Program Overview
BPN Biologics, part of the NIH Blueprint for Neuroscience Research, aims to advance the development of novel biologics-based drugs for nervous system disorders. The program covers diverse biotherapeutics modalities, including antibodies, proteins, peptides, oligonucleotides, gene and cell therapies, and other emerging modalities. Support is provided for projects from lead optimization to first-in-human clinical trials through participation from multiple NIH Institutes and Centers.
In addition to funding, BPN Biologics provides integrated project support to help academic and small company labs bridge critical gaps. Awarded projects receive:
- Assistance from NIH-funded drug development consultants with extensive industry and regulatory experience
- The option to run industry-standard nonclinical, manufacturing, and early-phase clinical activities through NIH-funded contract research organizations (CROs).
Applicants may choose how many and which R&D activities to conduct through BPN contractors in addition to grant-funded activities.
BPN Biologics Funding Opportunities
- PAR-24-293 (UG3/UH3) | Open to all eligible applicants
- PAR-24-294 (U44) | SBIR Fast-Track open to eligible U.S. small businesses
Features of the UG3/UH3 & U44 Mechanisms
- Cooperative agreements: Funding is provided through cooperative agreements. Unlike grants, cooperative agreements have substantial Program staff involvement.
- Award phases: The UG3/UH3 and U44 (combined SBIR Phase I/Phase II) are phased awards. Applications must include Aims and budget for both award phases and require a fully developed UH3 or U44 Phase II at the time of submission.
- Milestone-driven: Definitive milestones with quantitative go/no-go criteria are developed with NIH staff prior to award and are based on project Aims and feedback from the review process. The final plan is included in the Notice of Award.
- Interim evaluation: Program staff assess milestone progress at the end of the first award phase and determine if projects are sufficiently de-risked to advance.
- Seamless transition: If approved, projects advance to the second award phase without a break in funding.
Determine the Appropriate Mechanism
While the UG3/UH3 (PAR-24-293) and U44 (PAR-24-294)cover the same scope and offer the same NIH-contracting support, there are a few key differences.
Note: the U44 is an SBIR Fast-Track (Phase I/Phase II). BPN does not offer STTR funding or other small business paths (e.g., direct to Phase II).
Comparing BPN Biologics Cooperative Agreements
| Key Information | UG3/UH3 | U44 SBIR Fast-Track |
|---|---|---|
| Eligibility | Higher Education Institutions, Nonprofits, Local and Federal Government, Small Businesses & Other For-Profit Organizations | Only eligible U.S. small businesses |
| Duration | Up to 5 years total ≤ 2 years UG3 ≤ 4 years UH3 | Up to 5 years total ≤ 2 years Phase I ≤ 3 years Phase II |
| Budget | Not limited*; must reflect actual project needs | No hard cap but rarely exceeds: $500K/year Ph. I $1.5M/year Ph. II |
| *Large budget prior approval | Required if direct costs >$500K in any year. Contact Program staff. | No specific requirements |
| Principle investigator | No specific employment requirements | Primary employment (>50%) must be with the small business |
| Foreign institutions | Contact Program staff. | Not eligible |
| Non-U.S. components of U.S. organizations | Eligible. Contact Program staff. | Not eligible |
| Commercialization plan | Developed during funding period | Required for application submission |
BPN U44 vs. Traditional SBIR Mechanisms
| Key Information | BPN U44 | SBIR Omnibus Program |
|---|---|---|
| Mechanisms | U44 SBIR Cooperative Agreement | R43 and R44 SBIR grants |
| Award phases | Fast-track (combined Phase I/Phase II) only | Phase I, Phase II, Direct-to-Phase II, Fast-Track |
| NIH staff involvement | Substantial involvement | Not directly involved in project |
| Award support | Funding plus access to NIH-funded consultants, CROs and project managers | Grant funding only. Additional support available through NIH SEED Office |
| Biomedical products | Biotherapeutics only (e.g., proteins, ASOs, gene and cell therapies,) | Broad (e.g., therapeutics, diagnostics technologies, and tools) |
| Indications | Aligns with participating NIH Institute/Center mission | Extremely broad |
| Drug development stages | Lead optimization through first-in-human trials | All stages of discovery, preclinical development, and early-stage clinical testing |
| Milestones | Set by PI & Program staff after peer review | Included in Fast-Track applications only |
Lead Development Teams (LDT)
LDTs are assembled to support each investigator-driven project and include the investigator’s research and development team, NIH Program staff, NIH-contracted drug development consultants, and CROs. Bi-weekly team meetings and frequent email communication facilitate study planning and coordination, troubleshooting, and achieving project milestones.
Investigators are expected to lead the project team, regularly present research and development updates, and actively participate in planning NIH-contracted work.
