Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Alcohol Binge Drinking Addex Therapeutics : Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Alcohol Binge Drinking Geneva, Switzerland, 29 October 2012 – (SIX:ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today positive preclinical data for its GABA-B receptor positive allosteric modulator (PAM) oral small molecule, ADX71441, in a validated rodent model of alcohol binge drinking. ADX71441 demonstrated robust, dose-dependent and long-lasting suppression of alcohol intake in animals compared to naltrexone, the most-commonly prescribed treatment of alcoholism on the market. “These data are extremely encouraging and superior to naltrexone in our pre-clinical model, and warrant further exploration as a novel treatment for alcoholism,” said Professor Klaus Miczek at Tufts University (USA) in whose laboratory the study was performed. Both clinical and pre-clinical data suggest that activation of the GABA-B receptor offers a unique therapeutic opportunity to address largely unmet needs of patients with alcohol and drug abuse by (1) reducing the alcohol or drug intake; (2) alleviating many physical signs (pain, Gastrointestinal/urinary disturbances) and emotional symptoms (anxiety) associated with withdrawal; and (3) maintaining abstinence by reducing alcohol or drug craving. ADX71441, which has potential for once daily dosing and selectively activates the GABA-B receptor, was evaluated in a mouse model of alcohol binge drinking. Acute, oral administration of ADX71441 (3, 10, 30 mg/kg) resulted in a dose-dependent suppression of alcohol intake, achieving 80% reductions at higher doses (10, 30 mg/kg) in comparison to vehicle treatment. Reductions in alcohol consumption in response to ADX71441 treatment were present for the entire 4hour alcohol access period. The effect of ADX71441 in this model was more robust and longer-lasting than that seen in mice treated with naltrexone, which was used in the study as a positive control. This is the first study showing efficacy of a GABA-B receptor PAM in a rodent model of alcohol binge drinking. “Alcoholism is an important unmet medical need as current treatments offer marginal efficacy in reducing alcohol intake and are associated with significant side effects,” noted Dr. Graham Dixon, CSO at Addex. “We are excited by the robustness of the data and look forward to the filing of a CTA for ADX71441 by the end of 2012 and initiating Phase 1 testing in Q1 2013.” Oral small molecule GABA-B receptor PAMs have potential in treating multiple indications and Addex has previously demonstrated positive proof of concept in a broad range of preclinical models, including those of pain, anxiety, obsessive-compulsive disorder and overactive bladder (OAB). Addex is positioning ADX71441 as a treatment for spasticity, with multiple sclerosis (MS) being an initial focus of the clinical development program. “The advancement of ADX71441 towards the clinic clearly illustrates our strategy to bring forward innovative oral small molecule NCEs addressing validated targets with broad therapeutic potential,” said Bharatt Chowrira, CEO at Addex. “GABA-B receptor is one such exciting target whose activation has been validated in a broad range of indications. We plan to initially focus on evaluating ADX71441 for the treatment of spasticity in MS patients who currently are not adequately treated for this debilitating disease.” Addex Therapeutics (Addex Therapeutics : about addex) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (ADX48621, an mGluR5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed by our partner Janssen Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients suffering from major depressive disorder. Addex also is advancing several preclinical programs including: GABA-BR PAM for spasticity in MS, OAB and other disorders; mGluR4 PAM for Parkinson's, MS, anxiety and other diseases. In addition, Addex is applying its proprietary discovery platform to identify highly selective and potent allosteric modulators of a number of both GPCR and non-GPCR targets that are implicated in diseases of significant unmet medical need.