Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (February 2024)
43 slides from Addex Therapeutics's investor presentation, February 2024
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders February 2024 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 Multiple high value ➢ ADX71149 Phase 2 epilepsy study (J&J) - data expected Q2 2024 ➢ GABAB PAM for cough (Addex) & SUD** (Indivior) in CCS* programs reaching ➢ M4 PAM for schizophrenia and other psychosis in CCS* significant milestones ➢ Dipraglurant for post-stroke recovery phase
Slide 4: What are Allosteric Modulators?
What are Allosteric Modulators? Endogenous Ligands Active Site Active Site Outside Cell Negative Positive Cell Allosteric Allosteric Membrane Modulator Modulator Inside Cell NAM PAM Reduces signal Increases signal No activation in the absence of the endogenous ligand 4
Slide 5: Advantages of Allosteric Modulation Vs Orthosteric Drug Discovery
Advantages of Allosteric Modulation Vs Orthosteric Drug Discovery Conventional Nucleic acid- Biologics Gene Allosteric Allosteric modulators small based /peptides therapies modulators ➢ Address: molecules therapies ‒ “Undruggable” targets, such as Selectivity + ++ +++ +++ ✓ GPCRs, RTKs, cytokine Dif
Slide 6: Advancing a Broad Allosteric Modulator Pipeline in Neuroscience
Advancing a Broad Allosteric Modulator Pipeline in Neuroscience Molecule / Stage Partner Milestone MoA Discovery IND Studies Phase 1 Phase 2 In house Lead Programs IND enabling studies GABAB PAM Chronic cough expected to start H1 2024 Schizophrenia / IND enabling studies M4 PAM other psychosis expec
Slide 7: GABAB PAM for Chronic Cough
GABAB PAM for Chronic Cough Going beyond baclofen to treat cough with improved safety and tolerability
Slide 8: Cough - Unmet Medical Need and Commercial Opportunity
Cough - Unmet Medical Need and Commercial Opportunity ➢ Chronic cough ➢ 10% in the general population4 – Lasting > 8 weeks1 ➢ Persists >1 year in 60% of – >700 coughs/day patients ➢ Multiple comorbidities Disease Prevalence Market 1.45B by 20252 Competition: Standard of P2X3 Care inhibitors ➢ Ineffe
Slide 9: Standard of Care in Cough - Strengths and Weaknesses
Standard of Care in Cough - Strengths and Weaknesses GABAB Dextro- Gabapentin Agonist Addex Use / side-effects metorphan Opioids & pregabalin Amitriptyline P2X3* Baclofen PAM Treatment type Chronic Acute Acute Acute Chronic Acute Chronic Risk of Abuse Yes Yes Yes Yes No No No Respiratory No Yes Yes
Slide 10: GABAB Receptor - Validated Target in Cough
GABAB Receptor - Validated Target in Cough ➢ GABAB receptor – Expressed throughout the cough neural circuit – Activation reduces neuronal excitability – Potential for broad application in cough patients ➢ Baclofen, an orthosteric agonist – Used off-label in patients with chronic cough – Clinical stu
Slide 11: Target Product Profile, Project Status and Development Plan
Target Product Profile, Project Status and Development Plan ➢ A first-in-class GABAB PAM to treat Cough – Once-a-day oral dosing suitable for chronic treatment – Reduction in cough bouts and severity and improvement in quality of life – Superior tolerability with no taste related side-effects ➢ Stat
Slide 12: M4 PAM for Schizophrenia
M4 PAM for Schizophrenia Selectively targeting the M4 receptor to treat psychosis related symptoms with improved safety and tolerability compared to standard of care
Slide 13: Schizophrenia - Unmet Medical Need and Commercial Opportunity
Schizophrenia - Unmet Medical Need and Commercial Opportunity ➢ Multi-cause mental disorder - ➢ 1% of general population psychosis, social withdrawal and ➢ ~24 M patients worldwide1 cognitive impairment ➢ Lifelong burden for patients and caregivers Disease Prevalence Market $12.5B in 20322 Standard
Slide 14: M4 PAM Mode of Action in Schizophrenia
M4 PAM Mode of Action in Schizophrenia 3) 3 Activation of M4 1) 1 M4 auto-receptor receptor indirectly activation with a PAM leads to activation of or agonist prevents Ach pre-synaptic CB2 release receptor and further reducing dopamine signaling 2) 2 Decreased Ach 4) 4 Activation of M4 binding to ni
Slide 15: Selective M4 PAM - Differentiated Approach to Treat Schizophrenia
Selective M4 PAM - Differentiated Approach to Treat Schizophrenia M4 PAM selectivity and high brain penetration offers potential improvements Muscarinic ➢ Xanomeline (M1/M4 agonist) shows efficacy in Effects / Side Standard Non- Selective schizophrenia and Alzheimer’s patients Effects of Care select
