Development of BIO 300 as a MCM for lethal radiation pneumonitis/fibrosis

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Project Summary 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 300’s 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 300’s 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.