Cortex Pharmaceuticals, Inc. Animal Studies Demonstrate Reversal of Memory Loss In Huntington’s Disease

Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) recently reported that preclinical studies from the laboratory of Professor Gary Lynch at the University of California Irvine, one of the scientific founders of the company, demonstrated that AMPAKINE® molecules show promise in the treatment of memory loss in Huntington’s disease. The studies were performed in mice harboring the genetic mutation found in humans that is responsible for Huntington’s disease. The related results demonstrated that treating mice with CX929, a high impact AMPAKINE, produced dramatic increases in the brain’s chemical processes for creating and storing memories. These studies were published in the early online version of the prestigious, peer-reviewed journal, Proceedings of the Nati onal Academy of Sciences (PNAS).

Huntington’s disease is a progressive, hereditary brain disease that affects men and women alike, with some thirty thousand patients in the U.S. and another one hundred fifty thousand at risk. It is caused by the death of specific brain cells and is characterized by the gradual development of involuntary muscle movements, progressive deterioration of cognitive processes and memory (dementia), and severe behavioral disturbances. The memory impairments include altered organization, generally slowed processing of information by the brain, and executive function – that is, the ability to plan, abstract thinking and multi-tasking.

“One protein in particular, brain-derived neurotrophic factor (BDNF), is reduced in Huntington’s disease. We know that BDNF plays an essential role in maintaining the health of the brain,” commented Professor Lynch. “And our studies now demonstrate that we can restore levels of BDNF by treating mice with an AMPAKINE, which reverses the memory impairments.”

Mark A. Varney, President and CEO stated that, “Professor Lynch’s studies in mice support the rationale for Cortex to develop AMPAKINE molecules to address the memory deficits in patients suffering from Huntington’s disease. Also, the link to BDNF may play an important role in other neurodegenerative diseases such, as Alzheimer’s disease.”

View the abstract of the paper.

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 clini cal 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 $7 million cash available (as of Sep. 30, 2008), and no debt on balance sheet
• In Phase II clinical development with its lead compounds, CX717 and CX1739
• Recently resumed Phase IIa study in an Alzheimer’s disease brain imaging PET-scan study
• 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.
• Five-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.