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Addex and the Charcot-Marie-Tooth Association enter collaboration to advance ADX71441 in Charcot-Marie-Tooth 1A disorder

 

Geneva, Switzerland, 21 October 2014 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today entering a collaboration with the Charcot-Marie-Tooth Association (CMTA) to evaluate the pharmacology of ADX71441, a GABA-B receptor positive allosteric modulator (PAM) in a battery of preclinical models of Charcot-Marie-Tooth 1A disorder (CMT1A), a rare hereditary motor and sensory demyelinating peripheral neuropathy.

The CMTA consortium will evaluate the efficacy of ADX71441 as a pharmacological agent in preclinical neurological and behavioral models of CMT1A and will assess the potential of ADX71441 to impede the development of motor and sensory control defects associated with normal disease progression.

Patrick Livney, CEO of the CMTA notes: “The Foundation has assembled the scientific and clinical key opinion leaders in CMT disorders, and the research tools necessary to validate therapeutic opportunities for their clinical potential. We have set out to engage drug makers to work together with the CMTA to advance new therapeutic approaches to our patients, and our STAR network that combines this world class research expertise with an operational capability has been highly enabling to the formation of collaborative alliances for this purpose. Currently, there are no therapies for the different CMT disorders to halt either the onset or progression of the disease. This Addex collaboration represents an exciting opportunity for the CMTA to both de-risk and accelerate development of a novel drug class for the treatment of CMT1A, the most prevalent of the genetic neuropathies.”

“CMTA and its network of experts have made significant contributions to our understanding of the underlying pathology of CMT disorders and have coordinated development and validation of a large battery of preclinical models.  The profiling of ADX71441 will provide Addex with invaluable information for its further development.” said Tim Dyer, CEO at Addex. “This is our first collaboration with CMTA and another example of us executing our strategy to advance our pipeline through collaborations with patient advocacy groups.”
 
Both clinical and pre-clinical data suggest that activation of GABA-B receptors offers a unique therapeutic opportunity to address the needs of patients with CMT1A. Addex has previously announced a positive proof of concept in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A) with ADX71441 (press release 7 January & 3 October 2013), confirming previous observations obtained using a GABA-B receptor agonist and the GABAB1-/- knock-out mice. This model identified the importance of GABA-B receptors in inhibiting proliferation and reduction of synthesis of specific myelin proteins, in particular, in lowering the toxic PMP22 overexpression, which in turn, may delay disease progression.

About Charcot Marie Tooth Disease Type 1A (CMT1A)
CMT1A is a rare (1:5,000) hereditary motor and sensory demyelinating peripheral neuropathy (also known as Hereditary Motor and Sensory Neuropathy, HMSN) which is caused by an intrachromosomal duplication and consecutive toxic overexpression of the PMP22 gene on chromosome 17. CMT1A is one of the most common inherited peripheral nerve-related disorders which is passed down through families in an autosomal dominant fashion. CMT1A disease becomes evident in young adulthood and slowly progresses with distally pronounced muscle weakness and numbness. Pain can range from mild to severe. The disease can be highly debilitating with patients becoming wheel chair-bound and is often accompanied by severe cases of neurological pain. There is no known cure for this incapacitating disease.

About GABAB Activation and ADX71441
Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically & commercially validated. Generic GABAB receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for overactive bladder (OAB), but is not commonly used due to a variety of side effects of the drug and rapid clearance. 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 has demonstrated excellent preclinical efficacy and tolerability in several rodent models of pain, anxiety, addiction and OAB and has also proven efficacy in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441 differs from the generic drug baclofen in that it is a positive allosteric modulator rather than an orthosteric agonist at the GABAB receptor. ADX71441 only acts when the natural ligand (GABA) activates the receptor, and 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 (May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona et al. 2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al).

About Charcot-Marie-Tooth Association
The Charcot-Marie-Tooth Association (CMTA) is a registered 501c3 dedicated to serving an international patient community that suffers from rare and disabling neuropathies of genetic origin (http://www.cmtausa.org ).  The Foundation directly engages its STAR scientific and clinical research network in the identification, validation and clinical development of therapies for the different Charcot-Marie-Tooth disorders.

Patrick Livney, CEO
Charcot-Marie-Tooth Association
Tel: +1-312.750.9800
Email: pal(at)cmtausa.org
 
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a discovery and development stage company focused on advancing innovative oral small molecules utilizing its pioneering allosteric modulation-based drug discovery platform. The Company’s two lead products are being investigated in Phase 2 clinical testing: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson’s disease levodopa-induced dyskinesia (PD-LID) and dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. Addex also has several preclinical programs including: GABAB receptor positive allosteric modulator (PAM) for addiction, Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder, autism and other disorders; mGlu4 PAM for MS, Parkinson’s disease, anxiety and other diseases; mGlu2 NAM for treatment resistant depression and cognitive deficits; mGlu7 NAM for psychosomatic disorders, TrkB PAM for neurodegenerative disorders; and GLP1 PAM 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. The Company uses its proprietary discovery platform to target receptors and other proteins that are recognized as essential for the therapeutic modulation of important diseases with unmet medical needs. The Company is currently focused on preserving the value of its assets, including the intellectual property surrounding its portfolio of allosteric modulator drug candidates and its proprietary allosteric modulator technology platform, while pursuing a strategy to secure the resources necessary to advance the pipeline and maximize value for shareholders. In parallel the Company continues to enter collaborations with academic institutions, government organizations and patient advocacy groups to advance its portfolio of drug candidates for the benefit of patients.

Tim Dyer, Chief Executive Officer
Addex Therapeutics
Telephone: +41 22 884 15 61
PR(at)addextherapeutics.com

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.

 

 

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-

Dyskinesia: Hope on the Horizon

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Soutien américain au biotech à Genève

ADDEX.Le titre a bénéficié d'un regain d'intérêt des investisseurs outre-Atlantique.
La direction plaide encore la sous-évalutation.

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- Seminal Research Provides Greater Insight into the Role of Selective mGluR4 Modulation on Motor Symptoms