Naurex Announces Initiation of Phase I Trial for Second-Generation NOVEL ANTIDEPRESSANT AGENT NRX-1074

Naurex Inc., a clinical-stage company developing innovative treatments to address unmet needs in psychiatry and neurology, has announced that it has begun patient dosing in a Phase I trial of its novel, orally active agent NRX-1074. NRX-1074 is a follow-on to Naurex’s firstgeneration compound GLYX-13, which has demonstrated good safety, robust efficacy and rapid onset of effect within hours of a single dose in a Phase IIa trial. NRX-1074 and GLYX-13 are NMDA receptor functional partial agonists, a new class of CNS-active compounds identified by Naurex scientists, who have generated multiple series of novel drug candidates based on these discoveries.

The Phase I trial is a randomized, placebo-controlled, ascending dose study that will assess the safety and pharmacokinetics of NRX-1074 in normal volunteers. NRX-1074 is several thousand times more potent than GLYX-13, and preclinical studies have shown that it is active when administered orally. NRX-1074 has in vivo mechanistic activity similar to GLYX-13, including a ketamine-like efficacy signature with rapid onset and long-acting duration of antidepressantlike effect. Similar to GLYX-13, in animal studies NRX-1074 has demonstrated good safety with no signs of CNS-related side effects. Naurex’s initial development focus for this fast-acting, potent, orally available compound is in major depression.

“NRX-1074 is the first orally available agent from our novel platform of highly selective NMDA receptor modulators to enter human trials,” said Derek Small, CEO of Naurex. “In preclinical studies it has demonstrated a similar profile to GLYX-13, with the ketamine-like attributes of rapid onset and prolonged antidepressant effect but without any evidence of ketamine’s limiting side effects. We are delighted to have begun testing NRX-1074 in humans at the same time that our Phase IIb trial of GLYX-13 is proceeding well. We expect to report results from the Phase I study in 2014.”

In the Phase IIa trial, a single administration of GLYX-13 produced statistically significant reductions in depression scores in subjects who had failed treatment with current antidepressants. The reductions were evident within 24 hours and persisted for an average of seven days. A measure of the antidepressant efficacy of GLYX-13 observed at 24 hours and at seven days was nearly double that seen with most antidepressants after 4-6 weeks of repeated dosing. In this study, GLYX-13 was also well tolerated.

Reported side effects were mild to moderate and were consistent with those observed in subjects receiving placebo. GLYX-13 did not produce any of the schizophrenia-like psychotomimetic effectsassociated with other drugs that modulate the NMDA receptor. 1,2 Naurex’s CNS programs are based on the work of company founder, Joseph R. Moskal, PhD and his colleagues at the Falk Center for Molecular Therapeutics at Northwestern University.

1. A Phase 2, Randomized, Double Blind, Single Intravenous Dose Study of GLYX-13, an NMDA Receptor Glycine Site Functional Partial Agonist, in Subjects with Major Depressive Disorder with Inadequate Response to Antidepressant Medication, Ronald M. Burch, Naurex, Oral Presentation, Special Symposium, “Beyond Ketamine, Can Selective Targeting of the NMDA Receptor Produce Antidepressant Response without Psychotomimetic Effects: Clinical Results with Three Novel Compounds”, Chair, Gerard Sanacora, ACNP Annual Meeting 2012, December 5, 2012
2. GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects, Jeffrey Burgdorf, Xiao-lei Zhang, Katherine L Nicholson, Robert L Balster, J David Leander, Patric K Stanton, Amanda L Gross, Roger A Kroes and Joseph R Moskal.
Neuropsychopharmacology (2013) 38, 729–74 doi:10.1038/npp.2012.246; published online 30 January 2013