Addex Dipraglurant Dosed in First Subject in Receptor Occupancy Study in Collaboration with Johns Hopkins University and with Funding from The Michael J. Fox Foundation
Geneva, Switzerland, 22 July 2015 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today that enrollment has been initiated and the first subject has been dosed with dipraglurant (ADX48621) in a receptor occupancy study in healthy volunteers. Dipraglurant is a novel small molecule inhibitor of the metabotropic glutamate receptor 5 (mGluR5) that has successfully completed Phase II proof-of-concept testing in Parkinson's disease (PD) patients suffering from debilitating levodopa-induced dyskinesia (LID).
The study, which is underway under the direction of lead investigator Dean F. Wong, MD, PhD, of the Departments of Radiology, Psychiatry and Neuroscience at Johns Hopkins University, is designed to study brain mGluR5 occupancy by positron emission tomography (PET) following dosing of dipraglurant in healthy subjects and to assess the relationship between dipraglurant plasma concentration and brain mGluR5 occupancy. The Michael J. Fox Foundation for Parkinson’s Research (MJFF) provided funding for the trial.
"The development of treatments to prevent or ease dyskinesia remains a priority for our Foundation," said Maurizio Facheris, MD, MSc, MJFF Senior Associate Director of Research Programs. "Innovative therapies against this common side effect hold great potential for improved quality of life for the millions living with Parkinson’s disease.”
“The understanding of brain mGluR5 occupancy is an important step in the clinical development of dipraglurant,” said Sonia Poli, PhD, Chief Scientific Officer of Addex. “The results of the study will further contribute to our knowledge of the product and will support a rationale design of the Phase IIB studies that are currently being finalized.”
"We look forward to reporting the results from the study and moving forward the development of dipraglurant in PD-LID," said Tim Dyer, Chief Executive Officer of Addex. "The support of MJFF demonstrates the promise of dipraglurant as a potential treatment for Parkinson’s disease levodopa-induced dyskinesia.”
The study is an open label, non-randomized, PET study investigating mGluR5 occupancy after single or double oral dosing of ADX48621 in 15 healthy subjects using [18F]-FPEB. The study consists of two parts:
- A receptor occupancy dose curve will be obtained by using an adaptive design. Subjects will undergo two [18F]-FPEB PET imaging sessions: at baseline and after treatment with one dose of ADX48621. The second scan will be taken at Tmax for ADX48621 (one hour post dose). The initial dose will be 100 mg as this has been proven to be efficacious in a Phase IIA study in Parkinson's patients. The maximum dose given will be 200 mg.
- The time course of receptor occupancy will be studied for the dose that gives 70 percent receptor occupancy as determined in the first part of the study. Two subjects will receive a single daily dose of ADX48621 on two separate days and undergo three [18F]-FPEB PET imaging sessions: a baseline scan and two post-dose scans. Subjects will be given ADX48621 one hour before the first post-dose scan. The second dose will be given approximately four to six hours before the second post-dose scan. The maximum dose to be given will be 400 mg (200mg twice).
ClinicalTrials.gov Identifier: NCT02447640
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 II 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 and 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, the Clinical and Patient Global Impression of Changes scales, and an evaluation of the patient’s mood using the Hospital Anxiety and Depression Scale. 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 (mGluR5 negative allosteric modulator or NAM) has successfully completed a Phase IIA POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter Phase IIB for PD-LID. In parallel, dipraglurant’s therapeutic use in dystonia and treatment resistant depression is being investigated. Addex second clinical program, ADX71149 (mGluR2 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 I and is being investigated for therapeutic use in Charcot-Marie-Tooth (Type 1A) disease, alcohol use disorder and nicotine dependence; mGluR4PAM for drug abuse and dependence, Parkinson’s disease and other neurodegenerative diseases; mGluR2NAM for treatment resistant depression and cognitive deficits; mGluR7NAM 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.