The NeuroNEXT Small Business Innovation in Clinical Trials funding opportunity, issued by the National Institute of Neurological Disorders and Stroke (NINDS) under the National Institutes of Health (NIH), seeks to support small businesses conducting exploratory clinical trials or biomarker validation studies. These studies are intended to generate data that can justify and inform the design of future clinical trials. The focus is on investigational agents, including drugs, biologics, surgical therapies, or devices, that align with the NINDS strategic research priorities. Successful applicants will gain access to the NeuroNEXT infrastructure, which includes a Clinical Coordinating Center (CCC) for study implementation, a Data Coordinating Center (DCC) for statistical and data management support, and a network of clinical sites for patient recruitment and protocol execution. Applicants are not required to be part of the existing NeuroNEXT infrastructure, but they must integrate their studies into this network and use established master clinical trial agreements and a central Institutional Review Board (IRB).

The primary purpose of this funding opportunity is to advance therapies and interventions for neurological disorders, excluding stroke, which has a separate NIH clinical trials network. Studies can include Phase II trials for dose optimization, safety, pharmacokinetics, and proof-of-mechanism evaluations. Applications focused solely on Phase I or Phase III clinical trials, natural history studies, or animal studies are not eligible under this program. Rare disease trials, particularly those affecting populations under 200,000 in the U.S., are encouraged, and applicants may propose adaptive or innovative trial designs to address recruitment and data analysis challenges. Biomarker validation studies should clearly define their intended context of use and demonstrate how they will inform future clinical trials.

Eligible applicants are limited to U.S.-based small business concerns (SBCs), including partnerships, corporations, joint ventures, and other legal entities operating primarily within the United States. These businesses must be majority-owned by U.S. citizens, permanent residents, or qualifying venture capital firms, with no single foreign entity owning more than 50%. Performance benchmarks for Phase I to Phase II transitions and commercialization rates must also be met, as outlined by the Small Business Administration (SBA). Foreign organizations and non-domestic components of U.S. organizations are not eligible to apply, although foreign components may be included in the research plan if justified.

The maximum award budget is $3,000,000 per year in total costs, with a project duration of up to five years. Applicants are strongly encouraged to contact NINDS program staff before submission to discuss feasibility and ensure alignment with program goals. Applications must include a Community Engagement and Research Inclusion (CERI) Plan, detailing strategies for community involvement in study design, execution, and evaluation. Applications lacking this plan will not be considered for review.

Applications must comply with NIH submission guidelines and can be submitted via the NIH ASSIST system, institutional system-to-system solutions, or Grants.gov Workspace. Standard NIH application due dates apply, with submissions accepted three times per year: January 5, April 5, and September 5. Scientific merit reviews will follow these deadlines, with advisory council reviews occurring shortly thereafter. The earliest project start dates will be approximately six months after submission. Applicants are advised to submit proposals well before the deadline to allow time for corrections to submission errors.

In summary, this funding opportunity supports small businesses in advancing therapies for neurological disorders through exploratory clinical trials or biomarker validation studies. With access to the NeuroNEXT infrastructure, applicants have an opportunity to efficiently implement their studies in collaboration with NINDS. Prospective applicants should carefully review eligibility requirements, ensure their project aligns with the program's goals, and include all mandatory components, such as the CERI Plan, to maximize their chances of success.