HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] (U19 Clinical Trial Not Allowed) | RFA NS 22 052

Opportunity Information: Apply for RFA NS 22 052

The National Institutes of Health (NIH) is offering this funding opportunity under the HEAL (Helping to End Addiction Long-term) Initiative to push forward the early translational steps needed to create safer, effective, non-addictive pain medicines. The award mechanism is a U19 cooperative agreement, which means NIH staff will typically have an active partnership role in guiding scientific and programmatic progress, and the work is expected to be organized as a coordinated, team-based effort rather than a single-investigator project. Clinical trials are not allowed under this announcement, so the focus stays on preclinical and translational-enabling activities that set a strong foundation for later-stage development.

The core purpose of the program is to support the practical, nuts-and-bolts work that helps a promising idea become a credible drug development candidate. That includes building and refining scientifically sound assays, establishing screening approaches, and carrying out early optimization to move from an initial "hit" to a more mature "lead." The FOA also explicitly welcomes projects that identify and validate pharmacodynamic markers (signals that show the drug is engaging its target and producing the intended biological effect), and projects that conduct pharmacokinetic and pharmacokinetic/pharmacodynamic (PK/PD) studies to understand exposure, dose-response relationships, and how biological activity tracks with drug levels. In other words, this opportunity is aimed at bridging the gap between basic discovery and a development-ready package by generating the kind of evidence needed for credible decision-making in drug development.

A key milestone expectation is that, by the end of the project period (up to five years), the team will have advanced a hit or lead far enough that it could meet the entry criteria for a follow-on HEAL FOA focused on non-addictive analgesic therapeutic development for small molecules and biologics (referenced as RFA-NS-21-010, UG3/UH3 clinical trial optional). This makes the U19 an earlier stepping-stone: the work should be designed so that, if successful, it naturally hands off into a more advanced development track, with a candidate that is supported by rigorous data, credible assays, and a clear biological rationale.

The scientific expectations emphasize rigor around target rationale and disease linkage. Applications need to lay out a clear plan for developing analgesics grounded in strong biology and validated experimental systems. If the target is not yet firmly tied to the proposed pain indication, the application is expected to include a compelling strategy to generate that missing evidence. That means demonstrating, with data, that the proposed target is relevant to the pain condition and that changing the target's activity is likely to produce meaningful, beneficial outcomes. The message is that this program is not just funding screening for its own sake; it is funding development-oriented research where assays, markers, and PK/PD are used to de-risk the program and justify continued investment.

The program is intentionally broad with respect to pain conditions. It is not restricted to a single disorder area, and it invites therapeutic development concepts spanning many types of pain. Examples specifically mentioned include acute and chronic pain, painful neuropathies (including diabetic neuropathy and chemotherapy-induced neuropathy), musculoskeletal pain, headache disorders, osteoarthritis, eye pain, sickle-cell pain, post-surgical pain, cancer pain, visceral pain, obstetric and gynecologic pain, post-stroke pain, myofascial pain, and painful disorders affecting the orofacial region, among others. This breadth gives applicants flexibility to propose projects matched to their expertise, as long as the translational plan and rationale meet the program's bar.

The scope includes both small molecules and biologics, signaling that NIH is open to multiple therapeutic modalities as long as they are aimed at non-addictive analgesia and can be advanced through early translational development. Practically, competitive projects under this FOA would typically describe an integrated workflow: assay development and validation, screening and hit identification, early medicinal chemistry or biologic optimization, development and qualification of pharmacodynamic markers, and PK/PD studies that connect compound properties to target engagement and functional outcomes in relevant models. Because clinical trials are not allowed, the emphasis remains on generating the preclinical and translational evidence package that positions a candidate for later clinical-stage programs.

In terms of eligibility, the announcement is open to a very wide range of applicant organizations. Eligible applicants include various levels of government (state, county, city/township, and special district), public and private institutions of higher education, independent school districts, Native American tribal governments (federally recognized) and other tribal organizations, public housing authorities/Indian housing authorities, nonprofits (both 501(c)(3) and non-501(c)(3)), for-profit organizations (other than small businesses), and small businesses, as well as other categories. The FOA also highlights additional eligible groups 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, U.S. territories or possessions, and even non-U.S. (foreign) entities. This broad eligibility aligns with the team-science intent, encouraging participation from diverse institutions and collaborative structures.

Administratively, the opportunity is listed as RFA-NS-22-052, offered by NIH as a discretionary funding program using a cooperative agreement funding instrument. The original closing date shown is October 10, 2023, and the listed award ceiling is $1,500,000. The FOA is associated with multiple CFDA numbers (including 93.121, 93.213, 93.233, 93.393, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, and 93.867), reflecting the multi-institute nature of HEAL-related investments across NIH.

Overall, this FOA is best understood as a structured push to help teams do the early translational work that turns a plausible non-addictive pain target and modality into a development-ready lead. It prioritizes strong biological justification, robust assays, translational biomarkers, and PK/PD-driven decision-making, with the explicit intention that successful projects will be ready to enter a later HEAL program focused on more advanced therapeutic development within a five-year window.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] (U19 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, 93.233, 93.393, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2022-04-22.
• Applicants must submit their applications by 2023-10-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $1,500,000.00 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 22 052

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