dipraglurant (ADX-48621) / Addex - LARVOL DELTA

Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Addex Pharma S.A. | Recruiting ➔ Completed | Phase classification: P2a ➔ P2

Phase classification • Trial completion • CNS Disorders • Dystonia • Movement Disorders

Open-label Safety Study of Dipraglurant (ADX48621) in Patients With Parkinson's Disease Receiving Levodopa-based Therapy (clinicaltrials.gov) - P2/3 | N=17 | Terminated | Sponsor: Addex Pharma S.A. | N=140 ➔ 17 | Recruiting ➔ Terminated; Terminated prior to completing enrollment goals due to COVID-related difficulties in recruiting patients

Enrollment change • Trial termination • CNS Disorders • Movement Disorders • Parkinson's Disease

Dipraglurant (ADX48621) for the Treatment of Patients With Parkinson's Disease Receiving Levodopa-based Therapy (clinicaltrials.gov) - P2/3 | N=25 | Terminated | Sponsor: Addex Pharma S.A. | Phase classification: P2b ➔ P2/3 | N=140 ➔ 25 | Recruiting ➔ Terminated; Terminated prior to completing enrollment goals due to COVID-related difficulties in recruiting patients

Enrollment change • Phase classification • Trial termination • CNS Disorders • Movement Disorders • Parkinson's Disease

Characterization of Rat Models of Headache in Support of the NIH PSPP Program (IASP 2024) - "Here, we describe one such effort to characterize the pharmacology of rat models of vascular headache and trigeminal sensitization involving administration of isosorbide dinitrate or dural infusion of inflammatory soup (IS)...For the model of trigeminal sensitization, rats received single or multiple infusions of inflammatory soup (IS; 2 mM serotonin, histamine, bradykinin, 0.2 mM PGE2) onto the dura under acute isoflurane anesthesia...Pharmacology was examined by evaluating the effects of pretreatment with the reference compounds morphine sulfate (6 mg/kg), naproxen (30 mg/kg), sumatriptan (1 mg/kg), olcegepant (1 mg/kg), SNC80 (30 mg/kg), and dipraglurant (50 mg/kg)... The data demonstrate that transient facial allodynia in rat models of vascular headache and trigeminal sensitization persists for a longer duration in female rats compared to male rats. Clinically effective treatments for headache and migraine, including 5-HT1B/1D receptor agonists and CGRP receptor..."

Preclinical • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Migraine • Pain • Psychiatry

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm. (PubMed, Mov Disord) - "Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm."

Clinical • Journal • CNS Disorders • Dystonia • Movement Disorders • Parkinson's Disease

Addex Reports 2023 Half Year and Second Quarter Financial Results and Provides Corporate Update (GlobeNewswire) - "Addex Therapeutics...today reported its half-year and second quarter financial results for the periods ended June 30, 2023 and provided a corporate update...GABAB PAM Indivior strategic partnership for substance use disorders extended through to end June 2024 with CHF2.7 million of committed research funding - multiple drug candidates in clinical candidate selection phase...R&D expenses decreased by CHF 5.9 million to CHF 3.6 million in the first half of 2023 compared to CHF 9.5 million in the first half of 2022 and by CHF 3.9 million to CHF 1.8 million in the second quarter of 2023 compared to CHF 5.7 million in the second quarter of 2022. The decrease in R&D expenses is primarily due to decreased dipraglurant related external research and development activities."

Commercial • Licensing / partnership • Chronic Cough • CNS Disorders • Cough • Pain • Parkinson's Disease • Respiratory Diseases

Effect of the Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulator Dipraglurant on Motor and Non-Motor Symptoms of Parkinson's Disease. (PubMed, Cells) - "In vivo, dipraglurant dose-dependently reduced haloperidol-induced catalepsy, increased punished licks in the Vogel conflict-drinking model, decreased immobility time in the forced swim test, decreased the number of buried marbles in the marble-burying test, but had no effect on rotarod performance or locomotor activity. These findings suggest that dipraglurant may have benefits to address some of the highly problematic comorbid non-motor symptoms of PD, in addition to its antidyskinetic effect demonstrated in PD-LID patients."

