Addex And NIDA Enter Collaboration To Advance ADX71441 & ADX88178 In Drug Abuse And Addiction

GENEVA, Nov. 4, 2013 (GLOBE NEWSWIRE) --
Addex Therapeutics (SIX: ADXN), a leadingcompany pioneering allosteric modulation-based drug discovery and developmentannounced today entering a collaboration with the National Institute on DrugAbuse (NIDA), a component of the National Institutes of Health (NIH) to evaluatethe pharmacology of ADX71441, a GABAB receptor positive allosteric modulator(PAM), and ADX88178, an mGlu4 PAM in preclinical models of drug abuse andaddiction. The collaboration will evaluate Addex drug candidates, ADX71441 andADX88178 in a battery of preclinical models to study their potential astreatments for nicotine and cocaine addiction."NIDA has made significant contributions to our understanding of the underlyingpathology of drug abuse and addiction and has coordinated development andvalidation of a large battery of preclinical models which will provide Addexwith invaluable information for the further development of ADX71441 andADX88178," said Tim Dyer, CEO at Addex. "This is our first collaboration withNIDA and another example of us executing our strategy to advance our pipelinethrough collaborations with cutting edge academic and governmental researchgroups."Both pre-clinical and clinical data suggest that activation of GABAB receptorsoffers a unique therapeutic opportunity to address the needs of drug abusepatients by reducing drug intake, by maintaining abstinence, and by reducingdrug craving. Moreover treatment with a GABAB activator can alleviate manyphysical signs (GI/urinary disturbances) and emotional symptoms (anxiety)associated with withdrawal. Addex recently reported positive data with ADX71441in 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). The data have been published online onAugust 22 (L.S. Hwa et al. Psychopharmacology)."Alcohol and nicotine addiction are often comorbid, and therefore the data fromthis collaboration with NIDA will help us define the best clinical developmentpath for our lead programs," said Sonia Poli, VP translational science at Addex."We are also excited to learn more about the potential utility of both GABAB PAMand mGlu4 PAM in further aspects of drug addiction"About Drug Abuse and Drug AddictionScientific advances have revolutionized our understanding of addiction as achronic, relapsing disease and not a moral failure. Drug addiction is a complexillness which is characterized by intense and, at times, uncontrollable drugcraving, along with compulsive drug seeking and use that persist even in theface of devastating consequences. Addiction affects multiple brain circuits,including those involved in reward and motivation, learning and memory, andinhibitory control over behavior. While a person initially chooses to takedrugs, over time the effects of prolonged exposure on brain functioningcompromise that ability to choose, and seeking and consuming the drug becomecompulsive, often eluding a person's self-control or willpower. Because drugabuse and addiction have so many dimensions and disrupt so many aspects of anindividual's life, treatment is not simple. Addiction treatment must help theindividual stop using drugs, maintain a drug-free lifestyle, and achieveproductive functioning in the family, at work, and in society. Patientstypically require long-term or repeated episodes of care to achieve the ultimategoal of sustained abstinence and recovery of their lives.About GABAB Activation and ADX71441Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family Cclass of GPCR, is clinically & commercially validated. Generic GABAB receptoragonist, baclofen, is marketed for spasticity and some spinal cord injuries, andused for overactive bladder (OAB), but is not commonly used due to variety ofside effects of the drug and rapid clearance. ADX71441 is a potent selectivepositive allosteric modulator (PAM) which potentiates GABA responses at theGABAB receptor. ADX71441 is a novel, first-in-class, oral, small molecules thathas demonstrated excellent preclinical efficacy and tolerability in severalrodent models of pain, anxiety, addiction and OAB and have also proven efficacyin a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441differs from the generic drug baclofen in that it is a positive allostericmodulator rather than an orthosteric agonist at the GABAB receptor. ADX71441only acts when the natural ligand (GABA) activates the receptor, and thereforerespecting the physiological cycle of activation. It has been proposed that PAMsproduce 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; Ahnaou et al).About mGlu4 Activation and ADX88178The metabotropic glutamate receptor 4 (mGlu4) belongs to the Group III mGluRs(Class C G-Protein Coupled Receptor) and is negatively coupled to adenylatecyclase via activation of the Gai/o protein. It is expressed primarily onpresynaptic terminals, functioning as an autoreceptor or heteroceptor and itsactivation leads to decreases in transmitter release from presynaptic terminals.MGlu4 is currently receiving much attention based primarily upon its uniquedistribution in key brain region involved in many CNS disorders. MGlu4 PAM isemerging as a promising target for the treatment of motor and non motor