Early-Stage Therapy Development for ADRD (R61/R33 Clinical Trial Not Allowed) | RFA NS 22 059

Opportunity Information: Apply for RFA NS 22 059

The Early-Stage Therapy Development for ADRD (R61/R33 Clinical Trial Not Allowed) funding opportunity (RFA-NS-22-059) is an NIH grant program aimed at moving new therapeutic ideas for Alzheimer’s disease and related dementias (ADRD) from early discovery toward the point where they are ready for more advanced translational development programs. It is run under the National Institute of Neurological Disorders and Stroke (NINDS) mission scope and focuses specifically on novel small-molecule drugs and biologic therapeutics. The dementias of interest include frontotemporal degeneration (FTD, including Pick’s disease and progressive supranuclear palsy), Lewy body dementias (including dementia with Lewy bodies and Parkinson’s disease dementia), vascular contributions to cognitive impairment and dementia (VCID), and multiple-etiology dementias (MED). A key constraint is embedded in the title: clinical trials are not allowed under this FOA, meaning the supported work is preclinical and early translational rather than human testing.

The structure of the award is a phased, milestone-driven R61/R33 mechanism designed to create a clear, staged path through early therapy discovery and development. The program is organized into four stages, each with explicit go/no-go milestones, so projects are expected to demonstrate concrete progress and meet predefined performance bars before advancing. Applicants can enter at the stage that best matches their current level of readiness, rather than being forced into a one-size-fits-all starting point. This design is meant to support projects that already have some groundwork laid, as well as projects that still need enabling tools (like assays) before meaningful compound or biologic optimization can happen.

The R61 phase supports the preparatory and enabling work that falls into stages 1 through 3. Stage 1 is about building or refining in vitro and/or ex vivo assays that can credibly support therapeutic screening, which usually means developing robust experimental systems with reproducible readouts that reflect the biology relevant to the chosen ADRD indication. Stage 2 focuses on screening efforts to identify and characterize potential therapeutic agents, which can include hit identification and early characterization steps that differentiate real signal from noise and begin to establish relationships between a candidate agent and the targeted mechanism. Stage 3 covers therapeutic optimization and foundational translational profiling, including pharmacodynamics and pharmacokinetics work, which is where candidates are typically refined to improve potency, selectivity, stability, exposure, and other properties needed for in vivo testing. Collectively, these stages are intended to turn an initial idea into a candidate that is sufficiently well-supported to justify efficacy testing in an animal model.

The R33 phase supports stage 4, which is in vivo efficacy studies in an animal model of disease. This is where the program expects projects to test whether the optimized therapeutic candidate produces meaningful effects in an established model relevant to the ADRD subtype being pursued. While the FOA does not support clinical trials, the R33 phase is still meant to be rigorous and translationally informative, emphasizing study designs and outcome measures that can credibly support a later step into larger-scale translational pipelines.

A major purpose of the FOA is to position successful projects for competitive follow-on applications, particularly those that meet entry criteria for later-stage, structured translational programs such as the Blueprint Neurotherapeutics Network, Blueprint Biologics, or similar programs. In practical terms, this means the work supported here is expected to generate the kind of data package and development maturity that de-risks the therapy and makes it more fundable for advanced preclinical development efforts, rather than stopping at basic discovery.

Eligibility is broad and includes many types of institutions and organizations. Beyond common NIH-eligible entities such as universities, nonprofits, for-profits (other than small businesses), and small businesses, the FOA explicitly recognizes a wide range of applicants including state, county, city/township, and special district governments; independent school districts; public housing authorities/Indian housing authorities; federally recognized tribal governments and other tribal organizations; and a variety of mission- or community-focused organizations. It also notes eligibility for entities such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, eligible federal agencies, and even non-U.S. (foreign) organizations, as well as U.S. territories or possessions. The award instrument is a discretionary grant under NIH, associated with CFDA numbers 93.853 and 93.866.

Key administrative details included with the listing are that the FOA was created on 2022-08-02 and had an original closing date of 2022-10-31. The listed award ceiling is $500,000. The number of expected awards is not specified in the provided source data. Overall, the opportunity is best understood as a milestone-gated bridge between early discovery and more advanced translational development, focused on producing strong preclinical packages for ADRD therapeutics while explicitly excluding clinical trial activity.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Early-Stage Therapy Development for ADRD (R61/R33 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): 93.853, 93.866.
• This funding opportunity was created on 2022-08-02.
• Applicants must submit their applications by 2022-10-31. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $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.

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