Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) | PAR 24 223

Opportunity Information: Apply for PAR 24 223

The Alzheimer’s Drug-Development Program (U01 Clinical Trial Optional), funding opportunity number PAR-24-223, is a National Institutes of Health (NIH) cooperative agreement designed to move promising Alzheimer’s disease therapeutics through the practical, development-focused steps needed to reach first-in-human testing. The central aim is to support preclinical development and early stage clinical development (up to and including Phase I) for novel small-molecule drugs and biologic candidates intended to prevent Alzheimer’s disease, slow disease progression, or treat cognitive and behavioral symptoms associated with Alzheimer’s. This program is positioned for projects that already have a credible therapeutic concept and are ready for the kind of translational work that bridges the gap between academic discovery and clinical evaluation.

Because the award mechanism is a cooperative agreement (U01), applicants should expect substantial NIH program involvement compared with a standard research grant. In practice, that typically means an emphasis on milestone-driven development plans, clear go/no-go decision points, and active coordination with NIH staff to keep projects aligned with the program’s development objectives. The clinical trial component is listed as “optional,” which signals that an application may propose a package of IND-enabling preclinical work only, or may extend into initial Phase I clinical testing if the program timeline, readiness, and development plan justify it.

The NOFO is specifically oriented toward the key activities required for therapy development rather than exploratory science. Supported activities include medicinal chemistry and lead optimization work aimed at improving developability; pharmacokinetics (PK) and ADMET (absorption, distribution, metabolism, excretion, and toxicology) studies; efficacy testing in relevant animal models; and development of biomarkers used for target engagement, which are critical for demonstrating that a candidate drug is hitting its intended biological target. The scope also includes formulation development and chemistry, manufacturing, and controls (CMC) activities such as chemical synthesis under Good Manufacturing Practices (GMP), which are necessary to produce clinical-grade material. In addition, the program supports Investigational New Drug (IND)-enabling studies and can support initial Phase I clinical testing when appropriate. Overall, the opportunity is meant to fund the integrated set of experiments and documentation that regulators and clinical teams need to safely begin human studies.

Equally important, the NOFO draws a clear boundary around what it will not fund. Applications focused on basic mechanisms of disease biology or basic mechanisms of drug action are considered non-responsive, even if they are relevant to Alzheimer’s. It also excludes the development of risk, diagnostic, prognostic, predictive, prevention biomarkers when those biomarker projects are not tied directly to therapy development and target engagement for a specific candidate. The opportunity is not intended for devices or non-pharmacological interventions such as exercise programs, diet interventions, or cognitive training. It also does not support repurposed drugs, combination therapies, early discovery efforts like high-throughput screening, hit identification, hit-to-lead work, or hit optimization. Stand-alone clinical trials that are not part of a broader development package leading up from preclinical work are also outside the program’s scope. In short, this is a targeted development pipeline opportunity, not a broad Alzheimer’s research or general clinical trial funding announcement.

Eligibility is broad across public and private sectors in the United States, reflecting the program’s translational and product-development focus. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education where applicable); for-profit organizations (other than small businesses); small businesses; and other categories identified by NIH policy. The NOFO also explicitly highlights additional eligible applicant types 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), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

On the non-U.S. participation rules, the NOFO states that non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply as applicant organizations. However, non-domestic components of U.S. organizations may be included, and foreign components (as defined in the NIH Grants Policy Statement) are allowed, meaning portions of the work can be performed abroad under an eligible U.S. applicant when justified and compliant with NIH policy.

Key administrative details included in the source information are that this is a discretionary funding opportunity in the health category (CFDA 93.866) administered by NIH. The listed award ceiling is $1,500,000. The original closing date is 2027-11-05, indicating a multi-year window during which NIH expects to accept applications on the published due dates associated with the NOFO. While the number of expected awards is not specified in the provided text, the overall structure and emphasis suggest NIH is looking for a manageable set of milestone-ready therapeutic development projects rather than a large number of exploratory studies.

Taken together, PAR-24-223 is best understood as a development accelerator for Alzheimer’s therapeutics: it prioritizes candidates that are beyond discovery, need structured support to complete IND-enabling packages, and can credibly reach Phase I (or at least be positioned to do so) through a tightly planned set of translational activities tied to regulatory and clinical readiness.

• 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 2024-06-25.
• 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 24 223

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