Journal • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Obsessive-Compulsive Disorder • Parkinson's Disease • Psychiatry

Addex Publishes Dipraglurant Data Showing In Vivo Efficacy on Motor and Non-Motor Symptoms of Parkinson’s Disease (GlobeNewswire) - "Addex Therapeutics...today announced data showing that dipraglurant could have beneficial effects on non-motor symptoms (NMS) experienced by Parkinson’s patients in addition to its established positive effects on dyskinesias....In the current study, published in Cells, the effects of dipraglurant were investigated in a rodent motor symptoms model of PD, as well as anxiety, depression and obsessive-compulsive disorder, all of which are among the most prevalent NMS symptoms. Following oral administration, dipraglurant was rapidly absorbed and readily crossed the blood-brain barrier. In vivo, dipraglurant administration was found to dose-dependently impact the various NMS disease models, including reducing haloperidol-induced catalepsy, increasing punished licks in the Vogel conflict-drinking model, decreasing immobility time in the forced swim test and decreasing the number of buried marbles in the marble-burying test."

Preclinical • CNS Disorders • Parkinson's Disease

An overview of the pharmacotherapeutics for dystonia: advances over the past decade. (PubMed, Expert Opin Pharmacother) - "The most novel emerging therapies include daxibotulinumtoxinA, dipraglurant, and sodium oxybate. There is a strong clinical need for more effective therapeutic options in dystonia, which may involve the development of individualized treatment options based on dystonia subtype, etiology, or novel mechanisms of action that target specific underlying contributing features."

Journal • CNS Disorders • Dystonia • Movement Disorders

Addex Terminates Dipraglurant Phase 2b/3 Study in Patients with Dyskinesia Associated with Parkinson’s Disease due to Slow Recruitment Rate (GlobeNewswire) - "Addex Therapeutics Ltd...announced today that it has terminated the Phase 2b/3 study evaluating dipraglurant as a potential treatment for dyskinesia associated with Parkinson’s disease (PD-LID) due to the slow recruitment of patients. This has been attributed to the consequences of COVID-19 related patient concerns about participation in clinical studies as well as staffing shortages and turnover within study sites....In light of the Company’s termination of the dipraglurant program for PD-LID, the Company is suspending the Company’s financial guidance."

Trial termination • CNS Disorders • Parkinson's Disease

Addex Reports Q1 2022 Financial Results (BioSpace) - "Addex Therapeutics...today reported financial results for the quarter ended March 31, 2022....R&D expenses increased by CHF 1.0 million to CHF 3.8 million in the first quarter 2022 compared to CHF 2.7 million in the first quarter 2021, mainly due to CHF 0.5 million of increased outsourced R&D costs related to our dipraglurant PD-LID program and dipraglurant blepharospasm program."

Commercial • CNS Disorders • Parkinson's Disease

Open-label Safety Study of Dipraglurant (ADX48621) in Patients With Parkinson's Disease Receiving Levodopa-based Therapy (clinicaltrials.gov) - P2/3 | N=140 | Recruiting | Sponsor: Addex Pharma S.A. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Addex Reports Full Year 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Addex Therapeutics...today reported financial results for the full-year ended December 31, 2021 and provided a corporate update....Phase 2b/3 dipraglurant study in dyskinesia associated with Parkinson’s disease expected to report data in H1 2023"

P2/3 data • CNS Disorders • Parkinson's Disease

Addex Increases Issued Share Capital to Create Treasury Shares (BioSpace) - "Addex Therapeutics...announced today that it has increased its share capital from 49,272,952 to 65,272,952 through the issue of 16,000,000 new registered shares at a nominal value of CHF1 each to Addex Pharma S.A, its 100% wholly-owned subsidiary....'This transaction provides us with future financing flexibility as we execute on the development of dipraglurant for dyskinesia associated with Parkinson’s disease and blepharospasm as well as advancing multiple preclinical programs towards clinical studies...'"

