First in Human and Early Stage Clinical Trials of Novel Investigational Drugs or Neuromodulatory Device-based Interventions for Psychiatric Disorders (U01 Clinical Trial Required) | PAR 25 180

Opportunity Information: Apply for PAR 25 180

This NIH Notice of Funding Opportunity (PAR-25-180) supports milestone-driven, early stage clinical trials that test new investigational drugs and novel neuromodulatory device-based interventions for psychiatric disorders, specifically in areas where there are still major unmet treatment needs. The award mechanism is a U01 cooperative agreement, which typically means NIH staff will have substantial scientific and programmatic involvement during the project period, with an emphasis on clearly defined milestones, go/no-go decision points, and rapid learning that can guide subsequent development. The overall goal is practical and development-focused: generate convincing early human data that reduces uncertainty (often described as "de-risking") so that promising candidates are more likely to attract follow-on private investment or additional public funding and ultimately move toward FDA-approved treatment options.

A major focus of the NOFO is on first-in-human (FIH) and other early clinical studies in both adult and pediatric populations. For novel drugs, supported trials are expected to do more than simply report symptom change. FIH and Phase II-enabling work must include evidence of target engagement, such as demonstrating brain exposure or other indicators that the intervention is reaching and affecting the intended biological target in the central nervous system. Applications are expected to assess pharmacologic effects along with basic clinical safety and tolerability, producing the type of dataset needed to judge whether a program is ready to proceed to larger Phase II or proof-of-concept (PoC) studies in psychiatric indications. In Phase II/PoC contexts, the NOFO emphasizes measuring the drug's impact on clinically relevant physiological systems using functional measures, as well as tracking clinical indicators of effect, so that early signals are interpretable and actionable rather than purely exploratory.

The opportunity also explicitly supports device-based interventions, including first-in-human and early feasibility studies (EFS) of novel neuromodulatory devices. For devices, the expectation is similarly translational and milestone-oriented: show credible target engagement, characterize safety and tolerability, and produce early evidence related to efficacy. The NOFO also allows for device approaches and combination treatment strategies where appropriate, reflecting the reality that many psychiatric conditions may benefit from multimodal interventions. Across both drug and device categories, the intent is to rapidly assemble a high-quality early clinical package that answers the questions most likely to block development later, such as whether the mechanism is engaged in humans, whether there is a measurable functional effect consistent with the proposed biology, and whether the risk profile is acceptable.

A defining feature of this NOFO is its emphasis on collaborative partnerships between academic biomedical researchers and biotechnology or industry researchers. The program is designed to move beyond purely academic clinical experimentation and into development-oriented teamwork that can support manufacturing, regulatory planning, clinical operations, and eventual commercialization pathways. By encouraging these partnerships, NIH is signaling that applications should be positioned to move efficiently along the development pipeline, including the practical requirements for investigational product handling, device engineering controls, and the kinds of data packages investors and later-stage funders typically require.

Eligibility is broad within the United States and includes many organization types such as state, county, and local governments; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities; nonprofits (including both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses. The NOFO also highlights additional eligible applicant categories such as HBCUs, Hispanic-serving institutions, AANAPISIs, Tribal Colleges and Universities, Alaska Native and Native Hawaiian-serving institutions, faith-based or community-based organizations, eligible federal agencies, and U.S. territories or possessions. At the same time, it clearly excludes non-U.S. entities: foreign organizations are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by NIH policy are not allowed.

Administratively, the opportunity is issued by the National Institutes of Health under a health-related activity category (CFDA 93.242) and uses a cooperative agreement funding instrument. The original closing date listed is October 15, 2027. While an award ceiling and the expected number of awards are not specified in the provided listing, the structure and description make clear that NIH is prioritizing projects that can define and meet concrete milestones quickly, generate interpretable human evidence of mechanism and effect, and set the stage for the next development step toward treatments that could eventually gain FDA approval for psychiatric disorders.

• 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 Neuromodulatory Device-based Interventions 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 2024-11-26.
• Applicants must submit their applications by 2027-10-15.
• 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 25 180

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