Opportunity Information: Apply for RFA FD 26 004
The Food and Drug Administration (FDA), through its Oncology Center of Excellence (OCE), is offering a cooperative agreement funding opportunity called "Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers" (RFA-FD-26-004). The program is designed to tackle a core problem in oncology drug development: when a cancer affects only a few hundred people per year, the usual playbook for building evidence, running trials, and attracting sustained commercial investment often breaks down. For this notice of funding opportunity (NOFO), the FDA uses a strict definition of "ultra-rare" as cancers with an approximate annual U.S. incidence of 300 to 400 people or fewer. This is intentionally more stringent than the Orphan Drug Act framework, which is based on prevalence under 200,000 people in the U.S., because the practical barriers for extremely small patient populations are even more severe.
The opportunity sits within a broader FDA effort to speed innovation for hard-to-study cancers. OCE's Pediatric Oncology Program and Rare Cancers Program were created to facilitate and expedite drug development in pediatric and other rare cancers, and OCE's Project Catalyst focuses on connecting scientific expertise and creative early-stage product development ideas. The NOFO also aligns with the newly launched design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), a public-private partnership developed with NIH and the Foundation for the National Institutes of Health (FNIH), which aims to accelerate innovative treatment development for ultra-rare cancers.
The NOFO is motivated by recurring, well-known bottlenecks in ultra-rare cancer development. These include difficulty enrolling enough patients to conduct traditional clinical trials, weak financial incentives that can discourage sustained development programs, gaps in understanding disease biology and natural history, limited or delayed access to molecular testing that determines whether a patient can receive a targeted therapy, and the methodological challenge of designing trials that are still adequate to establish safety and effectiveness when sample sizes are inherently small. At the same time, the FDA is highlighting that new technologies, especially single-cell multi-omic approaches, are making it easier to define and subdivide cancers by their molecular drivers, which can open doors to targeted strategies even in tiny populations. Examples referenced include several molecularly defined or ultra-rare tumor types such as neuroectodermal tumors, pulmonary blastoma, desmoplastic small round cell tumor (DSRCT), epithelioid sarcoma, diffuse intrinsic pontine glioma (DIPG), fibrolamellar carcinoma, and malignant rhabdoid tumors, along with pediatric tumors driven by translocation-related fusion oncoproteins.
The main purpose of the funding is to support new, practical approaches that make therapeutic development more feasible in ultra-rare pediatric and adult cancers, including molecularly defined subsets of more common cancers. Rather than focusing on one specific drug or tumor type, the FDA is looking for projects that create reusable tools, evidence strategies, infrastructure, endpoints, or enabling technologies that can reduce friction for future development and, importantly, support regulatory decision-making. The scope is intentionally broad and includes both clinical development innovations and more translational or platform-oriented work, as long as the aim is to accelerate credible therapeutic development for ultra-rare cancers.
The NOFO lists several priority areas of interest. One major theme is building infrastructure: applicants can propose coordination networks and patient-level data repositories that aggregate information across institutions and even internationally. The point is to make scarce patient data more usable for trial planning, natural history understanding, external control arms, and other evidence packages that regulators and developers may rely on when randomized trials are impractical. A second theme is clinical endpoints: the FDA is interested in studies that explore, develop, and validate early clinical endpoints and other novel efficacy endpoints that could be appropriate for ultra-rare cancers, where conventional endpoints may be slow, noisy, or infeasible to measure at scale.
A third area is real-world data (RWD) generation using registry frameworks, with a particularly explicit callout for pediatric diffuse midline glioma (DMG), including DIPG. The NOFO encourages collaborative, multi-stakeholder efforts to generate and use RWD from registries in ways that can support therapy development, which typically means attention to data quality, consistent definitions, longitudinal follow-up, and governance models that allow the data to be used credibly in research and potentially in regulatory contexts.