Subject matter expert consultants provide technical recommendations and guidance on strategy, study designs, and regulatory package preparation. Consultants are assigned by Program staff based on the stage- and modality-specific needs for each project.
Determining If Your Project Is In Scope
BPN Biologics prioritizes both common and rare disorders of the nervous system. However, applications must focus on a single disorder that falls within the mission of a participating NIH Institute or Center (IC). Applicants are strongly encouraged to read Sections I.D and I.E of PAR-24-293 or PAR-24-294 for complete information on entry criteria and activities supported.
For small molecule approaches, see our companion Blueprint Neurotherapeutics funding opportunities (PAR-25-051 and PAR-24-063), which offer similar NIH-contracted resources.
Participating Institutes and Centers
Each participating BPN Biologics IC has specific disease areas of interest. Email the relevant IC Program staff for questions on IC priorities and instructions on pre-submission/prior approval requests, ideally 12 weeks before the application due date. NOTE: Prior approval is required for UG3/UH3 applicants requesting ≥$500,000 in direct costs in any one year.
- National Institute of Neurological Disorders and Stroke | Lauren Friedman, PhD
NINDS is interested in projects that focus on the development of novel biologics-based therapeutics for neurological and neuromuscular disorders relevant to its mission.
- National Eye Institute | Paek Lee, PhD; Tony Gover, PhD
NEI’s interest in BPN Biologics is to develop novel therapies to treat diseases and disorders of the visual system, especially blinding eye diseases such as glaucoma, age-related macular degeneration, retinitis pigmentosa and other conditions of the visual nervous system.
- National Institute on Aging | Shreaya Chakroborty, PhD
NIA is interested in projects developing new biologics aimed at modifying the behavioral symptoms in Alzheimer's disease (AD), delaying the onset or slowing the progression of AD, mild cognitive impairment (MCI), other dementias of aging and age-related cognitive decline. Biotherapeutic modality interests include gene, peptide/protein-based, cell-based and immunotherapies, genome editing, gene silencing, and PROTAC.
- National Institute on Alcohol Abuse and Alcoholism | Qi-Ying Liu, MD, MSci
NIAAA is interested in research aimed to develop pharmaceuticals targeting new molecular sites to provide effective therapy for alcohol use disorder. Recent research has discovered specific genetic variants that may contribute to the risk for alcoholism and/or render individuals with alcohol use disorder responsive to specific therapeutic agents. NIAAA is interested in supporting research to develop pharmaceuticals targeting individuals with identified genotypic and phenotypic characteristics to improve efficacy and safety.
- National Institute of Dental and Craniofacial Research | Melissa Ghim, PhD
NIDCR is interested in biologics development for craniofacial disorders and painful disorders of the orofacial region including temporomandibular joint disorders, trigeminal neuropathies, burning mouth syndrome, oral cancer pain, dental pain and other conditions.
- National Institute on Drug Abuse | Jason Sousa, PhD
NIDA is interested in developing new biotherapeutics for substance use disorders (SUD). Projects focused on cocaine, methamphetamine and marijuana use disorders are of high priority for NIDA because there are currently no FDA-approved treatments for these indications. NIDA will only support projects entering BPN Biologics at the “Discovery stage”.
- National Institute of Environmental Health Sciences | Jonathan Hollander, PhD
- National Institute of Mental Health| Yael Mandelblat-Cerf
NIMH is interested in applications proposing biologics as a therapeutic approach for mental disorders, including treatment-resistant depression, bipolar disorder, schizophrenia, PTSD, and autism spectrum disorder, and neurodevelopmental disorders that are aligned with NIMH genetics priorities. NIMH will only support projects entering BPN Biologics at the “Discovery stage”.
- National Center for Complementary and Integrative Health | Hye-Sook Kim, PhD
NCCIH is interested in projects focused on novel biologic therapies that involve natural product-derived components -- including microbial-based interventions (e.g., probiotics and live biotherapeutic products) and macromolecular natural products (e.g., peptides and toxins from marine and terrestrial plants, animals, and microbes) -- to modulate or manage symptoms of nervous system disorders such as chronic pain, stress, sleep disorders, anxiety disorders, and mild depression.
Entry Criteria
Projects can enter the program at one of two stages: lead optimization (“Discovery”) or candidate stage (“Development”).
Types of R&D Activities Supported
All projects start in the first award phase (UG3 / U44 Phase I) regardless of scientific entry point. For projects entering at Discovery-stage, final clinical candidate selection is required to move on to UH3 / U44 Phase II.
| Award Phase | Types of Activities Supported |
|---|---|
| UG3 / U44 Ph. I | Lead optimization and/or preparatory work for IND-enabling studies (e.g., bioanalytical assay qualification, process development, pre-IND package) |
| UH3 / U44 Ph. II | IND-enabling nonclinical studies, CMC, IND preparation and submission. Optional first-in-human (FIH) clinical trial |
At minimum, applicants should aim to reach IND filing by the end of UH3 / U44 Phase II. An FIH clinical trial may be proposed if completion of the study is feasible within the award period.
