Addex Therapeutics Validates Potential Efficacy Biomarker for Phase 1 Trial of Its GABA-B Positive Allosteric Modulator, ADX71441
Published: May 21, 2013
PLAN-LES-OUATES GENEVA, SWITZERLAND--(Marketwired - May 21, 2013) -
Addex Therapeutics / Addex Validates Potential Efficacy Biomarker for Phase 1 Trial of its GABA-B Positive Allosteric modulator, ADX71441.
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· ADX71441 produced dose-dependent changes on growth hormone (GH) plasma concentrations in a preclinical model
· The data confirms the role of gamma-aminobutyric acid (GABA) in modulating GH plasma concentrations previously reported in humans and animals
· GH plasma concentrations occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction
· ADX71441 on track to initiate Phase 1 testing in H1 2013
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development, announced today that its gamma-aminobutyric acid B (GABA-B) receptor positive allosteric modulator, ADX71441, caused dose dependent changes in growth hormone (GH) plasma concentrations compared to vehicle control in a rodent preclinical model. These data are consistent with published scientific literature demonstrating that GABA, the endogenous neurotransmitter for GABA-B receptors, plays both a stimulatory and inhibitory role in modulating the neuro-endocrine regulation of GH secretion in both animals and humans. GH plasma concentration changes occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction. "The data obtained with ADX71441 demonstrate that growth hormone can be used as a potential biomarker for an efficacy signal and fully supports its inclusion in our first-in-man program," stated Graham Dixon, Ph.D., CSO at Addex. "The use of growth hormone as a biomarker in the Phase 1 will allow us to obtain early information about target engagement, guide dose selection for further clinical development and possibly provide us an understanding of the therapeutic potential of ADX71441."
The study was performed on samples from single oral treatment studies where ADX71441 was given at doses of 5, 20 and 80 mg/kg. Assessment of GH and ADX71441 plasma concentrations were performed at 4 and 24 hours post-treatment. The results demonstrate a direct relationship between plasma concentrations of ADX71441 and effect on GH levels. GH changes occur at doses (< 10 mg/kg) and plasma concentrations (between 300 and 600 ng/mL) that have been shown to induce pharmacological and efficacious effects in several preclinical models, including CMT1A, anxiety, pain, overactive bladder and alcohol addiction.
About ADX71441 and GABAB Activation
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. Generic GABA-B 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 severe side effects of the drug and rapid clearance. Orthosteric GABA-B receptor agonists have also shown clinical validation in gastroesophageal reflux disease (GERD). Addex' GABA-B receptor PAMs have shown efficacy in multiple preclinical models including: CMT1a, OAB, pain, osteoarthritis pain and anxiety.
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.
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, potential efficacy or clinical promise of its products, 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-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.
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