Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (September 2025)
31 slides from Addex Therapeutics's investor presentation, Sep 1, 2025
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders September 2025 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 Phase 1 studies ➢ Leading allosteric modulator drug discovery platform
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 Brain injury recovery - post-stroke / TBI (mGlu5 NAM) study* ADX71149 Indication under evaluation New indication selection (mGlu2 PAM) GABAB PAM
Slide 5: Dipraglurant (mGlu5 NAM) for Brain Injury Recovery Post-Stroke / TBI
Dipraglurant (mGlu5 NAM) for Brain Injury Recovery Post-Stroke / TBI Targeting neuroplasticity early in rehabilitation to promote rebuilding of neuronal connections and sensorimotor 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 Brain Injury Recovery
mGlu5: An Innovative Target for Brain Injury Recovery Healthy brain mGlu5 NAM supports rebuilding of neuronal connections (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 ➢
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 population – Lasting > 8 weeks1 ➢ Persists >1 year in 60% of – >700 coughs/day patients ➢ Multiple comorbidities Disease Prevalence Market 1.45B by 20252 Standard of Competition Care ➢ P2X3 Inhibitors (Phase 3
Slide 15: Pharmacological treatment of chronic cough – efficacy vs tolerability
Pharmacological treatment of chronic cough – efficacy vs tolerability GABAB Use / side- Dextro- Nalbuphine Gabapentin Agonist Addex effects metorphan Opioids (Phase 2) & pregabalin Amitriptyline P2X3* Baclofen PAM Treatment type Chronic Acute ? Acute Acute Chronic Chronic+ Chronic Risk of Abuse 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: – Favorable developability – Pre-IND activities completed – CMC completed ➢ In vivo proof-of-concept in a broad range of cough m
Slide 18: Citric Acid Cough in Guinea Pigs – Total Number of Coughs
Citric Acid Cough in Guinea Pigs – Total Number of Coughs Compound ED50 Max Max (mg/kg) Efficacy Efficacy* Compound A 5.96 70% 70% Baclofen 0.93 60% 50% Nalbuphine 7.57 70% 65% Codeine 12.6 70% 40% ➢ Compound A results in a dose-dependent reduction in cough number reaching maximal effects similar or
Slide 19: Citric Acid Cough in Guinea Pigs – Latency to First Cough
Citric Acid Cough in Guinea Pigs – Latency to First Cough Compound ED50 Max Max (mg/kg) Efficacy Efficacy* Compound A 5.20 282 282% Baclofen 8.58 54 10% Nalbuphine 31.78 182 100% Codeine 4.91 357 226% ➢ Compound A results in a dose- dependent increase in cough latency reaching maximal effects simila
Slide 20: Citric Acid Cough in Guinea Pigs – Respiratory Rate
Citric Acid Cough in Guinea Pigs – Respiratory Rate ➢ Respiratory rate is a biomarker of sedation in rodents as well as humans ➢ Compound A had no effect on respiratory rate at up to 60 mg/kg, while other compounds resulted in marked reduction in respiratory rate at their highest doses ➢ Compound A
Slide 21: Citric Acid Cough in Guinea Pigs – Reduction in Body Temperature
Citric Acid Cough in Guinea Pigs – Reduction in Body Temperature ➢ Reduction in body temperature is a rodent biomarker of GABAB receptor occupancy in the CNS ➢ Compound A resulted in a minor (0.7°C) reduction in body temperature only at the highest dose (60 mg/kg), in contract to near 2°C reduction
Slide 22: Citric Acid Cough in Guinea Pigs – Growth Hormone
Citric Acid Cough in Guinea Pigs – Growth Hormone ➢ Growth hormone is a biomarker of GABAB receptor occupancy in the CNS ➢ Compound A did not increase growth hormone in plasma at up to 60 mg/kg, while baclofen caused more than 2x increases in growth hormone concentration ➢ Compound A shows less CNS
Slide 23: Citric Acid Induced Cough: Acute vs Sub-chronic Treatment
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. 23
Slide 24: Citric Acid Induced Cough: Sub-chronic Treatment Tolerability Readouts
Citric Acid Induced Cough: Sub-chronic Treatment Tolerability Readouts Respiratory Rate Body Temperature Growth Hormone Compound A (mg/kg) Compound A (mg/kg) ➢ No marked change in readouts linked to tolerability related biomarkers following sub-chronic dosing of Compound A 24
Slide 25: Compound A vs P2X3 inhibitor - Citric Acid + ATP Induced Cough
Compound A vs P2X3 inhibitor - 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 temperature and growth ho
Slide 26: 20% Equity Interest in Neurosterix
20% Equity Interest in Neurosterix Well funded preclinical portfolio of high value assets 26
Slide 27: Neurosterix
Neurosterix ➢ Addex spin-out company – Series A funding of $65 million in 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 advancing tow
Slide 28: Addex Financials and Stock
Addex Financials and Stock 28
Slide 29: Financials and Stock
Financials and Stock ➢ Cash at March 31, 2025: ➢ 128.26 M outstanding shares CHF 2.8M (USD 3.2M) – Armistice Capital LLC – 21.97%* – Cash runway through 2026 ➢ 184.35M shares incl. treasury shares ➢ No debt (254.03M fully diluted) – Management & board holds – 13.46%* ➢ Traded on SIX Swiss Exchange:
Slide 30: Summary
Summary ➢ GABAB PAM for substance use disorder (Indivior) candidate selected & IND Multiple high value enabling studies successfully completed partnerships ➢ 20% equity interest in Neurosterix (backed by Perceptive Advisors) ➢ Dipraglurant - brain injury recovery Phase 2a ready to start In house pro
Slide 31: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (September 2025) on 6ix