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Research & Development
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Naurex Pipeline
Naurex is developing a pipeline of small peptides and synthetic small molecules that modulate the NMDA receptor (NMDAR) at the glycine site. Naurex’s lead compound is GLYX-13, a novel NMDA receptor Glycine-site Functional Partial Agonist (GFPA), which is in development for the treatment of depression. GLYX-13 has shown promising results in a Phase I clinical trial and in preclinical studies. A Phase II trial is currently underway evaluating the use of GLYX-13 in patients who are not achieving adequate responses to their current antidepressant agents. The second-generation NRX-1050 series of novel GFPA agents is in preclinical development. It includes orally available compounds for the treatment of a variety of CNS disorders and includes a number of molecules that have demonstrated preclinical proof of concept.
Naurex’s NMDAR modulator platform technology includes these first- and second-generation GFPA programs as well as additional novel chemistries for modulation of the NMDA receptor. Naurex’s research has shown that compounds generated from the GFPA platform have the potential for therapeutic utility in a number of CNS conditions, including:
- Anxiety disorders
- Cognitive disorders
- Pain
- Addiction
NMDA Receptor Modulators as Potential CNS Drugs
The glutamate receptor subtype known as N-methyl-D-aspartic acid (NMDA) plays a central role in modulating aspects of brain activity in the central nervous system, such as synaptic transmission, synaptic plasticity and excitotoxicity. Major pharmaceutical firms have been developing NMDAR modulators for over 20 years, and a few, including memantine, ketamine, D-cycloserine and dextromethorphan are marketed for non-depression CNS indications, generating annual sales of more than $1 billion.
The antidepressant potential of modulating the NMDA receptor has been confirmed by data from clinical studies with known NMDAR antagonists, which produced significant reductions in depression scores in patients with treatment-resistant depression. These data have confirmed the NMDA receptor as a novel target of high interest in depression, representing a potentially entirely new way to treat patients who do not respond to current therapies. But, while the efficacy of these drugs is promising, they are also associated with significant toxicities at doses that are very close to the therapeutic dose. These toxicities include dissociative effects, such as hallucinations, as well as sedation and abuse and addiction potential. Until now, the narrow margin between therapeutic effects and adverse effects has limited the full therapeutic potential of these agents.
Glycine-Site Functional Partial Agonists: A Novel Approach with Encouraging Data
Naurex scientists designed the company’s novel Glycine-site Functional Partial Agonists (GFPAs) of the NMDA receptor to achieve the efficacy of previously known NMDAR modulators without their limiting side effects. In preclinical and clinical studies to date, the company’s GFPAs have demonstrated the therapeutic efficacy of classic NMDAR modulators with no evidence of these side effects.