Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (June 2019)
40 slides from Addex Therapeutics's investor presentation, June 2019
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders June 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 start in Q4 2019 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 digit & 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 Accountant 30 year
Slide 5: Pipeline with Lead Program Entering US Pivotal Study
Pipeline with Lead Program Entering US Pivotal Study Molecule / MoA Preclinical Phase 1 Phase 2 Phase 3 Dipraglurant-IR Parkinson’s disease levodopa-induced dyskinesia (mGlu5 NAM) Dipraglurant-ER Focal cervical dystonia (mGlu5 NAM) ADX71149 Epilepsy (mGlu2 PAM) GABAB PAM Addiction NAM = Negative All
Slide 6: Extensive Discovery Stage Pipeline Driving Long-Term Growth
Extensive Discovery Stage Pipeline Driving Long-Term Growth Molecule / MoA Hit to Lead Lead Optimization GABAB PAM Charcot-Marie-Tooth GABAB PAM mGlu7 NAM Psychiatric Disorders (PTSD & Hearing Loss) mGlu2 NAM Mild Cognitive Impairment mGlu4 PAM Parkinson’s Disease mGlu3 PAM Neurodegenerative Disorde
Slide 7: Dipraglurant in Parkinson's Disease
Dipraglurant in Parkinson’s Disease 7
Slide 8: The Dipraglurant Opportunity in Dyskinesia Associated with PD
The Dipraglurant Opportunity in Dyskinesia Associated with PD Pivotal studies on track to start in Q4 2019 Clear Development & Regulatory Manufacturing and planning ongoing Path Precedented FDA regulatory path >1M Parkinson’s disease patients in US of which >170,000 have dyskinesia Unmet Nee
Slide 9: 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 Dopamine replacement does not lead to dyskinesia per se, but lowers the triggering threshold for symptoms associated with the development of Dyskinesias result from the neurodegenerative process that u
Slide 10: 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 receptors are at STRIATUM L-DOPA L-dopa the basis of LID development (drug) Dopamine • In the striatum, LI
Slide 11: 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 DYSKINESIA • PK profile of dipraglurant mirrors that of levodopa L-DOPA peak • Dipraglurant inhibits abnormal glutamate stimulation during peak levodopa dose but releases the r
Slide 12: 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 Coordinating Investigator: Prof Olivier Rascol at University Hospital, Toulouse, France N= number of patients; R= randomization N= 24: Placebo Secondary obje
Slide 13: Dipraglurant Reduces LID Severity by 30%
Dipraglurant Reduces LID Severity by 30% Change from baseline in peak mAIMS at 90 min • Dipraglurant had a statistically significant MMRM model, changes over time, ITT population effect on the first day • Dipraglurant reduced dyskinesia compared to placebo at all visits over the 28 days • Placebo re
Slide 14: 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 15: Clinician Rated Global Impression of Change - Dyskinesia
Clinician Rated Global Impression of Change - Dyskinesia • Relatively simple scale that CGIC PBO reflects everyday clinical practice CGIC DIP • Assessment by treating physician and thus is a more objective assessment than the more subjective mAIMS • Assessment performed at end of study compared to b
Slide 16: 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 16
Slide 17: Dipraglurant Doses Demonstrated Safety and Satisfactory Tolerability
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 18: Phase 3 Trial on track to start Q4 2019
Phase 3 Trial on track to start Q4 2019 • 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 • Management of placebo response is a priority: Objective Strategy Minimize rater vari
Slide 19: Dipraglurant pivotal registration studies
Dipraglurant pivotal registration studies 1st Pivotal LID Study (301) 2nd Pivotal LID Study (302) N= number of patients; R= randomisation; LID= L-Dopa induced dyskinesia; OLE = open label extension The Primary and Secondary endpoints for both Secondary objectives trials are the same: (Safety & tol
Slide 20: Dipraglurant LID Opportunity
Dipraglurant LID Opportunity LID has a large unmet need and > 170K LID patients in US market opportunity ~$1.4bn US market opportunity for dipraglurant Gocovri (reformulation of generic amantadine): Approved on 24th August 17 – safety profile similar to generic Limited competition – only one
Slide 21: Promising Preclinical Pipeline
Promising Preclinical Pipeline 21
Slide 22: GABAB PAM Program for Charcot-Marie-Tooth 1A Neuropathy
GABAB PAM Program for Charcot-Marie-Tooth 1A Neuropathy • Rationale : – GABAB is the metabotropic receptor for GABA, main inhibitory neurotransmitter – Activation of GABAB is validated through the use of baclofen (GABAB orthosteric agonist) • Clinical efficacy in Charcot-Marie-Tooth type 1A (CMT1A)
Slide 23: mGlu7 PAM Program for PTSD & Hearing Loss
