Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (SBIR U44 Clinical Trial Not Allowed) | RFA AG 21 026

FAQs: NIH SBIR U44 - Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (RFA-AG-21-026)

What is the funding opportunity described here?

This opportunity is the NIH funding announcement titled "Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (SBIR U44 Clinical Trial Not Allowed)" with identifier RFA-AG-21-026. It is a discretionary, health-focused Small Business Innovation Research (SBIR) cooperative agreement intended to help small businesses advance promising geroscience therapies through key preclinical steps needed before first-in-human testing.

Which agency is offering this opportunity?

The sponsoring agency is the National Institutes of Health (NIH).

What is the CFDA number for this program?

The CFDA number listed for this opportunity is 93.866.

What is the main goal of this NIH SBIR award?

The main goal is to support preclinical development work that builds a credible evidence package for therapeutics aimed at fundamental biological mechanisms that drive aging. The intent is to mature candidates toward an IND-enabling trajectory and position them for subsequent clinical funding or partnerships, rather than to conduct human studies during the project.

What scientific area does this opportunity focus on?

The focus is geroscience: therapeutics targeting core biological mechanisms of aging, rather than approaches that only treat single diseases in isolation without tying the intervention to aging biology.

Which aging-related mechanisms are specifically highlighted?

The announcement highlights chronic inflammation, cellular senescence, and loss of proteostasis (the systems that maintain protein quality and function) as key aging-related processes of interest.

Does the FOA require that projects target aging mechanisms rather than only a single disease?

Yes. The emphasis is on interventions that target fundamental aging mechanisms and translate those mechanistic insights into therapeutic candidates, rather than focusing only on a single disease in isolation.

What kinds of health conditions are in scope?

Projects should be aimed at aging mechanisms and at conditions that are common in older adults.

What types of therapeutic modalities are eligible?

The scope is broad and can include novel small molecules (with senolytics given as a key example), biologics, and stem or progenitor cell-based approaches, as long as the work targets aging mechanisms and fits the preclinical development purpose of the program.

Are senolytics specifically mentioned as an example?

Yes. Senolytics are named as a key example within the eligible small-molecule modality category.

Can applicants propose drug repositioning or drug repurposing strategies?

Yes. The FOA explicitly welcomes translational strategies intended to reduce development risk and time, including repositioning investigational drugs (previously studied for another indication but not approved) and repurposing FDA-approved drugs for aging-related conditions when supported by a mechanistic geroscience rationale.

What is meant by "repositioning investigational drugs" in this context?

It refers to taking compounds that have already been studied for a different indication (but are not yet approved) and proposing them for an aging-related indication based on a rationale linked to aging mechanisms.

What is meant by "repurposing FDA-approved drugs" in this context?

It refers to evaluating an already FDA-approved drug for an aging-related condition, supported by a mechanistic rationale tied to geroscience and aging biology.

What stage of R&D does this opportunity support?

This program supports preclinical development activities. It is designed to move candidates through critical preclinical steps needed before first-in-human testing, while stopping short of initiating human clinical trials under this award.

What types of preclinical activities are specifically supported or encouraged?

Examples called out include target validation (linking the biological target to aging mechanisms and the intended disease context), lead optimization (improving potency, selectivity, stability, and developability), pharmacokinetics and drug disposition studies (ADME and tissue exposure), and preclinical safety and toxicology studies.

Does the program support target validation work?

Yes. Target validation is explicitly mentioned as an example of a supported activity, with an emphasis on demonstrating meaningful links to aging mechanisms and the intended disease context.

Does the program support lead optimization?

Yes. Lead optimization is explicitly listed, including improving potency, selectivity, stability, and overall developability of a candidate.

Are pharmacokinetics (PK) and drug disposition studies within scope?

Yes. The FOA highlights pharmacokinetics and drug disposition studies, including how a candidate is absorbed, distributed, metabolized, and excreted, and what exposures are achieved in relevant tissues.

Are preclinical safety and toxicology studies within scope?

Yes. Preclinical safety and toxicology studies are specifically called out as examples of supported work.

What kind of overall development package is the FOA trying to build?

The FOA aims to support a translational foundation that demonstrates mechanism-based activity, establishes a development-quality candidate profile, and addresses early safety and PK risks that commonly derail programs before they can enter clinical testing.

What does "U44 cooperative agreement" mean for how the project will be managed?

As a cooperative agreement, this is not a standard grant operated fully independently by the awardee. Cooperative agreements typically involve substantial scientific or programmatic involvement from NIH staff, which may include coordination, milestone-based oversight, and guidance aligned with program goals.

Are clinical trials allowed under this funding opportunity?

No. The FOA is designated "Clinical Trial Not Allowed," meaning the funded work must remain preclinical and should not include initiating human clinical trials within the project.

If clinical trials are not allowed, what is the intended next step after the project?

The intent is to mature therapeutic candidates to a stage where they are positioned for subsequent clinical funding or partnerships, rather than running clinical studies during the award period.

Who is eligible to apply?

Eligibility is centered on U.S. small businesses, consistent with SBIR requirements.

Are non-U.S. (foreign) institutions eligible to apply?

No. The announcement states that non-U.S. (foreign) institutions are not eligible to apply.

Are non-domestic components of U.S. organizations eligible?

No. The announcement states that non-domestic components of U.S. organizations are also not eligible.

Are any foreign components allowed at all?

The FOA notes that certain foreign components (as defined by the NIH Grants Policy Statement) may be allowed. This implies limited, well-justified foreign involvement could be permissible under NIH policy, but the applicant organization must be an eligible U.S. small business and the overall project must comply with NIH rules.

What is the original closing date listed for this opportunity?

The original closing date listed is 2020-11-10.

Is the scope limited to entirely new compounds, or can known drugs be proposed?

The FOA describes practical flexibility: applicants can propose anything from an entirely new compound series that needs lead optimization to a known drug being re-evaluated for an age-associated indication, as long as the rationale is tied to aging mechanisms and the work remains preclinical.