Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Institute on Drug Abuse (NIDA)

National Institute of Environmental Health Sciences (NIEHS)

Funding Opportunity Title
CCRP Initiative: Countermeasures Against Chemical Threats (CounterACT) Therapeutics Discovery and Early-Stage Development (UG3/UH3 Clinical Trial Not Allowed)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-22-209
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853, 93.867, 93.279, 93.855, 93.113, 93.846
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) solicits applications for the early-stage development of therapeutics to mitigate the adverse health effects resulting from toxic chemical exposure. Chemical threats are toxic compounds that could be used in a terrorist attack or accidentally released from industrial production, storage or shipping. They include specific chemical warfare agents, toxic industrial chemicals, pesticides, and pharmaceutical-based agents. The overall scope of this solicitation includes validation of therapeutic targets and preclinical characterization of lead compounds. The UG3 phase of this FOA supports target validation and characterization of initial lead compound(s); UH3 phase activities include candidate optimization and in vivo demonstration of activity and efficacy in relevant post-exposure models. At the conclusion of the overall UG3/UH3 funding period, projects are expected to deliver at least one well-characterized therapeutic candidate.

Key Dates

Posted Date
July 06, 2022
Open Date (Earliest Submission Date)
September 17, 2022
Letter of Intent Due Date(s)

30 days prior to application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 17, 2022 October 17, 2022 Not Applicable March 2023 May 2023 July 2023
October 17, 2023 October 17, 2023 Not Applicable March 2024 May 2024 July 2024
October 17, 2024 October 17, 2024 Not Applicable March 2025 May 2025 July 2025

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.

Expiration Date
October 18, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in 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 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. You must use one of these submission options to access the application forms for this opportunity.

  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. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Overview

The Chemical Countermeasures Research Program (CCRP) supports the discovery and early development of medical countermeasures (MCMs) to treat and/or prevent serious morbidities and mortality resulting from high consequence public health chemical emergencies. A high consequence public health chemical event is when a large number of civilians are either deliberately or accidentally exposed to highly toxic chemicals. In this case, the MCMs should be easily accessible to first responders and local public health authorities for use in a mass casualty pre-hospital setting and they should be safe and effective for adults, children, and the elderly or as follow-on treatments in-hospital, when appropriate. The civilian chemical threat spectrum includes chemical warfare agents, toxic industrial chemicals, pesticides, pharmaceutical-based agents, and others that have been identified by the United States Government (USG) as Chemicals of Concern (CoC). These compounds are highly toxic and MCMs are urgently needed to advance national medical and public health preparedness for, response to, and recovery from, chemical emergencies.

The CCRP is a trans-NIH initiative established by the NIAID in 2006 and involves partnerships with the NEI, NIAMS, NICHD, NIEHS, NIDA, and NINDS NIH Institutes to execute the overall NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Chemical Threats. Within the CCRP, the NIH Countermeasures Against Chemical Threats (CounterACT) program led by the NINDS in collaboration with the other CCRP Institutes supports research focused on civilian chemical MCMs. The NIH collaborates closely with sister federal agencies, such as the Biomedical Advanced Research and Development Authority (BARDA) under the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) to support the advanced research and development of promising MCMs.

Projects funded under this FOA are expected to deliver a characterized therapeutic candidate at the conclusion of the overall UG3/UH3 funding period.

A characterized therapeutic candidate, including repurposing of therapeutics for other indications, is a small molecule or biologic that is biologically active and synthetically feasible, where specificity, affinity, potency, target selectivity, pharmacokinetics/ pharmacodynamics, safety and post-exposure efficacy have been established. This includes demonstration of acceptable Absorption, Distribution, Metabolism, Elimination, Toxicity (ADMET) profile, in vivo efficacy, and validated target engagement for the proposed indication with clinically relevant results. For guidance on studies and metrics to identify a lead therapeutic candidate see the Early Drug Discovery and Development Guidelines: For Academic Researchers, Collaborators, and Start-up Companies.

