Review from Linköping University Published in Alcohol and 
Alcoholism Journal 
 
   Geneva, Switzerland, February 16, 2021 -- 
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Addex Therapeutics (SIX: ADXN and Nasdaq: ADXN), a clinical-stage 
pharmaceutical company pioneering allosteric modulation-based drug 
discovery and development, today announced that a review published in 
https://www.globenewswire.com/Tracker?data=bPTLX2Q6bgY5gPWPkfveNh-FpGZ6n7zXWUZdT0r9ScB9e753fS_PX2ojTLbemv-tC0ZyAvkRNpSokXXE1aP83VuAylW-UO5TWrhZ9V1McvjdlFo-ob-n4cJW7ymHC2KCuj9kyKqDTUNzGJE3YBSUG6ae2rICDUl-pMYd_i9XERp44znN65i2dtZJGGT1JwEG 
Alcohol and Alcoholism suggests that positive allosteric modulators 
(PAMs) of the gamma-aminobutyric acid B (GABA(B) ) receptor could offer 
a new treatment option for patients with severe alcohol use disorder 
(AUD). Direct, orthosteric, GABA(B) receptor agonists, such as baclofen, 
have been shown to attenuate addiction-related behaviors in preclinical 
studies. However, the therapeutic use of baclofen is very limited due to 
significant side-effects, including sedation, drowsiness and sleepiness. 
 
   Following analysis of a number of studies, the review emphasized that 
all preclinical behavioral results have shown the efficacy of GABA(B) 
PAMs for addiction treatment and offer similar mechanistic and 
therapeutic effects, while avoiding the tolerance and toxicity issues 
associated with baclofen. In particular, Addex's GABA(B) PAM, ADX71441, 
demonstrated efficacy on several alcohol-related behaviors in rat 
models. ADX71441 potently decreased binge-like drinking, reduced 
relapse-like drinking, and dose-dependently reduced alcohol 
self-administration as well as decreasing motivation to consume alcohol. 
These data support the hypothesis of GABA(B) PAMs offering a better and 
broader approach to address alcoholism symptoms. The high translational 
value of these preclinical studies strongly supports clinical testing of 
GABAB PAMs. 
 
   "The groundbreaking work carried out with ADX71441 in alcohol and other 
addiction disorders has laid a solid foundation supporting the 
development of our GABA(B) PAMs as novel treatment for addiction 
disorders. This review shows the growing body of research in this field 
and summarises data suggesting that the effects seen in preclinical 
models of AUD could translate to humans," said Robert Lütjens, Head 
of Discovery Biology of Addex. "Our research collaboration with Indivior 
evaluating new GABA(B) PAMs in addiction is progressing rapidly, with an 
aim to begin clinical studies in 2022." 
 
   Relevant publications: 
 
   Augier E. (2021) Recent Advances in the Potential of Positive Allosteric 
Modulators of the GABAB Receptor to Treat Alcohol Use Disorder. Alcohol 
and Alcoholism, 1--11; doi: 10.1093/alcalc/agab003 
 
   Hwa LS, Kalinichev M, Haddouk H, et al. (2014) Reduction of excessive 
alcohol drinking by a novel GABAB receptor positive allosteric modulator 
ADX71441 in mice. Psychopharmacology 231:333--43. 
 
   Augier E, Dulman RS, Damadzic R, et al. (2017) The GABAB positive 
allosteric modulator ADX71441 attenuates alcohol self-administration and 
relapse to alcohol seeking in rats. Neuropsychopharmacology 42:1789--99. 
 
