Addex Therapeutics /Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model ofAlcoholBinge Drinking. Processed and transmitted by Thomson Reuters ONE.The issuer is solely responsible for the content of this announcement.
* Data reinforces broad therapeutic potential of oral ADX71441
* Program on track for CTA filing before end of 2012
(SIX: ADXN), a leading company pioneeringallosteric modulation-based drug discovery and development, announcedtodaypositive preclinical data for its GABA-B receptor positive allostericmodulator(PAM) oral small molecule, ADX71441, in a validated rodent model ofalcoholbinge drinking. ADX71441 demonstrated robust, dose-dependent andlong-lastingsuppression of alcohol intake in animals compared to naltrexone, themost-commonly prescribed treatment of alcoholism on the market.
"These data are extremely encouraging and superior to naltrexone in ourpre-clinical model, and warrant further exploration as a noveltreatment foralcoholism," said Professor Klaus Miczek at Tufts University (USA) inwhoselaboratory the study was performed.
Both clinical and pre-clinical data suggest that activation of theGABA-Breceptor offers a unique therapeutic opportunity to address largely unmetneedsof patients with alcohol and drug abuse by (1) reducing the alcohol ordrugintake; (2) alleviating many physical signs (pain,Gastrointestinal/urinarydisturbances) and emotional symptoms (anxiety) associated withwithdrawal; and(3) maintaining abstinence by reducing alcohol or drug craving.
ADX71441, which has potential for once daily dosing and selectivelyactivatesthe GABA-B receptor, was evaluated in a mouse model of alcohol bingedrinking.Acute, oral administration of ADX71441 (3, 10, 30 mg/kg) resulted in adose-dependent suppression of alcohol intake, achieving 80% reductionsat higherdoses (10, 30 mg/kg) in comparison to vehicle treatment. Reductions inalcoholconsumption in response to ADX71441 treatment were present for the entire4houralcohol access period. The effect of ADX71441 in this model was morerobust andlonger-lasting than that seen in mice treated with naltrexone, which wasused inthe study as a positive control. This is the first study showing efficacyof aGABA-B receptor PAM in a rodent model of alcohol binge drinking.
"Alcoholism is an important unmet medical need as current treatmentsoffermarginal efficacy in reducing alcohol intake and are associated withsignificantside effects," noted Dr. Graham Dixon, CSO at Addex. "We are excitedby therobustness of the data and look forward to the filing of a CTA forADX71441 bythe end of 2012 and initiating Phase 1 testing in Q1 2013."
Oral small molecule GABA-B receptor PAMs have potential in treatingmultipleindications and Addex has previously demonstrated positive proof of conceptin abroad range of preclinical models, including those of pain, anxiety,obsessive-compulsive disorder and overactive bladder (OAB). Addex ispositioning ADX71441as a treatment for spasticity, with multiple sclerosis (MS) being aninitialfocus of the clinical development program.
"The advancement of ADX71441 towards the clinic clearly illustrates ourstrategyto bring forward innovative oral small molecule NCEs addressingvalidatedtargets with broad therapeutic potential," said Bharatt Chowrira, CEO atAddex."GABA-B receptor is one such exciting target whose activation has beenvalidatedin a broad range of indications. We plan to initially focus onevaluatingADX71441 for the treatment of spasticity in MS patients who currentlyare notadequately treated for this debilitating disease."
About Alcoholism
Alcoholism is a broad term for problems with alcohol, and isgenerallyindicative of compulsive and uncontrolled consumption of alcoholicbeverages. Itis medically considered a disease, specifically an addictive illness. TheWorldHealth Organization estimates that about 140 million people throughout theworldsuffer from alcohol dependence. Patients with alcoholism suffer majorchanges tothe brain structure and chemistry. Excessive alcohol consumption damagesalmostevery organ in the body and the cumulative toxic effects can cause bothmedical(cirrhosis of the liver, pancreatitis, heart disease, peptic ulcers,sexualdysfunction) and psychiatric (epilepsy, dementia, psychosis,anxiety &depression) problems. Treatment of alcoholism is complex with currentstandardof care typically being prescribed to patients with heavy drinking butlargelybeing unable to prevent them from relapsing.
