GENEVA, Switzerland, Oct. 3, 2013 (GLOBE NEWSWIRE) --
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today that ADX71441 dose dependently reduced PMP22 expression comparable to baclofen in a preclinical transgenic model of Charcot-Marie-Tooth 1A disease (CMT1A). ADX71441 was studied in the transgenic CMT1A rat model which displays a 1.6-fold PMP22 overexpression (mRNA level) and exhibits clinical abnormalities, such as reduced nerve conduction velocity and lower grip strength that closely mimic findings in CMT1A patients. In a 5 day comparative study with baclofen, a dose- response was successfully established for orally administered ADX71441. ADX71441 given orally once daily significantly reduced PMP22 mRNA expression at 3 mg/kg and 6 mg/kg (0.98-fold±0.49 and 0.93-fold±0.35, respectively). Baclofen given orally twice daily reduced PMP22 mRNA expression at 3mg/kg (0.91-fold±0.25). ADX71441 did not significantly reduced PMP22 mRNA expression at 1mg/kg (1.48- fold±0.26) compared to CMT vehicle group (1.6-fold±0.19). "These findings in the CMT1A transgenic rat model which show that ADX71441 has comparable efficacy to Baclofen are very promising," Professor Michael Sereda, of the Max-Planck Institute of Experimental Medicine, Göttingen, Germany, in whose laboratories the study was performed. "These results are consistent with previous reported data which suggest that intraperitoneal application of ADX71441 could lower toxic PMP22 overexpression and potentially delay the progression of the disease. Oral application of ADX71441 may therefore offer a unique therapeutic opportunity for CMT1A patients." 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 wheel chair-boundness and is often accompanied by severe cases of neurological pain. There is no known cure for this incapacitating disease. About GABA-B Activation and ADX71441 Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically & commercially validated. Generic GABA-B receptor agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and used for OAB, but is not commonly used due to severe side effects of the drug and rapid clearance. ADX71441 is a potent selective positive allosteric modulator (PAM) which potentiates GABA responses at the GABA-B receptor. ADX71441 is a novel, first-in-class, oral, small molecules that has demonstrated excellent preclinical efficacy and tolerability in several rodent models of pain, anxiety, addiction and overactive bladder (OAB) and have 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 GABA-B 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 Addex Therapeutics Addex Therapeutics ( www.addextherapeutics.com ) is a development stage company focused on advancing innovative oral small molecules against rare diseases 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 rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc., to treat both schizophrenia and anxiety as seen in patients suffering from major depressive disorder. Addex also has several preclinical programs including: GABA-B positive allosteric modulator (PAM) for Charcot-Marie-Tooth (Type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for MS, Parkinson's disease, anxiety and other diseases. 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. Tim Dyer Chief Executive Officer Addex Therapeutics +41 22 884 1561 PR@addextherapeutics.com Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "seek", "not pursue", "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such factors may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Addex Therapeutics will complete the restructuring and reduction of its liabilities or any financing nor that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws. [HUG#1733348]
