Addex Receives Approval to Initiate a Phase 1, First–In-Man, Clinical Study for ADX71441
ADX71441, a novel oral small molecule GABA-B receptor positive allosteric modulator, on track to initiate clinical testing in first half of 2013 and to deliver top-line safety, PK and biomarker data by year end
Geneva, Switzerland, 24 April 2013 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today that the regulatory authorities in the Netherlands have approved the clinical trial application (CTA) to initiate a Phase 1 study of ADX71441, a GABA-B receptor positive allosteric modulator (PAM). The Company plans to initiate clinical testing at the Centre of Human Drug Research in Leiden, in the first half of 2013 and expects to deliver top-line safety, pharmacokinetic and biomarker data by year end. Addex previously announced achievement of positive Proof of Concept for ADX71441 in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A) neuropathy as well as a number of other disease indications. The Company plans to move quickly to Phase 2a testing of ADX71441 for the treatment of CMT1A, an orphan disease, in 2014. The CTA was submitted to the authorities in March 2013.
“We are delighted to receive this approval for ADX71441 and to be able to initiate clinical development of this exciting molecule,” said Sonia Poli, Ph.D., Vice President, Translational Sciences and Project Leader for the ADX71441 program at Addex. “We believe the speed at which the Dutch authorities approved the CTA attests to the quality of our preclinical data and related material. We plan to seek orphan drug designation for this compound in the treatment of CMT1A and attempt to take advantage of a rapid development and regulatory path to market.”
ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically and commercially validated in several indications including spasticity, overactive bladder (OAB), spinal cord injuries and gastroesophageal reflux disease. However, generic GABA-B receptor agonists are not commonly used in certain disorders due to compliance-limiting drug side effects, receptor sensitization, rebound effect and rapid clearance. An oral once-daily small molecule activator of GABA-B receptor without the issues associated with the current GABA-BR agonists could dramatically change the treatment paradigm for a number of diseases. Allosteric modulation is ideally suited to overcome such limitations of an agonist. ADX71441 has shown efficacy in multiple preclinical models including: CMT1A, OAB, pain, obsessive-compulsive disorder, alcohol binge drinking and anxiety. The United States Patent and Trademark Office recently granted Addex a composition of matter patent covering ADX71441 and other GABA-B receptor PAMs. The claims of the issued patent also cover pharmaceutical composition and method of treatment using such GABA-BR PAMs.
“This is an important accomplishment for the company as we continue to execute on our strategy to focus on the clinical development of novel compounds to treat orphan diseases,” said Graham Dixon, Ph.D., Chief Scientific Officer at Addex. “With this CTA approval, our pipeline consists of four Phase 2 programs, one Phase 1 program and one preclinical program which we hope to advance to Phase 1 testing by the end of next year. This robust pipeline represents multiple, strong value drivers which we believe have the potential to generate significant shareholder value.”
About Charcot-Marie-Tooth 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, including being wheelchair bound, and is often accompanied by severe cases of neurological pain. There is no known cure for this incapacitating disease. Data obtained with ADX71441 and a GABA-BR agonist seems to suggest that positive modulation of the GABA-B receptor could lower toxic PMP22 overexpression and potentially delay the progression of the disease and offer a unique therapeutic opportunity for CMT1A patients.
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 (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 is also advancing several preclinical programs including: GABA-BR 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.
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Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "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, and/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 may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR 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 allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR 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-BR 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-BR 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.