symptomsas well as a disease-modifying agent in Parkinson's disease through a non-dopaminergic approach. Emerging data for other therapeutic indications such asanxiety, multiple sclerosis, neuropathic and inflammatory pain, schizophreniaand diabetes make mGlu4 a highly promising target for both CNS and non CNSdiseases. In particular, anxiety disorders are among the most prevalentpsychiatric disorders in the world. Addex has reported in 2010 that ADX88178demonstrated oral efficacy in two preclinical rodent models of anxiety: themarble burying test in mice and EPM in mice and rats. The mGlu4-mediatedspecific effect has been also confirmed in knock-out mice. Therefore, mGlu4activators may represent a new generation of anxiolytic therapeutics. Morerecently, mGlu4 PAM PHCCC demonstrated efficacy in a neuroinflammation model,the remitting-relapsing EAE model, by promoting regulatory T-cell (Treg)formation and reverse pro-inflammatory T-cell release. Therefore, positivemodulation of mGlu4 could potentially stop the destruction of myelin in MS in arobust and durable manner.About Addex TherapeuticsAddex Therapeutics ( is a development stage companyfocused on advancing innovative oral small molecules against rare diseasesutilizing its pioneering allosteric modulation-based drug discovery platform.The Company's two lead products are being investigated in Phase 2 clinicaltesting: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is beingdeveloped by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allostericmodulator or PAM) is being developed in collaboration with JanssenPharmaceuticals, Inc., to treat both schizophrenia and anxiety as seen inpatients suffering from major depressive disorder. Addex also has severalpreclinical programs including: GABAB receptor positive allosteric modulator(PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients withmultiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4PAM for MS, Parkinson's disease, anxiety and other diseases. Allostericmodulators are an emerging class of small molecule drugs which have thepotential to be more specific and confer significant therapeutic advantages overconventional "orthosteric" small molecule or biological drugs. The Company usesits proprietary discovery platform to target receptors and other proteins thatare recognized as essential for the therapeutic modulation of important diseaseswith unmet medical needs.Tim DyerChief Executive OfficerAddex Therapeutics+41 22 884 1561PR@addextherapeutics.comDisclaimer: The foregoing release may contain forward-looking statements thatcan be identified by terminology such as "seek", "not pursue", "not approvable","continue", "believes", "believe", "will", "remained open to exploring","would", "could", or similar expressions, or by express or implied discussionsregarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, itsbusiness, the potential approval of its products by regulatory authorities, orregarding potential future revenues from such products. Such forward-lookingstatements reflect the current views of Addex Therapeutics regarding futureevents, future economic performance or prospects, and, by their very nature,involve inherent risks and uncertainties, both general and specific, whetherknown or unknown, or any other factor that may materially differ from the plans,objectives, expectations, estimates and intentions expressed or implied in suchforward-looking statements. Such factors may in particular cause actual resultswith allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutictargets to be materially different from any future results, performance orachievements expressed or implied by such statements. There can be no guaranteethat Addex Therapeutics will complete the restructuring and reduction of itsliabilities or any financing nor that allosteric modulators of mGlu2, mGlu4,mGlu5, GABA-BR or other therapeutics targets will be approved for sale in anymarket or by any regulatory authority. Nor can there be any guarantee thatallosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutictargets will achieve any particular levels of revenue (if any) in the future. Inparticular, management's expectations regarding allosteric modulators of mGlu2,mGlu4, mGlu5, GABA-BR or other therapeutic targets could be affected by, amongother things, unexpected actions by our partners, unexpected regulatory actionsor delays or government regulation generally; unexpected clinical trial results,including unexpected new clinical data and unexpected additional analysis ofexisting clinical data; competition in general; government, industry and generalpublic pricing pressures; the company's ability to obtain or maintain patent orother proprietary intellectual property protection. Should one or more of theserisks or uncertainties materialize, or should underlying assumptions proveincorrect, actual results may vary materially from those anticipated, believed,estimated or expected. Addex Therapeutics is providing the information in thispress release as of this date and does not undertake any obligation to updateany forward-looking statements contained in this press release as a result ofnew information, future events or otherwise, except as may be required byapplicable laws.[HUG#1740130]