AEOL-10150

For our latest coverage on healthcare-related developments regarding the evolving crisis in Ukraine click here. Two months after the nuclear accidents at the Fukushima power plant following the earthquake and the tsunami that hit Japan in March 2011, the risks of potential radiation poisoning continue to make headline news. The pictures of the damaged nuclear reactors have raised memories of the Chernobyl disaster and the plight of the reactor workers has emphasised the need for powerful anti-radiation drugs like never before. In the weeks after the disaster, potential buyers from Asia have swamped western bio-tech companies with requests for any anti-radiation drugs currently available. They have responded by donating hundreds of thousands of doses of radiation blocking drug potassium iodide to Japan. On top of that, US customers, whose fears of a radiation cloud reaching the west coast of the nation were sparked by scaremongering media reports, rushed to buy up anything they could. Even though there had never been a shortage of iodine supply before, panic buyers have caused a temporary shortage, affecting supply to the irradiated zones in northern Japan. Related Those recent events, as terrible as they are for the East Asian nation, have triggered a discussion about the radiation drugs market and the readiness of countries for a potential nuclear disaster. The anti-radiation salt: potassium iodide “Potassium iodide is not really an anti-radiation drug as such; it just minimises the uptake of radioactive iodine.” The most commonly used ‘drug’ currently available on the market is potassium iodide, also called KI, a salt of stable, not-radioactive iodine. The salt, manufactured by the two FDA-approved companies Anbex and Fleming Pharmaceuticals in the US, protects thyroid glands from radioactive iodine. A human thyroid cannot tell the difference between stable and radioactive iodine and will absorb both. The salt works by blocking the radioactive iodine from entering the thyroid gland as it becomes ‘full’ with the stable iodine and cannot take up any more of the substance – either stable or radioactive. Environmental sciences programme manager at the Royal Society of Chemistry (RSC), Brian Carter, explains: “In an incident such as Fukushima, Iodine-131 will be the most common radionuclide released into the atmosphere. Iodine-131 is particularly dangerous to the thyroid gland because it may lead to thyroid cancer.” However, the salt will only be effective if it is taken prior to exposure, blocking the radioiodine uptake by the thyroid for the next 24 hours. Carter, who was among the scientists warning the public after the incident in Japan against a nuclear panic, says: “Potassium iodide is not really an anti-radiation drug as such; it just minimises the uptake of radioactive iodine. It doesn’t stop the radiation.” “Research in this area would not be a high priority for pharma companies as it would not generate much in the way of revenue.” Nevertheless, stockpiling of potassium iodide is recommended by health officials worldwide to prevent thyroid cancer of those exposed to radioactive iodine in the event of a nuclear reactor accident or detonation of a nuclear bomb. For instance, a US policy was set by a 2002 law that called for the distribution of the salt to residents up to 20 miles away from reactors. “The only possible pharmaceutical weapon against a nuclear crisis we are aware of is potassium iodide,” says Carter. Nevertheless in 2008, the Bush administration dropped the regulation saying that evacuation would be a much better option. And the salt, available in pharmacies and health food shops without prescription, is far from being a magic medicine against exposure to high levels of direct radiation. Reawakening research for new drugs The serious radiation leaks at the damaged Fukushima nuclear power plant have rekindled public fears about acute radiation syndrome (ARS) or radiation sickness and shown the need for the exploration of a powerful drug against radiation exposure. Some small biotechnology companies, mostly working under contracts from the US government to develop drugs to treat ARS, have been put into the spotlight in the aftermath of the incidents. Aimed at treating people after a military or terrorist attack involving nuclear or radioactive weapons, research has accelerated since the crisis, as the drugs could also be used in case of nuclear accidents. “However, research in this area would not be a high priority for pharma companies as it would not generate much in the way of revenue,” says Carter. The interest in developing a new drug lies therefore with the government and the military. In the US, the National Institutes of Health (NIH) and the Department of Defense (DoD) have subsidied basic research into the field. In 2006, Congress passed legislation to establish the Biomedical Advanced Research Development Authority (BARDA). Since 2008, the official body has invested $164m into anti-radiation drug candidates. Countermeasures against ARS under development in companies and funded by federal programmes currently range from stem cell treatments to toll-like receptor agonists. The Maryland-based stem cell company Osiris Therapeutics has recently received a contract from the DoD to develop its Prochymal stem cell therapy as a medical countermeasure to nuclear terrorism and other radiological emergencies. Working on a class of catalytic antioxidant compound (AEOL 10150) to reduce oxidative stress, inflammation and tissue damage is Aeolus Pharmaceuticals, a small California-based biotech company. In February 2011, BARDA awarded the company a contract to develop AEOL 10150 as a medical countermeasure against the pulmonary sub-syndrome of ARS. One day after the news about the nuclear crisis in Japan became public, about 5.6 million shares of the company changed owner – over 1,000 times the company’s usual trading volume. However, the research process is slow and faces one major problem: the drugs cannot be tested in human clinical trials as it is considered highly unethical to expose people to large amounts of radiation. The FDA in the US has therefore developed an abbreviated pathway for approval, called the animal efficacy rule. Only drugs tested under this process, which includes showing efficacy in animals, safety in humans and biomarkers to show that the mechanism is common to both animals and humans get approval and will be released on the market. Cleveland Biolabs’ protectan CBLB-502 Another American biotechnology company developing a new drug against radiation sickness is the Buffalo-based Cleveland Biolabs (CBLI). Scientists there have developed CBLB-502, a ‘protectan’ that derives from the bacterial protein flagellin and fools the body into believing there has been a salmonella infection. The body responds by producing substances that help to repair the immune system and gastrointestinal tract. “The serious radiation leaks at the damaged Fukushima nuclear power plant have rekindled public fears about radiation sickness.” After the events in Japan, the company experienced a spike in its trading interest and the research of CBLB-502 was fast-tracked by the FDA. According to an interview of the Wall Street Journal’s Market Watch with CLBI chief executive Michael Fonstein, the new medicine has also been offered free of charge for the use in any humanitarian efforts in Japan – even though the treatment has yet to emerge from the testing phase. Tested under the FDA animal efficacy rule with funding from the DoD and the BARDA, the drug is at least two years away from approval, as Cleveland BioLabs is aiming to submit it to the FDA by late 2012. Regardless of the current research efforts Carter, remains cautious, saying that the drugs need more clinical trials before conclusions on their potential benefits can be made. He believes that western countries are well-prepared for the case of a nuclear disaster. “The UK for instance is likely to be okay given that the sites of nuclear power stations are away from well populated areas. The supply of potassium iodide is also readily available,” he says. However, the outlook for the introduction of a powerful drug in the very near future is not a very positive one; most are about two to five years away from regulatory approval. And because they cannot be tested in human clinical trials, there is the slight danger that they might not even work in the case of high radiation exposure.

