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

Pre-application for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules (X02)    

Activity Code

X02 Preapplication

Announcement Type

Reissue of PAR-14-213

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-TR-17-001

Companion Funding Opportunity

RFA-TR-17-002,UG3/UH3 Exploratory/Developmental Phased Innovation Awards Cooperative Agreement

RFA-TR-17-003, UG3/UH3 Exploratory/Developmental Phased Innovation Awards Cooperative Agreement

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.350, 93.242 

Funding Opportunity Purpose

The NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules [New Therapeutic Uses (NTU)] program is designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutics development. This innovative program matches researchers with a selection of pharmaceutical industry assets to test ideas for new therapeutic uses with the ultimate goal of identifying promising new treatments for patients. The program was designed to enable efficient 3-way drug repositioning partnerships between academic, government, and pharmaceutical partners.

NCATS is issuing a new round of Funding Opportunity Announcements (FOAs) that support clinical testing of new therapeutic uses for experimental drugs or biologics (Assets) across a broad range of human diseases in adult and pediatric populations.

This FOA invites X02 pre-applications for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules.  The X02 pre-application is the first step in the application process for companion FOAs, RFA-TR-17-002 and RFA-TR-17-003; applicants should read the companion FOAs. The X02 pre-applications will be evaluated by outside experts.

Investigators whose X02 pre-applications are judged to be the most meritorious will be notified of the opportunity to submit an UG3/UH3 under RFA-TR-17-002 or RFA-TR-17-003 in the case of adult or pediatric indications, respectively.    

Key Dates
Posted Date

February 15, 2017

Open Date (Earliest Submission Date)

March 17, 2017

Letter of Intent Due Date(s)

March 17, 2017

Application Due Date(s)

April 17, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

Not Applicable

Advisory Council Review

Not Applicable

Earliest Start Date

Not Applicable

Expiration Date

April 18, 2017

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. 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.

  3. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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. Funding Opportunity Description

NCATS is issuing a new round of Funding Opportunity Announcements (FOAs) that support clinical testing of new therapeutic uses for experimental drugs or biologics (Assets) across a broad range of human diseases in adult and pediatric populations. This innovative program matches researchers with a selection of pharmaceutical industry assets to test ideas for new therapeutic uses with the ultimate goal of identifying promising new treatments for patients. The program was designed to enable efficient 3-way drug repositioning partnerships between academic, government, and pharmaceutical partners.

This FOA solicits X02 pre-applications for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules.  The X02 pre-application is the first step in the application process for companion FOAs, RFA-TR-17-002 or RFA-TR-17-003; applicants should read the companion FOAs. The X02 pre-applications will be evaluated by outside experts.

Applicants whose X02 pre-applications are identified as being highly meritorious and relevant to NIH program priorities will be notified of the opportunity to submit a UG3/UH3 under RFA-TR-17-002 or RFA-TR-17-003 in the case of adult or pediatric indications, respectively. Such applicants will also be put in contact with the appropriate pharmaceutical company so that they can work with their institutional technology transfer or sponsored research office to finalize the terms and conditions of the collaborative research agreement (CRA) and confidential disclosure agreements (CDA) with the pharmaceutical company partner for the selected Asset, prior to submitting an UG3/UH3 application.

Background

Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) is a collaborative program designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutics development. This innovative program matches researchers with a selection of pharmaceutical industry assets to test ideas for new therapeutic uses with the ultimate goal of identifying promising new treatments for patients. The program was designed to enable efficient 3-way drug repositioning partnerships between academic, government, and pharmaceutical partners. Strategies used to accomplish this include posting limited confidential information about investigational Assets [new molecular entities (NMEs) and biologics] offered by pharmaceutical companies to a public website. This facilitates crowdsourcing of ideas for new therapeutic uses from academic medical centers or companies in the form of grant applications to NCATS. The program has shortened the time needed to establish collaborations to 3 to 4 months (from the typical 9 months to a year) by publicly posting template collaborative research agreements (CRAs) and template confidential disclosure agreements (CDAs) that are executed between the applicant institution and the pharmaceutical company that is providing the Asset for testing a new therapeutic use.

