Atom | 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)

Funder: National Institutes of Health

Funding Amounts: No budget limit; project period up to 2 years (UG3) + up to 3 years (UH3), max 5 years total.

Summary: Supports milestone-driven, combined Phase 1/2a clinical trials of novel drugs (excluding amyloid/tau targets) for Alzheimer's disease and related dementias.

Key Information: Applications must bundle both UG3 (Phase 1) and UH3 (Phase 2a) activities and include go/no-go safety milestones; definitive efficacy (Phase 3) trials are not eligible.

Description

This opportunity from the National Institutes of Health (NIH), led by the National Institute on Aging (NIA), funds seamless early-stage clinical drug development for novel therapeutic agents targeting Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). The program is designed to accelerate the evaluation of promising pharmacological interventions—specifically those that engage non-amyloid/non-tau mechanisms and address cognitive and/or neuropsychiatric symptoms across the full spectrum of disease, from pre-symptomatic to severe stages.

The funding mechanism (UG3/UH3) supports a bundled approach: applicants must propose both Phase 1 and Phase 1b/2a clinical trials in a single application, with clear, prespecified safety and tolerability milestones that determine progression from Phase 1 (UG3) to Phase 2a (UH3). The goal is to streamline early-stage clinical development and generate data to inform further clinical advancement of novel or repurposed drugs for AD/ADRD.

Due Dates

Letter of Intent (optional): January 21, 2025
Upcoming Application Deadlines:
- June 23, 2025 (New)
- July 23, 2025 (Renewal/Resubmission/Revision)
- October 20, 2025 (New)
- November 20, 2025 (Renewal/Resubmission/Revision)
- February 20, 2026 (New)
- March 20, 2026 (Renewal/Resubmission/Revision)
- June 22, 2026 (New)
- July 22, 2026 (Renewal/Resubmission/Revision)
- October 19, 2026 (New)
- November 19, 2026 (Renewal/Resubmission/Revision)

All applications are due by 5:00 PM local time of the applicant organization.

Funding Amount

Budget: No specific budget limit; budgets must reflect actual project needs.
Project Period:
- UG3 (Phase 1): up to 2 years
- UH3 (Phase 2a): up to 3 years
- Combined maximum: 5 years
Number of Awards: Contingent on NIH appropriations and the number of meritorious applications.

Eligibility

Eligible applicants include:

Public and private institutions of higher education
Nonprofits (with or without 501(c)(3) status)
For-profit organizations (including small businesses)
State, county, city, township, and special district governments
Independent school districts
Public housing authorities/Indian housing authorities
Native American tribal governments and organizations (federally recognized and other)
Faith-based and community-based organizations
Regional organizations
U.S. territories and possessions
Non-domestic (non-U.S.) entities and foreign components

Note: Applicant organizations must complete all required registrations (SAM, eRA Commons, Grants.gov, etc.) before applying.

Application Process

Application Submission: Use NIH ASSIST, an institutional system-to-system solution, or Grants.gov Workspace.
Required Application Components:
- Single application for both UG3 and UH3 phases
- Prespecified, quantitative go/no-go safety and tolerability milestones
- Data Management and Sharing Plan
- Resource Sharing Plan (biosamples and data)
- Inclusion plans for women and minorities
- Letters of support (if applicable)
Page Limits: Follow NIH How to Apply - Application Guide and Table of Page Limits.
Contact NIA Program Staff: Strongly encouraged at least 12 weeks before submission, especially for projects requesting $500,000 or more in direct costs in any year.

Additional Information

Scope: Only applications proposing both UG3 and UH3 activities are eligible. Applications for definitive efficacy (Phase 3) trials or for only one phase will be withdrawn.
Research Focus: Interventions must target non-amyloid/non-tau mechanisms and may include small molecules, biologics, or repurposed drugs. Exploratory efficacy may be a secondary aim, but not the primary focus.
Data Sharing: Timely sharing of trial data and biosamples is required (within 9 months of database lock or at publication).
Review Criteria: Scientific merit, innovation, rigor, feasibility, investigator expertise, and resource environment.

External Links

Contact Information

Contact Type	Name/Email	Phone
Scientific/Research Contact	Akanni Clarke, Ph.D. akanni.clarke@nih.gov	301-496-9350
Scientific/Research Contact	Laurie Ryan ryanl@mail.nih.gov	301-496-9350
Peer Review Contact	Ramesh Vemuri ramesh.vemuri@nih.gov	301-402-7700
Grants Management Contact	Philip Smith philip.smith2@nih.gov	301-402-3465
General Grants Info	GrantsInfo@nih.gov	301-480-7075
eRA Service Desk	eRA Service Desk	301-402-7469 or 866-504-9552