UDysRS verses mAIMS
Dyskinesia Rating Scales: UDysRS verses mAIMS UDysRS mAIMS • Recommended scale by Movement Disorder Society • FDA regulatory NDA precedent (Adamas - Gocovri) • mAIMS alone was identified as suboptimal • Contains anchored objective clinician in detecting treatment-related changes Characteristics eval
Slide 23: Dipraglurant 1st Pivotal LID Study (301)
Dipraglurant 1st Pivotal LID Study (301) Primary objective: efficacy in reducing LID N=85 Pacebo Change over time in UDysRS (wk13 from baseline) N=170 Moderate to R Secondary objective: severe PD-LID safety & tolerability, additional efficacy parameters, PK Change over time in MDS-UPDRS N= 8
Slide 24: Dipraglurant 2nd Pivotal LID Study (302)
Dipraglurant 2nd Pivotal LID Study (302) Primary objective: N=85 Placebo efficacy in reducing LID Change over time in UDysRS (wk13 from baseline) N=170 Moderate to R Secondary objective: severe PD-LID safety & tolerability, additional efficacy parameters , PK Change over time in MDS-UPDRS N=
Slide 25: Dipraglurant LID Opportunity
Dipraglurant LID Opportunity • LID has a large unmet need and market opportunity – > 170K LID patients in US – ~$1.4bn US market opportunity for dipraglurant • Limited competition – only one FDA approved medicine – Gocovri (reformulation of generic amantadine): Approved on 24th August 17 – safety pr
Slide 26: Financials
Financials Therapeutics
Slide 27: Financials and Stock
Financials and Stock • Cash runway through 2021 – Proforma cash of CHF47M at 31 March 2018. • Traded on SIX Swiss Exchange: ADXN (ISIN:CH0029850754) • 28,564,031 shares outstanding (37.7M fully diluted) – New Enterprise Associates - 16% – New Leaf Ventures – 5.6% – CAM Capital – 5.6% – Management &
Slide 28: Allosteric modulators for human health
Allosteric modulators for human health www.addextherapeutics.com 28
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