Positive Data on AEOL 11207 in Pre-Clinical Epilepsy Model Published in the Journal of Neurobiology of Disease
Aeolus Pharmaceuticals Compound Significantly Decreases Both the Frequency and Duration of Spontaneous Seizures; Increase in Average Life Span; Protected Against Neuronal Death
MISSION VIEJO, CA--(Marketwire -02/07/12)- 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 11207 inepilepsy in Neurobiology of Disease. The article, titled "Mitochondrial oxidative stress and epilepsy in SOD2 deficient mice: Attenuation by a 2 lipophilic metalloporphyrin," was authored by Li-Ping Liang, Simon Waldbaum, Shane Rowley, Ting-Ting Huang, Brian J. Day and Manisha Patel, of the University of Colorado, National Jewish Health, Stanford University and the VA Palo Alto Health Care System, and was sponsored by a grant from the National Institutes for Health (NIH) and the CURE Foundation.
Epileptic seizures are a common feature associated with inherited mitochondrial diseases. The study investigated the role of mitochondrial oxidative stress in epilepsy resulting from mitochondrial dysfunction using cross-bred mutant mice lacking mitochondrial manganese superoxide dismutase (MnSOD or SOD2) and a lipophilic metalloporphyrin catalytic antioxidant.
AEOL11207 treated Sod2 -/- mice showed a decrease in the average number and duration of spontaneous behavioral seizures based on daily observation from 17 to 20 days old compare to vehicle treated Sod2 -/- mice. Only 60% of AEOL 11207-treated Sod2 -/- mice exhibited spontaneous seizure activity compared to 100% of vehicle-treated Sod2 -/- mice. Seizures from AEOL11207- treated Sod2 -/- mice occurred less frequently and had shorter duration as compared to vehicle-treated Sod2 -/- mice. Furthermore, the continuous seizure event those last longer than 60 s was not observed in AEOL 11207 treated Sod2 -/- mice. The AEOL 11207 group showed no detectable adverse events up to 20 days of treatment and no mortality resulting from treatment. No differences were observed in seizure severity between vehicle and AEOL 11207-treated Sod2 -/- mice.
The occurrence of epileptic seizures in Sod2 42 -/- mice and the ability of catalytic antioxidant therapy to attenuate seizure activity, mitochondrial dysfunction, and ATP levels suggest that ongoing mitochondrial oxidative stress can contribute to epilepsy associated with mitochondrial dysfunction and disease. Removal of reactive oxygen species (ROS) with catalytic antioxidants, such as AEOL 11207, may provide new therapeutic strategies for epilepsy and other pathological manifestations of mitochondrial diseases. The data from these studies suggests potential implications for inherited mitochondrial disorders resulting in epilepsy such as mitochondrial encephalopathy with ragged red fibers (MERRF), mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) and other metabolic disorders associated with seizures. Aeolus' compounds, including AEOL 11207, contain a manganese center that is capable of detoxifying a wide range of ROS and lipid peroxide radicals. AEOL11207 has potent H2O2 scavenging activity and is a potent inhibitor of mitochondrial ROS production.
"This study is an important step in confirming the role of oxidative stress in epilepsy and the potential role of AEOL 11207 as an effective treatment," stated Brian Day, PhD, Chief Science Officer of Aeolus Pharmaceuticals, Inc. "We look forward to continuing research in this important area of medicine."
About AEOL 11207
AEOL 11207 is a novel orally available lipophilic, metalloporphyrin, catalytic antioxidant, with high potency for catalytic removal of endogenously generated reactive oxygen species. The AEOL platform of metalloporphyrin compounds contains a manganese center that is capable of detoxifying a wide range of ROS, including O2.-, H2O2, ONOO-, and lipid peroxide radicals (Day, 2004). AEOL 11207 has potent H2O2 scavenging activity and relatively modest SOD activity (Castello et al., 2007; Liang et al., 2007) and is a potent inhibitor of mitochondrial ROS production (Trova et al., 2003).
Data developed by Aeolus' scientists and Dr. Manisha Patel at the University of Colorado Anschutz Medical Campus indicate that when administered orally, AEOL 11207 is greater than 80% bioavailable, meaning that it is readily absorbed and reaches both the circulatory system and the brain in sufficient amounts to demonstrate biological activity.
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.
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.