Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required) | RFA TR 22 029

Opportunity Information: Apply for RFA TR 22 029

The NIH funding opportunity "Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required)" (RFA-TR-22-029) is designed to move promising therapeutic candidates into clinical testing using a basket trial approach, meaning a single clinical trial framework that enrolls patients across more than one rare disease when those diseases share the same underlying molecular cause. The core idea is to accelerate development by focusing on a shared mechanism (for example, the same pathway disruption, gene variant, or molecular target) rather than running separate, fully independent trials for each rare condition. This can be especially valuable in rare diseases where patient populations are small, recruitment is difficult, and traditional one-disease-at-a-time trials can be slow and expensive.

This FOA supports clinical trials specifically for drugs that are intended to act on these shared molecular etiologies across multiple rare diseases. In practical terms, applicants are expected to propose a clinical trial that tests a therapeutic intervention in more than one rare disease cohort under a unified protocol, with a scientific rationale showing why the drug should benefit each included disease based on the common molecular driver. Because the announcement is labeled "Clinical Trial Required," the project is not just planning or observational work; it must include an actual interventional clinical study.

The award mechanism is a U44 Cooperative Agreement, which is commonly used for Small Business Innovation Research (SBIR) projects that involve later-stage development and clinical evaluation. A cooperative agreement also signals that NIH staff will likely have substantial involvement during the project, such as providing input on milestones, trial design considerations, or coordination expectations. The eligible applicant pool is limited to small businesses, reflecting the SBIR-style focus on helping commercial entities translate biomedical innovations toward real-world products and therapies.

NIH indicates a clear preference for applications that can start up efficiently and make strong use of existing infrastructure and data. To that end, the FOA favors projects that focus on diseases already being studied within the Rare Disease Clinical Research Network (RDCRN) and that include collaborations with RDCRN clinical investigators. This preference is meant to reduce avoidable delays by leveraging established cohorts, natural history data, validated outcome measures, experienced sites, and investigators who already have rare disease trial expertise. In other words, proposals that can plug into an existing rare disease research ecosystem, rather than building everything from scratch, are positioned as more competitive.

In terms of eligibility and foreign involvement, the opportunity is not open to non-U.S. entities (foreign institutions) as direct applicants. It also excludes non-domestic components of U.S. organizations from applying. However, the FOA notes that foreign components, as defined under the NIH Grants Policy Statement, may be allowed in some circumstances, which typically means discrete parts of the project may be performed outside the U.S. if they provide a necessary capability or resource that cannot be readily obtained domestically, subject to NIH approval and policy compliance.

Key administrative details from the listing include that this is a discretionary funding opportunity administered by the National Institutes of Health under CFDA 93.350, with an award ceiling listed at $325,000. The original closing date shown is July 12, 2023, and the FOA was created on July 13, 2022. Overall, the program is aimed at enabling small businesses to run efficient, mechanism-driven basket trials in rare diseases, ideally in tight partnership with RDCRN investigators and leveraging existing rare disease clinical research assets to increase the likelihood of timely execution and interpretable outcomes.

• 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 2022-07-13.
• Applicants must submit their applications by 2023-07-12. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $325,000.00 in funding.
• Eligible applicants include: Small businesses.

Apply for RFA TR 22 029

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