Mr. McManus: Aeolus Pharmaceuticals is a biotechnology company that's focused on the development of a portfolio of catalytic antioxidants. Our lead drug, AEOL 10150, has been tested extensively as a treatment for radiation exposure, both in the context of cancer radiation therapy and in radiation exposure from a nuclear event. We're a company with a platform of 199 compounds, but the bulk of our work is on this lead drug in the area of radiation.
TWST: What is the science background on the application of antioxidants to oxidative stress? How does this particular focus of Aeolus fit into what we already know and may hope to find?
Mr. McManus: The technology that we are developing was created at Duke University by a team of scientists led by Dr. Irwin Fridovich. Dr. Fridovich is credited with the discovery of the superoxide dismutase (SOD) function for SOD proteins, and these SOD proteins are the body's natural defense against reactive oxygen and reactive nitrogen species, otherwise known as free radicals. So they did this work on the discovery of protective mechanisms within the body and then went about creating or trying to develop a technology that would offset levels that were out of balance - either when there were extremely high levels of free radicals or oxidative stress in the body because of injury or disease, or when the body's natural mechanisms were either shut down or underperforming. And that's where the idea behind the technology came from. They created this platform that we're developing, which basically has a manganese metal surrounded by a synthetic porphyrin. The library of compounds has different pendents that hang off the porphyrin that changes the activity and stability of the compound. The manganese center inside the porphyrin is the catalyst where electrons are exchanged with the free radicals, which basically neutralizes them by converting them to less-reactive species, such as oxygen and water. So as an example, if you have overproduction of superoxide, which is a reactive oxygen species and is damaging to the body, and you give AEOL10150, the manganese exchanges electrons with the superoxide and, essentially through a series of reactions, changes superoxide to oxygen and water. AEOL10150 treatments can dramatically lower the levels of oxidative stress in the body. We've collected a lot of animal data that demonstrates that AEOL10150 treatment lowers the measurements of oxidative changes to proteins, lipids and DNA. We also see a significant impact on markers of inflammation and, ultimately, we're seeing protection of lung cells, GI cells, and other systems and organs in the body from the damaging effects of things like radiation, sulphur mustard gas exposure and smoke inhalation.
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