Protean

The Defense Advanced Research Projects Agency (DARPA), through its Biological Technologies Office (BTO), has issued Research Announcement DARPARA2601 for a program titled Protean. This initiative represents a forward-thinking and scientifically ambitious effort aimed at developing novel medical countermeasures (MCMs) that restore or protect human protein function in response to chemical warfare agents. DARPA, a division of the U.S. Department of Defense, is well known for its role in fostering transformative innovations with national security implications. With Protean, the agency aims to address an urgent and evolving threat landscape in chemical and biological defense by funding the development of prophylactics and therapeutics capable of protecting against extreme chemical agent exposure. The Protean program seeks to overcome the limitations of traditional protective gear and symptom-management strategies by directly targeting the mechanistic effects of chemical threats at the protein level. Existing strategies are reactive and often impractical in forward-deployed or resource-limited environments. The scope of the challenge is significant: there are over 10 million potential chemical threat agents, yet only a limited number of human proteins are typically affected. By focusing on the structural and dynamic mechanisms through which these agents impair protein function, DARPA intends to develop interventions that can neutralize broad classes of threats. The program’s primary targets include Acetylcholinesterase, the Mu Opioid Receptor, and ion channels—proteins most commonly impacted by chemical threats. Protean is structured in two sequential phases spanning a total of 33 months. Phase 1 (18 months) centers on “Non-classical Protection” and is designed to explore novel molecular mechanisms to either protect or restore protein functionality following exposure to chemical agents. Researchers are expected to identify intervention points within the conformational landscape of targeted proteins, investigate protein-protein interactions, and understand how threat agent binding alters physiological function. Phase 2 (15 months), titled “Countermeasure Design,” focuses on the development and optimization of compounds capable of restoring protein activity in vivo. A significant goal is to produce interventions that provide over 10,000-fold protection relative to baseline exposure thresholds, validated through animal models. The application process is divided into two distinct submission stages. The first stage (Gate 1) requires a Video Abstract and an Abbreviated Technical Volume, both due by March 12, 2026. These early-stage materials are designed to demonstrate technical understanding, innovation potential, and alignment with DARPA’s mission, without requiring detailed budget information. Successful applicants from Gate 1 will receive an invitation to submit a full proposal by the second deadline (Gate 2) on May 7, 2026. Full proposals will include technical, administrative, and cost elements and will be the basis for award negotiations. Proposal components include milestones, deliverables, intellectual property declarations, and a science and technology protection implementation plan (S&T PIP). Awards under Protean will be structured as either Cooperative Agreements or Research Other Transactions (OTs), with fixed, milestone-based payments and a 33-month period of performance. No cost sharing or matching funds are required, although cost-sharing is encouraged when commercial applications are likely. All selected projects must adhere to Controlled Unclassified Information (CUI) protocols and comply with NIST 800-171 standards for data protection. External communications, including publications and investor interactions, must receive prior approval from DARPA to ensure compliance with national security and information control policies. The opportunity is open to all responsible organizations capable of fulfilling the program objectives, including U.S. and international entities. Small businesses, minority institutions, and historically black colleges and universities are encouraged to apply. All applications must be submitted via DARPA’s BAA website in compliance with instructions and security protocols. Technical and administrative inquiries may be directed to the program’s central email address, [email protected]. This funding opportunity does not recur annually; however, given its structure and impact, future iterations may be considered based on the program’s outcomes and strategic priorities.

Proposals must address both program phases; non-compliance leads to disqualification.