Addex and University of Geneva Collaborators Awarded Swiss Grant to Profile Addex TrkB Allosteric Modulators as Neuroprotective Agents
Geneva, Switzerland, 15 December 2015 – Addex Therapeutics (SIX: ADXN), a leading company pioneering allosteric modulation-based drug discovery and development announced today that it has been awarded a CHF440,762 grant from the Swiss Commission for Technology and Innovation (CTI) to advance the characterization of novel tyrosine receptor kinase subtype B (TrkB) positive allosteric modulators (PAM) in preclinical models of neurodegenerative diseases. Addex will collaborate over a period of 2 years with the group of Prof. Karl-Heinz Krause from The University of Geneva Medical Center (CMU). The project will characterize Addex unique and selective TrKB PAM’s in Professor Krause’s group’s battery of highly specialized and well recognized in vitro, ex vivo and in vivo models of neurodegeneration.
"TrkB is a very exciting target for neurodegeneration and having access to Addex selective TrkB PAMs offer a unique opportunity for us to demonstrate the quality of our neurodegeneration models" commented Prof. Karl-Heinz Krause. "We very much look forward to collaborating with Addex discovery group and helping them advance this promising program.”
“Collaborating with Professor Krause’s laboratory, a recognized center of excellence in neurodegeneration, will provide Addex with invaluable information to help us advance our TrkB PAM program toward clinical candidate selection,” commented Dr Robert Lütjens, Head of Discovery at Addex. “Addex TrkB PAM were discovered using our proprietary allosteric modulator discovery platform and represent the first selective small molecules for this exciting target.”
“This collaboration and CTI grant represents another example of how we are executing our strategy to advance our leading allosteric modulator discovery programs forward with non-dilutive funding,” commented Tim Dyer, CEO at Addex.
About TrkB and Addex TrkB PAMS
Tyrosine receptor kinase B is the high affinity catalytic receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3). As such, TrkB mediates the multiple effects of these neurotrophic factors which include supporting the survival of existing neurons as well as helping growth and differentiation of new neurons and synapses. While the identification of small molecule BDNF agonists has remained elusive, allosteric modulation represents probably the only approach to enhance TrkB activation. Addex has identified several novel chemical series of TrkB positive allosteric modulators (PAM) from a high through put screening of its proprietary screening platform. The compounds identified by Addex therefore constitute unique starting points for the discovery of a small molecule equivalent of BDNF, which could potentially be used as a neuroprotective treatment for several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s Disorders and Amyotrophic Lateral Sclerosis.
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for neurological disorders. Addex lead drug candidate, dipraglurant (mGluR5 negative allosteric modulator or NAM) has successfully completed a Phase IIa POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter Phase III for PD-LID. In parallel, dipraglurant’s therapeutic use in dystonia is being investigated. Addex second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for Epilepsy. Addex also has several preclinical programs including: ADX71441 (GABAB receptor PAM) which has received regulatory approval to start Phase I and is being investigated for therapeutic use in Charcot-Marie-Tooth (Type 1A) disease, alcohol use disorder and nicotine dependence; mGluR4PAM for drug abuse and dependence, Parkinson’s disease and other neurodegenerative diseases; mGluR2NAM for treatment resistant depression and cognitive deficits; mGluR7NAM for psychosomatic disorders, TrkBPAM for neurodegenerative disorders; and GLP1PAM 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. Addex allosteric modulator drug discovery platform targets receptors and other proteins that are recognized as essential for therapeutic intervention – the Addex pipeline was generated from this pioneering allosteric modulator drug discovery platform.
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