Aeolus Pharmaceuticals Initiates Study of AEOL 10150 as a Countermeasure to Radiation Exposure in Non-Human Primates
Aeolus Pharmaceuticals, Inc. (OTC Bulletin Board:AOLS) announced today that it has initiated a study to confirm the efficacy of AEOL 10150 as a countermeasure to nuclear and radiological exposure in non-human primates. AEOL 10150 has previously demonstrated a statistically significant survival advantage when given to mice after exposure to radiation. The new study is designed to test the efficacy of AEOL 10150 as a treatment for damage to the lungs due to exposure to radiation and to begin establishing an animal model that can be validated and could be utilized by the U.S. Food and Drug Administration (US FDA) for approval of a countermeasure for Pulmonary Acute Radiation Syndrome under the "Animal Rule".
The new study builds on results from previous studies in rats and mice where it was shown that doses in the range of 5 to 30 mg/kg AEOL 10150 given daily up to 24 hrs after irradiation and administered for as long as 10 weeks mitigate functional lung injury in rats and led to a statistically significant survival advantage in mice. Investigators will examine both the acute and latent effects of radiation on the lungs and the impact that AEOL 10150 has on mitigating those effects. In rodents, non-human primates and humans, radiation of the lungs can cause reduced breathing capacity, pneumonitis, fibrosis, weight loss and death and is characterized by oxidative stress, inflammation and elevated macrophage counts. AEOL 10150 has proven to be an effective countermeasure to radiation exposure of the lungs in mice and rats.
"Initiating this study is a critical milestone for Aeolus, as we have seen positive results in mice and are now beginning work in the second animal model that we expect will be necessary for approval of AEOL 10150 as a countermeasure for Acute Radiation Syndrome ("ARS") under the FDA's Animal Rule," stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. "We look forward to the results of this study, as we expect that non-human primates will be one of the two species necessary for approval of AEOL 10150 as a countermeasure to nuclear threats under the US FDA's Animal Rule."
The FDA Animal Rule outlines criteria whereby the US FDA can rely on animal efficacy data when "evidence is needed to demonstrate efficacy of new drugs against lethal or permanently disabling toxic substances when efficacy studies in humans, ethically cannot be conducted."
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 two human clinical trials, and has an extensive pre-clinical safety and toxicology package completed.
-- Safe and Easily Stored - 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.
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.