Geneva, Switzerland, 31 January 2017 - Addex Therapeutics (SIX: ADXN) announced today that The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded the Company an $835,000 grant towards the discovery and development of tyrosine receptor kinase B (TrkB) positive allosteric modulators (PAMs) as potential novel treatments for Parkinson’s disease.
“We are honored to receive this award from MJFF, representing an important validation of both the capabilities of Addex’ proprietary allosteric modulation platform and the quality of our TrkB PAM program,” said Tim Dyer, CEO of Addex. “This is yet another example of our successful strategy to collaborate with important patient advocacy organizations to advance Addex portfolio of allosteric modulators for the potential future benefit of patients.”
“Supporting research that can potentially protect the brain cells affected by Parkinson’s disease is an important priority area at MJFF,” said Marco Baptista, PhD, MJFF director of research programs. “The development of such a therapy would be life changing for the millions living with or at risk for this disease. The Addex allosteric modulator discovery platform has identified promising TrkB PAM compounds toward that goal, and we look forward to its continued progress.”
“The success of our allosteric modulation platform to discover highly selective small molecule TrkB PAMs is an important step towards developing a drug candidate for this drug target that has significant potential in the field of neurodegeneration, including Parkinson’s disease,” said Robert Lutjens, Head of Discovery at Addex. “The Addex TrkB PAM program is an excellent demonstration of the broad potential of Addex proprietary biology and chemistry capabilities for identifying and optimizing allosteric modulators across diverse classes of drug targets.”
TrkB is the high-affinity receptor for neurotrophins, including Brain Derived Neurotrophic Factor (BDNF), which is involved in processes such as neurogenesis, neuronal survival and differentiation. Identifying small molecules that directly act on TrkB has remained elusive, until now. Allosteric modulation has demonstrated the potential to enhance TrkB activation. Addex has identified unique TrkB PAM starting points from its allostery-biased corporate library of small molecules, using its proprietary biological screening tools. The funds awarded by MJFF will support the necessary biology and chemistry efforts required to deliver compounds with characteristics allowing testing in invivo models of Parkinson’s disease, which represents an important initial step towards the development of a new treatment.
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, 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 of TrkB may be the most promising approach. Addex has identified several novel chemical series of TrkB PAM from a high through put screening using its proprietary screening platform. The compounds identified by Addex represent 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 including Parkinson’s disease.
The Michael J. Fox Foundation is the world’s largest nonprofit funder of Parkinson’s research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson’s disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson’s patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $650 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson’s research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson’s disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson’s awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.
Addex Therapeutics (www.addextherapeutics.com) is a biopharmaceutical company focused on the development of novel, orally available, small molecule allosteric modulators for neurological disorders. 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’s 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. Addex’s lead drug candidate, dipraglurant (mGluR5 negative allosteric modulator or NAM) has successfully completed a Phase 2a POC in Parkinson’s disease levodopa-induced dyskinesia (PD-LID), and is being prepared to enter registration trials for PD-LID with support from the Michael J. Fox Foundation for Parkinson’s Research (MJFF). In parallel, dipraglurant’s therapeutic use in dystonia is being investigated with support from the Dystonia Medical Research Foundation (DMRF). Addex’s second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc for epilepsy. In addition, ADX71441 (GABAB receptor PAM) has received regulatory approval to start Phase 1 and is being investigated for its therapeutic use in Charcot-Marie-Tooth Type 1A disease (CMT1A), cocaine and alcohol use disorder and nicotine dependence. Discovery programs include mGluR4PAM, mGluR7NAM, TrkBPAM and mGluR3NAM & PAM.
