Addex Therapeutics and Collaborators Awarded Swiss CTI Grant to Develop Allosteric Modulators for Neurodegenerative and Psychiatric Diseases
Published: Oct 02, 2012
GENEVA, SWITZERLAND--(Marketwire - October 02, 2012) - Grant to Further Characterize Allosteric Modulators Against mGluR4 and mGluR7
Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based oral small molecule drug discovery and development, announced today that it has been awarded a CHF700,000 grant from the Swiss Commission for Technology and Innovation (CTI) to develop allosteric modulator therapeutics for neurodegenerative and psychiatric diseases. Addex will collaborate with the Center for Psychiatric Neuroscience at the University of Lausanne and at the Laboratory for the Study of Neurodegenerative Diseases (LEN) at Ecole Polytechnique Fédérale de Lausanne (EPFL).
The objective of the project is the characterization and optimization of potent and selective allosteric modulators targeting Group III of metabotropic glutamate receptors, mGluR4 and mGluR7. Drug candidates targeting mGluR4 will be assessed in animal models replicating human Parkinson's disease. Electrophysiological studies will be carried out with allosteric modulators targeting both mGluR4 and mGluR7 to investigate their role in modulating synaptic transmission. Data from the project will contribute to the selection of the best candidate compounds for clinical development.
"We are thrilled by this opportunity to collaborate with Addex, a leader in allosteric modulator discovery, and to help advance these two exciting neuroscience programs" commented Dr Ron Stoop, Center for Psychiatric Neuroscience at the University of Lausanne. "Testing Addex proprietary compounds in our models will bring essential understanding of the significant role mGluR4 and mGluR7 may play in a number of important human diseases."
Addex is currently characterizing a number of novel, selective, orally available mGluR4 positive allosteric modulators (PAMs), which have demonstrated efficacy in several different rodent models of Parkinson's disease, anxiety and most recently in the industry standard neuroinflammation model of multiple sclerosis, the Relapsing-Remitting Experimental Allergic Encephalomyelitis (RR-EAE) model. Addex is currently advancing this lead series towards identification of a clinical candidate compound. The Company's mGluR7 negative allosteric modulator (NAM) program is currently in lead optimization phase where compounds representing multiple chemical series have been shown to be efficacious in animal models of anxiety. There are currently no described mGluR7 NAM compounds and therefore Addex is uniquely positioned to potentially unravel the role of this receptor in the brain.
"This grant will enable us to characterize further the role of mGluR4 and mGluR7, believed to play an important role in several neurodegenerative and psychiatric diseases," explained Dr. Robert Lütjens, Vice-President of Biology at Addex. "Allosteric modulators targeting mGluR4 and mGluR7 have the potential to offer a more precise way to regulate brain function in a number of large unmet medical needs. Working with the world class academic labs of Doctors Ron Stoop (UNIL) and Bernard Schneider (EPFL) will significantly improve our scientific understanding of the mode of action of our compounds."
The mGluR4 belongs to the Group III mGluRs (Class C G-Protein Coupled Receptor) and is negatively coupled to adenylate cyclase via activation of the Gai/o protein. It is expressed primarily on presynaptic terminals, functioning as an autoreceptor or heteroceptor and its activation leads to decreases in neurotransmitter release from presynaptic terminals. The mGluR4 is uniquely distributed in key brain regions involved in multiple CNS disorders. In particular, mGluR4 is abundant in striato-pallidal synapses within the basal ganglia circuitry a key area implicated in movement disorders, like Parkinson's disease. In the immune system mGluR4 has been found on dendritic cells (DCs). Emerging data implicate mGluR4 in multiple indications such as multiple sclerosis, Parkinson's disease, anxiety, neuropathic and inflammatory pain, schizophrenia and diabetes.
The mGluR7 receptor is the most highly conserved of all mGluR subtypes, exhibiting the widest distribution in the brain. It is localized pre- synaptically at a broad range of glutamatergic and GABAergic synapses and is thought to be one of the most important mGluR subtypes in regulating CNS function. Preclinical data suggest that mGluR7 antagonism could alleviate stress-related anxiety and depressive symptoms and deficits in amygdala- dependent behaviors (fear response and conditioned taste aversion). These data are consistent with the abundant localization of mGluR7 in brain regions involved in the control of fear and emotion.
Addex Therapeutics (www.addextherapeutics.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, 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 address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (ADX48621, an mGluR5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed by our partner Janssen Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients suffering from major depressive disorder. Addex also is advancing several preclinical programs including: GABABR PAM for overactive bladder and other disorders; mGluR4 PAM for Parkinson's, MS, anxiety and other diseases. In addition, Addex is applying its proprietary discovery platform to identify highly selective and potent allosteric modulators of a number of both GPCR and non-GPCR targets that are implicated in diseases of significant unmet medical need.
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 mGluR2, mGluR4, mGluR5, GABABR 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 mGluR2, mGluR4, mGluR5, GABABR 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 mGluR2, mGluR4, mGluR5, GABABR 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 mGluR2, mGluR4, mGluR5, GABABR 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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