Financing • CNS Disorders • Parkinson's Disease

Levodopa-induced dyskinesia: a brief review of the ongoing clinical trials. (PubMed, Neurodegener Dis Manag) - No abstract available

Clinical • Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Addex Therapeutics : Provides Year End Pipeline Development Update - Form 6-K (Market Screener) - "Addex Therapeutics...today provided an update on progress in its product pipeline....Dipraglurant Study 301 for Parkinson's disease levodopa-induced dyskinesia....We expect to report top-line data at the end of Q4 2022....mGlu2 NAM for mild neurocognitive disorders associated with Alzheimer’s disease, Parkinson’s disease and depressive disorders: We are in late lead optimization phase with multiple series of compounds and expect to enter clinical candidate selection phase early in 2022."

P2/3 data • Preclinical • CNS Disorders • Parkinson's Disease

Open-label Safety Study of Dipraglurant (ADX48621) in Patients With Parkinson's Disease Receiving Levodopa-based Therapy (clinicaltrials.gov) - P2/3; N=140; Recruiting; Sponsor: Addex Pharma S.A.

Clinical • New P2/3 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm (clinicaltrials.gov) - P2a; N=15; Recruiting; Sponsor: Addex Pharma S.A.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Dystonia • Movement Disorders

Addex Reports Q3 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Addex Therapeutics...today reported its Q3 2021 financial results for the periods ended September 30, 2021 and provided a corporate update...Q3 22 - Phase 2a data: ADX71149 for epilepsy. Q4 22 - Phase 2b/3 data: dipraglurant for dyskinesia associated with Parkinson’s disease."

P2/3 data • P2a data • CNS Disorders • Parkinson's Disease

Addex Therapeutics Initiates Phase 2 Clinical Study with Dipraglurant in Blepharospasm (GlobeNewswire) - "'We are now poised for a significant year of reporting data in 2022...top-line data from our pivotal study of dipraglurant in levodopa induced dyskinesia in Parkinson’s and for ADX71149 in epilepsy later in 2022.'"

Clinical data • CNS Disorders • Epilepsy • Parkinson's Disease

Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm (clinicaltrials.gov) - P2a; N=15; Not yet recruiting; Sponsor: Addex Pharma S.A.

Clinical • New P2a trial • CNS Disorders • Dystonia • Movement Disorders

Dipraglurant (ADX48621) for the Treatment of Patients With Parkinson's Disease Receiving Levodopa-based Therapy (clinicaltrials.gov) - P2b; N=140; Recruiting; Sponsor: Addex Pharma S.A.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

Addex Therapeutics Initiates Pivotal Phase 2b/3 Study with Dipraglurant for Dyskinesia Associated with Parkinson’s Disease (GlobeNewswire) - "Addex Therapeutics...announced today that screening of patients has started for its pivotal Phase 2b/3 study with dipraglurant for dyskinesia associated with Parkinson’s disease (PD-LID)....The registration program comprises two placebo-controlled studies. The first, Study 301, is a double-blind, placebo-controlled, parallel group design Phase 2b/3 pivotal clinical trial of dipraglurant (100 mg tid) in 140 PD-LID patients at approximately 50 sites in the U.S. The primary endpoint will evaluate efficacy in reducing PD-LID symptoms as measured by the Unified Dyskinesia Rating Scale, or UDysRS at week 12 compared to baseline."

Trial status • CNS Disorders • Parkinson's Disease

Dipraglurant-IR: Topline data from P2b/3 trial for levodopa induced dyskinesia in Parkinson’s disease in Q4 2022 (Addex Pharmaceuticals) - Corporate Presentation

P2/3 data • CNS Disorders • Parkinson's Disease

Rescue of striatal long-term depression by chronic mGlu5 receptor negative allosteric modulation in distinct dystonia models. (PubMed, Neuropharmacology) - "Our findings suggest that distinct dystonia genes may share common signaling pathway dysfunction. More importantly, they indicate that dipraglurant might be a potential novel therapeutic agent for this disabling disorder."

Journal • CNS Disorders • Depression • Dystonia • Mood Disorders • Movement Disorders • Psychiatry