The FDA also wants projects that rethink how therapies are sourced for ultra-rare cancers, especially through drug repurposing or rescuing abandoned assets. This includes biologically driven approaches to identify new clinical development opportunities for previously approved drugs or biologics, as well as compounds whose development was discontinued. Relatedly, the NOFO seeks novel strategies to preserve availability of drugs where commercial developers have stopped adult development even though the agent may have strong potential in an ultra-rare cancer setting, but lacks sufficient financial incentive to continue. This emphasis reflects a real-world pattern in rare oncology where promising agents can disappear from practical access because market dynamics do not support ongoing manufacturing, labeling work, or trials.
Another practical development barrier the NOFO targets is patient access to trials, especially when eligible patients are geographically dispersed. The FDA is therefore interested in methods that incorporate telemedicine and pragmatic trial design elements, such as allowing lab work and imaging to be collected at local facilities rather than requiring repeated travel to major centers. The aim is to reduce participation burden, expand catchment areas, and improve enrollment feasibility without undermining data integrity.
The NOFO also includes examples of more technology-forward translational research priorities. One is nanoparticle-based delivery of therapeutic nucleic acids targeting oncogenic fusion transcription factors in metastatic tumor animal models, using targeted bioPROTAC degradation strategies or genomic editing approaches. The FDA describes concrete success criteria for such efforts: demonstrating effective in vivo delivery and expression in tumor cells, meaningful downregulation of the target transcription factor protein, minimizing off-target effects, and reducing unwanted nanoparticle sequestration by the liver, spleen, and lungs. Another listed area is comprehensive characterization of the "surfaceome" (plasma-membrane protein expression) of an ultra-rare cancer and its healthy tissue of origin, including resident tissue stem cells, using single-cell transcriptomics and proteomics. These studies should be designed to identify combinatorial plasma-membrane protein signatures unique to the tumor, which can be particularly valuable for targeted therapeutics such as antibody-drug conjugates, bispecifics, CAR-T or other cell therapies, and imaging/diagnostic targeting. Tumors specifically mentioned for surfaceome work include sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT).
Structurally, this is a discretionary funding opportunity administered by the FDA under a cooperative agreement mechanism, which typically implies substantial involvement by the agency during the project compared to standard grants. The opportunity lists a maximum award amount (award ceiling) of $500,000 and anticipates making about 3 awards. The application closing date is June 15, 2026, and the opportunity was posted May 4, 2026. Eligibility is broad and includes many types of U.S. entities: state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (including those other than small businesses); and small businesses. In practice, this means the FDA is open to proposals from academic centers, hospitals and research consortia, patient registry operators, nonprofits and foundations, and industry teams, including smaller biotech groups, provided the project aligns with the NOFO priorities.
Overall, the grant is aimed at solving the enabling problems that keep ultra-rare cancer therapy development slow and fragile: fragmented data, inadequate or impractical trial designs, unclear endpoints, limited patient access, and weak market incentives. The projects the FDA is signaling interest in are the ones that can create durable infrastructure, credible evidence strategies, and scalable technical approaches that make it realistically possible to evaluate and advance therapies for the smallest and most underserved cancer populations.Apply for RFA FD 26 004
- The Food and Drug Administration in the agriculture, consumer protection, food and nutrition sector is offering a public funding opportunity titled "Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
- This funding opportunity was created on 2026-05-04.
- Applicants must submit their applications by 2026-06-15. (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 $500,000.00 in funding.
- The number of recipients for this funding is limited to 3 candidate(s).
- Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses.
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FAQs: Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers (RFA-FD-26-004)
What is this funding opportunity?
This is an FDA Oncology Center of Excellence (OCE) cooperative agreement funding opportunity titled "Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers" (RFA-FD-26-004). It supports projects that make it more feasible to develop therapies for ultra-rare cancers by creating practical, reusable approaches that can be used across diseases and programs.
Which FDA office is offering this program?
The program is offered by the Food and Drug Administration (FDA) through the Oncology Center of Excellence (OCE).
What does the FDA mean by "ultra-rare" cancer in this NOFO?
