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Aeolus Pharmaceuticals' AEOL 10150 Significantly Increases Survival in Mice Exposed to Radiation when Administered After Exposure

Data to Be Presented at the 55th Annual Meeting of the Radiation Research Society in October

MISSION VIEJO, Calif.--(BUSINESS WIRE)--Jul 6, 2009 - Aeolus Pharmaceuticals, Inc. (OTC Bulletin Board:AOLS) announced today that data from a study in which AEOL 10150 was administered to 40 mice who had been exposed to radiation show a statistically significant increase in survival rates among mice who were treated with AEOL 10150 compared to controls. Additionally, mice receiving AEOL 10150 experienced a reversal in weight loss seen in the untreated mice. The six month study, led by Zeljko Vujaskovic, M.D. Ph.D. of Duke University Medical Center, was designed to test the efficacy of AEOL 10150 as a treatment for damage to the lungs due to exposure to radiation. At 45 days, all of the animals in the untreated group had either died or had to be sacrificed based on animal care rules. The remaining animals that received AEOL 10150 did not need to be sacrificed based on animal care rules, but a majority were sacrificed in order to increase the numbers that could be compared to the untreated animals sacrificed at 45 days, since there would be no untreated animals for comparison at the end of six months. A number of treated animals continued to be monitored until the end of six months and analysis of those animals is currently underway. Specific data related to this study will be presented by Dr. Vujaskovic at the 55th Annual Meeting of the Radiation Research Society in October 2009 in Savannah, Georgia. AEOL 10150 is under development as a countermeasure for nuclear and radiological exposure and as a protective agent in cancer patients receiving radiation therapy.

“AEOL 10150 has consistently shown a protective effect against the harmful effects in radiation, including when the drug is administered up to 72 hours after exposure,” stated Zeljko Vujaskovic, M.D. Ph.D. of Duke University. “We have now seen the drug protect in both mice and in rats, and it has protected multiple organ systems in the body. Our objective now is to determine how long after exposure we can administer the drug and achieve significant benefits and to more clearly identify the appropriate dose and dosing regimen.”

The study protocol called for four groups of animals, two of which would be studied for 6 weeks to look at the acute effects of Lung ARS and the potential efficacy of AEOL 10150 as a countermeasure, and two which would be studied for six months to look at the chronic effects of Lung ARS and the potential efficacy of AEOL 10150 as a countermeasure. In total 60 animals were exposed to 15 gy single dose radiation to the whole thorax. Twenty animals were untreated and 20 animals received a 20 mg loading dose of AEOL 10150 two hours after exposure and then received 10 mg of AEOL 10150 three times per week for four weeks. Twenty animals received a 40 mg loading dose of AEOL 10150 two hours after exposure and then received 20 mg of AEOL 10150 three times per week for four weeks.

In addition to the statistically significant (P< 0.05) survival advantage, statistically significant differences in body weights and wet lung weights were seen over the first six weeks of the study. Untreated mice experienced a steady decline in body weight over the six weeks, while treated animals experienced weight gain that was just slightly less than that seen in the controls (animals not receiving radiation). AEOL 10150 also demonstrated statistically significant reductions in markers for oxidative stress and inflammation – secondary endpoints for the study.

Results to date from this study will be used in the second two parts of the Duke study which will look at dosing, duration of treatment and the maximum length of time after exposure that the drug can be given. These results have also been used to design a proof of principle study in non-human primates, which is expected to begin within the next thirty days. In previous studies it has been shown that doses in the range of 5 to 30 mg/kg AEOL 10150 given daily starting up to 24 hrs after irradiation and administered for as long as 10 weeks mitigate functional lung injury in Fischer 344 rats. Doses in the range of 5 to 10 mg/kg/d showed a more potent effect including more significant mitigation as assessed by histopathology and immunohistochemistry.

“AEOL 10150 continues to demonstrate significant, protective effects when administered after exposure to radiation,” stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. “We believe AEOL 10150 could be a compelling countermeasure for Acute Radiation Syndrome (“ARS”) and are committed to working with our partners at Duke University, the University of Maryland and the National Institutes of Health (NIH) National Institutes of Allergies and Infectious Diseases (NIAID) to accelerate the development and approval of this product with the goal of providing protection against nuclear and radiological threats to the citizens of our country.”

