Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (August 2024)
36 slides from Addex Therapeutics's investor presentation, August 2024
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders August 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 (Addex) & SUD1 (Indivior) in CCS2 programs reaching ➢ Dipraglurant for PD-LID & post-stroke/TBI3 recovery – Phase 2 ready significant milestones ➢ Neurosterix portfolio advancing towards IND enabling studies ➢ Leading allosteric modulator drug discov
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- Allosteric modulators Biologics Gene Allosteric small based /peptides therapies modulators ➢ Address: molecules therapies ‒ “Undruggable” targets, such as Selectivity + ++ +++ +++ ✓ GPCRs, RTKs, cytokine rec
Slide 6: 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 2b/3 PD-LID (mGlu5 NAM) study* Dipraglurant Ready to start Phase 2a Post-stroke/TBI recovery (mGlu5 NAM) study* ADX71149 Indication under evaluatio
Slide 7: Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease (PD-LID)
Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson’s Disease (PD-LID) First-in-class program ready to start Phase 2b/3
Slide 8: Compelling Rationale to Develop Dipraglurant for PD-LID
Compelling Rationale to Develop Dipraglurant for PD-LID ➢ Large underserved patient population in need of improved treatment options ➢ Significant commercial opportunity with limited competition – 1M Parkinson’s disease patients in US of which >170,000 have dyskinesia – Orphan drug designation grant
Slide 9: Disability and Impact of PD-LID
Disability and Impact of PD-LID ➢ Dyskinesias caused by neurodegeneration Invariably associated with ➢ Dopamine replacement lowers the triggering threshold for symptoms long-term L-dopa use ➢ LID can become as disabling as the PD symptoms themselves ➢ Uncontrollable muscle contractions, twisting and
Slide 10: MoA Rationale for Targeting mGlu5 Inhibition in PD-LID
MoA Rationale for Targeting mGlu5 Inhibition in PD-LID ➢ Loss of substantia nigra neurons combined with the non-physiological, pulsatile stimulation of dopamine receptors with L-dopa are at the basis of LID development ➢ In the striatum, LID is the result of: A D1 receptor priming B Excess glutamate
Slide 11: Dipraglurant PK is a Key Advantage for Treating LID
Dipraglurant PK is a Key Advantage for Treating LID 3 Dipraglurant and L-Dopa plasma concentration 2,5 ➢ Dyskinesia symptoms are correlated to peak levels of L-dopa 2 Dyskinesia ➢ PK of dipraglurant allows control of glutamatergic (µg/ml) 1,5 tone ahead of L-dopa Cmax 1 Dipraglurant normalizes abnor
Slide 12: Dipraglurant Phase 2a Study in LID (in US and Europe)
Dipraglurant Phase 2a Study in LID (in US and Europe) ➢ Primary objective: N=24: Placebo safety & tolerability N=76 ➢ Secondary objective exploratory efficacy: N=52: Dipraglurant ‒ Modified Abnormal Involuntary Movement Scale (mAIMS) on days 1, 14 and 28 50 mg 100 mg 100 mg ‒ Clinician Global Impres
Slide 13: Dipraglurant Improves LID by 30%
Dipraglurant Improves LID by 30% Change from Baseline in Peak mAIMS at 90min 1 ➢ Statistically significant effects: 0 Day 1 (50mg) and Day 14 (100mg) ➢ Improvement maintained through (LS means +/- SE) -1 Day 28 ➢ Increasing placebo response caused p=0.041 -2 significance to be lost at Day 28 ➢ No pl
Slide 14: Responder Analysis Demonstrates Dipraglurant Significant Benefit
Responder Analysis Demonstrates Dipraglurant Significant Benefit Percent of patients with ≥ 30% improvement on mAIMS 60 p = 0.0132 p= 0.0474 50 Responder analysis Cumulative % of Responders (≥30% change of mAIMS from baseline) 40 Midday dose Dipraglurant Placebo 30 Day 1 (50 mg) n=13 26.0% n=3 12.5%
Slide 15: Significant Improvement on CGI-C
Significant Improvement on CGI-C 50% Dipraglurant Placebo 45% Improved 40% 71.2% 49.9% (p<0.05) 35% No 17.3% 45.8% change % of Patients 30% 25% ➢ Simple scale reflecting clinical assessment 20% by treating physician 15% ➢ More objective than mAIMS 10% ➢ Assessed at end of study compared to 5% baseli
Slide 16: Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients
Dipraglurant Demonstrated Good Safety and Tolerability in PD Patients ➢ Adverse events common in both treatment groups (dipraglurant 88.5%, placebo 75%) ➢ Most common AEs: Dipraglurant Placebo Worsening 21% 12.5% * 3 of 11 AEs of “worsening dyskinesia” occurred in the follow up period Dyskinesia (15
Slide 17: Dipraglurant PD-LID - Development Status
Dipraglurant PD-LID - Development Status ➢ Fast onset of action and short half-life - Ideally suited normalizes abnormal glutamate stimulation during peak levodopa dose ➢ Extensively profiled Phase 1 studies - 5 studies with >100 patients, including receptor occupancy (PET ligand study) ➢ Phase 2 st
Slide 18: Dipraglurant (mGlu5 NAM) for Post-Stroke Recovery
Dipraglurant (mGlu5 NAM) for Post-Stroke Recovery Targeting neuroplasticity early in rehabilitation to promote recovery
Slide 19: 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 20: 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 21: 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 22: 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 22
Slide 23: 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 24: 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 25: 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 26: GABAB PAM for Chronic Cough
GABAB PAM for Chronic Cough Going beyond baclofen to treat cough with improved safety and tolerability
Slide 27: 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 28: 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 29: 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 30: 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 31: 20% Equity Interest in Neurosterix
20% Equity Interest in Neurosterix Well funded preclinical portfolio of high value assets
Slide 32: 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 33: Addex Financials and Stock
Addex Financials and Stock Tretapeutics
Slide 34: Financials and Stock
Financials and Stock ➢ Cash at March 31, 2024: ➢ 128.26 M outstanding shares CHF 1.6M (USD 1.8M) – Armistice Capital LLC – 26.13%* – CHF 5M from sale of Neurosterix received – New Enterprise Associates – 3.03%* in April 2024 ➢ 184.35M shares incl. treasury shares ➢ No debt (254.03M fully diluted) –
Slide 35: Summary
Summary Multiple high value ➢ GABAB PAM for substance use disorder (Indivior) in clinical candidate selection partnerships ➢ 20% equity interest in Neurosterix (backed by Perceptive Advisors) ➢ Dipraglurant - PD-LID Phase 2b ready to start In house programs ➢ Dipraglurant - post-stroke recovery Phas
Slide 36: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (August 2024) on 6ix