For this notice of funding opportunity, the FDA uses a strict definition: ultra-rare cancers are those with an approximate annual U.S. incidence of 300 to 400 people per year or fewer.
How is this "ultra-rare" definition different from the Orphan Drug Act concept?
The Orphan Drug Act is based on prevalence under 200,000 people in the U.S. This NOFO uses a more stringent incidence-based definition because the practical development barriers become especially severe when only a few hundred people per year are diagnosed.
What problem is the FDA trying to solve with this grant?
The NOFO targets recurring bottlenecks that slow or derail therapy development for ultra-rare cancers, such as difficulty enrolling enough patients for traditional trials, weak financial incentives for sustained development, gaps in disease biology and natural history knowledge, limited or delayed access to molecular testing, and challenges designing adequate studies when sample sizes are inherently small.
What kinds of projects is the FDA looking for?
The FDA is looking for new, practical approaches that reduce friction for future therapeutic development in ultra-rare pediatric and adult cancers (including molecularly defined subsets of more common cancers). Projects can be clinical-development focused or translational/platform-oriented, as long as they support credible therapeutic development and regulatory decision-making.
Is the funding focused on a single drug or a single tumor type?
No. The purpose is not to fund one specific drug program or one tumor type. The FDA is signaling interest in reusable tools, evidence strategies, infrastructure, endpoints, and enabling technologies that can apply broadly across ultra-rare cancer development.
Does this opportunity cover pediatric cancers, adult cancers, or both?
Both. The NOFO explicitly targets ultra-rare pediatric and adult cancers, and it also includes molecularly defined subsets of more common cancers.
How does this NOFO connect to other FDA ultra-rare/rare oncology efforts?
The opportunity sits within broader FDA efforts to speed innovation in hard-to-study cancers, referencing OCE's Pediatric Oncology Program, Rare Cancers Program, and Project Catalyst. It also aligns with the design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), a public-private partnership developed with NIH and the Foundation for the National Institutes of Health (FNIH).
What are the main priority areas highlighted in the NOFO?
The NOFO highlights several priority areas, including: (1) infrastructure such as coordination networks and patient-level data repositories; (2) development and validation of early clinical endpoints and other novel efficacy endpoints; (3) real-world data (RWD) generation using registry frameworks, with a specific emphasis on pediatric diffuse midline glioma (DMG) including DIPG; (4) sourcing therapies through drug repurposing or rescuing abandoned assets; (5) improving patient access to trials using telemedicine and pragmatic trial elements; and (6) selected technology-forward translational approaches such as nanoparticle delivery of therapeutic nucleic acids and comprehensive tumor "surfaceome" characterization.
What does the NOFO mean by building "infrastructure"?
Infrastructure includes coordination networks and patient-level data repositories that aggregate information across institutions, including potential international aggregation. The goal is to make scarce patient data more usable for trial planning, natural history understanding, external control arms, and other evidence packages when randomized trials are impractical.
How might aggregated patient-level data be used in ultra-rare cancer development?
According to the NOFO, aggregated data can support trial planning, understanding natural history, and constructing external control arms and other evidence packages that regulators and developers may rely on when traditional randomized trials are not feasible.
What is the FDA looking for on clinical endpoints?
The FDA is interested in studies that explore, develop, and validate early clinical endpoints and other novel efficacy endpoints appropriate for ultra-rare cancers, where conventional endpoints may be slow to observe, too variable, or infeasible to measure at meaningful scale.
What is emphasized about real-world data (RWD) and registries?
The NOFO encourages collaborative, multi-stakeholder efforts to generate and use RWD from registry frameworks in ways that can support therapy development. It points to the importance of data quality, consistent definitions, longitudinal follow-up, and governance models that allow the data to be used credibly in research and potentially in regulatory contexts.
Is there a specific disease area called out for registry-based RWD work?
Yes. The NOFO includes a particularly explicit callout for pediatric diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), as an area for registry-based real-world data generation and use.
What does the NOFO say about drug repurposing or abandoned assets?
