- Single dose well tolerated up to 75 mg
- Analysis and Modeling of PK data suggests:
- Study report and protocol for single dose up to 200 mg and multiple day dosing to be submitted to the FDA Division of Medical Imaging products
- AEOL 10150 has been safe and well tolerated in 49 patients in three phase 1 studies for up to 7 days of treatment
MISSION VIEJO, CA / ACCESSWIRE / September 18, 2017 / Aeolus Pharmaceuticals, Inc. (AOLS), a biotechnology company developing compounds to protect against fibrosis, inflammation, nerve damage and infection announced today that AEOL 10150 was safe and well tolerated in a Phase 1 single, ascending dose escalation study in nine healthy subjects, meeting the primary endpoint of the study and enabling further dose escalation and a follow-on multiple dose study based on previous FDA guidance. Aeolus plans to submit the final study report to the FDA along with a protocol for dosing up to 200 mg and 7-day multiple ascending dosing shortly.
In addition to demonstrating that the new formulation of AEOL 10150 was safe and well tolerated in healthy subjects, the study provided pharmacokinetic ("PK") and pharmacodynamic data for the calculation of Human Equivalent Doses ("HED") based on optimal efficacy seen in Lung Acute Radiation Syndrome ("Lung-ARS"), sulfur mustard and soman gas animal studies. Based on these data, the HED for sulfur mustard and soman gas is estimated to be 40 to 50 mg and the HED for Lung-ARS is estimated to be 75 to 125 mg. PK data from the multiple dose study will confirm the estimated doses based on modeling of the single dose PK.
Safety was assessed by monitoring Adverse Events ("AEs") and concomitant medications and performing physical, neurological and injection site examinations, vital sign assessments, 12-lead ECGs, and clinical laboratory tests including plasma manganese levels. There were no Serious Adverse Events ("SAEs") or AEs requiring study discontinuation or hold reported. All drug-related AEs were injection site related and resolved prior to the end of the study and consisted of mild pain (5 patients), mild to moderate reddening (2 patients), mild swelling, discoloration and warmth (1 patient each). There were no clinically significant findings noted in any of the other safety parameters nor any significant abnormalities or trends identified in observed values or changes from baseline: in the continuous electrocardiogram monitoring, for vital signs, physical findings, and other observations related to safety, and there were no signs or symptoms of neurological symptoms and Uniform Parkinson's Disease Rating System examinations were normal.
"AEOL 10150 has been safe and well tolerated in 40 ALS patients and 9 healthy subjects and has demonstrated significant efficacy in animal models developed by BARDA and NIH as a broad spectrum medical countermeasure against radiation, sulfur mustard, soman, chlorine and phosgene gas exposure," said John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals, Inc. "We are grateful for NIH's continued support and commitment to move AEOL 10150 to approval in these indications. Aeolus and the US Government have invested more than $100 million to date and there are currently no treatments to address these very real threats that our country faces today. We also appreciate the collaboration, clear guidance and direction we have received from the FDA Division of Medical Imaging Products in establishing a pathway for approval under the Animal Rule."
About Acute Radiation Syndrome (ARS) and the Delayed Effects of ARS
AEOL 10150 is currently the only treatment in advanced development for Lung ARS. Statistically significant improvement in survival in both NHP and mouse models of Lung ARS have been demonstrated at HED's that have been safe and well tolerated in human safety studies. In June 2017, AEOL 10150 was granted Fast Track designation for Lung ARS by the FDA, and a special protocol assessment to reach agreement on the design of a pivotal ("adequate and well designed") study in the NHP will be submitted to the FDA shortly.
