National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional) | PAR 25 352

FAQs: National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (PAR-25-352)

What is PAR-25-352 (NCDDG) and what is it trying to fund?

PAR-25-352 is an NIH funding opportunity that supports focused, milestone-driven translational projects intended to move new therapeutics and neurostimulation ideas closer to real-world clinical impact. It is designed to push promising concepts through key steps such as discovery, preclinical development, and (when appropriate) early proof-of-concept (PoC) testing.

Is this opportunity new, or related to a previous NIH program?

This opportunity is a reissue of PAR-20-118. The reissue continues the same general intent: advancing promising drug/device concepts through defined translational stages using a milestone-based development approach.

What scientific areas and conditions are within scope?

The scientific scope covers mental disorders as well as substance use disorders (SUDs) and alcohol use disorder (AUD). Projects should be aligned with treatment development and/or enabling work that supports treatment development.

Does the program fund only treatments, or can it fund tools too?

In addition to treatment-focused candidates, the program supports creation of enabling tools (for example, novel ligands and circuit-engagement devices) when those tools help characterize existing targets or validate new targets for drug and device development.

What does “focused, milestone-driven” mean in practice?

The program is intended for projects with defined translational objectives, clear deliverables, and credible go/no-go milestones. The emphasis is on producing translational evidence that a candidate agent or stimulation approach is viable and worth advancing, rather than performing open-ended exploratory research.

What kinds of approaches does NIH expect applicants to take?

The program emphasizes rationally based approaches. Applicants are expected to build on a clear biological or circuit-level rationale, rather than relying on purely exploratory screening. Proposed work should connect the intervention (drug/biologic/device) to a defined mechanism or circuit-engagement concept relevant to psychiatric or addiction-related conditions.

What types of drug or biologics activities fit this NOFO?

Examples described in the opportunity include identifying or optimizing candidate agents with a defined mechanism, improving selectivity/potency/brain penetration, and completing preclinical packages that position a candidate for the next translational step.

What types of device activities fit this NOFO?

The opportunity explicitly highlights neurostimulation strategies and circuit-engagement technologies, reflecting interest in interventions that modulate brain circuits implicated in mental disorders and addiction-related conditions.

Is the goal mainly basic science, or development-ready evidence?

The overall intent goes beyond generating knowledge. The program aims to produce credible translational evidence (including PoC studies when appropriate) showing that a candidate therapeutic agent or stimulation approach is viable and worth advancing.

Are clinical trials required?

No. The NOFO is labeled “Clinical Trial Optional,” meaning a clinical study may be included when justified, but a clinical trial is not required for every application.

What funding mechanism is used for this opportunity?

The award uses the U01 cooperative agreement mechanism.

What does a U01 cooperative agreement imply for how the project will run?

A U01 cooperative agreement generally indicates substantial scientific or programmatic involvement from NIH staff compared to a standard research grant. Applicants should expect a more collaborative structure, clearer expectations for deliverables and project management, and ongoing coordination with NIH.

What kind of project is a U01 intended to support?

The U01 is meant for a discrete, specified, and circumscribed project led by named investigator(s). It is aligned with projects that have a defined endpoint and a coherent development plan.

When would a team consider the companion U19 instead of this U01?

If a team is proposing a broader, multi-project program with several interlocking components and a longer-term multidisciplinary strategy, the NOFO points applicants toward a companion U19 funding opportunity, which is better suited to complex program structures.

How important are academic-industry partnerships for this program?

Partnership is a central theme, and NIH strongly encourages academic-industry collaborations. The rationale is practical: therapeutic development often requires both academic strengths (mechanistic insight and innovative targeting) and industry strengths (development execution, manufacturing, regulatory strategy, and translational planning).

What characteristics of a collaboration are likely to align well with the NCDDG concept?

Applications tend to align well when roles are clearly defined and the team has access to necessary platforms and capabilities (examples mentioned include medicinal chemistry, device engineering, GMP considerations, biomarker development, and specialized assays), along with a credible path to downstream development.

Can the program support projects focused on validating targets or confirming circuit engagement?

Yes. The program allows projects that develop tools (ligands and devices) intended to validate targets or confirm circuit engagement. This type of work can de-risk later-stage therapeutic development by showing that a target is druggable, measurable, and tied to meaningful biological effects.

Who is eligible to apply?

Eligibility is broad and includes government, academic, nonprofit, and commercial sectors. Eligible applicants include state/county/local governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (outside higher education); for-profit organizations other than small businesses; and small businesses.

Are specific institution types (like HBCUs or HSIs) explicitly included?

Yes. The NOFO calls out additional eligible categories including 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 U.S. territories or possessions.

Can a non-U.S. organization apply as the main applicant?

No. Non-domestic (non-U.S.) entities are not eligible to apply as the applicant organization, and non-domestic components of U.S. organizations are not eligible to apply.

Are any international activities allowed at all?

Yes, in a limited way. “Foreign components” are allowed as defined in the NIH Grants Policy Statement, meaning certain project elements may be conducted outside the United States when appropriately justified and structured under NIH rules.

How can the foreign eligibility rules affect team structure and subcontracting?

The distinction between an ineligible non-U.S. applicant organization and an allowable “foreign component” can affect where work is performed and how international collaborators participate. Teams involving international collaborators typically need to plan carefully so the application remains compliant while still leveraging specialized expertise or unique resources.

Which NIH program classification details are provided (CFDA, activity area, instrument type)?

The opportunity is listed as a discretionary NIH funding opportunity under CFDA 93.242, categorized in the health funding activity area. The funding instrument is a cooperative agreement.

What are the key dates mentioned for this opportunity?

The record shows a creation date of January 15, 2025, and an original closing date of October 25, 2027.

Does the provided information include an award ceiling or the expected number of awards?

No. The excerpt does not provide an award ceiling or an expected number of awards.

How should applicants interpret the expected project size and scope given the U01 structure?

Based on the description, applicants should generally interpret the U01 structure as supporting well-scoped development projects with budgets and timelines that match defined translational objectives, rather than open-ended exploratory research.

What is the simplest way to summarize the program’s intent?

It functions like a translational pipeline for mental health and addiction therapeutics and neuromodulation: identify or refine a target and candidate, demonstrate meaningful engagement and functional impact, and generate preclinical and/or early clinical evidence that supports a credible next step toward treatment development.