HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional) | RFA NS 24 019

Opportunity Information: Apply for RFA NS 24 019

The NIH funding opportunity RFA-NS-24-019, titled "HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)," is a reissue of RFA-NS-20-010 and sits within the broader HEAL (Helping to End Addiction Long-term) Initiative. Its core aim is to push forward new pain treatments that are both effective and non-addictive, specifically by funding the preclinical optimization and early development of therapeutic candidates. The program is designed for teams that already have something tangible in hand: a promising small-molecule or biologic hit or lead, along with a clear biological rationale for why it should work for pain and a defined set of assays that can be used to optimize and evaluate the candidate as it is refined.

This FOA focuses on the work that bridges the gap between an early discovery and readiness to enter human studies. In practical terms, it supports activities such as lead optimization and early development (for example, improving potency, selectivity, and developability), followed by IND-enabling studies that generate the data package regulators typically expect before a first-in-human trial. The opportunity also explicitly includes assembling the Investigational New Drug (IND) application materials, which usually means pulling together pharmacology, toxicology, chemistry/manufacturing/controls information, and other required documentation in a coherent regulatory submission. While the notice is labeled "clinical trial optional," the thrust of the program is to accelerate candidates toward clinical trials by completing the key development steps that make a clinical entry feasible.

The award mechanism is a phased, milestone-driven cooperative agreement using the UG3/UH3 structure. The UG3 phase generally supports the earlier, more feasibility-focused portion of the project, where the team executes defined development and optimization milestones. Successful completion of those agreed-upon milestones can enable transition to the UH3 phase, which supports later-stage preclinical development and IND-enabling work. Because this is a cooperative agreement rather than a standard grant, NIH program staff are not passive funders; they participate in shaping the project plan and closely monitor progress against milestones. The milestone-driven structure is intended to keep projects on a product-development trajectory, with clear go/no-go decision points and accountability for advancing a candidate toward an IND.

Eligibility is broad and includes many types of U.S.-based entities: state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other organizations that meet NIH eligibility rules. The FOA also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, Tribally Controlled Colleges and Universities, eligible federal agencies, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions. However, non-U.S. (foreign) organizations are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible. 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 international elements within the project under NIH policy, even though a foreign organization cannot serve as the applicant institution.

Administratively, this is a discretionary funding opportunity from the National Institutes of Health and uses the cooperative agreement funding instrument. It is associated with multiple CFDA (now Assistance Listing) numbers, reflecting that more than one NIH institute or center may be participating or that the initiative spans multiple funding lines tied to NIH programs. The listing shows an original closing date of 2027-01-07, indicating a long application window or multiple receipt cycles through that date, although applicants typically need to confirm the specific due dates and cycles in the full FOA on NIH’s funding site. The award ceiling and expected number of awards are not specified in the provided excerpt, which usually means applicants must consult the full announcement for budget guidance, project period expectations, and any institute-specific caps or constraints.

Overall, the opportunity is aimed at translating credible, mechanistically grounded pain-therapeutic leads into IND-ready candidates through a structured development pathway. It is best suited for applicants who can demonstrate they have a real starting asset (not just a concept), can justify why targeting that biology should produce analgesia without addictive liability, and can lay out a rigorous, milestone-based plan that covers optimization, IND-enabling studies, and the concrete steps needed to assemble an IND package under close NIH collaboration and oversight.

• 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: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)" 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, 93.233, 93.273, 93.279, 93.313, 93.395, 93.837, 93.838, 93.839, 93.840, 93.846, 93.847, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2023-10-31.
• Applicants must submit their applications by 2027-01-07.
• 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 24 019

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