Ionizing radiation exposure through accidental release or detonation of a nuclear bomb leads to organ and tissue damage that may take months to manifest symptomatically. Direct or indirect damage to vital cellular macromolecules such as DNA, proteins, and lipids results in complex changes to molecular pathways leading to endothelial dysfunction, extravasation of plasma proteins, increased vascular contractility, vascular smooth muscle cell growth and apoptosis, monocyte migration, lipid peroxidation, inflammation, angiogenesis, epithelial-mesenchymal transition, and fibrosis in tissues. It is well documented that generation of free radicals leading to oxidative/nitroxidative modification of key intracellular signaling pathways facilitate the processes leading to radiation-induced toxicity.
The short-term clinical presentation of these cellular insults is known as Acute Radiation Syndrome or ARS, which occurs following whole- or partial-body exposure to high doses of radiation. Depending on the dose and anatomic region of exposure, the result can be acute damage to the hematopoietic system and/or gastrointestinal (GI) tract or delayed effects on the lung and kidney. Severe damage to these organ systems may lead to morbidity and mortality among the exposed population, due to immunosuppression, malabsorption, hemorrhage, infection, respiratory failure, or a combination of these injuries.
Hematopoietic ARS (H-ARS) and GI-ARS are the primary syndromes responsible for early‑onset morbidity and mortality following acute total-body irradiation. The US Government has acquired products such as Neupogen®, Neulasta® and Leukine® to treat H-ARS and Levofloxicin® and Ciprofloxicin® to treat GI-ARS. Radiation accident victims, treated with these types of products and supportive care, have survived both H-ARS and GI-ARS; however, they have then succumbed to delayed effects of acute radiation exposure, including lung injury presenting as pneumonitis and/or fibrosis. This has also been seen in mouse and non-human primate animal studies of the acute and delayed effects of total and partial body irradiation.
About AEOL 10150
AEOL 10150 protects tissue from damage and increases survival in animal models of lung damage after exposure to radiation, toxic chemicals, disease and trauma by mitigating and/or preventing cell death, inflammation and fibrosis through its action on oxidative stress and regulation of growth factors and chemokines, as well as impacting subsequent signaling pathways of reactive oxygen species production, apoptosis and fibrosis. We are developing 10150 as a MCM for national defense and for use in oncology and treating lung fibrosis.
AEOL 10150 has performed well in preclinical and non-clinical studies, demonstrating statistically significant survival efficacy in an acute radiation-induced lung injury model, and was well-tolerated in two human clinical trials in ALS patients and one human clinical trial in healthy subjects. The Company believes that AEOL 10150 could have a profound beneficial impact on people exposed to high-doses of radiation, whether from cancer therapy or a nuclear event, and potentially reduce lung damage in patients with idiopathic pulmonary fibrosis and people who inhale chemical vesicants, such as sulfur mustard gas. We also believe that AEOL 10150 could have a profound beneficial impact on people who have been exposed to nerve agents, based on the drug's demonstrated ability to protect nerve cells and cognitive ability. AEOL 10150 has received Fast Track designation and is at Technology Readiness Level (TRL) 7 for Lung ARS, TRL 6 for sulfur mustard and soman gas and TRL 5 for chlorine and phosgene gas exposure.
About Aeolus Pharmaceuticals
Aeolus Pharmaceuticals is developing a platform of novel compounds for use in biodefense, fibrosis, oncology, infectious diseases and diseases of the central nervous system. Its most advanced compound, AEOL 10150, is being developed, with funding by the US Department of Health and Human Services, 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 build public-private partnerships to develop dual use products that address unmet needs for both MCM and traditional medical indications. For more information, please visit Aeolus's corporate website at www.aolsrx.com
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 the effects of the Notification, the Company's proprietary technologies and research programs, and the Company's initiation of a phase 1 multiple dose study in healthy volunteers. 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 concerning the US Government, uncertainties of progress and timing of clinical trials, scientific research and product development activities; difficulties or delays in development, testing and 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; competition from other biopharmaceutical companies; and whether BARDA is ultimately able to exercise one or more additional options under its contract with Aeolus. 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, 2016. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof.
President and Chief Executive Officer
Aeolus Pharmaceuticals, Inc.
SOURCE: Aeolus Pharmaceuticals