Addex’s Clinical Programs and Discovery Platform Highlighted in Review of Allosteric Modulators for the Treatment of Neurodegenerative Diseases
Geneva, Switzerland, 6 February 2017 – Addex Therapeutics (SIX: ADXN) announced today the publication of a review summarizing the current status of allosteric modulators (AMs) as potential novel treatments for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, in Current Opinion in Pharmacology (http://www.sciencedirect.com/science/article/pii/S1471489217300061). This review highlights the important contribution Addex has made in the discovery of allosteric modulator compounds.
“Allosteric modulation is a clinically proven but differentiated pharmacological approach that has significant potential to deliver novel therapeutics across a broad range of disease areas,” said Robert Lütjens, Head of Discovery of Addex. “It is the combination of Addex’s proprietary biological assays and small molecule library that has enabled us to be so successful at finding drug like allosteric compounds.”
In particular, the paper reviews progress made by academic and industrial laboratories to deliver allosteric modulator compounds on important drug targets, such as purinergic, muscarinic acetylcholine, and metabotropic glutamate receptors. Addex’s dipraglurant for levodopa-induced dyskinesia associated with Parkinson’s disease is highlighted as one of the most advanced clinical compounds in the field. In addition, the important potential of a number of Addex programs, such as those targeting mGlu3, 4, 5, 7 and 8 receptors in neurodegenerative disease is recognized.
The review highlights the important steps that have been made to validate these targets through the use of pharmacological tool compounds for which Addex has been an important contributor. A special emphasis has been placed on the potential to treat symptoms of diseases, such as Parkinson’s and Alzheimer’s disease, while also confirming the potential disease-modifying effects observed with AMs in preclinical studies.
Addex, with its allosteric modulation technology platform and its rich pipeline of AMs addressing all metabotropic glutamate receptor subtypes, as well as other G protein-coupled Receptors (GPCR) and non GPCR targets, is well poised to deliver novel first-in-class compounds with a potential to substantially affect neurodegenerative disease symptoms as well as disease progression. This is highlighted in the recently announced grant of $835,000 from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to advance Addex’s positive allosteric modulators (PAMs) of the tyrosine receptor kinase B (TrkB), a target for neuroprotection with potential in Parkinson’s, Alzheimer’s and Huntington’s disease.
“While we focus on our clinical stage pipeline, including dipraglurant for levodopa-induced dyskinesia associated with Parkinson’s disease, we continue to advance our portfolio of discovery stage allosteric modulator programs with support from government, academic and patient advocacy organizations,” said Tim Dyer, CEO of Addex. “This review article and the recent grant from the MJFF are further validation of the capabilities of our allosteric modulator platform and portfolio of allosteric compounds.”
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.
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