Geneva, Switzerland, 13 December 2016 - Addex Therapeutics (SIX: ADXN), announced today that the pharmacological profile of ADX71441, gamma-aminobutyric acid subtype B (GABAB) receptor positive allosteric modulator (PAM), was published in Neuropharmacology, a leading peer reviewed journal.
The pharmacological results published in Neuropharmacology (Kalinichev et al, 2017; available online) describe the PAM mode of action of ADX71441 on rat and human GABAB receptors, its pharmacokinetic parameters, as well as the effect obtained after oral administration in rodent models of anxiety (marble burying and elevated plus maze models), and visceral pain-associated behaviors (acetic acid-writhing model). Minimal effective dose observed in these models was 3 mg/kg, corresponding to 340-440 ng/ml of compound in the plasma.
"ADX71441 is a first in class, Phase I-ready compound with a once-daily profile," said Robert Lutjens, head of discovery at Addex. "ADX71441's positive allosteric modulator pharmacological profile and absolute selectivity for the GABAB receptor make it potentially superior for indications that have been clinically validated by the orthosteric agonist, baclofen, such as addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, psychosis, over active bladder, spasticity and CMT1A."
About GABAB Activation and ADX71441 Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically & commercially validated. Generic GABAB receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for overactive bladder (OAB), but is not more widely used due to a variety of side effects and rapid clearance, requiring frequent dosing. ADX71441 is a potent selective positive allosteric modulator (PAM) which potentiates GABA responses at the GABAB receptor. ADX71441 is a novel, first-in-class, oral, small molecules that has demonstrated excellent preclinical efficacy and tolerability in several rodent models of pain, anxiety, addiction and OAB and have also proven efficacy in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441 differs from the generic drug baclofen in that it is a positive allosteric modulator rather than an orthosteric agonist at the GABAB receptor. ADX71441 only acts when the natural ligand (GABA) activates the receptor, therefore respecting the physiological cycle of activation. It has been proposed that PAMs produce less adverse effects and lead to less tolerance than direct agonists (May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona et al. 2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al).
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 neurological disorders. 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's 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. Addex's 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 registration trials for PD-LID with support from the Michael J. Fox Foundation for Parkinson's Research (MJFF). In parallel, dipraglurant's therapeutic use in dystonia is being investigated with support from the Dystonia Medical Research Foundation (DMRF). Addex's second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for epilepsy. In addition, ADX71441 (GABAB receptor PAM) has received regulatory approval to start phase I and is being investigated for its therapeutic use in Charcot-Marie-Tooth Type 1A disease (CMT1A), cocaine and alcohol use disorder and nicotine dependence. Discovery programs include mGluR4PAM for neurodegenerative diseases, mGluR7NAM for psychosomatic disorders and TrkBPAM for neurodegenerative disorders which are being advanced in collaboration with the Universities of Lausanne and Geneva under the Swiss CTI grant program; and mGluR3PAM which is being advanced in collaboration with Pierre Fabre Pharmaceuticals.
Press Contacts: Tim Dyer Chief Executive Officer Addex Therapeutics Telephone: +41 22 884 15 61 Email: PR@addextherapeutics.com
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