NIAID SBIR Phase II Clinical Trial Implementation Cooperative Agreement (U44 Clinical Trial Required) | PAR 21 082

Opportunity Information: Apply for PAR 21 082

The NIAID SBIR Phase II Clinical Trial Implementation Cooperative Agreement (U44 Clinical Trial Required) is a National Institutes of Health funding opportunity designed specifically for U.S. small business concerns that are ready to carry out an investigator-initiated clinical trial aligned with the National Institute of Allergy and Infectious Diseases (NIAID) mission. It sits at the SBIR Phase II stage, which generally means the project has already moved beyond early feasibility and is prepared for a more substantial, execution-focused effort. The award mechanism is a cooperative agreement (U44), so recipients should expect a more collaborative relationship with NIAID compared with a standard grant, including a clearer emphasis on predefined milestones, progress monitoring, and active federal involvement typical of cooperative agreements.

The core purpose of the program is to support hypothesis-driven, milestone-driven clinical trials. In practice, that means applicants are expected to propose a clinical study that tests a clear scientific or clinical hypothesis and lays out concrete, measurable milestones that demonstrate progress and de-risk the project over time. The FOA explicitly welcomes trials that are not considered high-risk, but it places particular emphasis on encouraging high-risk clinical studies, using a specific definition of "high-risk" that is about novelty and complexity rather than participant safety. In this context, high-risk refers to studies that include one or more distinctive features such as non-routine interventions, the administration of an unlicensed product, or the use of a licensed product for an unapproved indication. The announcement is careful to clarify that "high-risk" here does not mean higher risk to human subjects or patients; instead, it reflects greater uncertainty in scientific, operational, or regulatory pathways due to the innovative nature of the intervention or its use.

Another notable element is that the opportunity encourages mechanistic studies, meaning applicants can incorporate components aimed at understanding how or why an intervention works, not just whether it works. Mechanistic work can strengthen the scientific value of a trial by linking clinical outcomes to biological pathways, immune responses, pathogen dynamics, or other measurable processes relevant to NIAID priorities. This makes the program attractive for small businesses developing vaccines, therapeutics, diagnostics, or other infectious disease and immunology-related technologies that benefit from both clinical endpoints and supporting mechanistic evidence.

Eligibility is limited to small businesses, consistent with SBIR rules. Foreign institutions are not eligible to apply, and non-domestic (non-U.S.) components of U.S. organizations are also not eligible to apply, which signals that the primary trial activities and organizational components need to be U.S.-based. At the same time, the FOA notes that foreign components, as defined in the NIH Grants Policy Statement, may be allowed in some circumstances. That typically implies that certain discrete activities outside the U.S. could be permitted if they are strongly justified, unique, and necessary for the project, but they are not the default and would likely face higher scrutiny.

Administratively, this is an NIH discretionary funding opportunity in the health category, listed under CFDA number 93.855, and administered by NIH/NIAID. The opportunity number is PAR 21 082, and it was created on 2021-01-14, with an original closing date listed as 2024-01-13. The published excerpt does not specify an award ceiling or the expected number of awards, so applicants would need to consult the full FOA text and NIH budget guidance to understand typical budget ranges, project period expectations, and any institute-specific constraints. Overall, the program is aimed at helping qualified small businesses run well-structured, milestone-based clinical trials, especially those involving novel or non-standard clinical approaches that fit within NIAIDs research mission.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NIAID SBIR Phase II Clinical Trial Implementation Cooperative Agreement (U44 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2021-01-14.
• Applicants must submit their applications by 2024-01-13. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: Small businesses.

Apply for PAR 21 082

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