Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) | PAR 25 297

Opportunity Information: Apply for PAR 25 297

The National Institutes of Health (NIH) is offering a cooperative agreement opportunity called the Alzheimer's Drug-Development Program (U01 Clinical Trial Optional), listed as PAR-25-297 (CFDA 93.866). The aim is to move promising, novel therapeutic candidates for Alzheimer's disease (AD) forward through late preclinical work and into early human testing. Specifically, the program supports development of new small-molecule drugs and biologics intended to prevent Alzheimer's, slow or modify disease progression, or treat cognitive and behavioral symptoms associated with the disease. The focus is intentionally practical and milestone-driven, emphasizing the work needed to advance a candidate toward clinical readiness rather than open-ended research.

The funding is designed to cover the types of development activities that typically stand between a strong lead candidate and an Investigational New Drug (IND) application, and in some cases, the first-in-human Phase I study. Supported activities include medicinal chemistry and optimization (for small molecules), pharmacokinetics (PK), and ADMET (absorption, distribution, metabolism, excretion, and toxicology) studies; demonstration of efficacy in appropriate animal models; development of biomarkers specifically aimed at confirming target engagement; formulation development; and chemical synthesis and manufacturing under Good Manufacturing Practices (GMP). The program also supports IND-enabling studies and allows initial Phase I clinical testing, which is why the notice is labeled "Clinical Trial Optional." In other words, applicants can propose a package that ends at IND-enabling work, or one that continues into early Phase I, as long as the overall plan fits the program's drug-development purpose.

Just as important is what the NOFO does not fund. It is not intended for basic science studies on disease mechanisms or broad investigations into how a drug works at a fundamental level. It also excludes efforts focused solely on developing risk, diagnostic, prognostic, predictive, or prevention biomarkers (as standalone biomarker programs), as well as devices and non-pharmacological interventions such as exercise programs, dietary interventions, or cognitive training approaches. Repurposed drugs and combination therapies are considered non-responsive under this announcement, and so are discovery-stage activities like high-throughput screening, hit identification, and early hit-to-lead optimization when the work is still at the discovery stage. Stand-alone clinical trials that are not embedded in a broader preclinical-to-IND-to-Phase-I development pathway are also not a fit. The underlying message is that NIH wants applicants who already have a defined therapeutic candidate and a credible development plan to de-risk it and move it toward early clinical evaluation.

This opportunity uses the U01 mechanism, meaning it is a cooperative agreement rather than a standard grant. In practical terms, a cooperative agreement generally implies substantial involvement from the NIH program team during the project, often through active scientific and programmatic stewardship, alignment to milestones, and ongoing coordination around development decisions. For applicants, that typically means proposing clear deliverables and development checkpoints, and being prepared for a more collaborative, guided form of federal support than a traditional investigator-initiated research award.

Eligibility is broad across the U.S. research and development ecosystem. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (including those other than small businesses); and small businesses. The NOFO also highlights additional eligible applicant categories 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 eligible federal agencies.

On the international side, the rules are specific. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply as the applicant organization. However, non-domestic components of U.S. organizations are eligible, and foreign components are allowed as defined by the NIH Grants Policy Statement, meaning certain project elements can be performed abroad when appropriately justified and structured under a U.S.-based applicant.

Key administrative details include that the sponsoring agency is NIH, the opportunity category is discretionary, and the instrument type is a cooperative agreement (U01). The original closing date provided is 2027-11-05. The listed award ceiling is $1,500,000, indicating the maximum award amount under the announcement (with actual budgets typically depending on the scope, milestones, and NIH program priorities). Overall, this NOFO is best suited for teams with a novel AD therapeutic candidate that is beyond discovery, ready for rigorous preclinical development and IND-enabling work, and potentially positioned to enter initial Phase I clinical testing within the proposed project period.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Alzheimer's Drug-Development Program (U01 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 2024-12-04.
• Applicants must submit their applications by 2027-11-05.
• Each selected applicant is eligible to receive up to $1,500,000.00 in funding.
• 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 25 297

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