Aeolus Pharmaceuticals' AEOL 10150 Protects Lungs from Fractionated Radiation; Reduces Angiogenesis and InflammationLAGUNA NIGUEL, Calif.--(BUSINESS WIRE)--April 15, 2008 - Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) reported data published in the peer-reviewed journal, Free Radical Research, show the Company's lead compound, AEOL 10150, provided statistically significant protection of the lungs of Fisher 344 rats exposed to fractionated radiation in a study led by Zeljko Vujaskovic, M.D. Ph.D. of Duke University. The study also demonstrated that the compound reduced markers for tissue hypoxia, angiogenesis, inflammation and oxidative stress in rats studied in this experiment.
The primary objective of this study was to determine whether administration of AEOL 10150 reduces the severity of long-term lung injury induced by fractionated radiation. Fisher 344 rats were randomized into five groups: radiation therapy plus AEOL 10150 (2.5 mg/kg BID), AEOL 10150 (2.5mg/kg BID) alone, radiation therapy plus AEOL 10150 (5 mg/kg BID), AEOL 10150 (5 mg/kg BID) alone and radiation therapy alone. Animals received five 8 gray ("Gy") fractions of radiation therapy to the right hemithorax each day for five days. AEOL 10150 was administered 15 minutes before radiation exposure and 8 hours later each of the five days of radiation therapy treatment, followed by subcutaneous injections for 30 days, twice daily. Lung histology at 26 weeks revealed a significant decrease in lung structural damage and collagen deposition in the radiation therapy plus AEOL 10150 (5 mg/kg BID) group, in comparison to radiation therapy alone.
Immunohistochemistry studies revealed a significant reduction in tissue hypoxia (HIF-1a, CAIX), angiogenic response (VEGF, CD-31), inflammation (ED-1), oxidative stress (8-OHdG, 3-nitrotyrosine) and fibrosis pathway (TGFb1, Smad3, p-Smad2/3), in animals receiving radiation therapy plus AEOL 10150 (5 mg/kg BID). Administration of AEOL 10150 at 5 mg/kg BID during and after RT results in a significant protective effect from long-term radiation therapy-induced lung injury.
"In addition to its support for the potential use of AEOL 10150 in cancer radiation therapy, this data supports the possible use of AEOL 10150 against radiation-induced tissue damage from radiological or nuclear terrorism and nicely complements ongoing studies showing AEOL 10150 as a potentially protective agent against chemical terrorist agents such as mustard gas," stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. "These studies collectively suggest that AEOL 10150 may be a potent counteract agent against multiple terrorist threats."
Radiation therapy is used alone or in combination with surgery and chemotherapy in the care and management of nearly all adult and most pediatric patients with lung malignancies. Success in controlling lung cancer by radiation therapy hinges on being able to inactivate the cancer cells while preserving normal tissue function. The National Cancer Institute ("NCI") estimates that there will be approximately 215,000 new cases of lung cancer in the United States and approximately 162,000 deaths. According to the NCI, "results of standard treatment are poor except for the most localized cancers." The American Society for Therapeutic Radiology and Oncology reports that in 2004, nearly one million Americans made 23.4 million visits for radiotherapy treatments for cancer. The total market potential for an effective enhancement to current radiation therapy is estimated to be in excess of $1 billion.
The Potential for Metalloporphyrin Antioxidants in Radiotherapy for Cancer
Radiotherapy treatment in cancer has the positive effect of tumor destruction, but also has the negative effect of normal tissue damage. Optimal dosing in radiotherapy balances maximum tumor destruction with minimal toxicity and damage to normal tissue. The "ionizing radiation" used in cancer radiotherapy generates reactive oxygen species ("ROS") and other free radicals. These free radicals cause DNA damage and cell death. Catalytic antioxidants, such as Aeolus' AEOL 10150 and AEOL 10113 have been shown to neutralize free radicals and can reduce radiation-induced normal tissue damage. It is equally important that they also not protect the cancer from radiotherapy, which has been demonstrated in animal studies of both AEOL 10150 and AEOL 10113. A compound that protects healthy normal cells while not interfering with tumor destruction could provide patients and physicians the ability to either reduce side effects from cancer radiotherapy or to increase the radiotherapy dose, thus enhancing the potential for tumor destruction.
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. Additionally, the Company has plans to initiate 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, 2007. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.
Aeolus Pharmaceuticals, Inc.
John L. McManus
President and Chief Executive Officer
Posted: April 2008