AEOL 10150 increases regeneration of GI stem cells: NIAID study results

Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) announced today that recent experiments in preclinical models conducted by the National Institutes of Health’s (NIH), National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Medical Countermeasure Development program have shown that AEOL 10150 can effectively increase regeneration of gastro-intestinal (GI) stem cells, reduce the severity and duration of diarrhea and improve survival when administered at 24 hours after doses of total-body irradiation that produce the lethal GI syndrome. There are no published studies of agents that accomplish this enhanced stem cell regenerative effect while maintaining GI function and improving survival when administered post irradiation.

“The Aeolus drug AEOL 10150 passed our first phase of rigorous testing and showed definitive effects on crypt stem cells and other secondary parameters used to assess drug efficacy in ameliorating the acute GI syndrome,” stated Catherine Booth, Ph.D., Managing Director, Contract Research Services at Epistem, Ltd. “This is one of few drugs shown to affect 'both' stem cell crypt regeneration and survival in a syndrome that heretofore has been resistant to mitigation with drugs administered at 24 hours post lethal exposure.”

NIAID has a contract with the University of Maryland to provide product development support services for the development of countermeasures against radiation exposure. These studies are being conducted by Epistem, a subcontractor of the University of Maryland, in compliance with criteria of the FDA that are a pre-requisite for movement of the Aeolus drug along the pathway for FDA licensure to treat lethally irradiated persons in the event of a terrorist nuclear act. Epistem operates a major contract research organization and provides services to identify novel drugs that can protect or improve the repair of the gastrointestinal (GI) tract following exposure to irradiation and performed these studies as part of its US NIH’s program for the screening of a novel agents for bio-defense applications.

The NIH NIAID Radiation/Nuclear Medical Countermeasure Development program leads the U.S. effort to develop treatments for radiation sickness following a nuclear terrorist attack. GI-ARS is a massive, currently untreatable, problem following high-dose, potentially lethal radiation exposure. Agents that mitigate these effects would reduce sickness and hopefully prevent fatalities. The tests performed by NIH/NIAID are also likely to identify agents with oncology supportive care applications - agents that will reduce the severe ulceration and diarrhea (mucositis) experienced by patients during radio- and chemo-therapy. Risk of injury to the intestine is dose-limiting during abdominal and pelvic radiation therapy—interventions that limit post-irradiation intestinal dysfunction would have significant impact in large number of patients, estimated to be between 1.5 to 2 million cancer survivors with post-irradiation intestinal dysfunction. AEOL 10150 has previously demonstrated protective effects in protecting healthy normal cells from damage occurring due to cancer radiation therapy in preclinical models.

Radiation Damage to the GI Tract

The intestinal epithelium, a single layer of cells lining the surface of the GI lumen, is responsible for vital functions of nutrient absorption, maintaining fluid and electrolyte balance and protection of the body from bacteria, bacterial toxins and non absorbed materials. The functional integrity of the GI system is maintained via incessant production of epithelial cells from specialized stem cells located in crypts at the base of the epithelium. High-dose, total-body irradiation can result in a lethal GI syndrome that results in significant morbidity and mortality within days consequent to killing of the crypt stem cells and loss of the protective and absorptive epithelial barrier. There are no FDA-approved drugs or biologics to treat the acute GI syndrome.