A significant need exists for effective medical countermeasures for radiation-induced pneumonitis and pulmonary fibrosis associated with the delayed effects of acute radiation exposure. Of great importance are countermeasures that can be distributed for use without medical supervision, making orally effective countermeasures of high interest and importance. To address this unmet need, Humanetics Corporation is developing BIO 300 Oral Suspension (active ingredient genistein) to treat the delayed effects of acute radiation exposure (DEARE) in the lung. Genistein, a non-specific tyrosine kinase inhibitor, has a strong history of safety, and has substantial radioprotective effects linked to its strong antioxidant capacity, anti-inflammatory properties, and its effects on cell cycle division. In preclinical studies summarized in this proposal BIO 300 has been shown to significantly improve survival, mitigate lung tissue injury, and improve pulmonary function following whole thoracic lung irradiation. The aim of this proposal is to determine the optimum therapeutic dosing regimen of BIO 300 to reduce lung damage and maximize the likelihood for survival following acute radiation exposure to the thoracic region. Models in which the dose response and timecourse of radiation induced pulmonary damage are well defined will be used in the proposed studies. Studies are also proposed to further understand the effect that total or partial body irradiation has on BIO 300s pharmacokinetic properties. The overall goal of the proposed studies is to advance the development of BIO 300 as a medical countermeasure towards FDA approval. The proposed work builds on the R&D experience of Humanetics Corporation toward the development of BIO 300 as a medical countermeasure for acute radiation exposure. The main emphasis of future development will be to move BIO 300 development into large animal efficacy testing to determine if the positive efficacy data observed in the rodent model translates to a larger animal. Continued development of BIO 300 will undoubtedly expand the scientific knowledge base and support the continued evaluation and development of agents to prevent and/or treat the acute and chronic effects of radiation exposure. Moreover, with BIO 300s advanced development as a medical radiation countermeasure, and as an adjunct to cancer radiotherapy, it presents an opportunity for an accelerated development course through pivotal efficacy trials and to licensure.
Public Health Relevance Statement: Project Narrative Short-term exposure to a high dose of total or partial body irradiation, such as from a nuclear accident or act of terrorism, has both acute and delayed effects on bodily organs. Humanetics is developing a treatment for the delayed effects of acute radiation exposure to the lung. This drug, BIO 300, is a liquid formulation that is shelf-stable, safe, and can be administered without the need for medical supervision. In this proposal, Humanetics is working with experts at the University of Maryland, School of Medicine to determine the most effective treatment course for BIO 300. The goal is to continue BIO 300s development toward FDA approval as a drug to mitigate radiation-induced lung damage.
NIH Spending Category: Lung
Project Terms: Acute; Address; Adult Respiratory Distress Syndrome; Advanced Development; animal efficacy; Animal Model; animal rule; Animals; Anti-inflammatory; Anti-Inflammatory Agents; Antioxidants; Area Under Curve; Baltimore; Biological Availability; Blood; Body Weight; Bone Marrow; C57L/J Mouse; Caliber; cancer radiation therapy; Cell Cycle; Cell Cycle Progression; Cells; Characteristics; Chest; Chronic; course development; cytokine therapy; Data; Development; Development Plans; DNA Damage; Dose; drug development; Drug Kinetics; effective therapy; efficacy testing; efficacy trial; Evaluation; experience; Exposure to; Face; FDA approved; Fibrosis; Filgrastim; Formulation; Free Radicals; Future; gastrointestinal; gender difference; Genistein; Goals; Granulocyte Colony-Stimulating Factor; Hematopoietic; Histopathology; Human; improved; Individual; Inflammatory; Injury; interest; irradiation; knowledge base; Legal patent; Lethal Dose 50; Licensure; Life; Link; liquid formulation; Lung; lung injury; Maryland; Mediating; Medical; medical schools; Modeling; Morbidity - disease rate; mortality; Mus; nanoparticle; Nuclear Accidents; Oral; Oral Administration; Organ; Organ failure; oxidative damage; Particle Size; Pegfilgrastim; Pharmaceutical Preparations; Play; Positioning Attribute; preclinical study; prevent; Prevention; Property; Protein Tyrosine Kinase; Pulmonary Fibrosis; pulmonary function; Pulmonary Inflammation; Radiation; radiation effect; Radiation Injuries; Radiation Pneumonitis; Radioprotection; Rattus; Reaction; Recombinants; Recording of previous events; Regimen; repaired; research and development; respiratory; response; Rodent Model; Role; Safety; Self-Administered; Signal Pathway; Signal Transduction Pathway; Structure of parenchyma of lung; Supervision; Supportive care; Suspension substance; Suspensions; Syndrome; Terrorism; Therapeutic; Time; Tissues; Toxicokinetics; Translating; Tyrosine Kinase Inhibitor; Universities; Weight; Whole-Body Irradiation; Work
