Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Chronic Alcohol Dependence

Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of Chronic Alcohol Dependence

• Data reinforces broad therapeutic potential of ADX71441, an oral GABAB receptor Positive Allosteric Modulator
• Recent approval of Clinical Trial Application (CTA)  to initiate a Phase 1, first–in-man, clinical study
• Phase 1 initiation on track by July 2013
Geneva, Switzerland, 30 April 2013 – (SIX:ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today positive preclinical data for its GABAB receptor positive allosteric modulator (PAM) oral small molecule in a validated rodent model of chronic alcohol dependence (i.e. alcoholism). The Addex’ clinical candidate, ADX71441, demonstrated robust and dose-dependent suppression of alcohol intake in animals lasting 24 hours.

“These data support and expand those obtained previously in a mouse model of binge alcohol drinking with this molecule.  Taken together, they offer strong evidence that ADX71441 can be used as a treatment of binge drinking and chronic alcohol dependence,” said Professor Klaus Miczek at Tufts University (USA) in whose laboratory the study was performed.

ADX71441 is an oral small molecule, with potential for once daily dosing, which selectively activates GABAB receptor.  The compound was evaluated in an intermittent access to alcohol model of chronic alcohol dependence in mice.  This procedure generates excessive voluntary alcohol drinking after animals are given 24-hour access to alcohol concomitant to water every other day.   In animals with a history of 4 weeks of excessive drinking, oral ADX71441 (3, 10, 17 mg/kg), administered acutely, resulted in a dose-dependent suppression of alcohol intake, achieving 70% reductions at the higher doses (17 mg/kg) in comparison to vehicle treatment. Significant reductions in alcohol consumption in response to ADX71441 treatment were present for the entire 24-hour alcohol access period. The effect of ADX71441 in this model was more robust and longer-lasting than that seen in mice treated with naltrexone, used in the study as a positive control.  Also, the effect of ADX71441 was characterized with remarkable behavioral specificity since water consumption was not influenced by the treatment. 
“These data again support the potential of ADX71441 in a broad range of indications,” noted Dr Graham Dixon, CSO at Addex. “We believe that a, once-a-day, well-tolerated, efficacious oral treatment for alcoholism would represent a major advance in the treatment of this devastating condition.”

Oral small molecule GABAB receptor PAMs have broad potential in multiple indications and Addex has previously demonstrated positive proof of concept in a range of preclinical models including those of pain, anxiety, obsessive-compulsive disorder and overactive bladder (OAB). Based on ADX71441 current data package, Addex is positioning the drug candidate as a treatment for the rare disease CMT1a, a form of peripheral neuropathy as well as for patients with spasticity, e.g. in multiple sclerosis or spinal cord injury.

“We look forward to initiating the clinical testing for this compound,” stated Bharatt Chowrira, Ph.D., Chief Executive Officer at Addex. “We can see a huge market opportunity for a GABAB PAM in a variety of psychiatric and neurological conditions as well as a potential replacement therapy for baclofen.  We believe we can potentially build sustainable and valuable franchises around both ADX71441 and dipraglurant in that both represent treatments for a wide range of therapeutic indications.  We expect to deliver top-line safety, pharmacokinetic and biomarker data on ADX71441 by year end.”

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 a current standard of care typically being prescribed to patients with heavy drinking but largely being unable to prevent them from relapsing.  

About GABAB receptor Activation
Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically and commercially validated by generic GABAB receptor 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 and withdrawal syndromes. Orthosteric GABAB receptor agonists have also shown clinical validation in gastroesophageal reflux disease (GERD). Addex’ GABAR PAMs have shown efficacy in multiple preclinical models including: OAB, pain, osteoarthritis pain, anxiety and alcoholism.

About Addex Therapeutics
Addex Therapeutics ( is a development stage company focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform. The Company’s two lead products are being investigated in Phase 2 clinical testing: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson’s disease levodopa-induced dyskinesia (PD-LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. to treat both schizophrenia and anxiety as seen in patients suffering from major depressive disorder. Addex is also advancing several preclinical programs including: GABA-BR positive allosteric modulator (PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for MS, Parkinson’s disease, anxiety and other diseases. 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. The Company uses its proprietary discovery platform to target receptors and other proteins that are recognized as essential for the therapeutic modulation of important diseases with unmet medical needs.

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, 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, GABAB receptors 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, GABAB receptors 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, GABAB receptors 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, GABAB receptors 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; or 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.