Slide 16: Target Product Profile, Project Status and Development Plan
Target Product Profile, Project Status and Development Plan ➢ A best-in-class selective M4 PAM to treat schizophrenia and other psychosis – Once-a-day oral dosing suitable for chronic treatment – Improved tolerability in comparison to non-selective muscarinic agonists ➢ Status of program: clinical c
Slide 17: ADX71149 (JNJ-40411813) for Epilepsy
ADX71149 (JNJ-40411813) for Epilepsy Partnered with Janssen Pharmaceuticals, Inc
Slide 18: ADX71149 - Opportunity in Epilepsy
ADX71149 - Opportunity in Epilepsy ➢ Market projected to reach $20 billion by 20261 – Keppra & Briviact net sales in 2022 of €1.2 billion treating 2M patients2 Large market & unmet ➢ High proportion of refractory patients (¼ of new patients3) - combination medical need treatments have limited thera
Slide 19: ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model
ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model Validation in pharmaco-resistant mouse epilepsy model with high translational value: ED50 shift of Keppra by adding low dose of ADX71149 ED50 shift of ADX71149 by adding ED50 dose of LEV LEV alone ADX71149 alone LEV+10mg ADX71149 ADX71149 +350mg
Slide 20: ADX71149 Phase 2a Epilepsy Study
ADX71149 Phase 2a Epilepsy Study ➢ Double blind placebo controlled ➢ Establish 28-day seizure count (over 56-day Placebo baseline period) ➢ Primary endpoint: time to monthly baseline seizure ➢ Focal onset seizure with count suboptimal response to ➢ Period 1: 4-week acute efficacy phase levetiracetam
Slide 21: GABAB PAM for Substance Use Disorders (Indivior Partnership)
GABAB PAM for Substance Use Disorders (Indivior Partnership) Going beyond baclofen to treat substance use disorders with improved safety and tolerability
Slide 22: GABAB PAM for Substance Use Disorder
GABAB PAM for Substance Use Disorder ➢ High prevalence;1.8% of US population1 Large market & unmet ➢ Current treatments have undesirable side-effects and prone to relapse medical need ➢ Burden to society in US is >$600B annually2 ➢ Baclofen (GABAB agonist) used off label for alcohol use disorder ➢ A
Slide 23: Dipraglurant (mGlu5 NAM) for Post-Stroke Recovery
Dipraglurant (mGlu5 NAM) for Post-Stroke Recovery Targeting neuroplasticity early in rehabilitation to promote recovery
Slide 24: Post Stroke Recovery - Unmet Medical Need & Commercial Opportunity
Post Stroke Recovery - Unmet Medical Need & Commercial Opportunity ➢ Post stroke many suffer motor and ➢ >101 million ischemic stroke somatosensory impairment survivors worldwide1 ➢ Potential chronic disability & ➢ >12 million new strokes/yr low quality of life (1 every 3 seconds)1 Disease Prevalenc
Slide 25: mGlu5: An Innovative Target for Post-Stroke Recovery
mGlu5: An Innovative Target for Post-Stroke Recovery Healthy brain mGlu5 NAM supports post-stroke recovery (b) Recovery + mGlu5 NAM (a) mGlu5 brain Good inter & intra- distribution nodal connectivity mGlu5 Lesion effects: mGlu5 NAM promotes synaptic ➢ Densely expressed in the brain ➢ Confined neural
Slide 26: Preclinical Data: mGlu5 Inhibition Promotes Post-Stroke Recovery
Preclinical Data: mGlu5 Inhibition Promotes Post-Stroke Recovery MTEP treatment resulted in a significant Dipraglurant significantly restored functional recovery of functional control control in a one-week experiment Dipraglurant enhanced functional brain recovery in a rat model of experimental stro
Slide 27: MRI Imaging Data: Post-Stroke Resting State Functional Connectivity
MRI Imaging Data: Post-Stroke Resting State Functional Connectivity Intrahemispheric Connectivity Interhemispheric Connectivity mGlu5 inhibitors promote intra- and inter-hemispheric connectivity following stroke https://doi.org/10.1093/brain/awad293 27
Slide 28: Dipraglurant Development Status
Dipraglurant Development Status ➢ Fast onset of action and short half-life - Ideally suited for concurrent dosing with rehabilitation ➢ Extensively profiled Phase 1 studies - 5 studies with >100 patients - Including receptor occupancy (PET ligand study) ➢ Phase 2 studies conducted - Safe and well to
Slide 29: mGlu7 NAM for Stress Related Disorders - PTSD
