Project UPREG: DTRA's Push for Enhanced Protection Against Nerve Agents
The Defense Threat Reduction Agency’s (DTRA) Chemical and Biological Technologies Department, in its role as the Joint Science and Technology Office (JSTO), has launched Project UPREG, a bold initiative to develop next-generation medical countermeasures against organophosphorus nerve agents (OPNAs). These highly toxic compounds pose a significant threat to military personnel in both combat and homeland defense scenarios.
The Mission: Endogenous BuChE Upregulation
At the heart of Project UPREG is the goal to temporarily upregulate the body’s own production of butyrylcholinesterase (BuChE). BuChE is an enzyme that has shown broad-spectrum protective capabilities against OPNA intoxication. Rather than relying on recombinant or plasma-derived BuChE, which present scalability and reliability challenges, the project aims to trigger temporary, high-level expression of endogenous BuChE through a novel therapeutic approach. The desired result is protection against exposure levels up to 5X the lethal dose (LD50) across multiple OPNA classes for at least seven days following administration.
Performance and Regulatory Goals
The program is structured to lead all the way to an Investigational New Drug (IND) application with the FDA, including complete nonclinical development, safety, and pharmacokinetics studies. A successful product must meet strict criteria around storage, shelf life, and operational performance in austere field conditions — such as functionality after exposure to extreme temperatures and various delivery routes (intramuscular, subcutaneous, or oral).
Regulatory compliance is central to this effort. The Project Agreement Holder (PAH) must implement FDA-aligned quality systems (cGMP, GLP, GCP) and coordinate closely with JSTO on all communications with the FDA, ensuring full transparency and government review before submissions. This includes public health prioritization protocols such as potential Fast Track or Orphan Drug designations, and robust stability testing and data integrity strategies.
High Standards, High Stakes
Project UPREG places intense focus on risk management, quality assurance, and logistical readiness. This includes maintaining a Quality Management Plan (QMP), responding to site visits or audits, and providing comprehensive program reporting. The ability to perform under chemical surety regulations and manage chemical warfare agents for testing purposes is mandatory.
If successful, Project UPREG could transition into a follow-on production phase capable of delivering up to 100,000 doses annually which makes it a vital asset in national defense strategy.
What’s Next
Anticipated for award in FY26, Project UPREG represents a unique opportunity for the life sciences community to contribute to a cutting-edge defense need. DTRA is seeking partners capable of innovation, regulatory rigor, and operational execution.
As DTRA continues to shape the future of military medical readiness, EverGlade Consulting remains committed to helping organizations navigate this complex and highly technical space. Stay tuned for further insights on this and other transformational federal programs.
If your company has considered applying for DTRA funding, your federal funding journey starts here.