Cortex's AMPAKINE Compound, CX717, Achieves Primary Endpoints in Second Phase IIa Respiratory Depression Study in Germany.

CX717 Prevents Opioid-Induced Respiratory Depression While Maintaining Analgesia 

IRVINE, Calif. -- Cortex Pharmaceuticals, Inc. (NYSE Alternext US (COR)) reported that top-line data from its second Phase IIa study in opioid-induced respiratory depression (RD) demonstrated that a single oral dose of 1500mg of the AMPAKINE([R]) compound CX717 achieved statistical significance (p = 0.005) over placebo on the primary endpoint measure of spontaneous basal respiration without affecting opioid-induced analgesia. This placebo-controlled, double-blind, randomized two-way crossover trial (CX717-RD-01) was performed by one of the leading experts in the field, Professor Jorn Lotsch at the Institut fur Klinische Pharmakologie, Johann Wolfgang Goethe-Universitat in Frankfurt, Germany.

In this study, sixteen volunteers each received either 1500mg of CX717 or matching placebo that was orally administered two hours before each subject received an intravenous infusion of the opioid, alfentanil. The primary performance measures were the basal breathing rate, and the minute expiratory volume (VE) at 55 mmHg CO2 (VE55), and the lack of effect on analgesia. CX717 prevented the reduction in basal breathing rate induced by alfentanil, in comparison to placebo (p = 0.005). The degree of the reversal of the basal respiratory rate was similar to that obtained with the opioid antagonist, naloxone (Narcan[R]). At the same time, the analgesic properties of alfentanil were maintained in an acute pain model in the presence of CX717, whereas naloxone blocked the analgesic properties. The effect of CX717 on the VE55 numerically trended toward reversing, but did not reach statistical significance.

In August 2008, Cortex reported that in its first Phase IIa study in opioid-induced RD, 2100mg CX717 significantly reversed the VE55 measure of respiration. Spontaneous basal respiration was not an endpoint in the first Phase IIa study. "The primary objective of these two studies was to verify that this novel mechanism of action observed in animals would translate to humans," commented Mark A. Varney, President and CEO, "and we are pleased to see statistically significant effects with a single oral dose in these small proof of concept clinical studies." Dr. Varney went on to say, "AMPAKINE compounds may positively impact the ability of caregivers to optimize pain management for patients, as well as provide Cortex with a potentially large partnering opportunity and a good revenue stream when commercialized."

The incidence of RD in a clinical setting related to opioid administration has been estimated to be up to 17% when oxygen desaturation is used as the indicator. Professor Lotsch added, "There are still fatal outcomes after opioid administration even under controlled conditions in the clinical setting. The data from this study supports the possibility of using CX717 in the clinic to avoid life-threatening adverse effects associated with opioids."

These human results replicate data from animal studies generated by Dr. John Greer at the University of Alberta, which showed the utility of CX717 and other AMPAKINE compounds to prevent and treat opioid-induced RD without affecting their analgesic properties. Dr. Greer stated, "These advances will help patients whose pain cannot be treated effectively with opioids due to the unwanted side effect of a depression of breathing. Administration of AMPAKINE compounds can overcome this problem and lead to a significant improvement in pain management, as well as guard against deaths caused by opioid overdose. We are now extending our preclinical studies to determine whether AMPAKINE molecules can help the breathing problems in prematurely born babies and in adults with sleep apnea. This has been, and continues to be, an extremely productive collaboration with Cortex that is resulting in the translation of our basic scientific discoveries to clinical applications."

Cortex plans to continue the development of AMPAKINE compounds in opioid-induced RD. An intravenous dosage form of CX717 is being finalized, and a follow-on compound, CX1942, a water soluble pro-drug of a novel AMPAKINE compound with improved potency over CX717, will shortly enter preclinical development for RD. Additionally, a novel AMPAKINE molecule, CX1739, is currently in Phase I clinical trials and is targeted to begin Phase II clinical trials for ADHD in Q2 2009.

Cortex Pharmaceuticals, Inc.

Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for treating psychiatric disorders, neurological diseases and brain mediated breathing disorders. Cortex is pioneering a 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. Many psychiatric diseases, including schizophrenia, occur as a result of imbalances in the brain's neurotransmitter system. These imbalances may be improved by using the AMPAKINE technology. Cortex has an alliance with Schering-Plough Corporation who acquired Cortex's former partner N.V. Organon in November 2007. As a result of this acquisition, Schering-Plough has two AMPAKINE Phase II compounds Org24448 and Org 26576 for the treatment of schizophrenia and depression. In December 2006 Cortex terminated the research collaboration with Servier enabling Cortex to pursue the use of AMPAKINE compounds in the treatment of neurodegenerative diseases on a global basis. Servier retained the right to select up to three compounds developed during the collaboration for further development for the treatment of neurodegenerative diseases. Cortex may receive additional milestones and royalties if either Organon or Servier is successful in developing and commercializing AMPAKINE compounds. For additional information regarding Cortex, please visit Cortex Pharmaceuticals' website at http://www.cortexpharm.com.

Forward-Looking Statement 

Note - This press release contains forward-looking statements concerning the Company's research and development activities. The success of such activities depends on a number of factors, including the risks that the Company's proposed compounds may at any time be found to be unsafe or ineffective for the indications under pre-clinical or clinical tests and that such studies may at any point be suspended or take substantially longer than anticipated to complete. The forward-looking statements are necessarily subject to risks and uncertainties, all of which are difficult or impossible to predict accurately and many of which are beyond the control of Cortex, all as more fully described in the risk factors and other matters set forth in Cortex's Annual Report on Form 10-K for the year ended December 31, 2007, and Cortex's other filings with the Securities and Exchange Commission, As discussed in the Company's Securities and Exchange Commission filings, the Company's proposed products will require additional research, lengthy and costly clinical testing and regulatory approval. AMPAKINE compounds are investigational drugs and have not been approved for the treatment of any disease. Cortex disclaims any intent or obligation to update any forward-looking statements.