Press Release: Addex GABAB Positive Allosteric Modulator Demonstrates Promise in Alcohol Use Disorder

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

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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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(END) Dow Jones Newswires

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