 FOA

Type of research supported

Period of support (maximum)

X02

Pre-application (no research supported)

N/A

UG3/UH3

UG3: Pre-clinical studies and/or clinical trial document preparation

UH3: Phase I and Phase II clinical trials

Up to 1 year of support for UG3 and up to 3 years of support for UH3

UG3/UH3 Pediatrics*

UG3: Pre-clinical, pediatric toxicology, and/or clinical trial document preparation

UH3: Phase I and Phase II clinical trials

Up to 2 years of support for UG3 and up to 3 years of support for UH3

*In general, pediatric populations to be considered for this FOA refer to disease populations for which there is no adult equivalent and therefore, there is no adult population in which the drug could be tested prior to testing in children. However, trials in pediatric or juvenile populations for indications that also have an adult population (e.g., type 2 diabetes, autism, and osteoarthritis) may be considered if there is a strong scientific rationale that justifies why clinical trials in the pediatric population are required even though an adult patient population exists.

Research Objectives

This funding opportunity announcement (FOA) intends to identify meritorious pre-applications that propose testing of innovative ideas for the discovery of new therapeutic uses of existing Assets in previously unexplored diseases. Proposed human trials can include: 1) use of an Asset as a stand-alone intervention, or 2) as an adjunctive intervention with existing standard of care (if there is no evidence of drug-drug interactions with the proposed standard of care treatment). Strategies to inform the selection of patients for proposed new uses of the Assets are of interest.

For this FOA, Phase I and Phase II clinical trials are defined as follows:

  • Phase I clinical studies are conducted in the target patient population to evaluate safety, determine a safe dose range, and identify side effects prior to conducting a Phase II clinical trial.
  • Phase II clinical trials are conducted in a larger patient population, typically 150 subjects or less for trials in adults. The purpose of the Phase II clinical study is to provide a preliminary signal of efficacy.

Through the Limited Competition for the NIH-Industry Program: Discovering New Therapeutic Uses for Existing Molecules FOAs, RFA-TR-17-002 (UG3/UH3) or RFA-TR-17-003 (UG3/UH3), investigators will have an opportunity to investigate Assets with known pharmacologic mechanisms of action for clinical efficacy in new therapeutic areas. Investigators whose X02 pre-applications are judged to be the most meritorious will be notified of the opportunity to submit a UG3/UH3 application under these FOAs.

The UG3/UH3 RFA-TR-17-002 and RFA-TR-17-003 (pediatric) are single bi-phasic applications. The UG3 phase will support milestone-driven preclinical studies for making a go/no-go decision to progress to clinical trials and/or clinical trial document preparation and approvals (clinical trial protocol, manual of operations, consent forms, IND, detailed data and safety monitoring plan, data quality management plan, etc.). The duration of the UG3 project period for adult populations is anticipated to vary in time from 3 months up to one year. The duration of the UG3 project period for pediatric indications, which will also support pre-clinical juvenile drug toxicity studies in one or more species, may vary in time from one to two years depending on availability of juvenile toxicity data. UG3 projects that have met the scientific milestones and feasibility requirements will be eligible for rapid transition to the UH3, after NIH administrative review. 

The UH3 stage can be used for clinical trials using the selected company Asset in its existing formulation/route of administration to identify the dose or exposure of the Asset in the proposed patient group, and inform patient selection. During the UH3 stage, up to 1 year of support for Phase I clinical trials may be provided. Phase I trials that have met the scientific milestones and feasibility requirements will be eligible for transition to a Phase II clinical trial after NIH administrative review of the progress on negotiated milestones and go/no go criteria. The UH3 will provide up to 2 years of support for milestone-driven Phase II trials to demonstrate that the Asset, made available for this program by the pharmaceutical partners, modulates the target and has the potential to yield the desired clinical outcome in the proposed patient population – preliminary signal of efficacy. The project period for the UH3 (Phase I and Phase II clinical trial) may not exceed a total of three years.

