Addex Pharmaceuticals agreed collaboration and license agreement with pharma company Merck & Co., Inc. to develop drugs for the treatment of Parkinson’s disease and other central nervous system disorders.
The partners will work on allosteric modulators targeting the neurotransmitter glutamate receptor 4 (mGluR4), a target for treating Parkinson’s. The deal includes lead mGluR4 modulators discovered by Addex.
Current treatments for the disease focus on dopamine replacement strategies. However most patients reach a stage where these treatments are no longer effective, and there can also be debilitating side effects. The recent success of surgical approaches suggests that bypassing the dopamine system may provide a more effective treatment strategy. It is believed that selective activation of mGluR4 is one way to do this.
Under the terms of the agreement, Addex will receive $3 million upfront and is eligible for up to $106.5 million in research, development and regulatory milestones for the first product developed for multiple indications. Additional milestones of up to $61 million would be payable if a second and third product is developed, and Addex is eligible for royalties on sales of any products.
Addex and Merck will collaborate on preclinical development, with Merck being responsible for clinical development. Addex has an option to co-promote in certain European Union countries and will participate in the committee overseeing clinical development.
Addex, which floated on the Swiss Stock Exchange in May this year, was spun out of GlaxoSmithKline plc in 2002 to commercialise research looking at the role of glutamate in addiction. The GluR4 programme has reached lead optimisation.
Glutamate is a key neurotransmitter in the human brain, involved in control of multiple brain functions ranging from motor control to mood. Although there are marketed drugs that modulate specific receptors involved in both the dopaminergic and serotinergic systems, it has been difficult to develop drugs that target specific G protein coupled receptors.
Merck was the first to provide first evidence that mGluR4 activation has potential for treatment of Parkinson's disease, but has not succeeded in discovering compounds that are specific for this receptor.
Addex on the other hand has pioneered the development of selective small molecule drug candidates targeting glutamate receptors and has previously disclosed programs targeting two other receptors in this class, mGluR5 and mGluR2.
Research shows that mGluR4 activators could work via two distinct mechanisms to alleviate symptoms of Parkinson's disease firstly by triggering a compensatory mechanism that may spare or potentiate the use of dopamine receptor activators and secondly through a neuroprotective effect that helps to preserve the brain’s dopaminergic neurons.