Cortex Pharmaceuticals, Inc. Helps Sleep Apnea Sufferers Breathe Easy

Novel Therapy Believed To Provide Protection From Drug-Induced Respiratory Depression

The Greek word “apnea” literally means “without breath.” Sleep apnea is a common disorder characterized by short pauses in breathing during sleep. Each episode lasts long enough so that several breaths are missed, with such episodes occurring repeatedly throughout sleep. While there are three types of sleep apnea (obstructive, central, and mixed), each caused by different root causes, those suffering from the disorder stop breathing repeatedly during sleep, sometimes hundreds of times during the night, and often for a minute or longer.

Sleep apnea is a surprisingly common condition: according to the National Institutes of Health, the disorder affects more than twelve million Americans, making it as common as adult diabetes. Certain factors increase the risk of sleep apnea, such as being male, overweight, and over the age of forty, but sleep apnea can strike anyone at any age, including children. The vast majority of sufferers go undiagnosed and untreated. Untreated, sleep apnea can lead to high blood pressure and other cardiovascular diseases, memory problems, weight gain and diabetes, impotence, and headaches.

A special consideration for sufferers of sleep apnea concerns the use of anesthetic and analgesic agents during surgery. Many drugs and agents used during or after surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards, and these agents are known to make sleep apnea worse. Researchers at the University of Alberta and Cortex Pharmaceuticals, Inc., a neuroscience company based in Irvine, California, believe that a novel class of molecules known as AMPAKINE® compounds may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA-type glutamate receptor. Dr. John J. Greer of the University of Alberta demonstrated that certain AMPAKINE compounds stimulate primitive areas of the brain called the pre-Botzinger Complex that controls breathing, without causing side effects. In animal models, AMPAKINE compounds were shown to enhance the respiratory drive and breathing rhythm in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants. AMPAKINES could one day allow for improved safety and a more effective use of opiate analgesics and barbiturate sedatives, two important classes of central nervous system drugs.

Company Overview
Cortex Pharmaceuticals is a neuroscience company focused on the discovery, development and commercialization of novel drug therapies for the treatment of neurological and psychiatric disorders. Cortex’s primary technology platform is a novel class of proprietary pharmaceuticals called AMPAKINE® compounds, which act to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases. A number of psychiatric diseases, including schizophrenia, ADHD, and depression occur as a result of imbalances in the brain’s neurotransmitter system. These imbalances may be improved using the AMPAKINE technology. We also have found that these agents directly impact the center that is responsible for inspiration in the brain stem (Pre-Botzinger Complex). We recently completed two clinical trials in Europe with our lead compound, CX717, to demonstrate proof of concept for treatment of respiratory depression due to opiate analgesic therapy. Both trials achieved their clinical endpoints. Data from these studies suggest that AMPAKINE drugs may also be useful in treating respiratory depression caused by anesthetic agents and barbiturates and could potentially be a treatment for Obstructive Sleep Apneas. This platform technology is protected by strong Intellectual Property, which includes over 290 patent filings and 180 issued patents and additional filings being generated on a continuous.

Company Highlights

• Approximately $4.14 million cash available (as of Dec. 31, 2008), and no debt on balance sheet
• In Phase II clinical development with its lead compounds, CX717 and CX1739
  • Recently initiated a pilot Phase II clinical trial in sleep apnea
• Generated a robust portfolio of earlier-stage compounds in preclinical development
• Developing pharmaceutical products that address broad and large commercial market opportunities that would likely be partnered to larger Pharmaceutical companies for late stage development and commercialization (e.g. Alzheimer’s disease, schizophrenia, depression, ADHD, Parkinson’s disease, respiratory depression)
• Developing pharmaceutical products that address orphan diseases that could be rapidly developed and commercialized by Cortex (e.g. Huntington’s diseases, Fragile X, Rett’s syndrome)
• Strong intellectual property estate with over 290 Composition of Matter and Broad Use patents submitted with 180 issued to date

AMPAKINE® Technology

• An AMPAKINE compound is a small, drug-like molecule that enhances the effects of glutamate, a naturally occurring molecule in the central nervous system that is used to relay signals between nerve cells.
• Through enhancing the function of glutamate, an AMPAKINE compound facilitates communication between nerve cells, facilitating attention and memory.
• There are two chemical classes of AMPAKINE molecules – Low Impact (LI) and High Impact (HI) compounds, the latter of which can increase brain growth factors, termed neurotrophic factors, that have the ability to slow down or halt the progression of ongoing degenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.
• AMPAKINE molecules activate cells in the brain stem that control breathing, and reverse the depression of breathing induced by opiates such as morphine and fentanyl, and also may be an effective treatment for obstructive sleep apnea.
• In addition, AMPAKINE molecules may be effective treatments in a number of central nervous system diseases such as attention deficit-hyperactivity disorder (ADHD), Fragile X and autism spectrum disorders, depression, schizophrenia, and in restoration of nerve activity following damage (e.g. post ischemic stroke, traumatic brain injury and spinal cord injury).

Product Overview
CX717

• Demonstrated “Proof- of-Concept” in adult patients with Attention Deficit-Hyperactivity Disorder (ADHD).
• Demonstrated proof-of-concept in preventing opioid-induced respiratory depression in two pilot Phase II studies in the third quarter of 2008.
• CX717 demonstrated improvement in memory in classic animal models of Alzheimer’s disease (AD) and is currently being evaluated in mild to moderate AD patients in a PET brain imaging study.

CX1739

• A new, orally available, low impact AMPAKINE compound with excellent IP through 2028.
• Three-fold more potent than CX717 in animal models and appears to have a very favorable safety profile.
• Successfully completed Phase I studies – good safety and tolerability
• Phase IIa study initiated in sleep apnea
• Phase IIa studies in adult ADHD to start 2Q, 2009. 

CX1837

• First new high-impact compound which shows excellent safety margins in animal studies. 
• Currently being targeted for toxicology trials.
• Farampator (Org24448) & Org26576
• Two lead product AMPAKINE candidates that are currently being tested in Phase II studies for the treatment of schizophrenia and depression, respectively by Schering-Plough.
• Their clinical development resulted from a Research Discovery partnership with Schering-Plough (formerly Organon).
• This partnership has clinical development and regulatory milestones plus royalties upon commercialization.