Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, announced 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."

Date: October 29, 2012
Source: Addex Therapeutics