Chemicals of Concern (CoC)

The following chemicals of concern (CoC) identified by the Department of Homeland Security are organized within toxidromes established by the USG. Toxidromes group chemicals based on their primary modes of toxicity. One benefit of this approach is that a single MCM with broad spectrum activity can be used to treat multiple different chemical threats. The CoC toxidromes (with examples) are:

Anticoagulants (e.g., brodifacoum, bromadiolone)

Blood agents (e.g., hydrogen cyanide, hydrogen sulfide)

Cholinergic Warfare and Pesticides (e.g., sarin, soman, parathion, phorate, aldicarb)

Convulsant (e.g., picrotoxin, TETS, strychnine)

Hemolytic/Metabolic (e.g., arsenic trioxide, thallium sulfate, arsine)

Pulmonary (e.g., chlorine, phosgene, sulfur mustard, ammonia, sulfur dioxide)

Synthetic Opioids (e.g., fentanyl, carfentanil, acetylfentanyl, sufentanil, remifentanil)

Vesicants (e.g., sulfur and nitrogen mustard, Lewisite, phosgene oxime)

The above list of chemicals of concern are examples, the list is not limited only to these chemicals. Only projects that include chemicals that have been identified by the DHS as CoC will be supported by this FOA. Applicants are strongly encouraged to contact the Scientific/Research contacts provided in this FOA to confirm that the proposed chemical threat(s) is of interest to the program.

Scientific Scope/Research Topics

This FOA will only support research that is clearly relevant to the development of MCMs that will enhance national medical response capabilities during or after a large-scale chemical emergency. The scientific scope of this FOA in the UG3 phase includes target validation and characterization of preliminary candidate(s); UH3 phase activities include candidate optimization and non-GLP in vivo demonstration of activity and efficacy in relevant post-exposure models. Efficacy of the lead candidate therapeutic must be demonstrated in an appropriate model predictive of the human response in a mass casualty/ emergency setting, including an extended post-exposure treatment window and route of administration. Prophylactic therapeutic approaches that are administered before chemical threat exposure, are considered non-responsive to this FOA, and will not be reviewed as they to do not have practical utility during a mass casualty event.

In all cases, the proposed research must address acute exposures, not chronic exposures over a long period, e.g., environmental, occupational or residential exposures.

Research Relevant to this FOA:

  • Therapeutics that address acute lethal effects and are amenable for use in mass casualty situations, i.e., easily administered by first-responders and local health authorities.
  • Therapeutics to prevent long-term or delayed chronic effects after an acute exposure would also be considered and may be appropriate for administration after field evacuation and in-hospital, such as in-hospital treatment for long-term effects in survivors of the acute exposure.
  • Therapeutics must improve upon the current post-exposure MCM standard-of-care, if applicable.
  • The specific injuries caused by exposure to chemicals are often similar or identical to conditions observed in conventional clinical practice, e.g., respiratory depression, neovascularization, fibrosis, acute lung injury, seizure. Proposals seeking to expand indications of already approved/authorized drugs, i.e., therapeutic repurposing.
  • Therapeutics that have a broad spectrum of activity, i.e., "treat the symptoms of injury/disease regardless of etiologies".
  • Therapeutics for specific vulnerable subpopulations (e.g., pediatric, geriatric and pregnant) can be included in addition to primary studies targeted at adult populations if time and budget allow.

Minimum FOA Entry Criteria:

  • Rigorous data supporting the hypothesis that modulating the putative drug target or affected pathway will produce a desirable outcome for the intended disease indication.
  • Initial lead compounds, in hand, that will serve as a starting point for optimization.
  • Assays, in hand, to down-select to a single lead candidate for further optimization/characterization.
  • Lead compounds that can be advanced towards optimization and development with no obvious legal (e.g., intellectual property) constraints to pursuing the proposed chemical scaffold(s) and using the proposed assays and models for research purposes and/or commercial development, i.e., “freedom to operate”.

For projects that are proposing to repurpose FDA-approved drugs, many of the above entry criteria may already be met.

The UG3/UH3 Funding Mechanism

This FOA will use the UG3/UH3 Cooperative Agreement mechanism. As translational research is inherently high-risk, this mechanism uses milestones that will provide clear indicators of a project's continued success or emergent difficulties.

This mechanism will utilize both annual milestones as well as phase-transition milestones that govern transition from the UG3 to UH3 phases of the award. Milestones toward therapeutic intervention are not a description of specific aims and experiments, but rather are discrete goals that create go or no-go decision points that include quantitative success criteria. More information about milestones, including examples can be found on the CounterACT webpage. Annual milestones may be modified in negotiation with NIH program officials before an initial award is made, and during the review of annual non-competitive applications. Unmet annual milestones, unmet transition-phase milestones, or an incomplete data package that prevents an adequate evaluation of milestone progress may result in NIH ending project support.

