ACUTE RADIATION SYNDROME
Aeolus is developing AEOL-10150 under a five year, $118 million contract with the Biodmedical Advanced Research and Development Authority (BARDA), a division of the United States Department of Health and Human Services. The goal of the contract is to achieve FDA approval for AEOL-10150 as a treatment for the pulmonary sub-syndrome of Acute Radiation Syndrome (Lung-ARS) and the delayed effects of acute radiation exposure (DEARE) under the Animal Rule.
The FDA’s Animal Rule allows for approval of drugs using only animal models to demonstrate efficacy when there is no ethical way to run human studies. Generally, the Animal Rule requires efficacy studies in two animal species. For AEOL-10150, the FDA has concurred with Aeolus’ choice of mouse and non-human primate (“monkey”) models in Lung-ARS and DEARE. These studies are fully funded under the BARDA contract.
Both mouse and monkey studies in Lung-ARS last for six months to allow time for the sub-syndrome to develop and to track survival over an extended period. AEOL-10150 has successfully increased healthy survival in multiple animal studies to date.
In 2014, Aeolus announced positive results from six month study in rhesus macaque monkeys performed under the BARDA contract. Treatment with AEOL-10150 24 hours after exposure to acute, high dose radiation doubled survival at 180 days when compared with untreated animals. The survival data from this study will be a key component to a pre-Emergency Use Authorization application for AEOL-10150. An Emergency Use Authorization (EUA) is a determination by the FDA that an unapproved drug may be used in the event of an emergency.
BARDA has made the majority of its procurement for the Strategic National Stockpile prior to FDA approval following a pre-EUA application. Aeolus believes a successful pre-EUA filing could allow sales of AEOL-10150 to the U.S. Government as early as the second half of 2015.
The BARDA contract also funds additional human safety studies. AEOL-10150 has previously been tested in two Phase I studies that demonstrated no serious adverse effects and no maximum tolerated dose. An additional Phase I safety study is planned for early 2015. This study is another requirement for the pre-EUA application.
Large-scale, GMP manufacturing development is ongoing and funded by the BARDA contract. Aeolus believes it will meet the manufacturing requirements for the pre-EUA application in 2015.
Chemical Gas Exposure
AEOL-10150 is being developed by the National Institutes of Health’s Countermeasures Against Chemical Threats (CounterACT) program through direct grants to researchers affiliated with Aeolus. Multiple rodent studies have demonstrated a significant survival advantage when AEOL-10150 is administered following exposure to chemical vesicants such as mustard gas and chlorine gas.
Aeolus intends to meet with the FDA to discuss an appropriate large-animal model and prepare for an Investigational New Drug (IND) submission for this indication. The company expects that development will continue to be funded by NIH CounterACT.
In September 2013, NIH CounterACT awarded a $4.3MM grant to Dr. Manisha Patel of the University of Colorado to develop AEOL-10150 as a treatment for exposure to nerve gases such as sarin and soman. The grant was driven by a pilot study demonstrating that AEOL-10150 provides neuroprotection, decreases oxidative stress, and significantly improves survival in rats exposed to pilocarpine — a surrogate for the nerve agents — when administered with current standard of are for exposure.
Aeolus’ research partners are currently conducting further studies in this indication under the NIH funding.
The Company believes the positive data in chemical vesicant and nerve gas models offers an additional development pathway to FDA approval. More importantly, continued efficacy in these development programs will make AEOL-10150 more attractive as a drug for potential stockpiling as a treatment for multiple threats.
Idiopathic Pulmonary Fibrosis
Aeolus’s strategy is to leverage the significant government investment in the development of AEOL 10150 to develop the drug for use as a treatment for Idiopathic Pulmonary Fibrosis (“IPF”). IPF is a progressive, fatal disease characterized by rapid development of scarring, known as fibrosis, in the lungs. This development program is a direct outcome of the data generated in Lung-ARS under the BARDA contract. The animal models used in the BARDA program are models for the development of inflammation and fibrosis in the lungs and are, therefore, useful in evaluating potential treatments for other fibrotic lung diseases such as IPF.
In March 2015, the Company received notice from the Office of Orphan Products Development at the U.S. Food & Drug Administration (FDA) granting Orphan Drug Designation for AEOL 10150 "for treatment of idiopathic pulmonary fibrosis." Orphan Drug Designation entitles the sponsor to a seven-year marketing exclusivity period, clinical protocol assistance with the FDA, as well as federal grants and tax credits.
The Company intends to file an IND for 10150 in IPF in 2015 and begin clinical studies as soon as possible.
Radiotherapy for Oncology
Aeolus’s strategy is to leverage the significant government investment in the development of AEOL-10150 to develop the drug for use in combination with radiation therapy for cancer. One million patients in the US receive some form of radiation therapy for solid tumors each year. The efficacy of that therapy is often compromised by side effects from radiation. The company intends to pursue development of AEOL-10150 as a treatment for those side effects.
Additionally, pre-clinical studies have shown that administration of AEOL-10150 does not interfere with the effectiveness of either radiation or front-line chemotherapy drugs. More importantly, these studies have demonstrated that AEOl-10150 may have a tumor suppressive effect following radiation therapy. The company intends to pursue this potential effect in the design of its clinical program.
Following completion of the human safety studies under the BARDA contract, Aeolus intends to initiate one or more human studies in patients receiving radiation therapy for cancer.