SAN DIEGO, March 13 /PRNewswire-FirstCall/ -- Aeolus Pharmaceuticals, Inc. , a developer of a new class of disease-modifying compounds with potent activity in pre-clinical models of central nervous system diseases and oncology, announced today that it has received a milestone payment and equity consideration from ARCA Discovery, Inc., a privately held cardiovascular-focused company ("ARCA"). In 2003, CPEC, LLC ("CPEC"), a limited liability company owned by Aeolus (35%) and Indevus Pharmaceuticals, Inc. (65%), out-licensed all rights to a potential therapeutic compound referred to as "bucindolol" to ARCA. Both the cash payment and equity consideration received by Aeolus are based upon Aeolus' ownership interest in CPEC, and a renegotiation of certain terms of the 2003 agreement between CPEC and ARCA. Richard P. Burgoon, Jr., Chief Executive Officer to Aeolus, noted that, "The cash payment from this milestone will be used to further the development of Aeolus' catalytic antioxidant technology." Mr. Burgoon further commented that, "We are pleased to see progress in the development of bucindolol, a compound with potential for the treatment of heart failure." The $350,000 payment received by Aeolus was triggered by ARCA receiving investment funding. The equity consideration to Aeolus was consideration for a modification of the license agreement between CPEC and ARCA. Future milestone payments and royalty payments to Aeolus, if any, while provided for under the agreement between CPEC and ARCA, can not be assured nor guaranteed. Bucindolol was previously evaluated in Phase III clinical studies, and although the drug was found to be safe, these prior Phase III clinical studies were discontinued in 1999 following an interim analysis of the data. The interim data analysis revealed that some subpopulations within the study appeared to benefit from the drug, while other subpopulations did not. In total, bucindolol has been evaluated in Phase III clinical trails involving more than 3,000 patients with advanced heart failure and myocardial ischemia. About Aeolus Pharmaceuticals Aeolus is developing a variety of therapeutic agents based on its library of 200 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 has shown the ability to scavenge a broad range of reactive oxygen species, or free radicals. As a catalytic antioxidant, AEOL 10150 mimics and thereby amplifies the body's natural enzymatic systems for eliminating these damaging compounds. Aeolus has completed a Phase I dose escalating safety study of AEOL 10150 in patients diagnosed with Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease), which demonstrated that the drug is safe at the tested doses with no serious adverse events, and has to date complete two multiple dose cohorts of a planned three dose- multiple dose study-the completed doses were 40 mg, twice daily (80 mg total per day) for 6 days and a single 40 mg administration on the 7th day, and 60 mg, twice daily (120 mg total per day) for 6 days and a single 60 mg administration on the 7th day. In both cases the drug was safe with no serious adverse events. Because oxygen-derived free radicals are believed to have an important role in the pathogenesis of many diseases, Aeolus' catalytic antioxidants are believed to have a broad range of potential therapeutic uses. The Aeolus Pipeline Initiative, begun in the third calendar quarter of 2005, is an internal development initiative focused on advancing, in addition to AEOL 10150, several of the most promising catalytic antioxidant compounds from Aeolus' proprietary library of 200 compounds. The initial therapeutic focus areas for the Aeolus Pipeline Initiative are: Parkinson's disease; Cystic Fibrosis; Chronic Obstructive Lung Disease; Radioprotection; Tumor Suppression/Bone Marrow Transplantation; and Stroke. These therapeutic focus areas were selected based upon preliminary data developed using Aeolus catalytic antioxidant compounds. 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' Quarterly Report on Form 10-Q for the quarter ended December 31, 2005. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Please visit our website at . Aeolus Pharmaceuticals, Inc. CONTACT: Richard P. Burgoon, Jr., Chief Executive Officer of AeolusPharmaceuticals, Inc., +1-949-481-9825 Web site: