NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Not Allowed)

The Department of Health and Human Services, through the National Institutes of Health (NIH), has reissued the NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Not Allowed), Funding Opportunity Number PA-25-304. This program is administered in collaboration with multiple NIH Institutes and Centers, including the National Eye Institute, National Human Genome Research Institute, National Institute on Aging, and many others, with participation from the Office of Data Science Strategy. Additional Institutes joined participation in June and August 2025. Applicants must ensure their proposals align with the mission and research priorities of the participating Institutes and Centers. The NIH R21 program is designed to support early-stage, exploratory, and developmental research projects that may involve significant risk but hold the potential for substantial impact in biomedical, behavioral, or clinical research. Projects should be novel, break new ground, or extend prior discoveries into new directions, rather than incremental expansions of existing research. Studies funded under this mechanism may lead to breakthroughs or the development of innovative methods, models, tools, or applications. The program specifically does not accept applications proposing clinical trials. Applications are open to a broad range of U.S. and foreign entities, including higher education institutions, nonprofits with or without 501(c)(3) status, small and other for-profit businesses, various government entities, tribal organizations, faith-based and community-based organizations, and regional organizations. Non-domestic (non-U.S.) entities and foreign components of U.S. organizations are eligible to apply. All applicants must complete and maintain registrations in SAM.gov, eRA Commons, and Grants.gov before submission. The combined budget for direct costs for the two-year project period may not exceed $275,000, with no more than $200,000 requested in any single year. The maximum project period is two years. The number of awards depends on available appropriations and the submission of a sufficient number of meritorious applications. Matching funds are not required. Funding may be used for allowable costs under NIH policy, and all NIH grants policies, including data management and sharing requirements, apply. Applications follow the NIH standard submission cycle with three annual deadlines for new, renewal, resubmission, and revision applications. For 2025, deadlines include February 16, June 16, and October 16, with corresponding AIDS-related deadlines one month later. Scientific merit reviews, council reviews, and award start dates follow NIH’s established review and funding timeline. The final expiration date for this NOFO is January 8, 2028, and applications are due by 5:00 PM local time of the applicant organization on the deadline dates. Review criteria emphasize the importance of the research’s significance and innovation, the rigor and feasibility of the approach, and the expertise and resources of the investigators and institutions. Applications are evaluated by appropriate NIH Scientific Review Groups, with written critiques provided. Funding decisions consider scientific merit, availability of funds, and program priorities. Applicants are strongly encouraged to contact relevant NIH program staff to discuss the alignment of proposed research with the interests of participating Institutes or Centers before applying. Applicants must submit electronically via ASSIST, institutional system-to-system solutions, or Grants.gov Workspace, following all instructions in the How to Apply – Application Guide and this NOFO. Inquiries about application submission should be directed to the eRA Service Desk, GrantsInfo, or Grants.gov Customer Support, while scientific and grants management contacts for each participating IC are listed on the R21 IC-Specific Scientific Interests and Contact website.