Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required) | PAR 25 226

Opportunity Information: Apply for PAR 25 226

This NIH funding opportunity (PAR-25-226) supports a streamlined, "seamless" early clinical development path for new drug candidates intended for Alzheimer’s disease (AD) and AD-related dementias (ADRD). The core idea is to reduce delays between early studies by having applicants propose a bundled clinical program that includes a Phase 1 trial alongside a subsequent Phase 1b/Phase 2a trial plan, rather than treating these as disconnected efforts. The award uses a cooperative agreement mechanism, meaning NIH is expected to have substantial involvement during the project (for example, in oversight, coordination, or milestone-driven decision-making), and it is explicitly a clinical trial required NOFO.

The scientific focus is on pharmacological interventions that work through non-amyloid and non-tau mechanisms. In other words, proposals centered on amyloid or tau targets would not match the stated intent; the program is looking for alternative biological pathways and therapeutic strategies. Eligible interventions can include modalities such as small molecules and biologics, as long as the drug’s mechanism aligns with the non-amyloid/non-tau requirement. The clinical intent is also clearly patient-centered: supported projects should aim to improve cognitive symptoms and/or neuropsychiatric symptoms. Importantly, the program is designed to cover the full clinical spectrum, meaning studies may target participants ranging from pre-symptomatic individuals through those with more advanced disease stages, as long as the proposed development plan is appropriate to the stage being studied.

A defining feature is the UG3/UH3 phased award structure. The UG3 phase generally corresponds to the earlier portion of the work (here, the Phase 1 component and associated start-up activities), and the UH3 phase supports the later-stage clinical work (the Phase 1b/2a component). Progression from UG3 to UH3 is not automatic. Applications must include clear, prespecified go/no-go milestones, with particular emphasis on safety and tolerability thresholds. These milestones function as gating criteria: if the intervention does not meet the agreed-upon safety/tolerability benchmarks, the project should not advance into the next clinical stage under this program. This milestone-driven design is meant to protect participants, concentrate resources on the most viable candidates, and accelerate decision-making in early development.

From an applicant standpoint, eligibility is broad and includes many organization types across government, academia, nonprofit, and industry. Eligible applicants include state, county, and local governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits with and without 501(c)(3) status; for-profit organizations (including those other than small businesses) and small businesses; public housing authorities/Indian housing authorities; and federally recognized tribal governments as well as other tribal organizations. The NOFO also highlights additional eligible groups such as HBCUs, Hispanic-serving institutions, AANAPISIs, Tribal Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). The administering agency is the National Institutes of Health, the activity category is Health, and the CFDA listing is 93.242.

Timing-wise, the listed closing date is 2026-11-19, and the NOFO record indicates a creation date of 2024-11-22. An award ceiling and expected number of awards are not specified in the provided source data, so applicants would need to consult the full NOFO text for any budget guidance, institute-specific considerations, and detailed application requirements. Overall, the opportunity is designed for teams that already have a promising therapeutic agent with a credible early clinical package and that can propose a tightly integrated Phase 1 through Phase 2a strategy, complete with concrete safety-based decision points and a clear rationale for addressing AD/ADRD symptoms through non-amyloid/non-tau biology.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2024-11-22.
• Applicants must submit their applications by 2026-11-19. (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 PAR 25 226

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