Development of a field-deployable tocoflexol-based countermeasure for multi-organ radiation mitigation

The National Institute of Allergy and Infectious Diseases (NIAID) awarded $299,882 to Tocol Pharmaceuticals LLC on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop and test tocoflexol-based radiomitigator formulations for multi-organ protection against lethal radiation exposure.

Tocol Pharmaceuticals will conduct Phase I research demonstrating the field-deployability of tocoflexol as a radiomitigator, addressing an unmet clinical need for safe, stockpilable countermeasures to nuclear disaster. The company has designed tocoflexol, a tocotrienol analogue with extended duration of action through superior binding to a key transporter protein that reduces elimination rate. Preliminary mouse model studies show tocoflexol provides 100 percent survival when administered 24 hours before lethal total-body irradiation and 70 percent survival against lethal doses (LD80 of 8.5 GY) when given 24 hours after irradiation, with evidence of multi-organ protection and hematopoietic system recovery. The company has developed fast-release (tocoflexol-FR) and extended-release (tocoflexol-XR) formulations to overcome pharmacokinetic limitations of existing radiomitigators while retaining radioprotective properties.

Work is performed in Arkansas. The award period runs from September 1, 2026, through August 31, 2028.

Abstract

An intentional or accidental nuclear disaster would have catastrophic consequences to potentially millions of people. However, there are no safe and effective radiomitigator products that offer multi-organ protection and are practical for stockpiling, which is an urgent unmet clinical need. For example, FDA-approved radiomitigators such as filgrastim or romiplostim only protect the hematopoietic system, and they are expensive biologics with cold storage requirements which are difficult to handle in the field. Tocol pharmaceuticals scientists have designed tocoflexol as a novel radiomitigator. Tocoflexol is a tocotrienol analogue aimed to overcome their pharmacokinetic limitations while retaining their powerful multi-organ radioprotective properties. Our computational analysis showed that tocoflexol has extended duration of action through superior binding capacity to a key transporter protein that reduces the elimination rate of tocols. We have shown that is a strong antioxidant, has rapid cell uptake, and induces radioprotective signaling factors. Using mouse models, we have shown that provides 100% survival when given 24 hours before lethal total-body irradiation, with evidence of multi-organ protection. In radiomitigation studies, tocoflexol given 24 hours after lethal irradiation provides 70% survival against lethal doses (LD80) of total body irradiation (8.5 GY). Our preliminary results show that tocoflexol strongly promotes recovery of the hematopoietic system. This is the first time any tocol has shown radiomitigation efficacy when given 24 hours after irradiation. In this phase i proposal, our goal is to demonstrate the potential of tocoflexol as a field-deployable multi-organ radiomitigator against lethal radiation. We have developed a fast-release (tocoflexol-FR) and an extended- release (tocoflexol-XR) formulations, and we propose that subcutaneous CO-administration of these two formulations will provide rapid and sustained therapeutic activity during acute radiation syndrome and yield improved multi-organ radiomitigation efficacy. First, we will conduct a pharmacokinetics analysis to determine the optimal dose level of the CO-administered formulations that provides therapeutic plasma levels within 1 hour and sustain them for 15 days. Then, we will test the radiomitigation efficacy of the CO-administered tocoflexol formulations for improving survival outcomes, mitigating GI-ARS, promoting hematopoietic recovery after h- ARS, and protecting other organs from radiation injury. We will use mouse models of lethal irradiation, with tocoflexol CO-administration starting 24 h after radiation exposure. Our goal is to commercialize tocoflexol as a multi-organ radiomitigator in a field-deployable countermeasure kit. Our product is designed for practical stockpiling and rapid deployment to civilian and military populations during nuclear emergencies. We will seek FDA approval for tocoflexol as a multi-organ radiomitigator under the FDA animal efficacy rule. Phase II sbir projects will develop a field kit prototype and complete the GLP toxicology, pharmacokinetics, and pharmacology studies needed as part of the IND submission.