About AEOL 10150

AEOL 10150 is a small molecule that catalytically consumes reactive oxygen and nitrogen species (free radicals). The compound is a manganoporphyrin that contains a positively-charged manganese metal ion that is able to accept and give electrons to and from reactive oxygen species (“ROS”) and reactive nitrogen species (“RNS”). Research has shown that ROS and RNS have important cell signaling roles, and through its interaction with RNS and ROS, AEOL 10150 appears to have multiple mechanisms of action including anti-oxidant, anti-inflammatory and anti-angiogenic activities. In animal studies AEOL 10150 has demonstrated reductions in the markers for tissue hypoxia, angiogenesis, inflammation and oxidative stress. Specifically, AEOL 10150 is able to down-regulate oxidative stress and severe inflammation, which is responsible for much of the tissue destruction that occurs as a result of radiation exposure.

AEOL 10150 offers several unique advantages as a countermeasure for the treatment of ARS, mustard gas and chlorine gas for civilian and military populations. These include:

-- Flexible Treatment Paradigm – AEOL 10150 is intended for the treatment of patients post-exposure, even in those who are already exhibiting symptoms, eliminating the need for immediate administration in a predefined treatment window. This approach has the added benefit of not requiring biodosimetry (a means of laboratory analysis of the blood to determine the level of radiation exposure).

-- Advanced Development Stage – AEOL 10150 has demonstrated safety in three human clinical trials, and has an extensive pre-clinical safety and toxicology package completed. The product also has an established stability profile that permits long-term storage.

-- Large scale manufacturing – Aeolus has contract capacity with a large manufacturing site to mass produce large quantities of AEOL 10150 under GMP conditions.

-- Multiple Applications – AEOL 10150 has demonstrated protective effects against radiation and mustard gas exposure, and within these indications has shown the ability to treat multiple organ systems.

-- Commercial Application – Additionally, AEOL 10150 is being developed for use as an adjunct to cancer radiation therapy, and animal data suggest that the compound protects healthy normal cells from the effects of radiation without compromising the efficacy of the radiation in killing tumor cells.

Potential for AEOL 10150 as a Countermeasure Against Multiple Terrorist Threats

AEOL 10150 has shown significant protective effects against radiation and mustard gas in animal models. Additionally, based on its mechanism, it is believed that the compound may potentially protect against exposure to chlorine gas. Studies will shortly be initiated to further explore AEOL 10150's ability to protect the skin and lungs from damage due to exposure to mustard gas, and to protect the lungs from exposure to chlorine gas. A compound with the potential to protect against multiple threats would be of significant benefit in both the military and civilian efforts to protect citizens against potential threats. The FDA has a special “Animal Rule” under which compounds may be approved for use against chemical and nuclear threats on the strength of animal efficacy studies, which allows the potential for an accelerated approval path versus conventional pharmaceutical applications.

About Aeolus Pharmaceuticals

Aeolus is developing a variety of therapeutic agents based on its proprietary small molecule catalytic antioxidants, with AEOL 10150 being the first to enter human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic antioxidant that mimics and thereby amplifies the body's natural enzymatic systems for eliminating reactive oxygen species, or free radicals. Studies funded by the National Institutes for Health are currently underway evaluating AEOL 10150 as a treatment for exposure to mustard gas and will shortly be initiated to evaluate the compound as a treatment for exposure to chlorine gas. Additionally, the Company has initiated animal studies necessary to seek approval of the compound as a treatment to protect the lungs from exposure to radiation.

The statements in this press release that are not purely statements of historical fact are forward-looking statements. Such statements include, but are not limited to, those relating to Aeolus' product candidates, as well as its proprietary technologies and research programs. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Aeolus' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. Important factors that could cause results to differ include risks associated with uncertainties of progress and timing of clinical trials, scientific research and product development activities, difficulties or delays in development, testing, obtaining regulatory approval, the need to obtain funding for pre-clinical and clinical trials and operations, the scope and validity of intellectual property protection for Aeolus' product candidates, proprietary technologies and their uses, and competition from other biopharmaceutical companies. Certain of these factors and others are more fully described in Aeolus' filings with the Securities and Exchange Commission, including, but not limited to, Aeolus' Annual Report on Form 10-K for the year ended September 30, 2008. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.

 

 

Contact: Aeolus Pharmaceuticals, Inc.
John L. McManus, President and Chief Executive Officer
1-949-481-9825

 

 

Posted: July 2009

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