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) | PAR 23 274

FAQs: NIH PAR 23-274 (UG3/UH3) Early Clinical Development for AD/ADRD Therapeutics

What is PAR 23-274 funding?

PAR 23-274 is a National Institutes of Health (NIH) funding opportunity that supports a streamlined early clinical development path for new drug candidates intended to treat Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD).

What is the main goal of this opportunity?

The goal is to reduce delays between separate early-stage clinical studies by having applicants propose a coordinated package of clinical protocols that moves efficiently from a first-in-human or phase 1 trial into a subsequent phase 1b and/or phase 2a trial.

What stages of clinical development does this program support?

This opportunity is focused on the earliest clinical steps where safety, tolerability, dosing, and initial signals of clinical or biological activity are established, specifically spanning first-in-human/phase 1 and then phase 1b and/or phase 2a testing.

Does the application need to include multiple protocols?

Yes. Applicants are expected to propose a coordinated package of clinical protocols designed to transition from a first-in-human or phase 1 study into a subsequent phase 1b and/or phase 2a study, rather than treating each study as a separate, disconnected effort.

What kinds of therapeutic mechanisms are required?

Supported candidate interventions must target non-amyloid and non-tau mechanisms. The program is intended to expand the AD/ADRD therapeutic pipeline beyond approaches that primarily focus on amyloid beta or tau biology.

Are amyloid or tau targeting therapies eligible?

Based on the stated scientific requirement, the funded candidates must target non-amyloid and non-tau mechanisms, meaning the opportunity is specifically aimed at approaches other than amyloid beta- or tau-focused interventions.

What types of interventions or modalities are allowed?

The interventions can include different therapeutic modalities, such as small molecules or biologics, as long as they are pharmacological interventions and align with the non-amyloid/non-tau focus described in the opportunity.

What symptoms or outcomes should the proposed therapy aim to address?

Projects should aim to address cognitive symptoms and/or neuropsychiatric symptoms associated with AD/ADRD, and they may also evaluate initial signals of clinical or biological activity during early clinical testing.

What participant populations can be enrolled in the proposed studies?

Proposed studies may enroll individuals across the disease spectrum, ranging from pre-symptomatic populations to people with more advanced impairment.

What award mechanism does this opportunity use?

The opportunity uses the UG3/UH3 phased award mechanism, which supports a two-stage progression with clear accountability from an earlier phase into a later phase of clinical testing.

What is the UG3 phase intended to support?

The UG3 phase generally supports the earlier stage of work, often including phase 1 activities and readiness steps needed to begin and complete the initial early clinical component.

What is the UH3 phase intended to support?

The UH3 phase supports the later-stage clinical testing component, such as phase 1b and/or phase 2a studies, following successful completion of the UG3 phase requirements.

How does a project move from UG3 to UH3?

Applicants must prespecify go/no-go milestones, with particular emphasis on safety and tolerability thresholds, that determine whether the project can advance from the initial UG3 phase into the later UH3 phase.

What are go/no-go milestones in this program?

Go/no-go milestones are predefined, concrete decision points (especially focused on safety and tolerability) used to determine whether a therapeutic candidate is allowed to proceed from early work into later-phase clinical evaluation under the UH3 component.

Why does NIH require prespecified safety and tolerability milestones?

These milestones help ensure that later-stage resources are concentrated on interventions that have cleared essential early risk checks, and they provide accountability for advancing only candidates that meet predefined criteria.

Is this award a standard grant or a cooperative agreement?

It is a cooperative agreement, which typically indicates substantial scientific and/or programmatic involvement by NIH during the project period compared with a standard grant.

What is the activity category for this opportunity?

The activity category listed is health.

What CFDA number is associated with this opportunity?

The CFDA number listed is 93.866.

Is this opportunity discretionary funding?

Yes. The opportunity is categorized as discretionary funding.

What is the closing date for this opportunity?

The posted original closing date is 2026-11-19.

Is there an award ceiling or an expected number of awards stated?

The source listing information provided does not specify an award ceiling or expected number of awards in the provided fields. Applicants would generally need to consult the full NOFO text and any accompanying NIH institute guidance for budget expectations and related details.

Who is eligible to apply?

Eligibility is broad and includes many types of applicants such as state, county, and local governments; 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; public housing authorities and Indian housing authorities; tribal organizations that are not federally recognized tribal governments; nonprofit organizations with and without 501(c)(3) status (excluding those that are institutions of higher education in the specific category listing); for-profit organizations (other than small businesses); and small businesses.

Are minority-serving institutions and community-based organizations eligible?

Yes. The announcement highlights additional eligible categories including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), and faith-based or community-based organizations.

Are federal agencies eligible to apply?

Yes. Eligible applicant categories include eligible federal agencies.

Are US territories eligible to apply?

Yes. Eligible applicant categories include US territories or possessions.

Are foreign organizations eligible to apply?

Yes. The eligibility description includes non-US entities (foreign organizations).

What is the program trying to improve compared to traditional early clinical development?

The program is intended to make early clinical development more efficient by minimizing delays between separate early-stage studies and requiring an upfront plan that links phase 1 to phase 1b/phase 2a in a coordinated way.

What kinds of evidence are expected from these early studies?

The early clinical steps supported by this opportunity are where safety, tolerability, dosing, and initial signals of clinical or biological activity are established.

What should applicants do to confirm budget expectations and detailed requirements?

Because the provided listing does not include an award ceiling or expected number of awards, applicants would generally need to consult the full NOFO text and any accompanying NIH institute guidance for budget expectations, scope alignment, and review considerations.