The FDA is interested in biologically driven approaches to identify new clinical development opportunities for previously approved drugs or biologics, as well as compounds whose development was discontinued. The NOFO also highlights strategies to preserve availability of drugs where commercial developers stopped adult development even though an agent may have strong potential in an ultra-rare cancer setting.
Why does the NOFO emphasize "preserving availability" of certain agents?
The NOFO reflects a pattern in rare oncology where promising agents can become practically inaccessible because market dynamics do not support continued manufacturing, labeling work, or trials, even when scientific rationale remains strong for ultra-rare cancer use.
How does the NOFO address patient access and geographic barriers to trials?
The FDA is interested in methods that incorporate telemedicine and pragmatic trial design elements, such as allowing lab work and imaging to be collected at local facilities instead of requiring repeated travel to major centers. The intent is to reduce participation burden, expand catchment areas, and improve enrollment feasibility without undermining data integrity.
Are there any specific advanced technology or translational research examples included?
Yes. The NOFO includes examples such as nanoparticle-based delivery of therapeutic nucleic acids targeting oncogenic fusion transcription factors in metastatic tumor animal models, including targeted bioPROTAC degradation strategies or genomic editing approaches. It also includes comprehensive characterization of a tumor "surfaceome" (plasma-membrane protein expression) and the healthy tissue of origin using single-cell transcriptomics and proteomics.
What success criteria are described for the nanoparticle delivery example?
The NOFO describes criteria such as demonstrating effective in vivo delivery and expression in tumor cells, meaningful downregulation of the target transcription factor protein, minimizing off-target effects, and reducing unwanted nanoparticle sequestration by the liver, spleen, and lungs.
What is meant by "surfaceome" characterization in this NOFO?
Surfaceome characterization refers to comprehensive profiling of plasma-membrane protein expression in an ultra-rare cancer and its healthy tissue of origin, including resident tissue stem cells, using single-cell transcriptomics and proteomics. The goal is to identify combinatorial plasma-membrane protein signatures unique to the tumor.
Why is identifying tumor-specific surface protein signatures important?
The NOFO notes these signatures can be valuable for targeted therapeutics and targeting strategies, including antibody-drug conjugates, bispecifics, CAR-T or other cell therapies, and imaging/diagnostic targeting.
Which tumors are specifically mentioned for surfaceome work?
The NOFO specifically mentions sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT) as tumors for surfaceome characterization work.
What examples of ultra-rare or molecularly defined tumors are referenced?
Examples referenced include neuroectodermal tumors, pulmonary blastoma, desmoplastic small round cell tumor (DSRCT), epithelioid sarcoma, diffuse intrinsic pontine glioma (DIPG), fibrolamellar carcinoma, malignant rhabdoid tumors, and pediatric tumors driven by translocation-related fusion oncoproteins.
What is the award mechanism for this opportunity?
This is a cooperative agreement, which typically implies substantial FDA involvement during the project compared to standard grant mechanisms.
What is the maximum award amount?
The award ceiling listed for this opportunity is $500,000.
How many awards does the FDA expect to make?
The opportunity anticipates about 3 awards.
When was the opportunity posted?
The opportunity was posted on May 4, 2026.
What is the application closing date?
The application closing date is June 15, 2026.
Who is eligible to apply?
Eligibility is broad and includes many types of U.S. entities: state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (including those other than small businesses); and small businesses.
What kinds of organizations does the FDA seem to expect will apply?
Based on the eligibility list and described priorities, the NOFO is open to proposals from academic centers, hospitals and research consortia, patient registry operators, nonprofits and foundations, and industry teams including smaller biotech groups, as long as the project aligns with the NOFO priorities.
What is the overall goal of the funded projects?
The overall goal is to solve enabling problems that keep ultra-rare cancer therapy development slow and fragile, such as fragmented data, impractical trial designs, unclear endpoints, limited patient access, and weak market incentives, by creating durable infrastructure, credible evidence strategies, and scalable technical approaches that support therapeutic development and regulatory decision-making.
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