Addex Initiates Dipraglurant Receptor Occupancy Clinical Study in Collaboration with Johns Hopkins University with Funding from The Michael J. Fox Foundation
Geneva, Switzerland, 23 February 2015 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today approval by the ethics committee of the Johns Hopkins University to conduct a receptor occupancy study with dipraglurant in healthy volunteers. The lead investigator for the study is Dean F. Wong, MD, PhD, of the Departments of Radiology, Psychiatry and Neuroscience at Johns Hopkins University and the study will be conducted in collaboration with Lorena Gapasin, RN, CCRP; Hiroto Kuwabara, MD, PhD; and Anil Mathur, MD, CCRP. The study is supported by a grant from The Michael J. Fox Foundation for Parkinson's Research (MJFF).
Dipraglurant — a novel, small molecule inhibitor of the metabotropic glutamate receptor 5 (mGluR5) — has successfully completed Phase 2 proof of concept in Parkinson's disease (PD) patients suffering from debilitating levodopa-induced dyskinesia (LID). The data from the Phase 2 study showed that dipraglurant exhibits a good safety and tolerability profile in PD patients. Dipraglurant also demonstrated a significant reduction in severity of both components of LID (chorea and dystonia) with both 50mg and 100mg doses. The objectives of the current study are to quantify the brain mGlu5 receptor occupancy by positron emission tomography (PET) following single oral dosing of dipraglurant in healthy subjects and to assess the relationship between dipraglurant plasma concentration and brain mGlu5 receptor occupancy. The results of this study will support the design of the Phase 2B study, which is currently being prepared.
“Dipraglurant has demonstrated robust Phase 2 efficacy in PD LID and along with data from preclinical models of motor and non-motor symptoms leads us to believe that dipraglurant has the potential to provide significant symptomatic relief to Parkinson’s patients,” said Sonia Poli, PhD., Chief Scientific Officer of Addex. “We are excited to be restarting the development of dipraglurant with this important study and look forward to rapidly moving into Phase 2B”
"Dr Dean F. Wong and his colleagues at the Johns Hopkins University are some of the world’s leading experts in brain imaging and we are proud to have the opportunity to work with them on this important study in the development of dipraglurant," said Tim Dyer, Chief Executive Officer of Addex. "The support of MJFF demonstrates the importance of dipraglurant as a potential treatment for Parkinson’s disease levodopa induced dyskinesia.”
"The development of treatments to prevent or ease dyskinesia remains a priority for our Foundation," said Todd Sherer, Ph.D., Chief Executive Officer of The Michael J. Fox Foundation. "Innovative therapies against this common side effect hold great potential for improved quality of life for the millions living with Parkinson’s disease”.
Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGluR5), a Class C G-Protein Coupled Receptor (GPCR), with potential to be used in combination with levodopa or dopamine agonists or as a standalone treatment for Parkinson's disease levodopa-induced dyskinesia (PD-LID), motor and non-motor symptoms of Parkinson's disease and other movement disorders. In a double-blind, placebo-controlled, US and European Phase 2 study in PD-LID, data showed that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant reduced dystonia severity in addition to chorea, the two major LID components. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS), patient diaries documenting "off-time" (impaired voluntary movement), "on-time" (with or without dyskinesia) and sleep. Additional endpoints include the Unified Parkinson's Disease Rating Scale (UPDRS), the Clinician & Patient Global Impression of Change (CGIC & PGIC), and an evaluation of the patients' mood using the Hospital Anxiety & Depression Score. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.
About The Michael J. Fox Foundation
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $450 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for central nervous system disorders. Addex lead drug candidate, dipraglurant (mGlu5 negative allosteric modulator or NAM) has successfully completed a Phase 2A POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter Phase 2B for PD-LID. In parallel, dipraglurant’s therapeutic use in dystonia and treatment resistant depression is being investigated. Addex second clinical program, ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. Addex also has several preclinical programs including: ADX71441 (GABAB receptor PAM) which has received regulatory approval to start Phase 1 and is being investigated for therapeutic use in Charcot-Marie-Tooth (Type 1A) disease, alcohol use disorder and nicotine dependence; mGlu4PAM for drug abuse and dependence, Parkinson’s disease and other neurodegenerative diseases; mGlu2NAM for treatment resistant depression and cognitive deficits; mGlu7NAM for psychosomatic disorders, TrkBPAM for neurodegenerative disorders; and GLP1PAM for type 2 diabetes. Allosteric modulators are an emerging class of small molecule drugs which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. Addex allosteric modulator drug discovery platform targets receptors and other proteins that are recognized as essential for therapeutic intervention – the Addex pipeline was generated from this pioneering allosteric modulator drug discovery platform.
Chief Executive Officer
Telephone: +41 22 884 15 61
Disclaimer / Forward-looking statements: This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Addex Therapeutics Ltd. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.