PAR-25-051: Blueprint Neurotherapeutics Network (BPN) Small-Molecule Drug Discovery (UG3/UH3)

PAR-25-051: Blueprint Neurotherapeutics Network (BPN) Small-Molecule Drug Discovery (UG3/UH3)

Status of this opportunity

This page is an archive entry for the PAR-25-051 cycle. The official National Institutes of Health notice lists July 15, 2026 as the last standard application due date for new applications and for renewal, resubmission, or revision applications as allowed. That date has passed. The notice also lists August 19, 2026 as its expiration date, but an expiration date is not a new application deadline. As checked for this refresh, the official notice does not announce a later PAR-25-051 application cycle. Readers should therefore use this page to understand the closed opportunity and its requirements, not as an indication that a submission can still be filed under the listed cycle.

The official source remains the NIH Guide notice at the URL in the front matter. A local request to that URL returned HTTP 403 during this refresh, so the page’s URL status records that access result. The official NIH content was reviewed through the published notice surfaced by NIH’s public funding pages. The URL itself remains the authoritative program page and has not been replaced in the metadata.

What the BPN was designed to support

The Blueprint Neurotherapeutics Network (BPN) invited neuroscience investigators to advance small-molecule drug discovery and development projects toward the clinic. The program was not a general-purpose mechanism for disease biology or an unrestricted compound-screening project. Its center of gravity was the difficult translational work between a credible chemical starting point and a development candidate that can proceed through preclinical safety work and, where appropriate, Phase I testing.

The notice describes two entry paths. A project could enter at a Discovery stage such as exploratory work, hit-to-lead, or lead optimization. In that path, the team would characterize and optimize promising hits, establish structure-activity and structure-property relationships, and develop evidence about properties such as metabolism, selectivity, and toxicity. A project could also enter at a Development stage when it already had a sufficiently profiled candidate and needed to progress toward IND-enabling toxicology and Phase I clinical testing.

The small-molecule boundary matters. The notice is intended for compounds that can be readily synthesized and chemically modified if optimization is required. It is not designed for biologics or biotechnology products such as proteins and oligonucleotides, or for devices. The notice also identifies activities that are nonresponsive, including screening solely to identify hit compounds, basic research and disease-mechanism studies, animal-model development, diagnostic or biomarker development, development of biologics, and studies directed beyond Phase I clinical testing.

The disease focus must fit the mission of at least one participating NIH Institute or Center. Participating components listed in the notice include NINDS, NEI, NIA, NIAAA, NIDCR, NIDA, NIMH, and NCCIH. Program fit is therefore both technical and institutional: a strong compound-development plan still needs a nervous-system indication that matches the mission and priorities of a participating component.

Funding and project structure

PAR-25-051 uses an UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement. The notice does not set a numeric award ceiling. Instead, it says application budgets are not limited but must reflect the actual needs of the proposed project. A realistic budget still needs to match the work the applicant will perform, the proposed period of support, and the stage-specific plan. “No stated limit” should not be read as permission to submit an unsupported or inflated request.

Applicants could seek up to one year of UG3 funding. The UH3 phase could not exceed four years, and the total project period could not exceed five years. The actual duration depended on successful achievement of milestones and the conditions described in the program overview. The transition from UG3 to UH3 was not automatic. The program established go/no-go milestones, typically every six months but at least annually, and NIH program staff with technical input from an External Oversight Committee evaluated whether a project should advance.

The continuation decision considered successful milestone achievement, the overall feasibility of further advancement, the competitive situation for the disease indication and target, program priorities, and availability of funds. If a funded project failed to make sufficient progress toward agreed milestones, funding and access to BPN contract resources could be discontinued. A proposal therefore needed more than a promising target: it needed measurable decision points, evidence appropriate to its entry stage, and a credible plan for handling failed experiments or a change in development direction.

The cooperative-agreement model also creates meaningful NIH involvement after award. NIH assembles a customized Lead Development Team, normally co-chaired by the PI and an NIH-contracted drug-development consultant, with members from the applicant team, additional consultants, and NIH staff. The team helps establish strategy, propose milestones, coordinate contractor work, and interpret results. If the project reaches clinical development, the Lead Development Team is replaced by a Clinical Development Team that includes the PI, clinical consultants, and NIH staff.

What support could be coordinated through BPN

The applicant remained responsible for studies involving disease- or target-specific assays, models, and research tools in the applicant’s own laboratory. Depending on the team’s expertise and resources, the application could request support for additional work in the applicant’s laboratory, while collaborating with BPN contractors for specialized activities. The notice names medicinal chemistry, pharmacokinetics, toxicology, formulation development, chemical synthesis under current Good Manufacturing Practice, and Phase I clinical testing among the areas that contractors and consultants may support.

This arrangement was intended to accommodate different starting points. A team with strong medicinal chemistry capacity could retain more chemistry work and seek support for ADMET, in vivo pharmacokinetics, manufacturing, or IND-enabling toxicology. A team with limited drug-development infrastructure could propose to use more of the available contractor network. Applicants were expected to explain what their own group would do, what collaborators would do, and where NIH-provided resources would be needed.

The program’s intellectual-property structure was another important planning issue. The recipient institution retains its assignment of IP rights and gains assignment of IP rights from BPN contractors and consultants for drug candidates developed through the program. The institution is expected to take responsibility for patent filings, maintenance, licensing, and commercialization planning. Academic applicants needed to involve the technology-transfer or business-development office early enough to address existing rights, prior art, licensing constraints, and any arrangements among multiple institutions.

