Addex Therapeutics Ltd · SIX:ADXN
Addex Therapeutics — Investor Presentation (June 2023)
32 slides from Addex Therapeutics's investor presentation, June 2023
Slide 1: Innovative Treatments for Central Nervous System Disorders
Innovative Treatments for Central Nervous System Disorders June 2023 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 • Phase 2 epilepsy study (J&J) – IRC* recommends continuing study Multiple high value • Dipraglurant (mGlu5 NAM) – Phase 2 ready & indication under evaluation programs reaching • GABAB PAM for SUD (Indivior), chronic cough, pain & CMT1A significant milestones • mGlu7 NAM for stress
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 4
Slide 5: Advantages of Allosteric Modulation Versus Orthosteric Drug Discovery
Advantages of Allosteric Modulation Versus 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
Slide 6: Addex Pipeline
Addex Pipeline Molecule / MoA Indication Partner Pre-clinical Phase 1 Phase 2 Phase 3 Milestone ADX71149 Epilepsy Update in H2 2023 (mGlu2 PAM) Dipraglurant PD-LID*, post-stroke recovery, SUD* & Indication under (mGlu5 NAM) pain evaluation IND enabling Substance use disorders expected 2024 GABAB PAM
Slide 7: Experienced Team
Experienced Team Leadership Team Tim Dyer Dr Roger Mills Dr Robert Lutjens Dr Jean-Philippe Rocher Dr Mikhail Kalinichev CEO / CFO Chief Medical Officer Head of Discovery Biology Head of Discovery Chemistry Head of Translational Science Co-Founder of Addex Developed Nuplazid for PD Member of Addex f
Slide 8: ADX71149 (JNJ-40411813) for Epilepsy
ADX71149 (JNJ-40411813) for Epilepsy Partnered with Janssen Pharmaceuticals, Inc. 8
Slide 9: ADX71149 Opportunity in Epilepsy
ADX71149 Opportunity in Epilepsy • Market projected to reach $20 billion by 2026* – Keppra & Briviact net sales in 2022 of €1.2 billion treating 2M patients** Large market & unmet • High proportion of refractory patients (¼ of new patients***) - combination medical need treatments have limited thera
Slide 10: ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model
ADX71149 Preclinical Efficacy in Epilepsy - 6Hz Model • Preclinical 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 AD
Slide 11: ADX71149 Phase 2a Epilepsy Study
ADX71149 Phase 2a Epilepsy Study Placebo • Double blind placebo controlled Cohort 1 n=20 • Establish 28-day seizure count (over 56-day baseline period) • Primary endpoint: time to monthly baseline seizure • Focal onset seizure with suboptimal response to count levetiracetam • Period 1: 4-week acute
Slide 12: Dipraglurant (mGlu5 NAM) – Phase 2 Ready
Dipraglurant (mGlu5 NAM) – Phase 2 Ready Indications Under Evaluation: PD-LID, SUD, Post-Stroke Recovery, Pain and NDD 12
Slide 13: Dipraglurant Phase 2 Ready Opportunity in Multiple Indications
Dipraglurant Phase 2 Ready Opportunity in Multiple Indications Significant target • PD-LID: 200,000 patients in US, Orphan drug designation granted in US patient populations • SUD: 20 million patients in US and 2.2% of adult population worldwide and commercial • Pain: up to 10% of adult population
Slide 14: 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 15: 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 16: 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 17: 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 (µg/ml) 1,5 glutamatergic tone ahead of L-dopa Cmax 1 Dipraglurant normalizes abnor
Slide 18: 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: ‒ Modified Abnormal N=52: Dipraglurant Involuntary Movement Scale (mAIMS) on days 1, 14 and 28 50 mg 100 mg 100 mg ‒ Clinician Global Impre
Slide 19: 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 p=0.041 • Increasing placebo response caused -2 significance to be lost at Day 28 -3 p=0.
Slide 20: 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 21: 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% 10% • More objective than mAIMS 5% • Assessed at end of study compared to 0% bas
Slide 22: 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 23: Dipraglurant PD-LID – Status of Development
Dipraglurant PD-LID – Status of Development • Pivotal registration program –Study 301 & 12-month Open Label Study (302) terminated in June 2022 due to slow recruitment rate attributed to COVID related constraints • Future development under evaluation, including: –PD-LID –Post-stroke recovery –Substa
Slide 24: Other Preclinical Programs: GABAB PAM and mGlu7 NAM
Other Preclinical Programs: GABAB PAM for Substance Use Disorders (Indivior Partnership) & Chronic Cough mGlu7NAM Stress related disorders & Schizophrenia 24
Slide 25: GABAB PAM for Substance Use Disorder
GABAB PAM for Substance Use Disorder • High prevalence;1.8% of US population* Large market & unmet • Current treatments have undesirable side-effects and prone to relapse medical need • Burden to society in US is >$600B annually** • Baclofen (GABAB agonist) used off label for alcohol use disorder •
Slide 26: GABAB PAM for Chronic Cough
GABAB PAM for Chronic Cough • Widespread prevalence – Up to 10% of adult population worldwide* Large market & unmet – More prevalent (10-20%) in Europe, America and Australia than in Asia (5%)* medical need • Opioid drugs (codeine) offer suboptimal relief and are linked to undesirable side effects,
Slide 27: mGlu7 NAM for Stress Related Disorders (including PTSD) and Schizophrenia
MGlu7 NAM for Stress Related Disorders (including PTSD) and Schizophrenia • PTSD affects approximately 3.5% of U.S. adults Large market & unmet • Current treatments are primarily based on psychotherapy, medication is nonspecific (off-label use of anxiolytics and medical need antidepressants) and usu
Slide 28: Addex Financials, Stock and Milestones
Addex Financials, Stock and Milestones 28
Slide 29: Financials and Stock
Financials and Stock • Cash at March 31, 2023: CHF 5.6M • 88.71M outstanding shares (USD 6.1M) – Armistice Capital LLC – 48.32%*/** – CHF 4.5M (USD 5.0 M) raised on April 3, 2023 – New Enterprise Associates – 8.47%* – New Leaf Venture Partners – 2.92%* • No debt • 115.34M registered shares incl. tre
Slide 30: Milestones
Milestones Milestone Timing ADX71149 for epilepsy Phase 2a – Part 1 IRC* recommends to continue study 10th May 2023 Further update on progress H2 2023 GABAB PAM for substance use disorders Start IND enabling studies 2024 GABAB PAM for chronic cough, pain & CMT1A Start IND enabling studies 2024 mGlu7
Slide 31: Summary
Summary • Phase 2 epilepsy study (J&J) ongoing • Dipraglurant Phase 2 ready - multiple indications under evaluation Multiple high value • GABAB PAM for substance use disorder (Indivior) and other indications programs • mGlu7 NAM for stress related disorders (PTSD) and schizophrenia • M4 PAM for schi
Slide 32: Allosteric Modulators for Human Health
ALLOSTERIC MODULATORS FOR HUMAN HEALTH www.addextherapeutics.com
Addex Therapeutics — Investor Presentation (June 2023) on 6ix