Facilitating T1 Translational Aging Research: Preclinical and Early Phase Human Studies (UG3/UH3 Clinical Trial Optional) | RFA AG 25 027

Opportunity Information: Apply for RFA AG 25 027

The National Institute on Aging (NIA) is offering a cooperative agreement funding opportunity (RFA-AG-25-027) to push aging-related therapeutics from early translational work toward the clinic, specifically emphasizing T1 research that moves discoveries from the lab into first-in-human (FIH) testing. The core aim is to support milestone-driven projects that can credibly advance a candidate intervention along a practical development path for aging-related conditions and functional deficits. Examples called out in the announcement include sarcopenia, heart failure with preserved ejection fraction (HFpEF), and immune aging issues such as immunosenescence, but the overall intent is broader: build a bridge between strong preclinical rationale and early clinical evaluation when the science and development plan justify it.

The NOFO supports two main project types, each designed to fill common gaps that prevent promising aging biology from turning into real therapies. The first track is traditional, de novo therapeutic development, meaning new chemical entities or new molecular/biologic candidates rather than reusing an existing drug. For these projects, NIA allows entry into the pipeline at three different stages, depending on how mature the program is: (1) screening through preclinical validation, where the work focuses on identifying and validating a candidate with convincing activity; (2) hit-to-lead development through the Investigational New Drug (IND)-enabling stage, where optimization, early safety, and development readiness are central; and (3) late-stage preclinical development through FIH studies, for programs that are far enough along to justify moving toward initial human testing under a tightly justified plan.

The second track focuses on data-driven, computational drug repurposing, where applicants use systematic analytics (for example, large-scale omics, real-world data, network biology, machine learning, or other computational approaches) to identify new uses for drugs that are already FDA-approved or investigational. In this NOFO, repurposing is explicitly defined as finding alternative uses beyond the drug’s original intended indication. Importantly, NIA is not looking for purely in silico predictions; the computational work must be followed by experimental validation and proof-of-concept evidence, typically through relevant animal models and/or human in vitro systems. The expectation is that computational hypotheses are converted into testable biology and then into translationally meaningful evidence that supports moving forward.

A key structural feature is the two-phase UG3/UH3 design, which is built around go/no-go milestones. The UG3 phase supports planning and early translational studies that set up the later, more resource-intensive work. This can include establishing feasibility, refining the candidate selection strategy, developing or qualifying assays, demonstrating early signals in appropriate models, or generating preliminary data needed to justify subsequent pharmacology and safety steps. Transition to the UH3 phase is not automatic; it depends on whether the team achieves the milestones they proposed and that were agreed upon for the UG3 period. If the project successfully transitions, the UH3 phase is intended to fund more comprehensive translational development activities, including expanded pharmacology and/or toxicology work, replication studies to confirm preliminary findings, and in the repurposing track, direct experimental testing to validate predictive models. The overall logic is to fund projects in a way that rewards disciplined development plans, clear decision points, and reproducible evidence.

Because this is a cooperative agreement, awardees should expect substantial scientific and programmatic involvement from NIH/NIA compared with a standard research grant. That typically means closer coordination, milestone oversight, and an emphasis on deliverables that keep the program moving toward readiness for IND-enabling packages or early clinical studies, depending on the chosen entry point. Clinical trials are optional under this announcement, which signals that both advanced preclinical packages and early human studies can fit, as long as the proposed activities are appropriate for the project’s stage and the milestones are well defined.

Eligibility is broad across U.S.-based organizations and includes many public and private entities: state, county, and local governments; special districts; independent school districts; public housing authorities; public and private institutions of higher education; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and federally recognized tribal governments as well as other tribal organizations. The announcement also highlights additional eligible applicant types 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), along with faith-based or community-based organizations and U.S. territories or possessions. At the same time, it clearly restricts foreign involvement: non-U.S. entities cannot apply, non-U.S. components of U.S. organizations are not eligible, and foreign components (as NIH defines them) are not allowed.

Administrative details provided include the agency (National Institutes of Health, via NIA), the funding instrument (cooperative agreement), the activity category (health), and the CFDA number (93.866). The original application closing date listed is January 10, 2025, and the opportunity was created on October 28, 2024. Overall, the program is aimed at teams that can bring a therapeutics-focused mindset to aging research, with a realistic plan to generate the kind of evidence regulators, clinicians, and translational stakeholders need to justify advancing a candidate from promising biology to early-stage human evaluation.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Facilitating T1 Translational Aging Research: Preclinical and Early Phase Human Studies (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): 93.866.
• This funding opportunity was created on 2024-10-28.
• Applicants must submit their applications by 2025-01-10. (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 AG 25 027

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