Insomnia Focus Investor Meeting
September 25, 2007
Palace Hotel, New York

http://phx.corporate-ir.net/phoenix.zhtml?c=96629&p=IROL-eventDetails&EventId=1642397

Session Highlights

Tom Roth, PhD, Director, Sleep Disorders Center, Henry Ford Hospital
 “GABA is in fact -- has and always will be, the mainstay (of sleep therapeutics) because the sleep center of the brain is the ventral lateral pre-optic area, the VLPO, and it is GABAergic...Very clearly, there are a lot of compounds being developed, but again, GABA is the basic transmitter system of the ventral lateral preoptic area and will always be the mainstay of sleep-promoting agents.”

Alan Lankford, PhD, President and CEO, Sleep Disorders Center of Georgia
“I was an investigator on both (adipiplon studies) 202 and 203…One of the things we do in these trials, and it's a fairly reliable kind of thing, particularly in recent years--we elicit data on sleep quality with questionnaires that we use to ask patients about sleep quality.

“In the 100-plus trials that I've done over the last several years, these are the first trials that I've ever had where patients volunteered that they had slept better. We didn't have to ask them. Now, not every patient did this, but a number of patients would say, wow, I slept better and, wow, I feel better. And this happened not only in 202, but it happened in 203… I actually have two trial sites, and we had these reports from both of the trial sites.

“What is this about? Well, since there are some data that indicate that this compound has an effect on the (GABA) subunit responsible for the reduction of anxiety and anxiety seems to be a component associated with insomnia fairly regularly, the anxiolytic effect may very well be part of what's going on that's eliciting these reports from the patients about improvements in sleep quality and how they feel.”

Andrew Krystal, M.D., Associate Professor, Psychiatry, Duke University Medical Center
“The issue is that there is a striking overlap of generalized anxiety disorder and insomnia, in my view…. we have clearly a greater rate of catastrophic worry in the population of people who have difficulties with sleep and meet insomnia criteria. And in one large study, worrying about sleep before onset, while lying in bed, was a very, very important predictor of whether people were going to have difficulties with their sleep or had sleep difficulties…

“I would submit that treating anxiety is an important part of what we do when we treat insomnia…these basic considerations suggest a unique potential, that is, that you have the potential for simultaneous enhancement of sleep and reduction of anxiety. But the reduction of anxiety is really valuable from my point of view in these people with insomnia in the period before sleep, before the blood level gets up to the point where you're out (asleep).”

“Now, I think that people often make the mistake and believe that there's a group of medications called benzodiazepines and they are all non-specifically having all the effects that benzodiazepines have, pharmacologically and clinically, and it's not true.

“So I'm going to disabuse you of that concept, and discuss a little bit some of the differences among them and how that might be an important consideration for thinking of an agent as an insomnia agent or as an anxiety agent or both, and how that might be valuable in treating insomnia…

“Of the ones (GABA-A receptor subtypes) that we think of as having important clinical effects…alpha-1 is the one that has received the most attention in terms of sleep. It looks like binding to the GABA receptors that have that alpha-1 configuration is particularly likely to promote sleep. But I want to draw your attention to number 3.

“The higher the alpha-3 (stimulation), the more anxiety reduction you're likely to experience versus sedation… Adipiplon has this unique separation between the alpha-3 and all the others.”