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

Opportunity Information: Apply for RFA AG 21 026

The NIH funding opportunity "Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (SBIR U44 Clinical Trial Not Allowed)" (RFA-AG-21-026) is a discretionary, health-focused Small Business Innovation Research (SBIR) cooperative agreement designed to help small businesses move promising geroscience therapies through key preclinical steps that are needed before first-in-human testing. The scientific focus is on therapeutics that target fundamental biological mechanisms that drive aging, rather than only treating single diseases in isolation. The announcement highlights core aging-related processes such as chronic inflammation, cellular senescence, and loss of proteostasis (the systems that maintain protein quality and function), and it encourages projects aiming to translate discoveries about these mechanisms into tangible therapeutic candidates.

The scope is intentionally broad in terms of what kinds of interventions can be supported, as long as the work is aimed at aging mechanisms and at conditions that are common in older adults. Eligible therapeutic modalities include novel small molecules (with senolytics named as a key example), biologics, and stem or progenitor cell-based approaches. The FOA also explicitly welcomes translational strategies that reduce development risk and time, such as repositioning investigational drugs (compounds that have already been studied for another indication but are not yet approved) and repurposing FDA-approved drugs for aging-related conditions. In practical terms, this means 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 based on a mechanistic rationale tied to geroscience.

The activities supported are squarely in the preclinical development lane, with an emphasis on generating the evidence package that typically supports an eventual IND-enabling trajectory. Examples called out in the announcement include target validation (showing that the proposed biological target is meaningfully linked to aging mechanisms and the intended disease context), lead optimization (improving potency, selectivity, stability, and developability of a candidate), pharmacokinetics and drug disposition studies (how the candidate is absorbed, distributed, metabolized, and excreted, and what exposures are achieved in relevant tissues), and preclinical safety and toxicology studies. Overall, the FOA is aimed at building a credible translational foundation: demonstrating mechanism-based activity, establishing a development-quality candidate profile, and addressing early safety and PK risks that commonly derail programs before they can enter clinical testing.

Because this is a U44 cooperative agreement, it is not just a standard grant where the awardee operates independently; cooperative agreements typically involve substantial scientific or programmatic involvement from NIH staff, which can include coordination, milestone-based oversight, and guidance aligned with the program goals. The "Clinical Trial Not Allowed" designation makes clear that the funded work must remain on the preclinical side; applicants should plan development packages that stop short of initiating human clinical trials under this award. The intent is to mature candidates to a stage where they are positioned for subsequent clinical funding or partnerships, rather than to run clinical studies within the project period.

Eligibility is centered on U.S. small businesses, consistent with SBIR requirements. The announcement states that non-U.S. (foreign) institutions are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible. At the same time, it notes that certain foreign components (as defined by the NIH Grants Policy Statement) may be allowed, meaning limited, well-justified foreign involvement could be permissible under NIH policy, but the applicant organization itself must be an eligible small business and the project structure must comply with NIH rules. Administrative details provided include the agency (National Institutes of Health), the CFDA number (93.866), and the original closing date listed as 2020-11-10.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Preclinical Development of Novel Therapeutics Targeting Aging Mechanisms (SBIR U44 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): 93.866.
• This funding opportunity was created on 2020-06-25.
• Applicants must submit their applications by 2020-11-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: Small businesses.

Apply for RFA AG 21 026

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