GENEVA, Jan. 7, 2015 (GLOBE NEWSWIRE) -- 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 Alcohol Abuse and Alcoholism (NIAAA), a component of the National Institutes of Health (NIH), to evaluate the pharmacology of ADX71441, a GABAB receptor positive allosteric modulator (PAM), in preclinical models of alcohol use disorder. The collaboration will evaluate Addex drug candidate, ADX71441, in a battery of preclinical models to study its potential as a treatment for alcohol use disorder.
Both clinical and pre-clinical data suggest that activation of GABAB receptors offers a unique therapeutic opportunity to address the needs of patients with alcohol use disorder by suppressing multiple alcohol-related behaviors, including intake, reward and motivation, and seeking behavior. GABAB receptor PAMs have a similar pharmacological profile to the orthosteric agonist, baclofen, while showing a more favorable tolerability profile.
Addex has published 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) (Hwa et al. Psychopharmacology 2014;231(2):333-343).
"The evaluation of ADX71441 in additional preclinical models established in the laboratory of clinical and translational studies at NIAAA will provide Addex with invaluable information to guide the clinical development of ADX71441 in alcohol use disorders," said Sonia Poli, CSO at Addex. "This is our first collaboration with NIAAA and another example of our strategy to advance our pipeline through collaborations with cutting edge governmental research groups."
About Alcohol Use Disorder
Problem drinking that becomes severe is given the medical diagnosis of "alcohol use disorder" or AUD. AUD 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 alcohol use disorder 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. Approximately 7.2 percent or 17 million adults in the United States age 18 and older had an AUD in 2012. This includes 11.2 million men and 5.7 million women. In addition, an estimated 855,000 adolescents age 12-17, in the United States, had an AUD in 2012.
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, used off label for overactive bladder (OAB) and alcohol use disorder, but use is limited 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 molecule that has demonstrated excellent preclinical efficacy and tolerability in several rodent models of pain, anxiety, addiction and OAB and has 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).
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for central nervous system disorders. Addex lead drug candidate, dipraglurant (mGlu5 negative allosteric modulator or NAM) has successfully completed a Phase 2A POC in Parkinson's disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter Phase 2B for PD-LID. In parallel, dipraglurant's therapeutic use in dystonia and treatment resistant depression is being investigated. Addex second clinical program, ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. Addex also has several preclinical programs including: ADX71441 (GABAB receptor PAM) which has received regulatory approval to start Phase 1 and is being investigated for therapeutic use in Charcot-Marie-Tooth (Type 1A) disease, alcohol use disorder and nicotine dependence; mGlu4PAM for drug abuse and dependence, Parkinson's disease and other neurodegenerative diseases; mGlu2NAM for treatment resistant depression and cognitive deficits; mGlu7NAM for psychosomatic disorders, TrkBPAM for neurodegenerative disorders; and GLP1PAM for type 2 diabetes. 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. Addex allosteric modulator drug discovery platform targets receptors and other proteins that are recognized as essential for therapeutic intervention - the Addex pipeline was generated from this pioneering allosteric modulator drug discovery platform.
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