Blueprint Neurotherapeutics Network (BPN): Small Molecule Drug Discovery and Development of Disorders of the Nervous System (UG3/UH3 Clinical Trial Optional)

The NIH’s Blueprint Neurotherapeutics Network (BPN) program invites applications from researchers focused on small molecule drug discovery and development for nervous system disorders. This program provides support to conduct disease-targeted studies in the applicant’s lab, while NIH-funded resources such as contract research organizations (CROs) and consultants offer specialized support in medicinal chemistry, pharmacokinetics, toxicology, formulation, and clinical testing under Good Manufacturing Practices (GMP). Projects can enter the BPN at either the Discovery or Development stages, depending on the readiness of the compound. Discovery stage projects focus on optimizing compounds to develop a drug candidate with favorable pharmacological properties, while Development stage projects concentrate on preparing a single candidate for FDA Investigational New Drug (IND) approval and Phase I clinical trials. The BPN initiative specifically targets small molecule compounds and does not support biologics or devices. The application must focus on a nervous system disorder within the missions of participating NIH institutes, such as NINDS, NIMH, NEI, NIA, and NIDA. The BPN program uses a UG3/UH3 phased award mechanism, where UG3 provides up to one year of preparatory funding to complete essential studies, and the UH3 phase (up to four additional years) advances projects through rigorous optimization and safety testing milestones. Intellectual property rights are retained by the recipient institutions, who also receive the IP rights for BPN contractor contributions, enabling control over patenting and licensing of the developed compounds. Eligible applicants include higher education institutions, nonprofits, government entities, and for-profit organizations both within and outside the U.S. To apply, organizations must complete registration with systems such as SAM, NCAGE (for foreign organizations), and eRA Commons. Applications should include detailed project plans, such as the specific aims and research strategy for both UG3 and UH3 phases, experimental designs, target product profiles, and intellectual property strategies. For Discovery stage entries, preliminary data on bioactivity, assay validation, and initial in vitro ADMET profiling are required, while Development stage entries should have fully characterized candidates and data supporting clinical relevance and feasibility of the compound. The NIH assigns a Lead Development Team (LDT) to each awarded project, co-chaired by the Principal Investigator and an NIH consultant. This team oversees project strategy, sets milestones, and coordinates activities between the applicant’s lab and NIH contractors. Projects undergo regular reviews, with Go/No-Go milestones every six months to assess progress and determine continuation. Milestones ensure that BPN resources are effectively used and that project goals are achievable within the program structure. Applications undergo rigorous review based on scientific merit, significance, feasibility, and innovation. High-risk projects are acceptable, particularly at early stages, but must demonstrate compelling scientific rationale and a viable path toward a drug candidate. The review process also considers the applicant’s institutional resources for managing intellectual property and commercializing the drug candidate. Awardees must comply with NIH policies for data management, human subject protection, and Good Laboratory Practices, ensuring data quality for regulatory approval. Deadlines are staggered across multiple submission cycles, with initial deadlines on January 27, 2025, and subsequent due dates extending through 2026. Prospective applicants are encouraged to submit a letter of intent 30 days before the application deadline and to consult NIH program contacts for guidance.