The UG3/UH3 funding mechanism has two phases, both of which are required in the application. Applications must include a milestone plan that proposes a well-defined set of annual milestones as well as a list of specific milestones for transition from the UG3 phase to the UH3 phase. When applicable, milestone reports should describe how measurable outcomes will be collected using rigorous and transparent experimental approaches. These approaches include, but are not limited to, randomization, blinding, use of statistically adequate sample sizes with biologically relevant effect sizes, minimization of potential bias, independent replication, and adequate reporting of experimental details and results as described at https://grants.nih.gov/policy/reproducibility/index.htm.

The total project period for the UG3/UH3 Cooperative Agreement mechanism cannot exceed 5 years and neither phase can exceed 3 years.

The UG3 Phase:

The UG3 phase should include hit to lead activities that enable down-selection from candidate therapeutics to a single lead compound. Examples of activities for the UG3 phase include, but are not limited to:

  • Validate target/pathway engagement, and optimization of hits/leads to develop therapeutics that can effectively reverse the deleterious effects of chemical threats, post-exposure.
  • In vitro demonstration of target engagement and appropriate biological activity of candidate therapeutics to counteract the effects of the threat agent.
  • Development and utilization of relevant post-exposure animal models to demonstrate preliminary proof-of-concept efficacy. Animal models should demonstrate an important clinical benefit and should simulate the ultimate clinical use of the candidate therapeutic in humans.
  • Demonstration of preliminary safety, pharmacodynamic/pharmacokinetic (PD/PK) properties of the candidate therapeutic.

Transition to the UH3 Phase:

An administrative review of the extent to which peer-reviewed milestones are satisfactorily met in the UG3 Phase will determine whether the UH3 Phase award will be issued. Applicants and recipients of UG3 funding should note that the UG3 award does not guarantee subsequent UH3 funding. The justifiable go/no go criteria to determine whether a UG3 Phase will transition into the UH3 Phase will be negotiated between NIH staff and the applicants prior to funding.

The UH3 Phase:

The UH3 phase should include optimization activities that enable characterization of the lead candidate for further development. Examples of activities for the UH3 phase include, but are not limited to:

  • Specificity, affinity, potency, target selectivity/uptake/engagement, post-exposure in vivo efficacy, ADME/Tox.
  • Demonstration of efficacy in animal model more predictive of the human condition and more easily scalable in terms of therapeutic dose, e.g., swine, non-human primates, etc.
  • In vivo dose-ranging and efficacy (non-GLP) studies against the chemical threat consistent with the product's intended therapeutic use regimen (i.e. dose, schedule, duration, route of administration, and route of threat agent challenge).
  • Determination of the route and time(s) of administration of the therapeutic consistent with the intended use in humans, including the likely environment where the drug would be administered (pre-hospital or in-hospital settings).
  • Development of assays, surrogate markers, correlates of protection, and endpoints to be used during non-clinical and clinical studies to further evaluate and characterize candidate(s).
  • Optimization of formulations and delivery systems (e.g., intranasal, intramuscular, intraosseous) that can be effectively employed by emergency responders on the field in a mass-casualty situation.
  • Optimization of pharmacokinetic and metabolic properties of lead candidates using a relevant formulation via the intended route of administration in animals using relevant post-exposure models.
  • Demonstration of proof of identity and purity of lead compound.
  • Draft preliminary Target Product Profile. Questions of shelf life, storage conditions, and packaging should be considered to ensure that anticipated use of the product is consistent with the intended use for which approval will be sought from FDA.

Chemical Safety Certification

Many of the chemical threat agents of interest are extremely hazardous to humans. All

applications must include a letter from appropriate institutional biosafety committee or institutional review entity indicating that studies are deemed safe for research personnel and the environment (See letters of support in Section IV). Special safety certifications may be required to conduct research with some chemical threat agents (e.g., chemical warfare agents). Therefore, applicants are encouraged to collaborate with laboratories and contract research facilities that are already certified to work with restricted chemical agents, when applicable. See Section 4.1.24.3 of the NIH Grants Policy Statement for agents regulated under the Chemical Weapons Convention. Applicants are strongly encouraged to contact the relevant Scientific/Research Contacts listed in this FOA for further information on working with restricted chemical agents.

Annual Countermeasures Against Chemical Threats (CounterACT) Network Research Symposium

Awardees funded under this FOA must participate in the annual network research symposium of CCRP-funded projects. Participation includes presentation of research progress achieved under the CCRP award. Some awardees may be asked by the NIH to host the annual meeting for the purpose of information exchange, sharing scientific progress, and formation of potential research collaborations. If requested to host the meeting, grantees may request funding support for this activity via an administrative supplement request to the NIH.

Applications Not Responsive to this FOA

Non-responsive applications will not be reviewed.