Research Areas of Interest

National Center for Advancing Translational Sciences (NCATS)

NCATS is "disease agnostic." Rather than focusing on a single disease or biological system, NCATS focuses on improving the translational science process.

NCATS will consider funding projects that address diseases that have no available treatment or an inadequate treatment, and for which there is strong scientific rationale for the new therapeutic use.

Application Process

The submission of an X02 pre-application is the first step in applying for an award under RFA-TR-17-002 or RFA-TR-17-003; applicants should read the companion FOAs prior to submitting an X02 pre-application. Each pre-application submitted to the FOA should identify a single Asset (or single mechanism of action in cases where there is more than one Asset available with the same mechanism of action) to be tested for a new use.  Pre-applications submitted to this FOA will be evaluated by outside experts. X02 applicants will receive feedback on the scientific merit (particularly the association between the Asset’s mechanism of action and the disease indication proposed), technical feasibility, expertise of the investigative team, medical need, and overall potential of the science proposed. No awards will be made for X02 pre-applications under this FOA. Investigators of  X02 pre-applications, which are identified as being highly meritorious and relevant to NIH program priorities, will be provided contact information for the appropriate pharmaceutical company based on the Asset or mechanism of action identified in their X02 pre-application. The X02 applicants and pharmaceutical company partner will jointly decide whether a UG3/UH3 application should be submitted.

X02 applicants put in contact with the pharmaceutical company partner(s) for the Asset or mechanism of action that was selected for studies in the X02 pre-application are expected to execute an appropriate Confidential Disclosure Agreement (see template CDAs). Under the CDA, the applicant and pharmaceutical company partner will exchange confidential information (e.g., additional information on the Asset and studies to test the proposed new therapeutic use of the Asset), as deemed necessary, to initiate discussions. Subsequently, it is anticipated that a Collaborative Research Agreement (CRA) between the applicant and the pharmaceutical company partner will be the vehicle through which the applicant obtains permission to work with the Asset on the research project plan for the UG3/UH3 application. As part of the UG3/UH3 application, the applicant must provide the NIH with documentation of access to the Asset and associated data needed for filing an investigator-sponsored Investigational New Drug (IND) Application and for conducting the proposed clinical trial (e.g., an executed CRA).

Partnership Information

A key aspect of this FOA is the formation of collaborative partnerships between the biomedical research community and industry partners. NCATS has executed a Memorandum of Understanding (MOU) with each of the pharmaceutical company partners to provide a framework under which specific proprietary Assets will be provided by these partners to the program awardees. Template agreements have been developed for this program: Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) between the pharmaceutical company partner and the applicant. These template agreements have been developed to streamline interactions among the parties for the Program, and it is anticipated that applicants will use the agreements.

UG3UG3

Assets Available for the Program

The list of Assets and non-confidential information can be found at http://www.ncats.nih.gov/ntu/assets/current. The Assets are posted in two separate tables: 1) Table of Assets for Adult Indications and 2) Table of Assets for Pediatric Indications. 

Please also refer to the http://ncats.nih.gov/ntu/funding/TR17001-3-faq as an additional source of information about the program. 

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

Section II. Award Information
Funding Instrument

 Other: A mechanism that is not a grant or cooperative agreement. Examples include access to research resources or pre-applications

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

No awards will be made under this announcement. Awards will be made through the companion FOAs, RFA-TR-17-002 and RFA-TR-17-003.

