Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, announced 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 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 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.

"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 programme."

"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 programme 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 programmes forward with non-dilutive funding," commented Tim Dyer, CEO at Addex.