Eligibility and registrations

The official eligibility list is broad. It includes public and private higher education institutions; nonprofit organizations; small businesses and other for-profit organizations; state, county, city, special-district, and tribal governments; eligible federal agencies; U.S. territories or possessions; independent school districts; public or Indian housing authorities; tribal organizations; faith-based or community-based organizations; regional organizations; and non-domestic entities. Foreign organizations and non-domestic components of U.S. organizations are eligible to apply, subject to the applicable NIH policies.

Eligibility also depends on administrative readiness. Applicant organizations must complete and maintain the registrations described in the NIH How to Apply - Application Guide before submitting. The notice specifically points applicants to the unique entity identifier, System for Award Management, eRA Commons, and Grants.gov requirements. Registration can take six weeks or more, and an incomplete registration is not a valid reason for a late submission. Each PD/PI must include a valid eRA Commons ID in the Credential field of the Senior/Key Person Profile form, and the UEI in the application must match the identifier used in the organization’s eRA Commons and SAM profiles.

The allowed application types are New, Resubmission, and Revision. Renewal applications are not listed as an allowed type in the notice. Applicants also needed to make sure the proposed condition fit a participating Institute or Center and that the work was responsive to the small-molecule drug-discovery scope. A project that primarily develops a biologic, a device, a diagnostic, or a disease model would need a different NIH opportunity.

Application route and materials

The notice offered three ways to prepare and submit an application: NIH ASSIST; an institutional system-to-system solution that submits to Grants.gov and uses eRA Commons for tracking; or Grants.gov Workspace with eRA Commons tracking. Paper applications were not accepted. After submission, the organization was responsible for tracking the application in eRA Commons, viewing it before the deadline, and correcting any errors by submitting a changed or corrected application to Grants.gov on or before the due date and time. A corrected application submitted after the deadline could be considered late.

Applicants had to follow the Research instructions in the NIH How to Apply - Application Guide, together with the program-specific instructions in PAR-25-051. The core Research Strategy needed to make the entry stage clear, establish the biological rationale and supporting evidence, describe the compound and its disease relevance, and define milestones that can support a go/no-go decision. The application also needed to distinguish work performed by the applicant from work that could be performed by BPN contractors.

The notice adds several materials that are especially relevant to this program. Academic applicants should include a letter of support from the technology-transfer official responsible for IP and licensing, including agreement to share relevant licensing details confidentially with NIH when needed to assess commercialization feasibility. If work would take place at more than one institution, each institution should provide a letter explaining how IP would be shared or managed without encumbering the program’s goals. Applications generating scientific data must address the Data Management and Sharing Plan, even when the direct-cost request for a year is small. Only limited Appendix materials are allowed, and publications or other material may not be added there except for blank questionnaires or blank surveys.

When human subjects research or a clinical trial is proposed, the application must include the required PHS Human Subjects and Clinical Trials Information forms. The notice calls for attention to dose levels, route of administration, and pharmacokinetic outcome measures, including CNS penetration and target engagement or modulation when appropriate. Clinical-trial plans should be proportionate to the stage: BPN supports up to Phase I, primarily human pharmacokinetics and tolerability, and the applicant is not expected to provide a Phase II design in this application.

How a strong application would have been prepared

The first planning question was stage fit. A Discovery-stage proposal needed a credible hit or lead, assay evidence relevant to the proposed indication, and a plan to establish the data needed for optimization. A Development-stage proposal needed a well-profiled and optimized candidate with in vitro and in vivo activity and ADMET properties appropriate to the intended clinical use. The proposal should explain why the intended route and exposure are plausible and how the candidate could reach IND-enabling work.

The second question was division of labor. Reviewers considered whether the PI team had the expertise and resources for the work it proposed to conduct itself and whether the PI could lead the collaboration with NIH staff and BPN consultants. It was reasonable to suggest contractors or consultants where specialized expertise was needed, but the applicant still had to own the disease-specific science, the key assays and models, the interpretation of results, and the milestone plan.

The third question was quality and compliance. IND-enabling nonclinical studies are expected to follow Good Laboratory Practice and applicable FDA guidance. Clinical trials must follow Good Clinical Practice and NIH data-and-safety-monitoring policy. Investigational products for clinical trials must be produced under current Good Manufacturing Practice. These are not post-award details to be left out of the proposal; they affect the schedule, facilities, contractor plan, and budget.

Finally, the application needed an IP and commercialization plan that was credible for the proposed chemical scaffold and disease indication. Reviewers considered prior-art or licensing constraints, the ability to develop and commercialize the candidate, and the management of IP across institutions. The notice also asks reviewers to consider biological rationale, drug-like properties, potential patient benefit, novelty, study rigor, and the likelihood of a path into the clinic.

Historical-reference guidance

PAR-25-051 should not be presented as an open opportunity after the July 15, 2026 deadline. The August 19, 2026 expiration date describes the life of the notice, not a later submission window. No later application date is stated in the official notice reviewed for this update. Researchers interested in a future BPN round should check the NIH Guide and the Blueprint Neurotherapeutics Network site for a separately published notice rather than reusing this page’s deadline.

The official NOFO remains useful for understanding the BPN model: small-molecule projects can enter at Discovery or Development, NIH can coordinate specialized contractor support, the award uses UG3 and UH3 phases, and continuation depends on milestones and program review. Those facts describe the published PAR-25-051 mechanism. They do not make the closed cycle available for a new submission.

Official source

• NIH official NOFO: https://grants.nih.gov/grants/guide/pa-files/PAR-25-051.html
• Program: Blueprint Neurotherapeutics Network, administered through participating components of the National Institutes of Health
• Archived cycle deadline: 2026-07-15
• Official expiration date: 2026-08-19

Use the official NIH notice for any future replacement announcement, updated application instructions, or Institute-specific contact guidance.