Novel approaches to support therapeutic development in ultra-rare cancers

The U.S. Food and Drug Administration (FDA), a division of the U.S. Department of Health and Human Services, has issued a forecasted discretionary funding opportunity titled "Novel approaches to support therapeutic development in ultra-rare cancers." This grant program is intended to foster innovative strategies that facilitate therapeutic development for ultra-rare cancers, both pediatric and adult, including specific molecular subsets of more common cancers. As part of the FDA's broader mission to protect public health and advance medical innovations, this initiative supports translational research, data infrastructure development, and stakeholder collaboration necessary to address the unique challenges in treating ultra-rare cancers. The funding opportunity will be issued under a cooperative agreement, with the FDA anticipating the issuance of two awards. Specific areas of interest include the development of a coordination network and data repository to aggregate and standardize patient-level data across institutions, potentially on a global scale. Such a network would facilitate drug development and regulatory decision-making processes by enhancing the evidence base for ultra-rare cancer treatments. Additionally, the FDA seeks projects that investigate and validate early clinical endpoints and novel efficacy measures that are critical to evaluating treatments in patient populations where traditional trial structures may not be feasible due to small sample sizes. Applicants may also propose collaborative frameworks that leverage real-world data, particularly for pediatric patients with conditions such as diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG). The agency is especially interested in efforts that repurpose previously approved or discontinued drugs, targeting new biological pathways relevant to ultra-rare cancers, where limited commercial incentive exists. Further topics of interest include strategies for integrating telemedicine and pragmatic trial designs to expand clinical trial access and participation, particularly for geographically isolated patient populations. Other eligible projects include the development of nanoparticle-based delivery systems for therapeutic nucleic acids, especially targeting onco-fusion transcription factors in metastatic tumor models. These methods must show successful in-vivo expression with minimal off-target effects. Studies that perform comprehensive proteomic and transcriptomic profiling of ultra-rare cancers are also encouraged, particularly for identifying unique plasma membrane protein signatures to support targeted therapy development. The FDA lists specific cancer types of interest under this initiative, including Sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT). The funding announcement does not currently specify award ceilings, floors, or total program funding. However, cost sharing or matching is not required. The application is not yet open, as this is a forecasted opportunity, with an estimated post date of August 4, 2025. The grant is associated with Assistance Listing 93.103, which encompasses FDA research. The program is available nationwide and is open to a wide array of eligible applicants, including local and tribal governments, nonprofits, small and for-profit businesses, educational institutions, and public housing authorities. Key contact for this opportunity is Patrick Johnson, Grants Management Specialist at the FDA, who can be reached at 301-796-0154. Further details, including application components, submission timelines, and evaluation criteria, will be published with the final Notice of Funding Opportunity (NOFO). Applicants are encouraged to begin preparing early by reviewing the scope and aligning proposed research with the FDA’s outlined priorities.