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.Apply for PAR 25 226
- 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.
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FAQs: NIH PAR-25-226 (Seamless Early Clinical Development for AD/ADRD Drug Candidates)
1. What is PAR-25-226 funding?
PAR-25-226 is an NIH funding opportunity designed to support a streamlined, "seamless" early clinical development program for new drug candidates intended for Alzheimer’s disease (AD) and AD-related dementias (ADRD). The key goal is to reduce delays between early clinical studies by supporting an integrated program rather than disconnected trials.
2. What is the main purpose of this opportunity?
The opportunity aims to speed early clinical development by having applicants propose a bundled clinical program that includes a Phase 1 trial and a subsequent Phase 1b/Phase 2a trial plan as part of one coordinated development path.
3. Is this a clinical trial funding opportunity?
Yes. It is explicitly a clinical trial required NOFO, meaning the proposed work must include clinical trial activity consistent with the program’s expectations.
4. What mechanism does NIH use for this award?
This opportunity uses a cooperative agreement mechanism. Under a cooperative agreement, NIH is expected to have substantial involvement in the project, such as oversight, coordination, and milestone-driven decision-making.
5. What scientific approaches are in scope?
The scientific focus is on pharmacological interventions that act through non-amyloid and non-tau mechanisms. The program is looking for alternative biological pathways and therapeutic strategies beyond amyloid and tau targets.
6. Are amyloid- or tau-targeting proposals eligible?
Proposals centered on amyloid or tau targets would not match the stated intent of this funding opportunity, which emphasizes non-amyloid/non-tau mechanisms.
7. What kinds of drug modalities can be proposed?
Eligible interventions can include modalities such as small molecules and biologics, as long as the drug candidate’s mechanism aligns with the non-amyloid/non-tau requirement.
8. What patient benefits should the proposed intervention aim to achieve?
Supported projects are expected to be patient-centered and should aim to improve cognitive symptoms and/or neuropsychiatric symptoms in AD/ADRD.
9. What disease stages can be studied?
The program is designed to cover the full clinical spectrum. 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.
10. What does "seamless" early clinical development mean here?
In this program, "seamless" refers to proposing an integrated development plan that includes Phase 1 together with a subsequent Phase 1b/Phase 2a plan, reducing downtime and friction that can occur when early studies are planned and executed as separate efforts.
11. What is the UG3/UH3 phased award structure?
The award is structured in two phases:
- UG3 phase: generally corresponds to the earlier portion of the work, including the Phase 1 component and associated start-up activities.
- UH3 phase: supports the later-stage clinical work, specifically the Phase 1b/Phase 2a component.
12. Does a project automatically move from UG3 to UH3?
No. Progression from UG3 to UH3 is not automatic. The application must include clear, prespecified go/no-go milestones that determine whether the project advances.
13. What kinds of milestones are required for UG3-to-UH3 transition?
Applications must include prespecified go/no-go milestones, with particular emphasis on safety and tolerability thresholds. These milestones act as gating criteria for whether the project should proceed into the next clinical stage under the program.
14. What happens if the safety/tolerability milestones are not met?
If the intervention does not meet the agreed-upon safety and tolerability benchmarks, the project should not advance to the next clinical stage (the UH3-supported Phase 1b/2a work) within this program.
15. Why is the program milestone-driven?
The milestone-driven design is intended to protect participants, concentrate resources on the most viable candidates, and accelerate decision-making in early clinical development.
16. Who is eligible to apply?
Eligibility is broad and includes many organization types across government, academia, nonprofit, and industry. Examples listed include:
- State, county, and local governments
- Special districts and 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
- Federally recognized tribal governments and other tribal organizations
- U.S. territories or possessions
- Non-U.S. entities (foreign organizations)
17. Are minority-serving institutions and community-based organizations included?
Yes. The NOFO highlights additional eligible groups such as HBCUs, Hispanic-serving institutions, AANAPISIs, Tribal Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, as well as faith-based or community-based organizations and regional organizations.
18. Can foreign (non-U.S.) organizations apply?
Yes. The eligibility list explicitly includes non-U.S. entities (foreign organizations).
19. Which agency administers this opportunity?
The administering agency is the National Institutes of Health (NIH).
20. What is the activity category and CFDA listing?
The activity category is Health, and the CFDA listing is 93.242.
21. What is the application deadline?
The listed closing date is 2026-11-19.
22. When was the NOFO record created?
The NOFO record indicates a creation date of 2024-11-22.
23. Is there a stated award ceiling or expected number of awards?
No. An award ceiling and expected number of awards are not specified in the provided source information. Applicants would need to consult the full NOFO text for any budget guidance and award details.
24. What should applicants consult the full NOFO for?
Based on the information provided, applicants should consult the full NOFO text for budget guidance, institute-specific considerations, and detailed application requirements.
25. What kind of team or project is this opportunity best suited for?
This 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, including concrete safety-based decision points and a clear rationale for addressing AD/ADRD symptoms through non-amyloid/non-tau biology.
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