Prepare Your Application
The information in this section is specific to applications for BPN Biologics funding.
- Carefully read the information in Section IV of PAR-24-293 or PAR 24-294
- Ensure that UG3 / U44 Phase I does not exceed 2 years.
- Provide budget and aims for both award phases
- Include a Gantt Chart and Intellectual Property Strategy as separate attachments
- Review differences in CROs: BPN-contracted vs. Grant-funded (see below)
- Specify project’s entry stage (Discovery vs. Development)
- Include Target Product Profile and Therapeutic Agent Profile tables
- For Discovery-stage only, include a Testing Funnel figure
- Does your application include Human Subjects? See below.
CROs: BPN-contracted vs. Grant-funded
Applicants may opt to use grant funding for CROs managed and selected by the investigator, BPN-contracted CROs paid for by NIH, or a combination of the two. In all cases, applicants may propose the number and types of activities to outsource.
Note: U44 applicants should review allowable SBIR outsourcing for Small Business programs. Work requirement percents are only applicable when calculating grant funding and should not include NIH contractors.
How to address CROs in your application:
| Key Information | BPN-contracted CROs | Grant-funded CROs |
|---|---|---|
| Funding | Through NIH contracts. (no cost to applicant) | Through subaward |
| Selection | By NIH managed contractor RFP after award | By the applicant |
| Contractors named in application | No (selected after award) | Yes |
| Solicit quotes before submission | No | Yes |
| Expenses in application budget | No | Yes |
| Detailed study designs in application* | No. Only include high-level descriptions and expected deliverables. | Yes |
| Evaluation of appropriate expertise | Not subject to peer review since selected after award | Peer reviewed |
| Time to finalize agreements | ~12 months (post-award) | 1-2 months |
| Management during award | Led by NIH staff | Led by PD/PI team |
*BPN-contracted CRO studies will be designed in collaboration with the investigator’s team, NIH staff, and BPN consultants after award.
Drug Development Consultants
All BPN Biologics projects will receive support from BPN-contracted consultants who will be matched to teams based on project needs. Applicants may use grant funding to support additional consultants who have become an integral part of the project team.
How to address consultants in your application:
| Key Information | BPN Biologics Consultants | Grant-funded Consultants |
|---|---|---|
| Funding | Through NIH contracts. (no cost to applicant) | Through subaward |
| Selection | By NIH based on project needs | By the applicant |
| Consultants named in application | No (selected after award) | Yes |
| Expenses in application budget | No | Yes |
Human Subjects Research (if applicable)
Follow the steps below if your application includes human subjects, specimens, and/or data, and refer to the instructions in the NIH Application Guide.
Step 1: Use the NIH’s Human Subjects Research decision engine to determine if your research meets the NIH definition.
Step 2: Determine whether grant funding will be used to conduct any aspect of the proposed Human Subjects Research. NOTE: Human Subjects Research application requirements do NOT apply to work proposed through BPN-contracted CROs.
Step 3: Respond to Question 1 in the application R&R Other Project Information Form. Answer “Yes” if any aspect of your application meets the Human Subjects Research definition AND if that work will be covered by grant funding (NOTE: Answer “No” if proposing to use BPN CROs for human subjects work).
Step 4: Determine if your grant-funded Human Subjects Research is “Delayed Onset”, which is defined as human studies anticipated during the award, but where definite plans are not known when applying.
NOTE: All grant-funded first-in-human clinical trials proposed for BPN Biologics should be marked as “delayed onset” since it is expected that the study details will be determined in consultation with your project team and feedback from regulatory agencies.
Application Support Library
- Gantt chart example(pdf, 171 KB)
- Target Product Profile (TPP) example(pdf, 189 KB)
- Therapeutic Agent Profile example(pdf, 100 KB)
- Testing Funnel example(pdf, 131 KB)
Intellectual Property (IP)
Recipient institutions/companies will retain the rights to existing IP and any new IP developed as part of the funded project. IP protection is essential in facilitating future outside investment or partnering to enable late-stage development and ultimately bring novel neurotherapeutics to patients.
Applicants must have existing patents for the proposed therapeutic or an IP strategy in place for future filings. Work closely with your business officials to develop a plan and consider any known constraints that could impede therapeutic development or future commercialization.
If the IP was developed by or licensed to a third party, applicants must include a letter of support that addresses agreements to provide the agent and describes any limitations on its use.