Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed) | RFA TR 25 002

Opportunity Information: Apply for RFA TR 25 002

The National Institutes of Health (NIH) is soliciting applications under the funding opportunity titled "Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number: RFA-TR-25-002). This is a discretionary grant opportunity using the R21 mechanism, focused on advancing early-stage therapeutic development for rare diseases through rigorous preclinical testing. The central purpose is to fund well-designed efficacy studies in an established rare disease preclinical model so applicants can generate convincing proof-of-concept data showing that a proposed therapeutic agent is promising enough to justify further development. Alongside efficacy testing, the NOFO also supports pharmacokinetic (PK) and pharmacodynamic (PD) studies, which are commonly needed to connect dosing and exposure to biological activity and therapeutic effects.

The program is aimed at moving projects beyond exploratory ideas and toward a stage where they can attract follow-on investment and partnerships. In practical terms, NIH is looking for projects that can produce a credible data package that supports the next major translational steps, such as enabling work toward a full Investigational New Drug (IND) application, or, in cases where the approach involves repurposing or repositioning an existing agent, generating enough evidence to justify moving toward clinical testing. Therapeutic agents of interest are broadly defined and include small molecules, biologics, and other biotechnology-derived products, reflecting the wide range of modalities being used in rare disease drug development.

As indicated by the title, clinical trials are not allowed under this R21. The work must remain preclinical, centered on established models of rare disease and the experimental evidence needed to demonstrate potential efficacy and characterize PK/PD relationships. The emphasis on an "established" model signals that the opportunity is meant for testing therapeutic hypotheses in systems that are already recognized as appropriate for the disease biology, rather than primarily building new models from scratch.

Eligibility is broad and includes many common U.S. applicant types: state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3), excluding higher education institutions in those nonprofit categories); for-profit organizations other than small businesses; and small businesses. The NOFO also explicitly calls out additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

At the same time, there are important limits related to foreign participation. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components are allowed as defined in the NIH Grants Policy Statement, meaning a U.S.-based applicant may be able to include certain foreign collaborations or elements when they meet NIH policy requirements and are appropriately justified.

Key administrative details provided include an original closing date of 2026-06-02 and an NIH CFDA number of 93.350. The opportunity was created on 2024-12-06. Information such as the award ceiling and expected number of awards is not specified in the provided source data.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.350.
• This funding opportunity was created on 2024-12-06.
• Applicants must submit their applications by 2026-06-02. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA TR 25 002

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