Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (December 2025)
34 slides from Addex Therapeutics's investor presentation, December 2025
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders December 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 ➢ GABAB PAM for cough ready to enter IND enabling studies High value ➢ Dipraglurant for post-stroke/TBI1 recovery – Phase 2 ready programs reaching ➢ Neurosterix portfolio advancing towards Phase 1 studies significant milestones ➢ Investment in Stalicla, clinical stage precision med
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 motor ➢ >101 million ischemic stroke and somatosensory impairment survivors worldwide1 ➢ Potential chronic disability & ➢ >12 million new strokes/yr low quality of life (1 every 3 seconds)1 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 A results in a dose-dependent reduction in number of coughs (MED 1 mg/kg) ➢ Compound A reaches maximal effects that are equal or higher than with reference compounds 18
Slide 19: Citric Acid Cough in Guinea Pigs – Latency to 1st Cough
Citric Acid Cough in Guinea Pigs – Latency to 1st Cough ➢ Compound A results in a dose-dependent increase in cough latency ➢ Compound A reaches maximal delays in the onset of cough that are similar or better than reference compounds, except codeine 19
Slide 20: Citric Acid Cough in Guinea Pigs – Respiratory Rate
Citric Acid Cough in Guinea Pigs – Respiratory Rate ➢ Biomarker of sedation ➢ 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 20
Slide 21: Citric Acid Cough in Guinea Pigs
Citric Acid Cough in Guinea Pigs Cough frequency Latency to 1st cough Compound ED50 Max Max Compound Max Max (mg/kg) Efficacy Efficacy* Efficacy Efficacy* Compound A 5.96 70% 70% Compound A 282 282% Nalbuphine 7.57 70% 65% Nalbuphine 182 100% Orvepitant 14.2 55% 51% Orvepitant 240 235% Baclofen 0.93
Slide 22: Citric Acid Cough in Guinea Pigs: PK/PD interaction
Citric Acid Cough in Guinea Pigs Growth hormone in plasma % Reduction in resp. rate Pharmacokinetic/pharmacodynamic interaction % Reduction in BT % Reduction in resp. rate Reduction in BT Growth hormone in plasma Antitussive activity of Compound A shows good PK/PD and correlation between tussive rea
Slide 23: Citric Acid Cough in Guinea Pigs – Reduction in Body Temperature
Citric Acid Cough in Guinea Pigs – Reduction in Body Temperature ➢ 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 seen with baclofen at 3 mg/kg. ➢ Compound A i
Slide 24: Citric Acid Cough in Guinea Pigs – Growth Hormone in Plasma
Citric Acid Cough in Guinea Pigs – Growth Hormone in Plasma ➢ 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 is likely to have less CN
Slide 25: ATP potentiated Citric Acid Cough in Guinea Pigs
ATP potentiated Citric Acid Cough in Guinea Pigs ➢ Compound A appears more Total number of coughs Cough latency potent than P2X3 inhibitor in the ATP – CA cough ➢ In a follow-up experiment involving co-administration of Compound A and P2X3 inhibitor isobolographic analysis revealed potentiation effe
Slide 26: ATP potentiated Citric Acid Cough in Guinea Pigs
ATP potentiated Citric Acid Cough in Guinea Pigs ➢ Both Compound A and P2X3 have no effect on respiratory rate, BT and growth hormone at up to 30 mg/kg ➢ Tolerability profile of Compound A is similar to that of P2X3 inhibitor, but without any taste-related side- effects 26
Slide 27: Citric Acid Cough in Guinea Pigs
Citric Acid Cough in Guinea Pigs ➢ Following sub-chronic treatment there were no signs of reduced potency or efficacy ➢ There were no marked changes in the respiratory rate, body temperature and growth hormone release in animals given Compound A acutely or sub-chronically Compound A (mg/kg) 27
Slide 28: Activity of Compound A in a Model of CA Induced Cough: Sub-chronic Treatment
Activity of Compound A in a Model of CA Induced Cough in Guinea Pigs : Sub-chronic Treatment SIDE EFFECTS-RELATED READOUTS Compound A (mg/kg) Compound A (mg/kg) Compound A (mg/kg) No marked changes in side effect related readouts following sub-chronic administration 28
Slide 29: 20% Equity Interest in Neurosterix
20% Equity Interest in Neurosterix Well funded preclinical portfolio of high value assets 29
Slide 30: 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 31: Addex Financials and Stock
Addex Financials and Stock 31
Slide 32: Financials and Stock
Financials and Stock ➢ Cash at September 30, 2025: ➢ 147.72 M outstanding shares CHF 2.2M (USD 2.75M) – Armistice Capital LLC – 19.57%* – Cash runway through mid 2026 ➢ 218.65M shares incl. treasury shares ➢ No debt (285.19M fully diluted) – Management & board holds – 11.99%* ➢ Traded on SIX Swiss E
Slide 33: Summary
Summary ➢ GABAB PAM for substance use disorder (Indivior) candidate selected & IND enabling studies successfully completed Multiple high value ➢ 20% equity interest in Neurosterix (backed by Perceptive Advisors) partnerships ➢ Investment in Stalicla, clinical stage precision medicine neurodevelopmen
Slide 34: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
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