Award Budget

Not Applicable

Award Project Period

Not Applicable  

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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)

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)
  • Eligible Agencies of the Federal Government including NIH Intramural Research Program
  • 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 Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – 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. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

Eligible PD(s)/PI(s) develop an X02 pre-application for the opportunity to submit a UG3/UH3 application. For these X02 pre-applications, the PD/PI listed on the X02 pre-application must be the same PD/PI listed on a subsequent UG3/UH3 application. For X02 pre-applications proposing multiple PD(s)/PI(s), the contact PD/PI listed on the X02 pre-application must be the same PD/PI listed on a subsequent UG3/UH3 application. The contact PD/PI is strongly encouraged to continue the multiple PD(s)/PI(s) leadership identified in the X02 pre-application if notified of the opportunity to submit a UG3/UH3 application.

NIH Intramural Research Program (IRP) investigators are eligible to submit an X02 pre-application, subject to the availability of intramural funds to support the project. IRP investigators can apply as PD(s)/PI(s), as multiple PD(s)/PI(s) in conjunction with extramural investigators (http://grants.nih.gov/grants/multi_pi/index.htm), or as collaborators with extramural academic or biotechnology company investigators.

If the applicant institution is an NIH Institute or Center, funds may not be requested for an extramural component/collaborator in the subsequent UG3/UH3 application.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

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.  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 NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. 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 Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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 IC 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:

Carol Lambert, Ph.D.
Telephone: 301-435-0814
Fax: 301-480-3660
Email: lambert@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

For this specific FOA, the Research Strategy section is limited to 4 pages.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.  

Type of Submission: Select "Pre-application".

Total Federal Funds Requested: Enter "0".

Total Federal and Non-Federal Funds: Enter "0".

Estimated Program Income: Enter "0".

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Are Human Subjects Involved: Answer "No".

Are Vertebrate Animals Used: Answer "No".

Other Attachments: Attach Asset information for the Asset selected for use in the project, available at http://www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/directory2014.html, and title it "Asset Information".

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed. 

Not Applicable

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.  

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

Specific Aims:  The Specific Aims section should include Aims delineated for the UG3 (pre-clinical and clinical trial planning) and UH3 (Phase I and Phase II clinical trial):

1. UG3

a. Define the aims of the pre-clinical studies, if pre-clinical studies are proposed.

b. Describe the goals to be achieved by the conclusion of the trial planning.

2. UH3 (Phase I and Phase II clinical trial)

a. Define the aims of the Phase I dosing, safety and tolerability clinical trial, if such a trial is proposed.

b. Define the aims of the Phase II preliminary effectiveness clinical trial.

1). The aims should address target modulation and efficacy.

2). The clinical data resulting from the UH3 stage should provide sufficient evidence that the drug candidate is safe and well-tolerated for administration in the proposed dose range; modulates the target/mechanism and a biomarker of PD effect; and has the potential to yield the desired clinical outcome in the disease population.

Research Strategy: Within the Research Strategy, provide the following information.

1. Background and Significance

a. Identify the proposed Asset (or identify the mechanism of action if multiple Assets are listed with the same mechanism of action) from among those made available for this Program that you are interested in using, its known pharmacologic mechanism of action or target, and the new therapeutic use which will be investigated.

b. Clearly describe the patient population to be studied. If the disease/condition exists in both children and adults, include strong scientific justification for testing the Asset in a pediatric patient population instead of testing in an adult patient population (e.g., the target in the pediatric population may differ from that in the adult or treatment of children may reduce progression or severity of the disease).

c. Provide the scientific rationale for selection of the Asset or mechanism of action and its proposed new therapeutic use.

d. Describe the potential impact of the novel therapeutic use of the Asset for the disease or disorder.

Describe how the mechanism under investigation differs from previous studies/trials for this indication. Include any information on ongoing or completed clinical trials investigating the same target/mechanism of action in the proposed patient population. What is the value added of the proposed studies?

e. Address the global burden of disease, which patients may benefit, how they may benefit, how use of the Asset might be superior to current therapy options, potential for impact on public health.

2. Preliminary Studies

a. The Preliminary Studies section may contain data and information that validate feasibility for conducting the proposed studies.

