First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Devices for Psychiatric Disorders (U01 Clinical Trial Required) | PAR 21 133

Opportunity Information: Apply for PAR 21 133

This NIH funding opportunity (PAR-21-133) supports milestone-driven, early stage clinical trials that test new investigational drugs and neuromodulatory devices for psychiatric disorders, especially in areas where current treatments fall short. It uses a cooperative agreement mechanism (U01), which typically means the NIH will have substantial scientific involvement during the project, with an emphasis on clear go or no-go decision points and rapid learning. The overall intent is practical and translational: generate the key human data needed to reduce risk (or "de-risk") for promising drug or device concepts so they become more attractive for follow-on investment and larger trials that could eventually lead to FDA-approved treatments.

The FOA is centered on first-in-human (FIH) and early Phase II work for drugs, and first-in-human plus early feasibility studies (EFS) for devices. For novel drugs, supported studies are expected to do more than just look at symptom change. They must demonstrate target engagement, including evidence tied to brain exposure or other convincing measures that the intervention is reaching and affecting the intended biological target. In addition, the trials need to characterize pharmacological effects along with basic clinical development requirements like safety and tolerability. The point of these early studies is to determine whether the intervention is feasible and sufficiently grounded in human biology to justify moving into Phase II or proof-of-concept testing in psychiatric populations.

For Phase II or proof-of-concept drug studies, the FOA expects applicants to evaluate impact on clinically relevant physiological systems using functional measures, alongside clinical indicators of effect. In practice, that means the program is looking for trials that connect mechanism to outcomes: objective or functionally meaningful measures that reflect the biological system a drug is meant to influence, paired with signals that patients may be improving in ways that matter clinically. The same general logic applies to devices. Device projects supported under this announcement should evaluate target engagement and early signals of efficacy while still prioritizing safety and tolerability, consistent with what is needed in early feasibility work for novel neuromodulatory technologies.

A notable feature of this FOA is its strong push for collaboration between academic or biomedical researchers and biotechnology or industry partners. The rationale is straightforward: early psychiatric drug and device development often stalls without coordinated expertise in clinical trial execution, regulatory planning, manufacturing or device engineering, and eventual commercialization pathways. By encouraging structured partnerships, the program aims to speed the transition from a promising idea to a development-ready asset with credible human data behind it.

The opportunity is open to a broad set of applicant organizations across the United States, including state and local governments, public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses, as well as eligible tribal governments and tribal organizations. It also explicitly highlights eligibility for several mission-focused institution types and community-based entities, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, tribally controlled colleges and universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, and faith-based or community-based organizations, among others. At the same time, it draws a firm boundary around foreign involvement: non-U.S. entities and foreign institutions are not eligible to apply, non-U.S. components of U.S. organizations are not eligible, and foreign components are not allowed under NIH policy for this announcement.

Administratively, this is an NIH discretionary grant in the health category (CFDA 93.242). The opportunity was created on 2021-03-02 and lists an original closing date of 2024-10-15. While the excerpt does not specify an award ceiling or expected number of awards, the emphasis on milestone-driven progress and de-risking suggests the program is geared toward well-structured projects with clear deliverables, rigorous early clinical endpoints (including target engagement), and a credible plan to move the intervention toward later-stage development if the data support it.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Devices for Psychiatric Disorders (U01 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 2021-03-02.
• Applicants must submit their applications by 2024-10-15. (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.

Apply for PAR 21 133

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