Jean-Philippe Rocher, Head of Discovery Chemistry at Neurosterix, presented an insightful overview of the company's recent advancements and strategic directions. Neurosterix, a spinoff of Addex Therapeutics, was established in 2024 with a focus on pharmaceutical development, particularly on mGlu allosteric modulators to address CNS disorders.
Rocher began by explaining the concept of allosteric modulation, highlighting its unique properties that differentiate it from classical drugs. Unlike traditional drugs that compete with endogenous ligands, allosteric modulators bind to distinct sites and act like a dimmer switch, increasing or decreasing signalling to restore neurotransmission to physiological levels. This approach allowed for high selectivity and the ability to design partial positive or negative allosteric modulators.
The presentation detailed the three main pillars supporting the discovery and design of allosteric modulators: a biology platform with proprietary assays, a chemistry platform with biophysical methods, and a translational platform with in vivo models and biomarkers. These platforms enabled Neurosterix to progress several molecules to clinical phases, including Raseglurant and Dipraglurant, although there were challenges in demonstrating efficacy in certain models.
Rocher also discussed the clinical progress of Neurosterix's molecules. Raseglurant showed positive clinical data for migraine and GERD but failed to demonstrate activity in dental anxiety. Dipraglurant produced robust preclinical data in a non-human primate model and translated into positive clinical Phase IIa results for PDLID, although it did not show efficacy in a small study for blepharospasm. The presentation highlighted the importance of addressing the translational gap between preclinical models and clinical outcomes.
Looking ahead, Neurosterix aim to develop new molecules, such as NTX94827, with promising bioavailability and activity in rodent models of PTSD. The goal is to progress these compounds to IND enabling studies. Rocher concluded by emphasising the progress made over the past 20 years and the potential of allosteric modulators to address CNS disorders, despite the complexity and challenges in the field.
