Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required) | RFA TR 21 010

Opportunity Information: Apply for RFA TR 21 010

The NIH funding opportunity "Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required)" (RFA-TR-21-010) is designed to support small businesses that want to run basket-style clinical trials in rare diseases. A basket trial is a clinical trial strategy where a single drug (or drug candidate) is tested across multiple distinct diseases or patient groups that share a common underlying molecular cause, such as the same genetic variant, pathway disruption, or molecular mechanism. The central aim is to speed up evaluation of targeted therapies by focusing on shared biology rather than traditional disease-by-disease silos, which is especially important in rare diseases where patient populations are small and recruitment can be difficult.

This opportunity uses a cooperative agreement mechanism (U44), meaning the funded project is not run as a standard, hands-off grant. Instead, NIH expects substantial scientific and programmatic involvement during the project, which often includes coordination on study design, trial execution milestones, and data-sharing expectations. The FOA explicitly requires a clinical trial, so proposals need to be built around an actual interventional human study rather than purely preclinical development or observational work. Because it is a U44, the program is tailored to small business applicants, typically supporting later-stage translational efforts where a company is positioned to execute a regulated clinical study and generate evidence of safety and effectiveness in one or more rare disease populations linked by a shared molecular etiology.

A major emphasis of the announcement is rapid and practical trial start-up, using existing infrastructure and data whenever possible. For that reason, the FOA states a preference for applications that focus on rare diseases already being studied within the Rare Disease Clinical Research Network (RDCRN) and that include active collaboration with RDCRN clinical investigators. The RDCRN is a NIH-supported network that brings together expert clinical sites, patient registries, natural history datasets, and established relationships with patient communities. Tapping into that ecosystem can reduce the time needed to finalize protocols, identify eligible participants, and select outcomes that matter clinically, all of which are common bottlenecks in rare disease trials.

Eligibility is limited to small businesses, consistent with the U44 mechanism and the program goal of advancing product-focused development. The FOA also clearly restricts foreign involvement at the applicant level: non-U.S. (non-domestic) entities are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible to apply. However, foreign components, as defined under the NIH Grants Policy Statement, may be allowed in some cases, which typically means discrete elements of the work may be conducted outside the U.S. if justified and permitted under NIH policy, even though the primary applicant organization must be U.S.-based. The sponsoring agency is the National Institutes of Health, the opportunity is categorized as discretionary funding in the health area, and it is associated with CFDA 93.350. The original closing date listed for submissions was January 12, 2022, and the opportunity was created on January 13, 2021.

In practical terms, a competitive application under this FOA would be expected to present a clear scientific rationale that links multiple rare diseases through a shared molecular mechanism, a strong justification for the chosen therapeutic candidate, and a clinical trial plan that can realistically recruit and evaluate participants across the selected disease "baskets." Strong applications would also typically show how existing RDCRN resources (such as cohorts, registries, biorepositories, and experienced investigators) will be used to accelerate initiation and strengthen interpretation of results, while laying out operational details like site selection, endpoints, statistical approach across baskets, and plans for handling heterogeneity between diseases that share a molecular driver but differ in clinical presentation.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (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): 93.350.
• This funding opportunity was created on 2021-01-13.
• Applicants must submit their applications by 2022-01-12. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: Small businesses.

Apply for RFA TR 21 010

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