We are developing a novel class of pharmaceuticals that are designed to enhance wakefulness and cognitive abilities in individuals that suffer from Narcolepsy or Excessive Daytime Sleepiness (EDS - which can be caused by a number of factors that cause aberrant or inefficient sleep patterns) or other conditions. Compounds that promote cognitive abilities are thought to have therapeutic potential for the treatment of other conditions as well, such as for the treatment of Attention Deficit Disorder (ADD or ADHD), or neurological conditions that reduce cognition. These compounds are designed to selectively act on a key receptor in the brain, the Histamine H3 receptor that is thought to play a key role in promoting wakefulness, attention and cognitive tone.
Individuals that suffer from narcolepsy or other conditions that result in excessive daytime sleepiness, or EDS, may experience persistent tiredness and lack of energy. As a result, such individuals may experience significant difficulty in performing certain tasks, and may suffer an impaired quality of life. More than 100,000 individuals in the U.S. suffer from narcolepsy or EDS. Historically, narcoleptics were treated with amphetamines and related stimulants that had substantial side-effects, but more recently have been prescribed Provigil (modafinil). This compound works by an unknown mechanism, but appears to be relatively free of the stimulant side-effects of amphetamines. In addition to its use for narcolepsy, Provigil is also approved for the treatment of shift work sleep disorder, or SWSD, and sleep apnea. Although Provigil appears to be an improvement over previous narcolepsy drugs, certain safety concerns were raised by the FDA when Cephalon, Inc. attempted to gain approval of modafinil for ADHD, and the company subsequently abandoned efforts in this market.
Similarly, individuals with attention or cognitive disorders may suffer from an inability to focus, solve problems, process information, communicate, and may have memory impairment. Attention and cognitive disorders include ADD / ADHD, Schizophrenia, Alzheimer’s disease and other forms of dementia. Datamonitor estimates that 23 million children in the seven major pharmaceutical markets (United States, France, Germany, Italy, Spain, United Kingdom and Japan) suffer from ADHD. Research also shows that 60% of children with ADHD maintain the disorder into adulthood. Despite the low rate of diagnosis, ADHD drug revenues reached $2.5 billion in 2004, 97% of which was generated within the United States. Currently available treatments cause side effects and do not adequately address the clinical need. Ritalin® (methylphenidate) is the most widely prescribed ADHD therapy. As a stimulant with abuse potential, it has been classified as a controlled substance by the FDA and the U.S. Drug Enforcement Agency. We believe there exists a tremendous market opportunity as diagnosis and awareness of ADHD is improved.
We are developing multiple classes of highly selective and potent compounds designed to block the H3 receptor and have established a program to develop non-stimulant, non-addictive, orally administered compounds for the treatment of narcolepsy or other conditions related to excessive daytime sleepiness. Recently, pharmaceutical companies such as Glaxo-SmithKline and Johnson& Johnson have advanced H3 antagonist programs into clinical development for the treatment of conditions such as narcolepsy and dementia, respectively.
Our histamine H3 receptor antagonists represent a new class of drugs that could have an improved efficacy and safety profile relative to existing drugs used for the treatment of narcolepsy and related sleep disorders. The H3 receptor regulates levels of histamine and other neurotransmitters in certain areas of the brain that play a direct role in regulating sleep and cognitive function.
In animal models, H3 receptor antagonists have been shown to increase histamine release in the brain and improve wakefulness, attention and learning. In preclinical studies conducted at independent sleep labs, we have tested some of our more advanced compounds in well validated rodent sleep models. During these studies, certain compounds significantly enhanced wakefulness without causing apparent adverse events. In comparison to modafinil or caffeine, these compounds were far more potent, achieving a comparable or better effect on wakefulness at substantially lower doses. In addition, certain compounds did not appear to cause hyperactivity or the excessive rebound sleepiness that is a characteristic of other agents used to promote wakefulness, such as amphetamines.
We intend to continue the study of H3 antagonists for potential applications in treating narcolepsy, excessive daytime sleepiness, and certain attention or cognitive disorders. In addition, we intend to conduct additional pharmacology and safety testing of our current compounds under evaluation. If these studies are successful, and depending on the availability of capital resources, we will consider filing an IND for the initiation of clinical trials.
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