   About GABA(B)  Activation with PAM 
 
   Activation of the GABA(B) receptor, a Family C class of GPCR, is 
clinically and commercially validated. The generic GABA(B)  receptor 
agonist, baclofen, is marketed for spasticity and some spinal cord 
injuries, and is used for overactive bladder (OAB), but it is not 
commonly used due to a variety of side effects of the drug and rapid 
clearance. Potent, selective oral positive allosteric modulators (PAM) 
that potentiate GABA responses at the GABA(B)  receptor, rather than an 
orthosteric agonist at the GABA(B) receptor, like baclofen, only act 
when the natural ligand (GABA) activates the receptor, therefore 
respecting the physiological cycle of activation. It has been proposed 
that PAMs produce less adverse effects and could 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., 2015). 
 
   About Addex Therapeutics 
 
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Addex Therapeutics is a clinical-stage pharmaceutical company focused on 
the development and commercialization of an emerging class of novel 
orally available small molecule drugs known as allosteric modulators for 
neurological disorders. Allosteric modulators offer several potential 
advantages over conventional non-allosteric molecules and may offer an 
improved therapeutic approach to conventional "orthosteric" small 
molecule or biological drugs. Addex's allosteric modulator drug 
discovery platform targets receptors and other proteins that are 
recognized as essential for therapeutic intervention. Addex's lead drug 
candidate, dipraglurant (mGlu5 negative allosteric modulator or NAM), is 
poised to start  a pivotal registration clinical trial for Parkinson's 
disease levodopa induced dyskinesia (PD-LID) in H1 2021. Addex is also 
investigating dipraglurant's therapeutic use in blepharospasm (a type of 
dystonia), for which a clinical trial is expected to be initiated in H1 
2021. Addex's third clinical program, ADX71149 (mGlu2 positive 
allosteric modulator or PAM), developed in collaboration with Janssen 
Pharmaceuticals, Inc, is scheduled to enter a phase 2a proof of concept 
clinical study for the treatment of epilepsy in Q2 2021. Addex's GABA(B) 
PAM program has been licensed to Indivior PLC who are focused on 
development for the treatment of addiction. Preclinical programs include 
GABA(B)  PAM for CMT1A, mGlu7 NAM for PTSD, mGlu2 NAM for mild 
neurocognitive disorders, mGlu4 PAM for Parkinson's disease and mGlu3 
PAM for neurodegenerative disorders. Addex is listed on the SIX Swiss 
Exchange and the NASDAQ Capital Market and trades under the ticker 
symbol "ADXN". 
 
   Press Contacts: 
 
 
 
 
Tim Dyer                                                          Mike Sinclair 
 Chief Executive Officer                                           Partner, Halsin Partners 
 Telephone: +41 22 884 15 55                                       +44 (0)20 7318 2955 
 Email: mailto:PR@addextherapeutics.com PR@addextherapeutics.com   mailto:msinclair@halsin.com msinclair@halsin.com 
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   Forward Looking Statements 
 
   Certain statements made in this announcement are forward-looking 
statements. These forward-looking statements are not historical facts 
but rather are based on the Company's current expectations, estimates, 
and projections about its industry; its beliefs; and assumptions. Words 
such as 'anticipates,' 'expects,' 'intends,' 'plans,' 'believes,' 'seeks, 
' 'estimates,' and similar expressions are intended to identify 
forward-looking statements. These statements are not guarantees of 
future performance and are subject to known and unknown risks, 
uncertainties, and other factors, some of which are beyond the Company's 
control, are difficult to predict, and could cause actual results to 
differ materially from those expressed or forecasted in the 
forward-looking statements. The Company cautions securityholders and 
prospective securityholders not to place undue reliance on these 
forward-looking statements, which reflect the view of the Company only 
as of the date of this announcement. The forward-looking statements made 
in this announcement relate only to events as of the date on which the 
statements are made. The Company will not undertake any obligation to 
release publicly any revisions or updates to these forward-looking 
statements to reflect events, circumstances, or unanticipated events 
occurring after the date of this announcement except as required by law 
or by any appropriate regulatory authority. 
 
 
 
 
 
 

(END) Dow Jones Newswires

February 16, 2021 01:00 ET (06:00 GMT)