DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Development of BIO 301 to Prevent Acute Radiation Syndrome and Mitigate the Delayed Effects of Acute Radiation Exposure

Principal Investigator: KAYTOR, MICHAEL D
Institution Receiving Award: HUMANETICS CORPORATION
Program: JWMRP
Proposal Number: JW180056
Award Number: W81XWH-19-2-0060
Funding Mechanism: Military Medical Research And Development Award
Partnering Awards:
Award Amount: $5,999,215.00


PUBLIC ABSTRACT

Fiscal Year 2018 Joint Warfighter Medical Research Program (JWMRP) Focus Area: This proposal is dedicated to the Radiation Health Effects Research Program. Specifically, the project will continue development of a leading medical countermeasure for the protection and prevention of injury caused by ionizing radiation exposure (prophylaxis).

Rationale and Scientific Objective: Individuals exposed to high doses of acute radiation face life-threatening injury. The objective of this proposal is to accelerate the development of BIO 301 toward Food and Drug Administration (FDA) approval as a preventative measure against the potentially lethal consequences of radiation exposure. As lethal radiation injury cannot be ethically studied in humans, medical countermeasures for such indications are developed according to the FDA’s “Animal Rule,” which stipulates that drug effectiveness must be demonstrated in two animal species, and then predicted to work in humans. Humanetics Corporation (Humanetics) is developing a radioprotective agent, genistein, which is able to prevent lethality from acute radiation exposure. In small animals (mice), a single dose of genistein 24 hours before radiation exposure can improve 30-day survival from ~15% to almost 100%. The original formulation of genistein, called BIO 300, has been transformed into a novel formulation, called BIO 301, through a currently funded Congressionally Directed Medical Research Programs Reformulation grant. The novel BIO 301 formulation has improved bioavailability over BIO 300, and is currently being developed into a tablet or capsule, such that it can be taken as a pill.

This new project funded by JWMRP will drive BIO 301 forward on all fronts. The completion of this proposed project would likely position BIO 301 for a pre-emergency use authorization (EUA) so that it could be acquired by the military in the case of emergency, and also move the product toward approval under the FDA Animal Rule. The studies proposed will demonstrate that BIO 300/BIO 301 can prevent the lethality of high doses of radiation in nonhuman primates, and determine the proper human dose for BIO 301, through a clinical trial with healthy human volunteers to establish what various doses of BIO 301 impact the drug exposure of blood in human subjects.

Military Benefits: The Department of Defense must be prepared to execute military missions in environments with excessive levels of radiation to manage crises associated with terrorist activities and consequences in the event of the detonation of a nuclear weapon. At present, there are no FDA-approved prophylactic medical countermeasures to prevent or lessen both acute and delayed injuries for Warfighters and first responders who may be exposed to radiation. The development of BIO 301 for radiation exposure that can be used prophylactically will significantly enhance the warfighting mission by sustaining unit effectiveness and is critical for operational preparedness in nuclear/radiological threat environments.

Clinical Applications: Humanetics has developed BIO 300 into a dual-use drug, both as a medical countermeasure for radiation exposure and as a supportive care drug for cancer patients undergoing radiation therapy for solid tumors. In addition to its prevention of acute radiation syndrome, the drug has also been shown to mitigate lung tissue injury resulting from whole thoracic lung irradiation when given before radiation exposure. Thus, Humanetics explored the potential of BIO 300 to be used to help cancer patients get through radiation therapy with less side effects caused by radiation toxicity. Humanetics performed experiments that showed that the radioprotective benefits of BIO 300 do not apply to tumor cells. Thus, radiation could be used to effectively kill tumors, and BIO 300 could be implemented to minimize the corresponding side effects. These studies have collectively enabled BIO 300 to achieve FDA Investigational New Drug (IND) status (IND 119322) as a potential agent to prevent the side effects associated with cancer radiation therapy, and it is currently being evaluated clinically as a supportive care drug for oncology patients treated with radiation therapy in a Phase 1b/2a clinical trial (NCT02567799).