mGlu7 NAM for Stress Related Disorders - PTSD Innovative approach targeting neuronal circuit in stress and fear to deliver an effective and safe treatment for patients with stress-related disorders
Slide 30: Medical Need & Commercial Opportunity in Stress Disorders - PTSD
Medical Need & Commercial Opportunity in Stress Disorders - PTSD ➢ Heterogenous mental disorder ➢ 8% of general population following exposure to trauma diagnosed with PTSD4 ➢ Often leads to stress, ➢ 5th most prevalent psychiatric behavioral imbalance & diagnosis dependance Disease Prevalence Marke
Slide 31: Selective mGlu7 NAM - Differentiated Approach to Treat Stress Disorders
Selective mGlu7 NAM - Differentiated Approach to Treat Stress Disorders ➢ Current treatments are primarily based on SSRI / mGlu7 psychotherapy Side-effects SNRI Ketamine MDMA NAM – Marginal efficacy and high relapse rate Withdrawal syndrome Yes 1,2 No Yes 3 No ➢ Medication is non-specific (Neuro)tox
Slide 32: mGlu7 NAM in Stress Related Disorders
mGlu7 NAM in Stress Related Disorders Brain regions involved in fear memory ➢ mGlu7 expressed throughout the stress/fear neural circuit ➢ mGlu7 KO mice exhibit – Reduced conditioned fear and anxiety1 – Reduced aggressivity and increased pro-social behaviors2 1 PFC & ACC 2 Hippocampus ➢ mGlu7 NAM tre
Slide 33: Target Product Profile, Project Status and Development Plan
Target Product Profile, Project Status and Development Plan ➢ A first-in-class mGlu7 NAM to treat PTSD – Once-a-day oral dosing suitable for chronic treatment – Reduction in symptoms and improvement in quality of life (social interaction, anxiety, depression, irritability/aggressivity) – Can be comb
Slide 34: mGlu2 NAM for Mild Neurocognitive Disorders
mGlu2 NAM for Mild Neurocognitive Disorders Innovative Approach for Treatment of Mild Neurocognitive Disorder (mNCD)
Slide 35: mNCD - Unmet Medical Need and Commercial Opportunity
mNCD - Unmet Medical Need and Commercial Opportunity ➢ Clinical state between normal cognition ➢ More prevalent as population ages and dementia – 6.7% in 65-69 yr. olds ➢ 3X higher risk of conversion to – 25% in 80-84 yr. olds dementia (Alzheimer disease) ➢ 2X higher risk of depression Disease Pre
Slide 36: mGlu2 NAM Mode of Action in mNCD
mGlu2 NAM Mode of Action in mNCD AMPAkines and mGlu2 NAM shared molecular pathways ➢ By increasing the excitability of neural circuits, AMPAkines/mGlu2 NAMs could counteract the synaptic deficits seen in mNCD This mechanism directly affects the strength of synaptic connections between neurons, poten
Slide 37: Depression a Major Co-morbidity in mNCD
Depression a Major Co-morbidity in mNCD Depression is often associated to mNCD and linked to a poorer prognosis ➢ mNCD patients with depression > more cognitive deficits ➢ Lower scoring in memory – executive/ lexicosemantic functions - immediate/delayed memory ➢ mNCD patients with depression > hig
Slide 38: mGlu2 NAM in mNCD - TPP and Development Plan
mGlu2 NAM in mNCD - TPP and Development Plan ➢ A novel mGlu2NAM to treat mild neurocognitive disorder – Once daily oral dosing – Better efficacy and tolerability than donepezil and AMPAkines – Effect on comorbidities such as depression ➢ Status – Our program is in lead optimization – Addex led conso
Slide 39: Addex Financials, Stock and Milestones
Addex Financials, Stock and Milestones
Slide 40: Financials and Stock
Financials and Stock ➢ Cash at September 30, 2023: CHF ➢ 125.19M outstanding shares 4.8M (USD 5.2M) – Armistice Capital LLC – 26.81%* – New Enterprise Associates – 3.11%* ➢ No debt ➢ 184.35M shares incl. treasury shares (247.60M fully diluted) ➢ Traded on SIX Swiss Exchange: ADXN – Management & boar
Slide 41: Milestones
Milestones Milestone Timing ADX71149 for epilepsy (Janssen funded) – results expected Q2 2024 GABAB PAM for chronic cough - start IND enabling studies H1 2024 M4 PAM for schizophrenia - start IND enabling studies H2 2024 Dipraglurant for post-stroke recovery – start Phase 2a in stroke patients 2024
Slide 42: Summary
Summary ➢ Phase 2 epilepsy study (J&J) ongoing Multiple high value ➢ GABAB PAM for cough and substance use disorder (Indivior) programs ➢ M4 PAM for schizophrenia and other psychosis ➢ Dipraglurant - post-stroke recovery phase 2 ready to start Technology and ➢ Pioneering allosteric modulation drug
Slide 43: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (February 2024) on 6ix