Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed)

Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed) is sponsored by National Center for Advancing Translational Sciences (NCATS/NIH). This R21 grant supports preclinical proof-of-concept studies specifically for rare diseases. The aim is to generate data that demonstrates the feasibility and potential of novel therapeutic approaches.

Clinical trials are not allowed.

RFA-TR-25-002: Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Advancing Translational Sciences ( NCATS ) Funding Opportunity Title Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed) R21 Exploratory/Developmental Research Grant June 5, 2026 Notice of Extension for RFA-TR-25-002 "Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not Allowed)".

See Notice NOT-TR-26-009 . March 31, 2025 - This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose This notice of funding opportunity (NOFO) provides funding to conduct efficacy studies in an established rare disease preclinical model to demonstrate that a proposed therapeutic agent warrants further development. In addition to preclinical efficacy, accompanying pharmacodynamic and pharmacokinetic studies would be supported.

Therapeutic agents include small molecules, biologics or biotechnology-derived products. The goal of this NOFO is to spur therapeutic development for a variety of rare diseases by advancing projects to the point where they would attract subsequent investment supporting full Investigational New Drug (IND) application development or progression to clinical trials in the case of repurposing or repositioning.

Open Date (Earliest Submission Date) Dates in bold and italics reflect changes per NOT-TR-26-009 Application Due Dates Review and Award Cycles New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date June 02, 2026 June 02, 2026 Not Applicable October 2026 January 2027 April 2027 June 02, 2027 June 02, 2027 Not Applicable October 2027 January 2028 April 2028 All applications are due by 5:00 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. New Date June 03, 2027 per issuance of NOT-TR-26-009 .

(Original Expiration Date: June 03, 2026 ) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 and Funding Purpose The NIH supports research on a broad range of diseases that are defined as rare; that is, diseases affecting fewer than 200,000 individuals in the United States.

While individually, each rare disease affects a limited number of individuals, when viewed collectively, rare diseases represent a significant unmet medical need. Approximately 30 million people in the United States are living with one of the estimated 10,000 rare diseases; many of which affect children and are serious or life-threatening.

Despite advances in our understanding of the mechanisms of many rare diseases, and large investments by pharmaceutical and biotech industries, effective treatments are available for fewer than 5% of diseases.

This dearth is a result of myriad interconnected factors including: 1) low disease prevalence resulting in fewer patients, clinicians, researchers; 2) fewer resources given a smaller market size; 3) high developmental failure rates resulting from a lack of high-quality preclinical data in disease-specific models.

Further, the transition from early drug discovery efforts (assay development, high-throughput screening, counter/orthogonal screening, medicinal optimization) to full IND-enabling work is hampered by a lack of funding to support high-quality efficacy testing. These pharmacology studies are expensive, particularly when the studies are designed for rigorous evaluation that would support progression to an IND-enabling enterprise.

This results in significant delays in development of potential therapeutics and leaves projects without a path forward. In order to address these issues, the National Center for Advancing Translational Sciences (NCATS) invites applications aiming to develop or repurpose therapeutics to treat a rare disease with an unmet medical need.

It is the intent of this opportunity to fund a diverse set of applications focused on a variety of rare disease indications. Research Objectives and Scope This notice of funding opportunity (NOFO) solicits applications that propose to conduct efficacy studies in an established rare disease preclinical model to demonstrate proof of concept that a proposed therapeutic agent warrants further development.

In addition to preclinical efficacy, accompanying pharmacodynamic (PD) and pharmacokinetic (PK) studies would be supported. In preclinical efficacy studies, a combination of efficacy, (PD) and (PK) measures are warranted to determine the feasibility of a candidate therapeutic agent to serve as a starting point for further therapy development.

Combined measures of PK and PD greatly increase the understanding of the in vivo efficacy of the therapeutic agent by exploring the relationship between the concentration of the agent at the site of action and the resulting efficacy measures.

For the purposes of this NOFO, efficacy measures reflect the effects of the therapeutic agent on endpoints that are closely tied to the desired clinical endpoints, but do not necessarily reflect target engagement. While PD measures may also reflect the effects of the therapeutic agent on endpoints closely tied to the desired clinical endpoint, they must also reflect target engagement.

PK measurements reflect the body’s effect on the absorption, metabolism, distribution and excretion of the therapeutic agent. While not required, PK to provide evidence that the therapeutic agent has the potential to be therapeutically viable and support the robustness of the efficacy data, is encouraged, if the limited R21 budget can accommodate such studies.

Efficacy studies should be conducted in an established and validated rare disease model. These models may include both in vivo models and/or in advanced in vitro models (e.g. tissue chip/microphysiologic systems). Data supporting relevance and validation of the model to the indicated rare disease should be included in the application.

Funding will not be provided for model development; evidence supporting access to the model, in suitable numbers to support rigorous efficacy studies, must be provided. A letter of support if the animals will be provided by a collaborator, or a quote for purchase must be included in the Letters of Support attachment.

To ensure both the relevance of the proposed development of the therapeutic agent, as well as the disease model, a plan for a partnership with a rare disease steering/oversight committee is required to submit to this NOFO.

However, neither the members of the committee nor the organizations that might partner should be named in the application This committee may be formed de novo with members having appropriate disease relevant expertise and/or experience and could include a potential financial backer.

The plan should include only a description of the type of individuals (expertise, patients and/or advocates, foundation representatives – do NOT name the foundation, etc.) and the planned interactions with the scientific team will need to be clearly described as an Other Attachment as part of the application. Further, developing therapeutics requires a multidisciplinary approach.

