Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (October 2024)
28 slides from Addex Therapeutics's investor presentation, October 2024
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders October 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 High value ➢ GABAB PAM for cough ready to enter IND enabling studies programs reaching ➢ Dipraglurant for post-stroke/TBI1 recovery – Phase 2 ready significant milestones ➢ Neurosterix portfolio advancing towards IND enabling studies ➢ Leading allosteric modulator drug discovery pla
Slide 4: Pipeline of In House Discovered Programs
Pipeline of In House Discovered Programs Molecule / Stage Partner Milestone MoA Discovery IND Studies Phase 1 Phase 2a Dipraglurant Ready to start Phase 2a Post-stroke/TBI recovery (mGlu5 NAM) study* ADX71149 Indication under evaluation Indication under review (mGlu2 PAM) IND enabling studies GABAB
Slide 5: Dipraglurant (mGlu5 NAM) for Post-Stroke / TBI Recovery
Dipraglurant (mGlu5 NAM) for Post-Stroke / TBI Recovery Targeting neuroplasticity early in rehabilitation to promote recovery 5
Slide 6: Post Stroke / TBI Recovery - Unmet Medical Need & Commercial Opportunity
Post Stroke / TBI Recovery - Unmet Medical Need & Commercial Opportunity ➢ Many stroke /TBI patients suffer ➢ >101 million ischemic stroke motor and somatosensory survivors worldwide1 impairment ➢ >12 million new strokes/yr ➢ Potential chronic disability & (1 every 3 seconds)1 low quality of life Di
Slide 7: 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 8: 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 9: 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 9
Slide 10: Dipraglurant for Post-stroke/TBI Recovery - Development Status
Dipraglurant for Post-stroke/TBI Recovery - 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 studi
Slide 11: 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 11
Slide 12: 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 13: GABAB PAM for Chronic Cough
GABAB PAM for Chronic Cough Going beyond baclofen to treat cough with improved safety and tolerability 13
Slide 14: 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 15: 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 16: 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 17: GABAB PAM for Cough – Program Status
GABAB PAM for Cough – Program Status ➢ Addex has a range of diverse potent and selective GABAB PAMs that were explored for cough indications ➢ Clinical candidate selected: – Favourable developability – Pre-IND activities completed – CMC completed ➢ In vivo proof-of-concept in a broad range of cough
Slide 18: Antitussive Effects of Cpd A vs Baclofen in Citric Acid Induced Cough
Antitussive Effects of Cpd A vs Baclofen in Citric Acid Induced Cough Compound A ➢ Compound A results in dose- dependent reductions in cough frequency and increases in cough latencies Compound A (mg/kg) BACLOFEN ➢ Baclofen affects only cough frequencies 18
Slide 19: Compound A vs baclofen on Biomarkers Related to Side-effects
Compound A vs baclofen on Biomarkers Related to Side-effects Reduction in body temperature (Δ°C) Compound A Brchs/min BACLOFEN ➢ Compound A has no effect on tolerability-related markers, including respiratory rate, body temperature and GH at up to 60 mg/kg. ➢ Baclofen showed reductions in respirator
Slide 20: Antitussive Activity of Compound A: Acute vs Sub-chronic Treatment
Antitussive Activity of Compound A in Citric Acid Induced Cough: Acute vs Sub-chronic Treatment ➢ There are no signs of tolerance in antitussive efficacy of Compound A after sub-chronic (7-day) treatment. ➢ A trend of reduced MED following sub-chronic treatment is seen in cough frequency and latency
Slide 21: Activity of Compound A in a Model of Citric Acid Induced Cough: Sub-chronic
Activity of Compound A in a Model of Citric Acid Induced Cough: Sub- chronic Treatment TOLERABILITY-RELATED READOUTS Compound A (mg/kg) Compound A (mg/kg) ➢ No marked change in readouts linked to tolerability related markers following sub-chronic dosing of Compound A 21
Slide 22: Antitussive effects of Compound A vs P2X3 inhibitor
Antitussive effects of Compound A vs P2X3 inhibitor in Citric Acid + ATP Induced Cough ➢ Compound A and a P2X3 inhibitor exhibit similar antitussive efficacy profiles. ➢ Compound A, similarly to a P2X3 inhibitor, show no marked effect on markers of tolerability, respiratory rate, reduction in body t
Slide 23: 20% Equity Interest in Neurosterix
20% Equity Interest in Neurosterix Well funded preclinical portfolio of high value assets 23
Slide 24: Neurosterix
Neurosterix ➢ Addex spin-out company – Series A funding of $63 million in April 2024 led by Perceptive Advisors – Addex contributed allosteric modulator drug discovery platform and portfolio of preclinical programs – Addex received CHF5 million and a 20% equity interest ➢ High value pipeline advanci
Slide 25: Addex Financials and Stock
Addex Financials and Stock 25
Slide 26: Financials and Stock
Financials and Stock ➢ Cash at June 30, 2024: ➢ 128.26 M outstanding shares CHF 3.79M (USD 4.20M) – Armistice Capital LLC – 26.13%* – CHF 5M from sale of Neurosterix received in April 2024 ➢ 184.35M shares incl. treasury shares – Cash runway beyond 2026 (254.03M fully diluted) – Management & board h
Slide 27: Summary
Summary Multiple high value ➢ GABAB PAM for substance use disorder (Indivior) candidate selected partnerships ➢ 20% equity interest in Neurosterix (backed by Perceptive Advisors) ➢ Dipraglurant - post-stroke/TBI recovery Phase 2a ready to start In house programs ➢ GABAB PAM for chronic cough ready
Slide 28: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (October 2024) on 6ix