Epilepsy represents a large and growing market opportunity. According to the Epilepsy Foundation, there is an estimated prevalence of 2.5 million patients in the United States, with approximately 180,000 new cases diagnosed in the United States each year. Worldwide sales of drugs currently marketed for the treatment of epilepsy totaled more than $8.9 billion during 2006. These sales included prescriptions of these drugs for both epilepsy and other indications, including neuropathic pain. Despite the variety of drugs currently available, approximately one third of the epilepsy patient population remains resistant to currently available medical treatments.

Leading drugs currently approved for the treatment of epilepsy in the United States include Topamax, Lamictal, Depakete, Lyrica, Keppra, Trileptal, Neurontin and Tegretol.  Some drugs are more effective against some types of epilepsy than others, and individual therapy must be tailored to the particular patient. Many patients require combination therapy to adequately control seizure activity. Each of these drugs is associated with side effects, such as dizziness, drowsiness, fatigue, nausea and depression as well as mood, attention and sleeping disorders, which limit their utility in the treatment of many patients.

There are many causes of epilepsy, including a history of trauma to the brain, tumor, bleeding, metabolic conditions and genetic conditions. There are three principal types of epilepsy, including: partial seizures, which affect a portion of the brain; generalized seizures, which affect the entire brain; and absence seizures, a type of generalized seizure that results in temporary loss of consciousness. Regardless of the underlying cause or the specific type of seizure activity, seizures are the result of abnormal excitability of neurons in the brain that generate and transmit electrical impulses inappropriately.

Electrical impulses are generated within and between neurons as a result of ion movements across cell membranes. During an epileptic seizure there may be an imbalance of ion channel activity due to, or leading to, an imbalance in electrical activity in various neurons in specific regions of the brain. By reducing abnormal neuronal excitability through the modulation of ion channels, drugs may prevent seizures.

Neuropathic pain is a particularly severe form of chronic pain that results from damage to the peripheral nervous system. Damage to the nervous system can result in neurons that are highly sensitized and that can produce pain in response to stimuli that would normally not be perceived as painful. The most common causes of neuropathic pain include diabetes and shingles, both of which are conditions in which there is damage to the peripheral nerves. Though rare, neuropathic pain may also be produced by damage to the central nervous system, particularly regions of the brain and spinal cord that are part of the normal pain pathways, including the thalamus. Neuropathic pain is often severe and notoriously unresponsive to standard pain treatments.

Lead Compounds
Icagen has discovered small molecule ion channel activators that target a potassium channel located primarily on the membrane of nerve cells, or neurons, present in particular regions of the central and peripheral nervous system. We are developing these lead compounds for the treatment of epilepsy and neuropathic pain.  We have retained worldwide rights to these compounds.

The ion channel target for our lead compounds is one of the potassium ion channels responsible for determining the excitability of neurons in the central and peripheral nervous systems. When this channel is activated, it permits the flow of positively charged potassium ions out of the nerve cells in which these channels reside, thereby making the resting membrane potential inside these cells more negative. This more negative resting membrane potential decreases the electrical excitability of the nerve cell, thereby decreasing the likelihood for inappropriate or excessive electrical signals, such as those which occur during epileptic episodes or in patients with neuropathic pain. Genetic evidence also suggests a role for this channel in maintaining an appropriate negative resting membrane potential in nerve cells.

In preclinical studies, our lead compounds

• increased the activity of the target potassium channel in a selective and specific manner;
• demonstrated broad spectrum anti-epileptic activity and activity in animal models of neuropathic pain.

The Company filed an Investigational New Drug application, or IND, for one of its lead compounds, ICA-105665, in July 2007.  ICA- 105665 is currently in Phase I clinical studies.