Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required) | RFA TR 24 001

Opportunity Information: Apply for RFA TR 24 001

The National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH), is offering a cooperative agreement funding opportunity to support basket clinical trials in rare diseases. The opportunity, titled "Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required)" (RFA-TR-24-001), is designed to speed the path from promising science to real-world clinical testing by running more efficient trials that can evaluate a single drug across multiple rare diseases that share the same underlying molecular cause. Instead of running separate, disease-by-disease trials, the basket approach groups patients by a common molecular mechanism, which can be especially valuable in rare diseases where patient populations are small and traditional trial recruitment can be slow and expensive.

A central goal of the program is not only to fund these trials, but also to actively identify and address the practical and scientific challenges of adapting a basket trial model that is widely used in oncology to the rare disease setting. This includes challenges such as selecting appropriate shared molecular targets, defining eligibility and molecular confirmation criteria across different disorders, standardizing endpoints when diseases present differently, handling small sample sizes while maintaining statistical rigor, and building operational trial infrastructure that can work across multiple sites and disease communities. Because the work is explicitly clinical trial focused, applicants are expected to have, or bring in, real expertise in designing and executing clinical trials in rare diseases, including the regulatory, operational, and patient-engagement complexities that typically come with them.

The funding instrument is a cooperative agreement (U44), which generally means NIH expects substantial involvement during the project, with NCATS working collaboratively with awardees rather than operating strictly as a pass-through funder. The NOFO is specifically open to small businesses, reflecting an emphasis on translation and development with a clear path toward clinical application. At the same time, applicants are expected to partner closely with clinical investigators at academic institutions, recognizing that many rare disease patients are concentrated in specialized academic centers and that these investigators often have the disease-specific knowledge and patient access needed to run successful trials.

NCATS strongly encourages collaborations with investigators involved in the Rare Disease Clinical Research Network (RDCRN), particularly for projects focused on diseases already studied within the network. RDCRN participation is positioned as an advantage because the network offers established clinical research infrastructure, experienced site teams, and connections to well-characterized patient cohorts, all of which can reduce startup friction and improve trial feasibility. Additional information about RDCRN is available at https://www.rarediseasesnetwork.org/.

In terms of eligibility and geographic scope, the NOFO is limited to U.S.-based small businesses. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible. However, foreign components (as defined under the NIH Grants Policy Statement) may be allowed, which typically means discrete parts of the project may be performed abroad under specific conditions and with appropriate justification, even though the primary applicant organization must be domestic and eligible.

Key administrative details from the listing include an original application closing date of 2024-03-15, an award ceiling of 306,872 (as provided in the source data), and classification under the health funding activity category with CFDA number 93.350. Overall, the opportunity is aimed at practical, trial-ready projects that use a shared molecular etiology strategy to test therapies across multiple rare diseases, while generating lessons and solutions that can make basket trials a more broadly usable tool for rare disease drug development.

• 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 2023-12-01.
• Applicants must submit their applications by 2024-03-15. (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 $306,872.00 in funding.
• Eligible applicants include: Small businesses.

Apply for RFA TR 24 001

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