ADDEX THERAPEUTICS LTD 
By Addex and NIDA enter collaboration to advance ADX71441 & ADX88178 in drug abuse and addiction
Geneva, Switzerland, 4 November 2013 - Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today entering a collaboration with the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH) to evaluate the pharmacology of ADX71441, a GABAB receptor positive allosteric modulator (PAM), and ADX88178, an mGlu4 PAM in preclinical models of drug abuse and addiction. The collaboration will evaluate Addex drug candidates, ADX71441 and ADX88178 in a battery of preclinical models to study their potential as treatments for nicotine and cocaine addiction.
"NIDA has made significant contributions to our understanding of the underlying pathology of drug abuse and addiction and has coordinated development and validation of a large battery of preclinical models which will provide Addex with invaluable information for the further development of ADX71441 and ADX88178," said Tim Dyer, CEO at Addex. "This is our first collaboration with NIDA and another example of us executing our strategy to advance our pipeline through collaborations with cutting edge academic and governmental research groups."
Both pre-clinical and clinical data suggest that activation of GABAB receptors offers a unique therapeutic opportunity to address the needs of drug abuse patients by reducing drug intake, by maintaining abstinence, and by reducing drug craving. Moreover treatment with a GABAB activator can alleviate many physical signs (GI/urinary disturbances) and emotional symptoms (anxiety) associated with withdrawal. Addex recently reported 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). The data have been published online on August 22 (L.S. Hwa et al. Psychopharmacology).
"Alcohol and nicotine addiction are often comorbid, and therefore the data from this collaboration with NIDA will help us define the best clinical development path for our lead programs," said Sonia Poli, VP translational science at Addex. "We are also excited to learn more about the potential utility of both GABAB PAM and mGlu4 PAM in further aspects of drug addiction"
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 used for overactive bladder (OAB), but is not commonly used due to variety of side effects of the drug 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 (May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona et al. 2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al).
About mGlu4 Activation and ADX88178
The metabotropic glutamate receptor 4 (mGlu4) belongs to the Group III mGluRs (Class C G-Protein Coupled Receptor) and is negatively coupled to adenylate cyclase via activation of the G
