Addex ADX71441 Demonstrates Statistically Signific

Geneva, Switzerland, 9 January 2017 - Addex Therapeutics (SIX: ADXN), announced today that ADX71441, a positive allosteric modulator (PAM) of the gamma-aminobutyric acid subtype B (GABAB) receptor demonstrated statistically significant efficacy in a highly translational preclinical model of chronic osteoarthritis pain.

ADX71441 and celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug were studied in the monosodium iodoacetate (MIA) model of chronic osteoarthritis pain for their anti-hyperalgesic effects. ADX71441 at doses of 0.3, 1, 3, and 15 mg/kg orally administered showed statistically significant efficacy 21 days post MIA administration. At 15 mg/kg the effect is similar to that observed with 30 mg/kg of celecoxib (P<0.01).

The study also demonstrated that ADX71943, a more peripherally restricted GABAB PAM compound, was more effective at early stages, presumably when the osteoarthritis pain is at a more inflammatory phase. While ADX71441, the more centrally active compound, was more effective at later stages, presumably when the osteoarthritis pain is at a more chronic neuropathic phase. Details of these data were published in European Journal of Pharmacology (Kalinichev et al, December 2016; available online).

"The efficacy demonstrated by ADX71441 in this chronic pain model, comparable to that obtained with the gold standard celecoxib, strongly supports the use of ADX71441 to treat chronic neuropathic pain," said Robert Lütjens, Head of Discovery at Addex. "ADX71441 has completed preclinical development and is scheduled to start Phase 1 this year."

"This recent publication in the European Journal of Pharmacology is a further demonstration of the quality of the science at Addex," said Tim Dyer, CEO of Addex. "While we focus on advancing ADX71441 in Phase 1 for addiction, we continue to profile other GABAB PAM compounds in multiple indications, including CMT1A neuropathy and pain."

GABAB receptor is clinically & commercially validated. Generic GABAB receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and French health authorities have approved its use for the treatment of alcoholism. Baclofen is also used off label for a number of other indications including overactive bladder (OAB), but its utility is limited due to variety of side effects and rapid clearance, requiring frequent administration of higher doses.

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 demonstrated excellent preclinical efficacy and tolerability in rodent models of pain, anxiety, OAB, alcohol use disorders, nicotine dependence and in a non-human primate model of cocaine use disorder. ADX71441 has also proven efficacy in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441 has a different molecular mechanism from the generic drug baclofen in that it is a positive allosteric modulator, rather than an orthosteric agonist at the GABAB receptor, with a longer half-life, suitable for once daily administration. ADX71441 only acts 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 lead to less tolerance than direct agonists.

Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for neurological disorders. 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's 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. Addex's lead drug candidate, dipraglurant (mGluR5 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 registration trials for PD-LID with support from the Michael J. Fox Foundation for Parkinson's Research (MJFF). In parallel, dipraglurant's therapeutic use in dystonia is being investigated with support from the Dystonia Medical Research Foundation (DMRF). Addex's second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for epilepsy. In addition, ADX71441 (GABAB receptor PAM) has received regulatory approval to start Phase 1 and is being investigated for its therapeutic use in Charcot-Marie-Tooth Type 1A disease (CMT1A), cocaine and alcohol use disorder and nicotine dependence. Discovery programs include mGluR4PAM for neurodegenerative diseases, mGluR7NAM for psychosomatic disorders and TrkBPAM for neurodegenerative disorders which are being advanced in collaboration with the Universities of Lausanne and Geneva under the Swiss CTI grant program; and mGluR3PAM which is being advanced in collaboration with Pierre Fabre Pharmaceuticals.

Contact: Tim Dyer Chief Executive Officer Addex Therapeutics Telephone: +41 22 884 15 61 Email: PR@addextherapeutics.com

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