Protean

The Defense Advanced Research Projects Agency (DARPA), under its Biological Technologies Office (BTO), has released the "Protean" funding opportunity (DARPARA2601), targeting advanced research in the field of medical countermeasures (MCMs) against chemical threat agents. This initiative seeks to move beyond traditional protective gear and reactive treatments by focusing on restoring or maintaining protein function disrupted by toxic exposures. The goal is to develop broad-spectrum prophylactics and therapeutics that intervene at the molecular level, particularly targeting proteins consistently affected by chemical threats. The effort underscores DARPA’s continued role in pioneering cutting-edge technologies that enhance national security and operational readiness, particularly in high-risk or austere environments where traditional medical support is unavailable. The program is structured into two sequential phases spanning a total of 33 months. Phase 1, lasting 18 months, focuses on identifying novel intervention points within protein conformations and signaling pathways. Applicants are expected to explore dynamic protein states and molecular mechanisms that underlie intoxication, targeting proteins such as acetylcholinesterase, mu opioid receptors, and ion channels. Phase 1 culminates in an in vitro demonstration that shows protection or restoration of protein function under chemical threat. Phase 2, which extends for 15 months, shifts toward the development and optimization of drug-like compounds based on findings from Phase 1. It aims to produce safe, effective chemical matter capable of preserving physiological function under extreme exposure scenarios, with final validation conducted in vivo using real chemical warfare agents. Proposals must address both phases to be considered for review. Submissions that only target one phase are deemed non-conforming. The program explicitly excludes approaches that focus solely on competitive inhibitors, agent-specific detoxifiers, genetic interventions, or strategies lacking mechanistic insights. DARPA emphasizes novel mechanisms of action, excluding black-box AI/ML models where internal logic is opaque. Awards will be structured either as cooperative agreements or Research Other Transactions (OTs), with performance evaluated against clear metrics at six-month intervals, including protein characterization, in vitro efficacy, and in vivo protection benchmarks. The application process consists of two gates. Gate 1 submissions, due by March 12, 2026, require both a video abstract and an abbreviated technical volume. These submissions are reviewed by a scientific board to determine eligibility for Gate 2. Full proposals (Gate 2) are due May 7, 2026, and may be preceded by a pre-award feedback session. Applications must be submitted via DARPA’s BAA website and adhere to the Controlled Unclassified Information (CUI) guidelines. Only one submission per proposer is allowed at Gate 1, and all documents must be unclassified or CUI. While cost sharing is not required, it is encouraged when a commercial application is anticipated. Eligible applicants include all responsible U.S. and non-U.S. sources capable of meeting the program's technical objectives, including but not limited to institutions of higher education, private companies, and nonprofit research entities. Special eligibility considerations apply to government entities, FFRDCs, and foreign institutions, which must comply with export laws and CUI handling protocols. Proposers are expected to submit a Science and Technology Protection Implementation Plan if selected for full proposals, and all dissemination of results must be coordinated with DARPA’s Public Release Center. The performance period is fixed at 33 months, beginning upon award. DARPA anticipates multiple awards, with the number contingent on proposal quality and available funding. While no matching funds are required, the agency reserves flexibility in award structure and milestone payment terms. The full solicitation, including attachments such as proposal templates and the CUI guide, is available on the DARPA BAA website, and questions may be directed to [email protected].

Avoid AI/ML black-box approaches; ensure proposal covers both phases; proposals lacking novel mechanistic insight will be rejected.