HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - Clinical Trial Not Allowed) | RFA NS 25 023

Opportunity Information: Apply for RFA NS 25 023

The HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - Clinical Trial Not Allowed) funding opportunity (RFA-NS-25-023) is a National Institutes of Health (NIH) grant designed to jump-start early, translation-focused research that can feed into a full pain drug discovery pipeline. It sits within the broader NIH HEAL (Helping to End Addiction Long-term) Initiative, which prioritizes the development of safer, more effective, and non-addictive options for treating pain. The central idea is to fund the practical, enabling steps that help investigators move from a promising pain-related biological concept to a credible, testable discovery program that can generate candidate therapeutic agents.

The scientific scope is tightly centered on the foundational work needed to identify and validate potential analgesic therapeutics before any clinical testing. Projects are expected to build and refine assays that can function as part of a clear screening and decision-making workflow, often described as a testing funnel. That typically means developing robust experimental systems that can reliably measure target engagement or pain-relevant biology, followed by screening efforts (for example, higher-throughput approaches) to find initial “hits” and then performing early characterization to understand whether those hits have real potential as therapeutic leads. The opportunity explicitly includes a wide range of therapeutic modalities, including small molecules, biologics, and natural products, as long as the work is aimed at producing and prioritizing credible lead matter for future development.

The mechanism is an R61/R33 phased award, which generally supports a milestone-driven transition from an initial, early-stage “launch” phase (R61) into a follow-on development phase (R33) if predefined objectives are met. In practice, applicants should expect to propose concrete, quantitative milestones that demonstrate their platform or discovery approach is working, such as assay performance benchmarks, screening quality metrics, evidence of reproducibility, and early structure-activity or functional profiling that helps justify advancement. This FOA is also labeled “Clinical Trial Not Allowed,” meaning the supported activities must remain preclinical or otherwise non-clinical in nature and cannot include prospective assignment of human participants to interventions to evaluate health-related outcomes.

Eligibility is broad across U.S.-based organizations and can include state, county, city, township, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside of higher education); for-profit organizations (other than small businesses); and small businesses. The notice also highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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. At the same time, it clearly excludes non-domestic (non-U.S.) entities from applying, and it also excludes non-domestic components of U.S. organizations, reinforcing that the work and applicant organization must be based in the United States.

Key administrative details provided include an original closing date of January 15, 2027, and an award ceiling listed as $350,000. The opportunity is categorized as a discretionary grant and spans multiple CFDA numbers associated with NIH programs (93.121, 93.213, 93.273, 93.393, 93.846, 93.847, 93.853, 93.865, 93.866, 93.867). Overall, this NOFO is best understood as a bridge between basic pain biology and a more advanced, programmatic therapeutic development effort, with funding aimed at the practical tools and early evidence needed to justify entry into later-stage NIH pain therapeutics development pathways.

• 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, 93.846, 93.847, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2024-09-18.
• 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 25 023

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