Addex Identifies New Potential Use of mGlu7 receptor NAMs to Treat Stress-Induced Visceral Pain
Geneva, Switzerland 3 June 2015 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today the publication of results obtained in collaboration with Professor John Cryan, University College Cork, Ireland, in the journal Neurobiology of Stress*. The collaboration has demonstrated the efficacy of ADX71743, a negative allosteric modulator (NAM) of the metabotropic glutamate receptor subtype 7 (mGlu7 receptor), in a rat model of stress-sensitive visceral hypersensitivity, representing the first pharmacological study to implicate mGlu7 receptor in visceral pain processes.
The Wistar Kyoto (WKY) rat strain has been characterized with a high-anxiety, and visceral hypersensitivity phenotype. It has been extensively used in the past years by Prof Cryan’s group to investigate the brain-gut axis. ADX71743 has already shown compelling results in animal models of anxiety**.
“Our data shows that mGlu7 receptor NAMs may represent an effective and novel approach in the pharmacological treatment of stress-induced visceral pain” said Prof. Cryan. “This is an exciting step forward in the validation of a potential utility of mGlu7 receptor NAM in an area of significant unmet medical need.”
"This collaboration is another example of Addex strategy to drive forward its discovery pipeline through collaboration with academic institutions." said Tim Dyer, CEO of Addex. “Addex allosteric modulator platform has identified unique compounds in the mGlu7 receptor NAM field and these data encourage us to move rapidly towards identifying a clinical candidate for further development.”
* Moloney et al., 2015. Neurobiology of Stress. 2:28-33
** Kalinichev et al. 2013. J Pharmacol Exp Ther. 344(3):624-36
About mGlu7 receptor and Visceral Pain
mGlu7 receptor is a subtype of the metabotropic glutamate receptor family, a group of eight G protein-coupled receptors involved in modulation of glutamatergic neurotransmission. Its low affinity for glutamate and its presynaptic expression suggests a negative autoreceptor role, being activated when excessive glutamate concentrations are reached in the synapse. With the discovery of ADX71743, a selective, orally available mGlu7 receptor NAM, it has been possible to investigate the function of this receptor in more details and to validate its therapeutic potential for CNS disorders, in particular stress-related disorders. There is a wealth of information relating to mechanisms underlying visceral pain, and excessive glutamatergic signaling has been implicated. Stress has been shown to be a critical factor in visceral pain pathophysiology, both in terms of increasing the risk to develop visceral hypersensitivity, and as an exacerbating or perpetuating factor. Functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS) are typified by heightened visceral sensitivity as well as altered bowel movements and bloating. Stressful life events both early in life and in adulthood have long been implicated in the pathophysiology of IBS. Visceral hypersensitivity means a general increase in pain sensation experienced in internal organs and is common in IBS sufferers. Current pharmacological treatments are not directly targeting visceral hypersensitivity and this indication remains a significant unmet medical need.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for central nervous system disorders. Addex lead drug candidate, dipraglurant (mGlu5 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 Phase 2B for PD-LID. In parallel, dipraglurant’s therapeutic use in dystonia and treatment resistant depression is being investigated. Addex second clinical program, ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. Addex also has several preclinical programs including: ADX71441 (GABAB receptor PAM) which has received regulatory approval to start Phase 1 and is being investigated for therapeutic use in Charcot-Marie-Tooth (Type 1A) disease, alcohol use disorder and nicotine dependence; mGlu4PAM for drug abuse and dependence, Parkinson’s disease and other neurodegenerative diseases; mGlu2NAM for treatment resistant depression and cognitive deficits; mGlu7NAM for psychosomatic disorders, TrkBPAM for neurodegenerative disorders; and GLP1PAM for type 2 diabetes. 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 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.
Chief Executive Officer
Telephone: +41 22 884 15 61
Disclaimer / Forward-looking statements: This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Addex Therapeutics Ltd. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.