Neurocrine to advance its NBI-98854 VMAT2 Inhibitor into a multiple repeated dose Phase 1 study

Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced their highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor, NBI-98854, will be advanced in clinical development.

The first trial in human subjects, NBI-98854-0801, was a single ascending dose trial in healthy male volunteers conducted in Canada under an approved Clinical Trial Application (CTA) with Health Canada. Preliminary data have now been reviewed; NBI-98854 was generally safe and well tolerated. There were no Serious Adverse Events, clinically significant drug-related laboratory abnormalities or clinically significant ECG findings. More critically, the characteristics of the compound met the pre-specified pharmacokinetic requirements: dose proportionality, low maximum concentration (Cmax) with adequate area-under-curve (AUC) for drug exposure, low variability, and a half-life which supports once per day dosing.

"The results of this first clinical trial in our VMAT2 inhibitor are exactly what we were seeking," said Chris O'Brien, Chief Medical Officer of Neurocrine Biosciences. "We will now move NBI-98854 into a multiple repeated dose Phase 1 study and begin preparation for Phase 2 proof of concept trial to be initiated later in 2010."

VMAT2 is a protein concentrated in the human brain that is primarily responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) among nerve cells. NBI-98854, developed in the Neurocrine laboratories, is a novel highly selective VMAT2 inhibitor that is effective in regulating the levels of dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines thereby reducing the likelihood of "off target" side effects. NBI-98854 is designed to provide low, sustained, plasma and brain concentrations of the active drug to minimize side effects associated with excessive dopamine depletion.

The next step for this VMAT2 development program is to complete a multiple, repeated dose Phase 1 study in healthy male volunteers after approval of the Canadian CTA submission. Once complete, Neurocrine will approach the FDA regarding the filing of an Investigational New Drug application in the United States with the express purpose of initiating the proof-of-concept study in patients with Tardive Dyskinesia late in 2010. In addition, NBI-98854 may well be useful in other disorders, such as Huntington's chorea, schizophrenia, Tourette's syndrome, and tardive dystonia.