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Department of Health and Human Services Part 1. Overview Information Participating Organization(s)

U.S. Food and Drug Administration (FDA)

NOTE: The policies, guidelines, terms, and conditions stated in this Notice of Funding Opportunity (NOFO) may differ from those used by the NIH. Where this NOFO provides specific written guidance that may differ from the general guidance provided in the grant application form, please follow the instructions given in this NOFO.

The FDA does not follow the NIH Page Limitation Guidelines or the NIH Review Criteria. Applicants are encouraged to consult with FDA Agency Contacts for additional information regarding page limits and the FDA Objective Review Process.

Components of Participating Organizations

Oncology Center of Excellence (OCE)

Funding Opportunity Title

Novel Approaches to Support Therapeutic Development in Ultra-Rare Cancers

Activity Code

U01

Announcement Type

New

Related Notices

None

Number (FON)

RFA-FD-26-004

Companion Funding Opportunity

None http://www.fda.gov/ https://www.fda.gov/about-fda/fda-organization/oncology-center-excellence http://grants.nih.gov/grants/funding/ac_search_results.htm?text_curr=u01&Search.x=0&Search.y=0&Search_Type=Activity

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Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.103

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to support new approaches for therapeutic development in ultra-rare pediatric and adult cancers, including molecularly-defined subsets of more common cancers.

Goals

This goal of this funding opportunity is to advance development of new tools, methods, or therapeutic approaches for ultra-rare cancers that can be broadly applied within the scientific community to benefit patients with ultra-rare cancers.

Key Dates Posted Date

Open Date (Earliest Submission Date)

May 01, 2026

Letter of Intent Due Date(s)

May 18, 2026

Application Due Date(s) June 15, 2026

All applications are due by 11:59 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

AIDS Application Due Date(s) Not Applicable

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Expiration Date

July 31, 2026

Advisory Council Review

Due Dates for E.O.

12372

Required Application Instructions Conformance to all requirements, both in the the Research (R) Instructions How to Apply - Application Guide and in the NOFO, is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV of this NOFO or an applicable related Notice posted to the Guide for Grants and Contracts.

When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents Part 1. Overview Information

Key Dates Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Background https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11164 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400

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The FDA Oncology Center of Excellence (OCE) aims to advance the development and regulation of oncology products for patients with cancer. The Pediatric Oncology Program and Rare Cancers Program were established to facilitate and expedite drug development for pediatric and other rare cancers. OCE’s Project Catalyst connects scientific knowledge, creative insight, and medical professionals to foster early-stage product innovation, which is particularly important to address the challenges related to product development for ultra-rare cancers. In collaboration with the National Institutes of Health (NIH) and the OCE, the Foundation for the National Institutes of Health (FNIH) recently launched the design phase of the Ultra-Rare Cancer Treatment Advancement Program (ULTRA), a new public-private partnership dedicated to accelerating the development of innovative ultra-rare cancer treatments.

For the purposes of this NOFO, the FDA OCE refers to cancers with an approximate annual incidence in the U.S. of 300 to 400 people or less as ultra-rare (a more stringent criterion compared to the threshold for a rare disease specified in the Orphan Drug Act based on a U.S. prevalence of <200,000 people).

Many of the challenges involved in drug development for ultra-rare cancers are similar to those for rare diseases and can include:

• Difficulty enrolling sufficient numbers of patients to clinical trials

• Limited financial incentives for drug development

• Insufficient understanding of the cancer pathophysiology, molecular characteristics, and natural history

• Limited or lack of timely access to molecular testing to determine eligibility for treatment with targeted therapies

• Complexities associated with designing clinical trials that are adequate to establish safety and effectiveness Advancing technologies such as single cell multi-omic analyses have helped define some ultra-rare cancers at the molecular level, providing new opportunities for targeted drug development. Pediatric oncology has several examples of tumor types with known translocation-induced, oncogenic driver fusion proteins. Other examples of ultra-rare cancers defined today by molecular pathology include:

neuroectodermal tumors, pulmonary blastoma, desmoplastic small round cell tumor (DSRCT), epithelioid sarcoma, diffuse intrinsic pontine glioma, fibrolamellar carcinoma, and malignant rhabdoid tumors.

Purpose and Research Objectives

The purpose of this NOFO is to support new approaches that can be applied to facilitate therapeutic development in ultra-rare pediatric and adult cancers, including molecularly-defined subsets of more common cancers.