About GABA-B Receptor Activation
Activation of gamma-aminobutyric acid subtype B receptor (GABABR), aFamily Cclass of GPCR, is clinically and commercially validated by a genericGABA-BRagonist, baclofen, which is marketed for spasticity in spinal cordinjurypatients. Baclofen has also shown clinical relevance in a number ofotherindications including overactive bladder, pain and is in early stageclinicaldevelopment for alcohol dependence and autism. Despite baclofen's broadclinicalvalidation, it is not commonly used due to multiple side effects,rapidclearance, development of tolerance to the drug, rebound andwithdrawalsyndromes. Orthosteric GABA-BR agonists have also shown clinicalvalidation ingastroesophageal reflux disease (GERD). Addex' GABA-BR PAMs have shownefficacyin multiple preclinical models including: OAB, pain, osteoarthritispain,anxiety and alcoholism.
Addex Therapeutics (www.addextherapeutics.com) discovers anddevelops anemerging class of small molecule drugs, called allosteric modulators, whichhavethe potential to be more specific and confer significant therapeuticadvantagesover conventional "orthosteric" small molecule or biological drugs. TheCompanyuses its proprietary discovery platform to address receptors and otherproteinsthat are recognized as attractive targets for modulation of importantdiseaseswith unmet medical needs. The Company's two lead products are beinginvestigatedin Phase 2 clinical testing: dipraglurant (ADX48621, an mGluR5negativeallosteric modulator or NAM) is being developed by Addex to treatParkinson'sdisease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2positiveallosteric modulator or PAM) is being developed by our partnerJanssenPharmaceuticals Inc. to treat schizophrenia and anxiety seen inpatientssuffering from major depressive disorder. Addex also is advancingseveralpreclinical programs including: GABA-BR PAM for spasticity in MS, OAB andotherdisorders; mGluR4 PAM for Parkinson's, MS, anxiety and otherdiseases. Inaddition, Addex is applying its proprietary discovery platform toidentifyhighly selective and potent allosteric modulators of a number of bothGPCR andnon-GPCR targets that are implicated in diseases of significant unmetmedicalneed.
Disclaimer: The foregoing release may contain forward-looking statementsthatcan 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 regardingAddexTherapeutics, formerly known as, Addex Pharmaceuticals, itsbusiness, thepotential approval of its products by regulatory authorities, orregardingpotential future revenues from such products. Such forward-lookingstatementsreflect the current views of Addex Therapeutics regarding future events,futureeconomic performance or prospects, and, by their very nature, involveinherentrisks and uncertainties, both general and specific, whether known orunknown,and/or any other factor that may materially differ from the plans,objectives,expectations, estimates and intentions expressed or implied in suchforward-looking statements. Such may in particular cause actual resultswith allostericmodulators of mGluR2, mGluR4, mGluR5, GABA-BR or other therapeutic targetsto bematerially different from any future results, performance orachievementsexpressed or implied by such statements. There can be no guaranteethatallosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR or othertherapeuticstargets will be approved for sale in any market or by any regulatoryauthority.Nor can there be any guarantee that allosteric modulators of mGluR2,mGluR4,mGluR5, GABA-BR or other therapeutic targets will achieve any particularlevelsof revenue (if any) in the future. In particular, management'sexpectationsregarding allosteric modulators of mGluR2, mGluR4, mGluR5, GABA-BR orothertherapeutic targets could be affected by, among other things, unexpectedactionsby our partners, unexpected regulatory actions or delays orgovernmentregulation generally; unexpected clinical trial results, includingunexpectednew clinical data and unexpected additional analysis of existing clinicaldata;competition in general; government, industry and general publicpricingpressures; the company's ability to obtain or maintain patent orotherproprietary intellectual property protection. Should one or more of theserisksor uncertainties materialize, or should underlying assumptions proveincorrect,actual results may vary materially from those anticipated, believed,estimatedor expected. Addex Therapeutics is providing the information in thispressrelease as of this date and does not undertake any obligation toupdate anyforward-looking statements contained in this press release as a resultof newinformation, future events or otherwise, except as may be required byapplicablelaws.
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This company has an outstanding allosteric modulator discovery platform. Buying and holding at CHF 10-11 range for sure... even a couple of drugs on the market and it's a 500% gain from here easy.
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