It is encouraged that academic investigators should form collaborations with those knowledgeable in the therapeutic development process, as well as those familiar with the desired properties of the end therapeutic product (such as biostatisticians, technical experts and clinicians).

Applicants should consider how they will identify and foster relationships with potential licensing and commercialization partners early in the therapy development process once an award is made.

Investigators are expected to work closely with their institutional technology transfer officials, if applicable, to ensure that royalty agreements, patent filings, and all other necessary intellectual property (IP) arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project.

Applications Not Responsive to this NOFO The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding. Please note: The scope of this NOFO differs from RFA-TR-23-016 .

Both New and Resubmission applications must meet the scope of this NOFO.

See non-responsiveness criteria below for restrictions on scope: Studies which do not clearly address a rare disease, defined as diseases affecting fewer than 200,000 individuals in the U.S. Evidence supporting rare disease classification may include references confirming the prevalence and additional information if the disease has been granted orphan status by the FDA.

Applications requesting support for development of the rare disease model. Applications focused on rare cancers. Applicants focused on rare cancers should seek guidance from NCI’s Preclinical Therapeutics Grants Branch within the Developmental Therapeutics Program at the Division of Cancer Treatment and Diagnosis.

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

Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed Resubmission - Resubmission of Applications submitted to RFA-TR-23-016, RFA-TR-24-023 and this NOFO 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. Not Allowed: Only accepting applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The NIH intends to commit up to $1,200,000 in FY26, contingent upon receiving scientifically meritorious applications. 3-5 awards are anticipated from this solicitation.

Future year amounts will depend on annual appropriations. The combined budget for direct costs for the two-year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.

The total project period may not exceed 2 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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 allowed. NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts.

All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16. 8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding.

This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

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 NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications 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. 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. 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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH 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 NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. 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.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

Other Attachments: The application must include the following attachment. Please use the filename suggested below. The filename provided for each document added to the section “Other Attachments” will be the name used for the bookmark in the electronic application in eRA Commons.

Each attachment is limited to 1-page maximum. Readiness of Agent (1-page maximum) A detailed overview demonstrating the readiness of the agent for thorough efficacy testing is required to submit to this NOFO.

This can include any data supporting selection of the therapeutic agent and any prior art thus far collected (i.e. prior screening data, suitable potency and selectivity, optimization of formulation or pharmacokinetic characteristics, etc.). Applications lacking a Readiness of Agent attachment will not be reviewed.

Partnership Plan (1-page maximum) A plan for a partnership with a rare disease steering/oversight committee is required to submit to this NOFO. However, neither the members of the committee nor the organizations that might partner should be named in the application This committee may be formed de novo with members having appropriate disease relevant expertise and/or experience and could include a potential financial backer.

Please include only a description of the type of individuals (expertise, patients and/or advocates, foundation representatives – do NOT name the foundation, etc.) Please clearly describe the planned interactions between this committee and the scientific team. Letters of support from committee members will be requested as part of the just-in-time package prior to issuing an award.

Applications lacking a Partnership Plan attachment will not be reviewed. SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Evidence Supporting Rare Disease Classification – The Significance section of the Research Strategy must include a paragraph with the heading, "Evidence Supporting Rare Disease Classification".

If the application does not include the following information, then it will be considered non-responsive and will not be reviewed.

This section should provide the evidence that the disease/condition being studied is classified as a rare disease; i.e., there are 200,000 or fewer patients in the U.S. This section may include one or more references confirming the prevalence of the disease/condition that is the primary focus of the research application. If the disease/condition has been granted orphan status by the FDA, provide this information in this paragraph.

Biological Rationale - The Research Strategy section should include a background section that clearly outlines the biological and therapeutic rationale for the application, including: 1) a description of the biological rationale linking the proposed therapeutic target and the rare disease of interest, 2) evidence for unmet medical need in the therapeutic disease area, 3) a brief description of any pertinent history for therapeutic development in the disease area, and 4) a summary of the project status, including data supporting the readiness of the therapeutic agents to be tested for efficacy (i.e. optimization of formulation or pharmacokinetic characteristics).

Therapeutic Rationale – The Research Strategy should provide the data supporting selection of the therapeutic agent and any prior art thus far collected. A summary of the project status should provide compelling preclinical evidence that a therapeutic candidate is ready to be tested for efficacy (i.e. prior screening data, suitable potency and selectivity, optimization of formulation or pharmacokinetic characteristics, etc.).

Rare Disease Model – The research strategy section must include a description of the rare disease model to be utilized, including validation of the model and evidence supporting relevance to the rare disease in question. Access to the model, in sufficient numbers to support testing, should be clearly described in the application.

A letter of support if the animals will be provided by a collaborator, or a quote for purchase must be included in the Letters of Support attachment. 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.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page.

The DMS Plan must address the elements in the structured format should not exceed two (2) pages. Where the DMS Plan Format Page requires a Yes or No response, no additional narrative is allowed. 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 NIH-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.

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. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 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 , NIH’s electronic system for grants administration.

NIH 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 NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

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. 5.

Intergovernmental Review (E. O. 12372) This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7. 9.

1 Selected Items of Cost. 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. 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 NIH.

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 Center for Scientific Review and responsiveness by components of participating organizations , NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at [email protected] when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application. Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award.

See Mandatory Disclosures, 2 CFR 200. 113 and NIH Grants Policy Statement Section 4. 1.

35 . Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected] . Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy Section V.

Application Review Information Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following: The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information.

Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will evaluate Factors 1, 2 and 3 in the