Specific areas of interest include, but are not limited to, the following examples:

• Development of infrastructure for a coordination network and data repository for patient-level data across institutions and internationally to support drug development and regulatory decision-making for one or more ultra-rare cancers.

• Investigations to explore opportunities to develop and validate early clinical endpoints and other novel efficacy endpoints for evaluation of treatments for ultra-rare cancers.

• Development and implementation of a collaborative multi-stakeholder effort to support generation and use of real-world data leveraging a registry framework for use in development of new therapies for pediatric patients with diffuse midline glioma (DMG) (including diffuse intrinsic pontine glioma, DIPG).

• Innovative approaches to identify new biologically-driven opportunities for clinical development of previously approved drugs or biologics (hereafter referred to as drugs), including drugs for which development has been discontinued, in ultra-rare cancers.

• Research to develop novel approaches to preserve the availability of drugs for which commercial developers have discontinued adult development that have strong potential in ultra-rare cancers but lack financial incentives for commercial development https://www.fda.gov/about-fda/fda-organization/oncology-center-excellence https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology https://www.fda.gov/about-fda/oncology-center-excellence/oce-rare-cancers-program https://www.fda.gov/about-fda/oncology-center-excellence/project-catalyst https://fnih.org/our-programs/ultra-rare-cancer-treatment-advancement/

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• Development of methods to incorporate use of telemedicine and/or pragmatic trial design elements (e.g., collecting laboratory and/or imaging data from local facilities) for patient assessments to facilitate enrollment of patients with ultra-rare cancers

• Development of nanoparticle-based delivery approaches for therapeutic nucleic acids targeting onco-fusion transcription factors in metastatic tumor animal models using targeted bioPROTAC degradation or genomic editing strategies. Successful efforts should demonstrate effective delivery and expression in-vivo to tumor cells, and downregulation of the target transcription factor protein while minimizing off-target effects and limiting sequestration of the nanoparticle by the liver, spleen, and lungs.

• Research to exhaustively characterize the plasma-membrane protein expression (surfaceome) of an ultra-rare cancer and the presumed healthy tissue of origin, as well as the resident-tissue stem cells, by single-cell transcriptomics and proteomics. These studies, and available correlative database analyses, should be designed to identify possible combinatorial signatures of plasma membrane proteins unique to the ultra-rare tumor. Tumors of interest include Sclerosing epithelioid fibrosarcoma and atypical teratoid rhabdoid tumors (ATRT).

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon FDA appropriations and the submission of a sufficient number of meritorious applications.

Award(s) will provide one (1) year of support and include future recommended support for up to two (2) additional year(s) contingent upon annual appropriations, availability of funding and satisfactory recipient performance.

FDA OCE intends to commit up to $1,500,000 in FY 2026 to fund 1-3 awards. Future year amounts will depend on annual appropriations.

http://grants.nih.gov/grants/guide/url_redirect.htm?id=11116 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82370

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Award Budget

Application budgets should reflect the actual needs of the proposed project and should not exceed the following in total costs (direct and indirect):

YR 01: $500,000

YR 02: $500,000

YR 03: $500,000

Award Project Period

The scope of the proposed project should determine the project period.

The maximum project period is three years.

HHS grants policies as described in the HHS Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information Eligible Organizations Higher Education Institutions

• Public/State Controlled Institutions of Higher Education

• Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)

• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses

• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments

• County Governments

• City or Township Governments

• Special District Governments

• Indian/Native American Tribal Governments (Federally Recognized)

• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

Other

• Independent School Districts

• Public Housing Authorities/Indian Housing Authorities

• Native American Tribal Organizations (other than Federally recognized tribal governments)

• Faith-based or Community-based Organizations

• Regional Organizations

Foreign Organizations https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf

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Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Required Registrations Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the HHS Grants Policy Statement for additional information

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

o Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process.

The same UEI must be used for all registrations, as well as on the grant application.

• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

The PD/PI should be an established investigator in the scientific area in which the application is targeted and capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD/PI will be expected to monitor and assess the program and submit all documents and reports as required.

2. Cost Sharing This NOFO does not require cost sharing as defined in the HHS Grants Policy Statement.

http://grants.nih.gov/grants/guide/url_redirect.htm?id=11118 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf https://grants.nih.gov/grants/guide/url_redirect.htm?id=82390 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11176 https://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82300 https://grants.nih.gov/grants/guide/url_redirect.php?id=82400

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Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The FDA will not accept duplicate or highly overlapping applications under review at the same time, per

2.3.7.4 Submission of Resubmission Application. This means that the FDA will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information Letter of Intent Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows FDA staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity

• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)

• Names of other key personnel

• Participating institution(s)

• Number and title of this funding opportunity

The letter of intent should be sent to:

Patrick Johnson Email:patrick.johnson@fda.hhs.gov

Page Limitations All page limitations described in the How to Apply - Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy section is limited to 30 pages.

