Purpose NINDS is committed to advancing diagnostics and treatments for people burdened by neurological diseases, and the NINDS Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs have provided the small business community with critical seed funding to support the development of a wide variety of technologies and therapeutics for the diagnosis and treatment of neurological diseases. The SBIR/STTR Programs are structured in three phases. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development (R&D) efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. At the conclusion of an SBIR/STTR Phase II, it is expected that the small business concern (SBC) will fully commercialize their product or technology using non-SBIR/STTR funds in Phase III. The development of medical biotechnology products is often impeded by a significant funding gap (known as the Valley of Death ). In particular, the development of regulated products such as therapeutics and medical devices often requires several years and substantial capital investments, due in part to the high costs of clinical trials. This FOA supports applications from Small Business Concerns (SBCs) for exploratory clinical trials that contribute to the justification for a future trial to establish definitive efficacy (such as a Phase 3 clinical trial or a Pivotal device trial). This includes Phase 1 and 2 studies of drugs and biologics, feasibility studies of devices, as well as preliminary studies of surgical, behavioral or rehabilitation therapies. A wide range of trials at different stages of development are allowed, including first-in-human (as defined by the Food and Drug Administration), Phase 1 and 2 single-site studies, and Phase 2b multicenter studies in certain cases. Applications must aim to generate data that inform further clinical development of the proposed intervention or diagnostic, and in the case of FDA-regulated clinical trials applications must demonstrate readiness by including FDA approval of the proposed study. The earliest clinical studies should be designed to provide important initial information regarding the intervention (e.g., safety, tolerability, dosing) or diagnostic. Midstage clinical studies will generally include randomization and blinding and should yield data that allow a clear go/no-go decision regarding whether the intervention should proceed to an efficacy trial. All applications must outline specific plans for future development in the event of promising results. This FOA is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy. Applications to implement definitive efficacy trials (e.g., Phase 3 clinical trials of drugs or Pivotal device trials) should be submitted to NINDS Efficacy Clinical Trials (U01). Renewal applications of SBIR Phase II awards (i.e., SBIR Phase IIB) to conduct Phase I and II clinical studies should be submitted to NINDS Renewal Awards of SBIR Phase II Grants (Phase IIB) for Pre-Clinical Research (R44). The goal of this FOA is to assist applicants in pursuing the next appropriate milestone(s) necessary to advance a product/technology that requires Federal regulatory approval or to bring a complex research tool to market. To achieve this goal, the FOA aims to facilitate the transition of clinical-stage projects to the commercialization stage by encouraging business relationships between NIH's SBIR/STTR awardees and third-party investors and/or strategic partners. Definitions For this funding opportunity announcement Phase 1 and 2 clinical studies or trials refer to the common phases of a clinical trial. SBIR Phase I and II refer to the project phases of the SBIR program. Specific Objectives Scientific/Technical Scope Examples of appropriate studies under this FOA include, but are not limited to, those designed to: Evaluate and optimize the dose, formulation, safety, tolerability or pharmacokinetics of an intervention in healthy volunteers or the target population. Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., target engagement, dose-response trends, pharmacodynamic response) in a human "proof of concept" trial. Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, biological activity, or preliminary clinical efficacy (e.g., futility trials). For devices: Establish proof-of-principle and optimize techniques, operation, and usability of a device; inform the final device design decisions; and estimate the magnitude of treatment effect. NINDS recognizes that devices can differ greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. A Pivotal device study, for example, could potentially be used in support of an off-label indication of an existing market approved device, or to provide evidence for a novel device design in support of a Pre-Market Approval (PMA), Humanitarian Device Exemption (HDE), 510(k) or 510(k) De Novo submission. Due to the broad scope of possible medical devices and the varied nature of the regulatory path, investigators considering applications to evaluate devices are strongly encouraged to contact Scientific/Research Staff as early as possible to discuss these issues and determine the suitability of their project for this funding mechanism. This PAR encourages applications from diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce. Fostering diversity by encouraging the participation of individuals from nationally underrepresented groups in the scientific research workforce is longstanding interest of Congress, and a key component of the NIH strategy to identify, develop, support, and maintain the quality of our scientific human capital (e.g., Public Law 114-329, American Innovation and Competitiveness Act of 2017, and Notice of NIH's Interest in Diversity, NOT-OD-20-031). Scientists and trainees from underrepresented backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. Increasing participation by socially and economically disadvantaged and women-owned small businesses is also critical to the success of the SBIR and STTR programs. Independent Third-Party Partners As significant funding is often needed to take regulated clinical projects to market beyond initial clinical studies, we encourage applicants to develop business relationships between applicant SBCs and third-party investors/strategic partners who can provide substantial financing to help accelerate the commercialization of promising new products and technologies initiated with NIH SBIR or STTR fundingThird-party partners include, but are not limited to, another company, a venture capital firm, an angel investor, a foundation, a university, a research institution, a state or local government, or any combination of the above. In light of these goals, the NINDS strongly encourages applicants to establish business relationships with investors and/or strategic partners that have appropriate prior experience in the commercialization of emerging biomedical technologies. That said, NINDS recognizes that companies developing products that have small potential revenue streams or that target small patient populations face additional barriers to market entry that make them less attractive to investors and strategic partners at preclinical or early clinical stages of development. Many of these technologies require complex clinical trial designs because of small and geographically diverse patient populations. For the purposes of this FOA, NINDS has defined small markets as development of novel products that: Address a rare disease, defined in the Rare Diseases Act of 2002 (Public Law 107-280) as a condition affecting fewer than 200,000 individuals in the United States; or Qualify as a Humanitarian Use Device, defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 persons in the United States per year; or Target a young pediatric population defined as including neonates (0-28 days), infants (
