HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - Clinical Trial Not Allowed) | RFA NS 25 012

Opportunity Information: Apply for RFA NS 25 012

The NIH HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - Clinical Trial Not Allowed) funding opportunity (RFA-NS-25-012) is a discretionary NIH grant designed to jump-start early, translational research that can feed directly into a stronger, later-stage pain drug discovery pipeline. It sits within the broader HEAL (Helping to End Addiction Long-term) Initiative, which emphasizes the development of safe, effective, and non-addictive treatments for pain. In practical terms, this opportunity is meant to help research teams do the enabling work that often determines whether a pain therapeutic concept can realistically mature into a bona fide discovery program, with the explicit intent of advancing projects toward the entry criteria for NIH's Pain Therapeutics Development Program.

The core scientific focus is on building the foundation for an organized discovery "testing funnel" rather than running clinical studies. Applicants are expected to concentrate on assay development and optimization, screening approaches to identify promising "hits," and the early characterization of those hits and potential therapeutic agents. The program explicitly allows a range of therapeutic modalities, including small molecules, biologics, and natural products. The kinds of activities that fit this scope typically include creating or refining robust, reproducible assays (for example, target engagement assays, phenotypic screening assays, or other translationally relevant test systems), establishing screening workflows and quality controls, conducting screening campaigns to uncover candidate hits, and performing initial follow-up work to understand whether those hits have properties consistent with a viable analgesic development path (such as early selectivity, basic structure-activity relationships, or preliminary mechanism-relevant validation). As the title notes, clinical trials are not allowed under this announcement, reinforcing that the work should remain in preclinical and discovery-enabling territory.

From a mechanism standpoint, the R61/R33 structure is a phased, milestone-driven approach commonly used by NIH to support early development projects that need to demonstrate concrete progress before transitioning to the next stage. While the notice text provided does not spell out specific milestone language, in general the intent of this type of structure is to support an initial, shorter "startup" or feasibility phase followed by a second phase that is contingent on meeting predefined progress criteria. For applicants, the practical takeaway is that the project should be planned as a stepwise program where the early work clearly de-risks the later work and produces outputs that would make the project competitive for downstream translational programs like the Pain Therapeutics Development Program.

The applicant eligibility is broad and includes many types of U.S.-based organizations: 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 other than federally recognized governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education when specified); for-profit organizations (other than small businesses); and small businesses. The opportunity also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions. However, there are important geographic restrictions: 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. At the same time, "foreign components" as defined by the NIH Grants Policy Statement are allowed, meaning a U.S. applicant may be able to include certain internationally performed elements under NIH policy, even though a foreign organization cannot be the applicant.

Administratively, the agency is the National Institutes of Health, and the opportunity is associated with multiple CFDA numbers (93.121, 93.213, 93.273, 93.393, 93.395, 93.846, 93.847, 93.853, 93.865, 93.866, 93.867), reflecting NIH's multi-institute participation in HEAL-related pain and translational science efforts. The opportunity was created on 2024-03-26, and the original closing date listed is 2027-01-15, indicating a multi-year window in which applications may be accepted according to the solicitation's schedule. The award ceiling listed is $350,000, which signals that projects should be designed with a focused, enabling scope: enough to establish validated assays, run targeted screening, and generate initial hit follow-up data, but not so broad as to cover extensive preclinical development or clinical testing.

Overall, this NOFO is best understood as a targeted on-ramp for analgesic discovery: it funds the nuts-and-bolts work of building screening-ready assays and generating early evidence around candidate analgesic agents so that the most promising projects can credibly move into more advanced translational development programs within NIH's pain therapeutics ecosystem, all while staying firmly outside of clinical trial activities.

• The National Institutes of Health in the education, food and nutrition, health, income security and social services sector is offering a public funding opportunity titled "HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - 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): 93.121, 93.213, 93.273, 93.393, 93.395, 93.846, 93.847, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2024-03-26.
• Applicants must submit their applications by 2027-01-15.
• Each selected applicant is eligible to receive up to $350,000.00 in funding.
• 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 NS 25 012

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