Addex ADX71441 Demonstrates Positive Results in Non-Human Primate Model of Cocaine Addiction
Geneva, Switzerland, 9 June 2016 – Addex Therapeutics (SIX: ADXN), announced today positive results with ADX71441, a GABAB receptor positive allosteric modulator, in a non-human primate model of cocaine self-administration. The results were obtained through the ongoing research collaboration with the US National Institute of Drug abuse (NIDA).
The effect of acute treatment with ADX71441 on intravenous (IV) cocaine self-administration was determined in rhesus monkeys that self-administered varying doses of cocaine (0.001–0.1 mg/kg/injection, IV). Specificity of the effect of ADX71441 was assessed by evaluating the response to food in sessions preceding and following the IV self-administration of cocaine phase of the experiments.
In the initial dose-ranging experiments, intra-muscular (IM) doses of ADX71441 (0.32-3.2 mg/kg) were administered 120 min before sessions in which 0.03 mg/kg cocaine was available for IV injection. The results indicate that ADX71441 dose-dependently decreased cocaine self-administration to approximately 10% of control values. The results further indicate that pretreatment with ADX71441 did not substantially effect food intake.
In the second set of experiments, the effect of 1.0 or 3.2 mg/kg of ADX71441 on self-administration behavior was evaluated at a range of IV doses of cocaine and IV saline. Data shows that ADX71441 decreased the self-administration of all doses of cocaine by 60-90% and had no effect on the IV self-administration of saline. In addition the effect was specific to cocaine.
These data demonstrate that acute treatment with ADX71441 may attenuate IV cocaine self-administration in a behaviorally selective manner.
“This remarkable data confirms the potential of ADX71441 as a treatment for addiction” said Sonia Poli, Chief Scientific Officer of Addex. “We previously demonstrated the ability of ADX71441 to reduce alcohol self-administration and are encouraged to see similar effects in models of cocaine addiction.”
“The NIDA and NIAAA teams have done an outstanding job characterizing ADX71441 in addiction” said Tim Dyer, Chief Executive Officer of Addex. “Based on the new data we are convinced that ADX71441 has a huge potential in multiple types of addiction and look forward to rapidly advancing ADX71441 into clinical studies.”
About Drug Abuse and Drug Addiction
Scientific advances have revolutionized our understanding of addiction as a chronic, relapsing disease and not a moral failure. Drug addiction is a complex illness which is characterized by intense and, at times, uncontrollable drug craving, along with compulsive drug seeking and use that persist even in the face of devastating consequences. Addiction affects multiple brain circuits, including those involved in reward and motivation, learning and memory, and inhibitory control over behavior. While a person initially chooses to take drugs, over time the effects of prolonged exposure on brain functioning compromise that ability to choose, and seeking and consuming the drug become compulsive, often eluding a person’s self-control or willpower. Because drug abuse and addiction have so many dimensions and disrupt so many aspects of an individual’s life, treatment is not simple. Addiction treatment must help the individual stop using drugs, maintain a drug-free lifestyle, and achieve productive functioning in the family, at work, and in society. Patients typically require long-term or repeated episodes of care to achieve the ultimate goal of sustained abstinence and recovery of their lives.
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 French health authorities have approved its use for the treatment of alcoholism on a "case by case" basis. Baclofen is also used off label for a number of other indications including overactive bladder (OAB), but its utility is limited due to variety of side effects and rapid clearance. 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, and 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. Addex has published positive data with ADX71441 in two models of alcohol abuse in mice, the ethanol binge-like drinking, drinking-in-the-dark (DID) and a model of long-term, excessive drinking, intermittent access to alcohol (IAA).
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. 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 III 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 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), 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. 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.
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