1). Evidence that the target or specific pathway is involved in the disease pathology. Examples may include but are not limited to:

(a) In vitro or in vivo evidence that a specific target/pathway is involved in the disease pathology.

(b) Evidence that modulation of the Asset’s target will have a positive impact on the disease or disorder proposed

2). Data to support the selection and relevance of the proposed models to assess the efficacy of the Asset in the new disease area (e.g., choice of assays, models, species, outcome or endpoints selected).

3. Approach

a. Provide a plan to assess the validity of the biological hypothesis for use of the Asset in the new disease area.

1). If pre-clinical studies are proposed, describe the types of approaches that will be used and how the results will be used to establish feasibility for moving from the UG3 to UH3 Phase I or Phase II clinical trial after a trial planning period (UG3).

b. Define go/no go decision points and milestones for advancing the Asset to Phase I and/or Phase II clinical trials to validate the new therapeutic use.

c. Describe the design of clinical trials to assess effectiveness of the Asset.

1). Provide appropriate metrics for determining feasibility to begin Phase II clinical trials.

2). Define the considerations and approach to be used to determine statistical end points and justification for the size of the trial.

4. Administration and Management

a. Provide an operational plan for managing the pre-clinical studies and clinical trials necessary to fully develop a new use for the Asset.

1). Describe institutional and/or team experience with FDA regulatory processes.

a. Phase I or II clinical trials will be dependent on the grantee filing an investigator-sponsored Investigational New Drug (IND) Application.

2). Explain the proposed contribution of each of the key participants in achieving the objectives of the project.

3). It will be important for the PD/PI to describe experience in meeting milestones.

b. Describe relevant experience and knowledge of public-private partnerships.

c. Describe the team's experience in the methods and approaches for design and implementation of human clinical trials and readiness to test the hypothesis.

d. Describe the team's requisite competencies and experience with clinical trials recruitment and execution and ability to recruit and enroll patients in the target disease population.

Letters of Support: Applicants MUST include a letter from an appropriate institutional official, generally a dean or provost, documenting institutional commitment to the project, including provision of resources, space, and available faculty. Include in the letter confirmation of the Institution’s willingness to engage in the necessary negotiations with the pharmaceutical company regarding the terms and conditions of the template CDA and CRA for the selected Asset or mechanism of action. A successful UG3/UH3 application will be contingent on the applicant’s ability to provide the NIH with documentation of access to the selected Asset and associated data needed for conducting the proposed pre-clinical studies and for filing an investigator-sponsored IND in order to conduct the proposed clinical trials (e.g., an executed CRA or letter from the pharmaceutical partner).

If multiple institutions are involved in an application, a letter must be provided by each participating institution.

For NIH Intramural Research Program (IRP) investigators, an official letter from the Scientific Director, which indicates approval of the IRP scientist's role as PD/PI or as collaborator in the project, must be included as a letter of support in the X02 application. The letter must specify the Scientific Director's commitment of intramural research funds to support the IRP investigator's proposed project or project component.  Although NCATS will not provide support for IRP components, NCATS may facilitate contact with the pharmaceutical company following meritorious review of an IRP-submitted X02 application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

A Resource Sharing Plan (Data Sharing Plan, Sharing Model Organisms, and GWAS Sharing Plan) is not applicable for this X02 FOA.

Appendix:

 Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Appendices are not allowed for this FOA and will not be accepted. Do not use the Other Attachments section to circumvent this limitation.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed. 

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. 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. Overview Information 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 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 SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at NCATSReferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Not Applicable

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process.

For this particular announcement, note the following:

The pre-application FOA is soliciting ideas for new therapeutic uses of existing molecules (Assets) from pharmaceutical company partners.  The pre-application is the first step toward gaining access to the Assets. Accordingly, reviewers will focus their evaluation on the scientific evidence that modulation of the Asset's target would positively impact the disease or condition, conceptual framework, the level of innovation, qualifications of the research team and the significance of the unmet medical need. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data on the target using alternative probes and methods.

