Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Alcohol Binge Drinking

Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Alcohol Binge Drinking


-Data reinforces broad therapeutic potential of oral ADX71441 

-Program on track for CTA filing before end of 2012

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.” 


About Alcoholism

Alcoholism is a broad term for problems with alcohol, and is generally indicative of compulsive and uncontrolled consumption of alcoholic beverages. It is medically considered a disease, specifically an addictive illness. The World Health Organization estimates that about 140 million people throughout the world suffer from alcohol dependence. Patients with alcoholism suffer major changes to the brain structure and chemistry. Excessive alcohol consumption damages almost every organ in the body and the cumulative toxic effects can cause both medical (cirrhosis of the liver, pancreatitis, heart disease, peptic ulcers, sexual dysfunction) and psychiatric (epilepsy, dementia, psychosis, anxiety & depression) problems. Treatment of alcoholism is complex with current standard of care typically being prescribed to patients with heavy drinking but largely being unable to prevent them from relapsing.   


About GABA-B Receptor Activation

Activation of gamma-aminobutyric acid subtype B receptor (GABABR), a Family C class of GPCR, is clinically and commercially validated by a generic GABA-BR agonist, baclofen, which is marketed for spasticity in spinal cord injury patients. Baclofen has also shown clinical relevance in a number of other indications including overactive bladder, pain and is in early stage clinical development for alcohol dependence and autism. Despite baclofen’s broad clinical validation, it is not commonly used due to multiple side effects, rapid clearance, development of tolerance to the drug, rebound and withdrawal syndromes. Orthosteric GABA-BR agonists have also shown clinical validation in gastroesophageal reflux disease (GERD). Addex’ GABA-BR PAMs have shown efficacy in multiple preclinical models including: OAB, pain, osteoarthritis pain, anxiety and alcoholism.


Addex Therapeutics ( 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.


Tim Dyer
Chief Financial Officer
Addex Therapeutics
+41 22 884 15 61


Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.