Instructions for Application Submission The following section supplements the instructions found in the How to Apply - Application Guide and should be used for preparing an application to this NOFO.

In addition to the sections normally required by PHS 398 Research Plan, applicants should propose a plan for scientific discussions and interactions with FDA to obtain regulatory science input to ensure that the project continues to address applied science of high interest to the FDA.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

http://grants.nih.gov/grants/guide/url_redirect.htm?id=82415 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82423 mailto:xxxx@mail.nih.gov https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=61134 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400

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• All applicants planning research (funded or conducted in whole or in part by the FDA) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or FDA-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered "Yes" to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record:

PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

4. Submission Dates and Times Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, FDA's electronic system for grants administration. FDA and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the FDA Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply - Application Guide.

6. Funding Restrictions All FDA awards are subject to the terms and conditions, cost principles, and other considerations described in the HHS Grants Policy Statement.

• Recipients must comply with all applicable federal anti-discrimination laws material to the government’s payment decisions for purposes of 31 U.S.C. § 3729(b)(4).

• Discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate:

https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/glossary.htm#DelayedOnsetStudy https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.html?id=82380 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf

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• racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation.

• denial by the recipient of the sex binary in humans or the notion that sex is a chosen or mutable characteristic.

• harm reduction

• illegal immigration; or

• any other initiatives that compromise public safety or promote anti-American values.

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations, and applicable judicial holdings.

Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate: racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety. If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

All research projects involving human subjects will have a restriction on use of funds for activities involving active recruitment of human subjects until both IRB approvals and FDA Human Subject Protection determinations from the FDA Office of the Chief Scientist have been completed.

Similarly, all research projects involving animals will have restrictions on use of funds for activities involving active animal research until Institutional Animal Care and Use Committee (IACUC) review has been completed for the project. There should be a formal written understanding that addresses responsibility for animal care and use, animal ownership, and IACUC review and oversight.

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply - Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to the FDA. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the assigned FDA Grants Management Specialist and responsiveness by FDA.

Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/how-to-apply-application-guide/due-dates-and-submission-policies/dealing-with-system-issues.htm https://grants.nih.gov/grants/how-to-apply-application-guide/due-dates-and-submission-policies/dealing-with-system-issues.htm http://grants.nih.gov/grants/guide/url_redirect.htm?id=11146

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Responsiveness

The following criteria will be used to determine whether an application is responsive to this NOFO.

• Primary goal of the research must NOT be to develop a specific therapeutic product; however, novel approaches (e.g., CRISPR CAS mediated genomic deletion of fusion genes) to target specific biological pathways directly involved in the genesis and maintenance of the neoplastic phenotype, or approaches applicable to multiple cancer types, are in scope.

• The disease to be studied is an ultra-rare cancer (consistent with the definition provided in the Background section, approximate U.S. annual incidence of 300-400 people or less) and is of high unmet medical need (no available treatments or existing therapies are inadequate). Studies of molecular subsets of more common cancers that meet this definition are within scope for this

NOFO.

• Proposed research does not involve an interventional trial. Observational trials, or studies of approaches/innovations to implement in interventional trials for ultra-rare cancers may be supported under this NOFO.

Applications should include information in the Specific Aims section to support fulfillment of each of the above criteria.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Post-submission materials are those submitted after submission of the grant application but prior to objective review. They are not intended to correct oversights or errors discovered after submission of the application. FDA accepts limited information between the time of initial submission of the application and the time of objective review. Applicants must contact the assigned Grants Management Specialist to receive approval, prior to submitting any post submission materials. Acceptance and/or rejection of any post submission materials is at the sole discretion of the FDA. Any inquiries regarding post submission materials should be directed to the assigned Grants Management Specialist. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria Only the review criteria described below will be considered in the review process. Applications submitted to the FDA in support of the FDA mission are evaluated for scientific and technical merit through the FDA objective review system.

Overall Impact Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Maximum Points: 20 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82299 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82299

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Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Approach & Innovation

Maximum Points: 30

Does the proposal contain specific, well-defined objectives and a clear plan to address each objective?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?

Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Does the proposal contain specific, well-defined objectives and a clear plan to aggregate, analyze, and disseminate data derived from the study? Does the proposal have plans to generate data that is generalizable to the U.S. patient population?