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).

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

Specific to this FOA: Does the proposed novel use of the Asset have the potential to affect pharmacologic intervention for a disease or disorder with unmet medical need? Is there a strong biological rationale for the proposed clinical trials?     

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Specific to this FOA: Do the PD(s)/PI(s) have the scientific and organizational vision and experience to serve effectively as the Director(s) of a therapeutic development effort? Is there evidence of sufficient management capabilities that include fiscal administration, personnel management, planning, and budgeting? Does the investigative team have the requisite competencies and experience with drug development including regulatory processes, clinical trials planning, recruitment and execution?  Does the team provide evidence to support their suitability to recruit and enroll patients from the target disease population? Do the PD(s)/PI(s) demonstrate relevant experience and knowledge of public-private partnerships?      

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: Are there ongoing or completed clinical trials modulating the same target/mechanism of action for this patient population?  How would this clinical trial be novel?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Specific to this FOA: Although the Asset itself was not accessible to the PD/PI, is sufficient evidence presented to support the scientific rationale for the proposed new use of the Asset (its pharmacologic mechanism of action or target) and relevance of the biology to therapeutic intervention in the proposed disease? If the applicant is proposing studies in a pediatric population for a disease/condition that exists in both children and adults, is there sufficient scientific justification for testing the Asset in a pediatric patient population instead of testing in an adult patient population? Are milestones, go/no go decisions clearly defined and appropriate to validate the new therapeutic use? Have the PD(s)/PI(s) provided an operational plan for managing the necessary collaborations between and among preclinical and clinical plan investigators, and the pharmaceutical company partner? If pre-clinical or Phase I trials are proposed, is there a plan for moving expeditiously to Phase II clinical trials once a new therapeutic use has been assessed for safety?.

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Environment

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?

Specific to this FOA:  Is there evidence of institutional commitment to the project? Is there institutional confirmation that the terms and conditions of the CDA and CRA for the selected Asset are acceptable to the technology transfer or sponsored research office (for example, through the letter documenting the Institution's willingness to enter into the necessary agreements with the pharmaceutical company partner)? Does the scientific environment indicate the potential for a multi-disciplinary approach involving teams of investigators?    

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

Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer. For additional information to assist you in making these determinations, please refer to the Guidelines for the Review of the Human Subjects Section.

Inclusion of Women, Minorities, and Children 

Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer. For additional information to assist you in making these determinations, please refer to the Guidelines for the Review of Inclusion on the Basis of Sex/Gender, Race, Ethnicity, and Age in Clinical Research.

Vertebrate Animals

Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer. For additional information to assist you in making these determinations, please refer to the Worksheet for Review of the Vertebrate Animal section (VAS).

Biohazards

Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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

Not Applicable

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

Not Applicable

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

Applications will be assigned to NCATS with potential secondary assignment, based on the proposed disease population, to the appropriate NIH Institute or Center.

Investigators whose X02 pre-applications are identified as being highly meritorious and relevant to program priorities will be notified of the opportunity to submit a UG3/UH3 application under RFA-TR-17-002 or RFA-TR-17-003.

3. Anticipated Announcement and Award Dates

Not applicable

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

Section VI. Award Administration Information
1. Award Notices

Not Applicable

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

Not Applicable

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Scientific/Research Contact(s)

We encourage inquiries and welcome the opportunity to answer questions from potential applicants.

For technical questions regarding the FOA (mechanisms, partnerships, application content or scientific management of the cooperative agreements), please contact:

Bobbie Ann Austin, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0824
Email: NewTherapeuticUses@mail.nih.gov

FAQs:
http://ncats.nih.gov/ntu/funding/TR17001-3-faq

 Review Contact(s)

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: Lambert@nih.gov

Financial/Grants Management Contact(s)

Julia Shriner
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-0853
Email: Julia.Shriner@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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