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

Frequently Asked Questions (FAQs)

What is this funding opportunity?

This opportunity is a National Institute on Aging (NIA) cooperative agreement Notice of Funding Opportunity (NOFO), RFA-AG-25-027, focused on advancing aging-related therapeutics from early translational work toward clinical evaluation, with an emphasis on T1 research leading to first-in-human (FIH) testing when appropriate.

What is the main goal of RFA-AG-25-027?

The goal 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, bridging strong preclinical rationale to early clinical evaluation when justified by the science and development plan.

What kinds of aging-related areas does NIA mention as examples?

Examples explicitly mentioned include sarcopenia, heart failure with preserved ejection fraction (HFpEF), and immune aging issues such as immunosenescence. The intent is broader than these examples and is aimed at aging-related conditions and functional deficits more generally.

What are the two main project types supported by this NOFO?

The NOFO supports (1) de novo therapeutic development (new candidates rather than reuse of an existing drug) and (2) data-driven, computational drug repurposing (finding new uses for already FDA-approved or investigational drugs, supported by experimental validation).

What does "de novo therapeutic development" mean in this NOFO?

It refers to developing new chemical entities or new molecular/biologic candidates, rather than repurposing an existing drug for a new indication.

At what stages can a de novo therapeutic development project enter the program?

NIA allows entry at three stages: (1) screening through preclinical validation; (2) hit-to-lead development through the IND-enabling stage; and (3) late-stage preclinical development through first-in-human (FIH) studies for programs ready to justify initial human testing.

What does the "screening through preclinical validation" entry stage focus on?

This stage focuses on identifying and validating a candidate with convincing activity, building the foundation needed to justify more advanced development steps.

What does the "hit-to-lead through IND-enabling" entry stage focus on?

This stage centers on optimization, early safety considerations, and development readiness, with the aim of moving a program toward IND-enabling work.

What does the "late-stage preclinical through FIH studies" entry stage cover?

This entry point is for programs far enough along that they can justify moving toward first-in-human studies under a tightly justified, milestone-driven plan.

What does NIA mean by "computational drug repurposing" in this NOFO?

It means using systematic, data-driven computational analytics (such as large-scale omics, real-world data, network biology, machine learning, or similar approaches) to identify alternative uses for drugs that are already FDA-approved or investigational, beyond the drug's original intended indication.

Are purely in silico repurposing projects responsive to this NOFO?

No. The NOFO indicates NIA is not looking for purely in silico predictions. Computational findings are expected to be followed by experimental validation and proof-of-concept evidence, typically using relevant animal models and/or human in vitro systems.

What types of validation are expected for repurposing projects?

The expectation is that computational hypotheses are converted into testable biology and then into translationally meaningful evidence, typically including experimental validation and proof-of-concept in relevant animal models and/or human in vitro systems.

What is the funding structure (UG3/UH3) for this opportunity?

The NOFO uses a two-phase UG3/UH3 cooperative agreement structure built around go/no-go milestones. The UG3 phase supports planning and early translational work, and the UH3 phase supports more comprehensive translational development activities if UG3 milestones are achieved.

Is the transition from UG3 to UH3 automatic?

No. Transition depends on whether the project achieves the milestones proposed by the team and agreed upon for the UG3 period.

What activities may be supported in the UG3 phase?

UG3 can support planning and early translational studies such as establishing feasibility, refining candidate selection strategy, developing or qualifying assays, demonstrating early signals in appropriate models, and generating preliminary data needed to justify later pharmacology and safety steps.

What activities may be supported in the UH3 phase?

If the project transitions, UH3 is intended to support more comprehensive translational development activities such as expanded pharmacology and/or toxicology work, replication studies to confirm preliminary findings, and for repurposing projects, direct experimental testing to validate predictive models.

Why does this NOFO emphasize milestones and go/no-go decisions?

The design is intended to reward disciplined development plans, clear decision points, and reproducible evidence, helping ensure projects move toward IND-enabling readiness and/or early clinical studies based on deliverables rather than open-ended exploration.

What does it mean that this is a cooperative agreement?

As a cooperative agreement, awardees should expect substantial scientific and programmatic involvement from NIH/NIA compared with a standard research grant, including closer coordination, milestone oversight, and an emphasis on defined deliverables.

Are clinical trials required under this opportunity?

No. Clinical trials are optional, meaning both advanced preclinical packages and early human studies can be proposed if they match the project stage and include well-defined milestones.

Who is eligible to apply?

Eligibility is broad across U.S.-based organizations, including state, county, and local governments; special districts; independent school districts; public housing authorities; public and private institutions of higher education; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses) and small businesses; federally recognized tribal governments; and other tribal organizations.

Are specific institution types highlighted as eligible?

Yes. The announcement highlights eligibility for HBCUs, Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIS), faith-based or community-based organizations, and U.S. territories or possessions.

Are foreign organizations eligible to apply?

No. Non-U.S. entities cannot apply under this NOFO.

Can a U.S. organization include a non-U.S. component in the application?

No. Non-U.S. components of U.S. organizations are not eligible under this NOFO.

Are foreign components allowed in any form?

No. The NOFO states that foreign components (as NIH defines them) are not allowed.

Which NIH institute is sponsoring this opportunity?

The opportunity is offered by the National Institutes of Health (NIH) through the National Institute on Aging (NIA).

What is the funding instrument and activity category?

The funding instrument is a cooperative agreement, and the activity category is health.

What is the CFDA number listed for this opportunity?

The CFDA number provided is 93.866.

What is the original application closing date provided?

The original closing date listed is January 10, 2025.

When was this opportunity created?

The opportunity was created on October 28, 2024.

What kind of teams or mindsets is this program aiming to support?

The program is aimed at teams that bring a therapeutics-focused mindset to aging research, with a realistic translational plan to generate evidence that supports advancement toward IND-enabling packages and/or early-stage human evaluation, depending on the chosen entry point.