Program Alignment

Does the project address a specific, practical problem of significance to regulatory science (defined as the science of developing new tools, standards and approaches to assess the safety, efficacy quality and performance of some FDA-regulated products) or regulatory decision making rather than expanding general knowledge? Does the proposal include robust support for how achievement of the research objectives will provide a meaningful, direct effect on drug development for one or more ultra-rare cancers?

Environment

Maximum Points: 10

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Will the scientific environment in which the work will be done contribute to the probability of success?

Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Vertebrate Animals The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research.

Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions Not applicable

Renewals Not applicable

Revisions Not applicable

Additional Review Considerations Not applicable http://grants.nih.gov/grants/guide/url_redirect.htm?id=11175 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11175 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11150

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Applications from Foreign Organizations Not Applicable.

Select Agent Research Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Objective Review Committee convened by the FDA, using the stated review criteria. Assignment to an Objective Review Committee will be shown in eRA Commons.

As part of the objective review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by objective review.

• Availability of funds.

• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates Successful applicants will be notified of additional information that may be required or other actions leading to an award. The decision not to award a grant, or to award a grant at a particular funding level, is discretionary and is not subject to appeal to any FDA or HHS official or board.

Information regarding the disposition of applications is available in the HHS Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

https://sharing.nih.gov/other-sharing-policies/model-organism-sharing-policy#policy-overview

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Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk. For more information on the Notice of Award, please refer to the HHS Grants Policy Statement.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in FDA-funded studies, the recipient must provide FDA copies of documents related to all major changes in the status of ongoing protocols.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in FDA-funded studies, the recipient must provide FDA copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements The following Federal wide and HHS-specific policy requirements apply to awards funded through FDA:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.

• All FDA grant and cooperative agreement awards include the HHS Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in the HHS Grants Policy Statement.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.

FDA may terminate awards under certain circumstances. See 2 CFR Part 200.340 Termination and HHS Grants Policy Statement.

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity. Visit https://www.ecfr.gov/current/title- 45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and

2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to HHS Grants Policy Statement for additional information.

https://grants.nih.gov/grants/guide/rfa-files/RFA-OD-25-003.html#FundingRestrictionsanchor https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf https://www.ecfr.gov/current/title-2/subtitle-A/chapter-II/part-200 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf https://www.ecfr.gov/current/title-2/subtitle-A/chapter-II/part-200/subpart-D/subject-group-ECFR86b76dde0e1e9dc/section-200.340 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B https://www.healthit.gov/topic/certification-ehrs/certification-health-it https://www.nist.gov/cyberframework https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf

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Cooperative Agreement Terms and Conditions of Award The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and FDA grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial FDA programmatic involvement with the recipients is anticipated during the performance of the activities.

Under the cooperative agreement, the FDA purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the FDA as defined below.

FDA staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones.

• Participating in interpretation of results and conclusions and planning for public dissemination of results (e.g., publications, presentations).

3. Data Management and Sharing Consistent with the FDA Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the HHS Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

FDA considers the sharing of research resources developed through FDA-sponsored research an important means to enhance the value and further the advancement of research. When research resources have been developed with FDA funds and the associated research findings published, those findings must be made readily available to the scientific community, regardless of whether the recipient is an institution of higher education, hospital, non-profit or for-profit organization.

Review of Project Outputs

Awardee must provide FDA co-authored materials (such as abstracts, manuscripts and reviews supported in part or in total under this cooperative agreement) for public disclosure to OCE PO prior to disclosure or submission for publication so that the Agency can review and clear the material (within an agreed upon timeframe between FDA and the awardee). For materials without an FDA co-author, the awardee must provide the materials to the OCE PO prior to public disclosure or submission for publication to allow FDA a review of the material (within an agreed upon timeframe between FDA and the awardee).

4. Reporting When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the HHS Grants Policy Statement.

All FDA grants require annual financial and performance progress reports as stated in Standard Terms & Conditions of Award. This award has additional performance reporting requirements as outlined below. In addition to the RPPR, awardees are required to submit Semi-annual progress reports each year of the cooperative agreement via email to the Program Official. These reports should be documented in an agreed upon format between FDA and the grantee.

https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf http://grants.nih.gov/grants/rppr/index.htm http://grants.nih.gov/grants/rppr/index.htm

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Semi-annual reports should describe progress made during the 6-month period of the cooperative agreement related to scientific progress and overall management of the project, including a summary of planned and completed presentations, abstracts, and manuscripts.