The NIH Blueprint Neurotherapeutics Network (BPN) for Biologics, through the Small Business Innovation Research (SBIR) U44 program (PAR-24-294), provides funding to U.S. small businesses for developing biologics-based therapeutics targeting nervous and neuromuscular system disorders. The program, structured as a milestone-driven cooperative agreement, supports biologics such as antibodies, peptides, gene therapies, and cell therapies from lead optimization to early clinical trials. Selected projects will benefit from in-kind resources provided by NIH-funded contract research organizations (CROs) and consultants with expertise in drug development, manufacturing, and regulatory compliance. Funding under this Notice of Funding Opportunity (NOFO) is intended for Phase I and Phase II SBIR stages, each with specific aims and transition milestones to advance biologics from discovery through initial clinical validation.

Eligible projects should focus on one neurological or neuromuscular disorder that aligns with the mission of participating NIH Institutes. Research should fall within either the “Discovery Stage” for optimizing one or more lead biologic agents or the “Development Stage” for advancing a selected clinical candidate. Discovery projects must show preliminary target engagement and efficacy in disease-relevant models and require minimal further optimization. Development projects must have a clinical candidate with established pharmacokinetics and in vivo efficacy, ready for IND-enabling studies and protected by intellectual property.

Activities funded in Phase I, lasting up to two years, include lead optimization, candidate selection, and IND-enabling preparations. In Phase II, which may span up to three years, the award supports nonclinical safety and pharmacology studies in compliance with GLP, cGMP production of the candidate, and potentially a first-in-human (FIH) clinical trial. Clinical trials under this NOFO are limited to initial trials that assess safety, pharmacokinetics, and pharmacodynamics, typically in a single-dose or ascending-dose protocol. Approval to progress from Phase I to Phase II will depend on milestone achievement, project feasibility, competitive landscape, and program priorities as assessed by NIH staff.

Small business applicants must provide a comprehensive plan, including a detailed budget that reflects only expenses for activities managed by the applicant team or chosen CROs. NIH funds BPN Biologics CROs and consultants directly, so these costs should not be included in the application budget. The program provides additional guidance on intellectual property (IP) requirements, mandating that businesses protect new IP developed during the project. Applicants are encouraged to establish licensing and commercialization strategies with potential industry partners early in the process, aligning with the program’s ultimate goal of advancing new therapies to market.

Applications for the U44 program must adhere to NIH guidelines for scientific rigor, transparency, and compliance with regulatory standards. Successful applications will propose robust, bias-minimizing experimental designs, address potential limitations in rigor and reproducibility, and include validated data to justify each stage. NIH strongly recommends consulting with program staff before submission to ensure alignment with program expectations and efficient use of BPN Biologics resources.

The U44 award offers flexible budgets based on project needs but generally should not exceed $500,000 per year in Phase I and $1.5 million per year in Phase II. The total project period for combined phases may not exceed five years. Applications from small businesses that comply with all SBIR eligibility requirements, including location in the U.S. and majority ownership by U.S. citizens or permanent residents, are encouraged. Key deadlines include an initial submission date of December 27, 2024, with subsequent biannual due dates through 2027.