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This Funding Opportunity Announcement (FOA) supports translational exploratory/developmental research that directly advances the discovery of novel treatment strategies, i.e., medical countermeasures (MCMs), that address serious morbidity and mortality after acute exposure to highly toxic chemical threats. Chemical threats are toxic compounds that could be used in a terrorist attack or accidentally released from industrial production, storage, or shipping. They include traditional chemical warfare agents, toxic industrial chemicals, pesticides, and ultra-potent synthetic (UPS) opioids. This FOA supports translational research that includes, but is not limited to, preliminary efficacy and/or early preclinical development studies towards discovery and validation of novel molecular entities or biologics as candidate MCMs. In addition to novel agents, new treatment strategies may involve repurposing already FDA-approved products or combinations of interventions based on established mechanisms of action. Projects supported by this FOA are expected to generate preliminary data that would facilitate the development of competitive applications for more extensive support from the NIH CounterACT Cooperative Agreement program and/or other related initiatives.