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Aeolus' AEOL 10150 Protects Lung Tissue From Radiation by Modulating PTEN Levels, Reducing Oxidative Stress and Apoptosis

 

MISSION VIEJO, CA--(Marketwire -02/08/12)- Aeolus Pharmaceuticals, Inc. (OTCQB: AOLS.OB - News) (Pinksheets: AOLS.OB - News)

  • Data published in the International Journal of Radiation Oncology, Biology, Physics provides explanation for drug's mechanism of action in radiation protection
  • AEOL 10150 had no effect on PTEN levels in healthy normal tissue
  • Key element required for FDA approval under the "Animal Rule"

Aeolus Pharmaceuticals, Inc. (OTCQB: AOLS.OB - News) (Pinksheets: AOLS.OB - News), a biotechnology company leveraging significant government funding to develop a platform of novel compounds in oncology and biodefense, today announced the publication of data on AEOL 10150 in the International Journal of Radiation Oncology Biology Physics. The article, entitled "Oxidative Stress Mediates Radiation Lung Injury by Inducing Apoptosis," was authored by Yu Zhang, Xiuwu Zhang, M.D., Ph.D., Zahad N. Rabbani, M.D., Isabel L. Jackson, B.S., and Zeljko Vujaskovic, M.D., Ph.D.

"Radiation pneumonitis and fibrosis are major obstacles for escalating radiation doses and improving overall patient survival in the treatment of thoracic tumors", stated Brian Day, Ph.D, Chief Science Officer of Aeolus Pharmaceuticals, Inc. "We have seen in studies in mice, rats and Non-Human Primates that AEOL 10150 increases survival and improves lung function, while reducing lung damage when administered up to 24 hours after radiation exposure. The data from this newly published study provide an explanation as to how the drug accomplishes this protection, and is another important step in its development as both a radiation countermeasure and a treatment for cancer radiation therapy patients."

PTEN, a protein, is a lipid phosphatase that regulates the balance between cell survival and cell death. This study evaluated whether PTEN levels contribute to epithelial and endothelial cell death in lung tissue six weeks after radiation exposure. The study also evaluated whether PTEN expression and its effect on PI3K-Akt driven pro-survival signaling is influenced by oxidative stress (the presence of higher than normal levels of reactive oxygen species, or free radicals). To test this hypothesis, irradiated mice were treated with AEOL 10150 and lung tissue was then evaluated for changes in oxidative stress, PTEN expression, and PI3K-Akt signaling.

The study found that death of cells exposed to radiation and untreated was associated with increased PTEN expression, inhibition of downstream PI3K-AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-beta1, Nox4, and oxidative stress were also increased. Therapeutic administration of AEOL 10150 returned PTEN signaling to normal levels, suppressed oxidative stress, and dramatically reduced the number of apoptotic cells. AEOL 10150's anti-oxidant properties are well established, and this study provides additional support for the drug's anti-inflammatory and anti-apoptotic effects, as well as insight into the mechanism behind these effects.

The investigators hypothesize that upregulation of PTEN is influenced by Nox4-derived oxidative stress. Importantly, AEOL 10150 had no effect on PTEN expression in normal, non-irradiated tissue. Studies are ongoing to determine the mechanism underlying the persistent overexpression of PTEN in response to radiation. The investigators believe this is the first study to highlight the role of PTEN in radiation-induced pulmonary toxicity.

"In addition to showing efficacy in two animal species and safety in humans, the FDA requires 'a reasonably well-understood mechanism for the toxicity of the agent and its amelioration or prevention by the product' for approval under the Animal Rule", stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. "This study is a critical step forward in addressing this requirement, and has the added benefit of demonstrating that AEOL 10150 does not negatively impact PTEN in healthy normal tissue. Thus, the data will be supportive of our IND filing and phase 1 safety study for Pulmonary Acute Radiation Syndrome and our IND for cancer, which we expect to make this year."

About AEOL 10150
AEOL 10150 is a broad-spectrum catalytic antioxidant specifically designed to neutralize reactive oxygen and nitrogen species. The neutralization of these species reduces oxidative stress, inflammation, and subsequent tissue damage-signaling cascades resulting from radiation exposure. AEOL 10150 could have a profound beneficial impact on people who have been exposed, or are about to be exposed, to high-doses of radiation in the treatment of oncology.

AEOL 10150 has already performed well in preclinical and non-clinical studies, was well-tolerated in two human clinical trials, and has demonstrated statistically significant survival efficacy in an acute radiation-induced lung injury model. The Company believes it could have a profound beneficial impact on people who have been exposed, or are about to be exposed, to high-doses of radiation, whether from cancer therapy or a nuclear event.

About Aeolus Pharmaceuticals 
Aeolus Pharmaceuticals is developing a new class of catalytic antioxidant compounds that protects healthy tissue from the damaging effects of radiation. Its first compound, AEOL 10150, is being developed for oncology indications, where it is used in combination with radiation therapy. It is also being developed, with funding by the US Government, as a medical countermeasure against chemical and radiological weapons, where its initial target indications are as a protective agent against the effects of acute radiation syndrome and delayed effects of acute radiation exposure. Aeolus' strategy is to leverage the substantial investment in toxicology, manufacturing, and preclinical and clinical studies made by US Government agencies in AEOL 10150, including the contract with BARDA valued, with options, at up to $118 million, to efficiently develop the compound for use in oncology.

Forward-Looking Statements 
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' amended Annual Report on Form 10-K/A for the year ended September 30, 2010. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.

Contact:

Russell Skibsted
Sr. Vice President and Chief Financial Officer
Aeolus Pharmaceuticals, Inc. 
            1-(949) 481-9825       
 
     
 
 
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