Exposure to ionizing radiation can cause life threatening health effects known as acute radiation syndrome (ARS). Medical countermeasures (MCMs) must be developed that can prevent ARS to prophylactically protect warfighters that respond to radiological or nuclear (R/N) events. BIO 300 is a prophylactic ARS MCM whose radioprotective properties were discovered by the U.S. Department of Defense (DOD). Humanetics Corporation has continued the advanced development of BIO 300 for ARS, which is governed by the U.S. Food and Drug Administration (FDA) Animal Rule. The development efforts described established the drug’s radioprotective properties and utility as an MCM. These include nonclinical studies in animal models, clinical safety, and plans for human dose selection, a key element of the FDA Animal Rule. Studies in ARS animal models have shown that BIO 300 improves survival post lethal radiation exposure, while also identifying candidate biomarkers for human dose selection. Clinical trials of BIO 300 have shown a robust safety profile. In addition, a trial of patients with lung cancer receiving radiotherapy found that BIO 300 mitigated therapy-related hematological toxicities, similar to those caused by ARS. In summary, the DOD has a unique opportunity to improve their approach to medical prophylaxis against ARS. Successful development of prophylactic ARS MCMs, such as BIO 300, will greatly benefit warfighters by improving force health protection and operational effectiveness in R/N environments. Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Uniformed Services University of the Health Sciences or the Department of Defense, USA. This research is supported by the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense contract W911SR-23-9-0018, Congressionally Directed Medical Research Programs (CDMRP) awards W81XWH-17-1-0584, W81XWH-19-2-0060, W81XWH-22-1-0516, JPC7 awards DM178016, VP000262-01. Michael Kaytor, Colin Chinn, Artur Serebrenik and Hannah Olson are employees of Humanetics Corporation. The other authors have no conflicts of interest. Disclaimer: Reference herein to any specific commercial products, process, or service by trade name, trademark, manufacturer, or otherwise, does not constitute or imply its endorsement, recommendation, or favoring by the United States government and shall not be used for advertising or product endorsement purposes.