GRX-917 HISTORY

(Deuterium Improved Etifoxine)

Early Beginnings

The original, non-deuterated drug (etifoxine) was originally developed to compete with tranquilizing and sedative BZs of the 1960’s, such as Valium and Librium. But it was mischaracterized as a mild benzodiazepine, because of its lack of typical benzodiazepine side effects, like sedation and ataxia. Hoechst sold the rights to the drug, without knowing its true efficacy and unaware of its dual mechanism of action. A small pharmaceutical distributor has been producing and distributing the drug off-patent since 1979, in limited markets. The drug was never developed in the U.S. or broader European markets.

Discovering the Extraordinary Dual Mechanism of Action

Contrary to what was originally believed, French researchers in the 2000’s discovered that etifoxine did not interact at the benzodiazepines site on GABA receptor coupled channels at all! It took sophisticated molecular biology techniques along with single cell electrophysiological experiments to demonstrate that the drug was very selective in enhancing GABA activity, through a unique interaction, and only working on a subset of GABA receptor coupled channels. Further research revealed a truly significant discovery: The drug was also increasing the levels of natural neurosteroids, like allopregnanolone (ALLO), also a highly potent and effective modulator of GABA channels, and that the clinically observed effects were a combination of the drug’s direct effect at GABA channels and an enhancement of GABA effects by ALLO. Scientists quickly took notice of this unique biological action and began to explore etifoxine in models of other indications where neurosteroids (like ALLO) had shown efficacy.

Etifoxine – No Patent Protection – Not Viable

The stage was set for an old drug to be rejuvenated but the original patents had expired and most of the therapeutic indications had already been disclosed (or patented). Without patent protection, there was no business rationale to re-develop the drug in any new markets, which explains why etifoxine was never introduced into the United States.

GRX-917 – Patent Protection – Viable

The Company has used deuteration technology to create a new and improved version of etifoxine, deuterated etifoxine (GRX-917), that has composition of matter patent protection, until 2036.