mGlu7 PAM Program for PTSD & Hearing Loss • Rationale : – Based on mGlu7 receptor knockout mice phenotype & mGlu7 receptor pharmacological inhibition studies, negative allosteric modulators show strong potential for anxiety related disorders such as PTSD – In addition, other potential indications in
Slide 24: mGlu2 NAM Program for Mild Cognitive Impairment
mGlu2 NAM Program for Mild Cognitive Impairment • Rationale : – Potential to treat medical conditions linked to lowered glutamate levels in the brain via restoration of a normalized glutamatergic tone • Alzheimer’s Disease (AD) : cognitive deficits and possible disease-modifying effect (slowing dise
Slide 25: mGlu4 PAM Program for Parkinson's Disease
mGlu4 PAM Program for Parkinson’s Disease • Rationale : – Novel non-dopaminergic approach to treat Parkinson’s disease with potential to treat both motor and non-motor symptoms, disease modifying neuroprotective potential: • Motor functions: in acute and chronic preclinical models of PD, mGluR4 PAM
Slide 26: mGlu3 PAM Program for Neurodegenerative Diseases
mGlu3 PAM Program for Neurodegenerative Diseases • Rationale : – Novel mechanism of action for treatment of neurodegenerative disorders & schizophrenia – Strong rational and preclinical validation through: • Schizophrenia: studies demonstrate GRM3 gene variants association; mGlu3 receptor KO mice ex
Slide 27: TrkB PAM Program for Neurodegenerative Diseases
TrkB PAM Program for Neurodegenerative Diseases • Overview : – TrkB is the receptor for BDNF (brain-derived neurotrophic factor) – TrkB activation is preclinically validated • neurodegenerative diseases - Alzheimer’s, Parkinson’s, or Huntington’s disease • potential for both disease-modifying and sy
Slide 28: Allosteric Modulation Becoming an Exciting Space
Allosteric Modulation Becoming an Exciting Space CONFIDENTIAL 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 world leading technology platform 29
Slide 30: Allosteric Compounds Provide Unique Opportunity
Allosteric Compounds Provide Unique Opportunity Orthosteric Allosteric • Allosteric drugs bind to a position away from the orthosteric (primary) binding site of a target protein • Allosteric sites can be targeted with great selectivity by allosteric modulators Affinity Modulation • When bound by an
Slide 31: Allosteric Modulators Could Unlock Multiple Undruggable Targets
Allosteric Modulators Could Unlock Multiple “Undruggable” Targets ~ 3000 Undrugged • Hitting previously undruggable targets is an increasingly Targets exciting space with the vast majority of well understood drug • Peptides/Biologics targets currently being undruggable • Nucleic acid based therapeut
Slide 32: Allosteric Approach Gathering Momentum
Allosteric Approach Gathering Momentum Number of papers published that reference allosteric modulators, by year 3,000 • Academic research into allosteric receptor modulators is 2,500 increasing – as shown by chart on right 2,000 1,500 • Ongoing research into identifying structural information about
Slide 33: Allosteric Approach Gathering Momentum
Allosteric Approach Gathering Momentum Multiple examples of allosteric modulators opening up new treatment possibilities • Novartis’ ABL001 is an allosteric modulator, and demonstrated strong anti-tumour responses as monotherapy in heavily pre-treated patients with Chronic Myeloid Leukemia (includin
Slide 34: Allosteric Space Heating Up
Allosteric Space Heating Up • HotSpot Therapeutics was co-founded by Nimbus employees who developed allosteric modulator GS-0976, which was acquired by Gilead for $1.2bn as part of Nimbus Apollo – HotSpot looks for natural regulatory sites on proteins, on the basis that evolution has perfected these
Slide 35: What Differentiates Addex's Allosteric Platform?
What Differentiates Addex’s Allosteric Platform? Physicochemical Comparison • Addex library of ~80k compounds is drug-like, but occupies distinct chemical space (see charts right) • Fast-hit library is used to validate the initial hit – increasing quality of candidates and saving on cost • Addex hit
Slide 36: 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 • GABAB is the metabotropic receptor for GABA, main inhibitory neurotransmitter • Activation of GABAB is validated throug
Slide 37: Financials
Financials Therepeutbes
Slide 38: Financials and Stock
Financials and Stock • Cash runway through 2021 – Cash of CHF41.7M at 31 December 2018 – Fully funded through dipraglurant study 301 readout • Traded on SIX Swiss Exchange: ADXN (ISIN:CH0029850754) • 28,564,031 shares outstanding 37.7M fully diluted) – New Enterprise Associated – 16% – New Leaf Vent
Slide 39: Upcoming Major Development Milestones
Upcoming Major Development Milestones Milestone Timing Dipraglurant – LID Phase 3 Registration Program Complete manufacturing of Drug Product Q3 2019 Study 301 – start dosing Q4 2019 Study 301 – Top line data Q3 2021 39
Slide 40: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH WWW.ADDEXTHERAPEUTICS.COM 40
Addex Therapeutics — Investor Presentation (June 2019) on 6ix