  • Applications that propose research on chemical threats that are not on the current Department of Homeland Security (DHS) List of Chemicals of Concern (check with Program staff prior to submission).
  • Applications that propose therapeutics unlikely to be amenable during or after a mass casualty scenario. This includes therapeutics that must be administered prophylactically or within the first 15-30 minutes of exposure.
  • Applications addressing health outcomes after chronic chemical exposure, i.e., this FOA only supports research on health effects after a single acute exposure event.
  • Applications lacking quantitative, go/no-go milestones and clear delineation of activities relevant to the UG3 or UH3 phase of the project.
  • Proposals that include advanced development activities such as 1) GLP IND-enabling safety studies; 2) Pivotal efficacy studies in animals; 3) cGMP production; 4) Human clinical trials.
  • Applications that propose assay development for discovery of novel therapeutic compounds.
  • Applications that propose screening to identify hit compounds.
  • Applications with a primary focus to develop de novo animal models.
  • Applications with a primary focus to develop diagnostics and/or devices.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

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

Award Budget

Applicants may request up to $350,000 direct costs annually for the UG3 phase and up to $450,000 direct costs for the UH3 phase per year.

It is expected that many applications will not need to request the maximum budget and the requested budget will need to reflect the actual needs of the proposed project.

Award Project Period

The proposed project period for the UG3 phase may not exceed 3 years (but may be shorter).

The proposed project period for the UH3 phase may not exceed 3 years (but may be shorter).

The maximum combined project period for both phases of an application submitted in response to this funding opportunity is five years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign 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.

  • 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 full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See Notice of NIH’s Interest in Diversity, NOT-OD-20-031, see also, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

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, per 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 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 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 instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide 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.

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:

Shardell M. Spriggs, PhD
Telephone: 301-443-8189
Email: shardell.spriggs@nih.gov

Page Limitations

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

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.

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.

Other Attachments:

Intellectual Property Strategy:

Applications should include an Intellectual Property (IP) strategy section that is no more than 1 page. It is advisable that this be prepared in consultation with their institution's technology transfer officials.

This section should describe the IP landscape surrounding their proposed therapeutic candidate(s). Applicants should describe any known constraints that could impede their therapeutic discovery and development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed. If the applicant proposes using a therapeutic candidate(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any obstacles to achieving the goals of the program and development and commercialization of the therapeutic candidate.

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable.

Applicants should discuss future IP filing plans, but any such action must be performed in accordance with the NIH Grants Policy Statement (NIHGPS). For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

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:

Introduction: Resubmission applications must include an “Introduction to Application” section that addresses the comments from the previous review (1 page).

Research Strategy

Significance: All proposed projects should have a strong biological rationale for the choice of the proposed injury mechanism and/or therapeutic(s) for the indication, supported by rigorous preliminary data. A well-structured application should, therefore, include clear rational experimental approaches that can yield significant data in support of the proposed indication. This section should describe how the research will lead to development of a characterized therapeutic candidate that can be used to reduce mortality and morbidity in a mass casualty event and is also an improvement over the current standard of care, if applicable.

The application should include a detailed description of the proposed characterized therapeutic candidate (to include detailed chemical structure information where applicable). The lack of structural information may adversely affect the assessment of the development potential. NIH has multiple safeguards to protect the integrity of and to maintain confidentiality in peer review.

Investigator: Applicants should describe the expertise within the team in preclinical and therapeutic discovery and development and expertise with chemical threat agents.

Innovation: Due to the nature of translational research supported by this FOA, some studies and methodologies may not be considered innovative even though they are essential components of the overall project. Examples of this type of research include routine preclinical safety/toxicity evaluations and the use of previously established models of chemical-induced injuries to identify potential differences between specific subpopulations (e.g. adults versus pediatrics). This FOA also supports and encourages repurposing products approved for other indications, as long as the therapeutic approach using that product is for a new indication.

Approach: The concept of use of the proposed therapeutic must be explained in the application as it is applicable in a mass casualty/emergency setting. Therefore, applicants should consider the rationale for the chosen model(s) and endpoints, adequacy of controls, including timing of therapeutic dosing and route of administration. Applicants should address effects of sex and age alone or in combination as biological variables in the proposed preclinical studies (see NOT-OD-15-102). Critical elements of a well-designed study include adequate scientific rigor, control of bias, reproducibility, dose-response, confirmation of mechanism, and transparency of reporting. As such, the NIH urges applicants to consider and directly address these elements in their application(s). Please see NOT-OD-15-103 for more information on enhancing reproducibility through rigor and transparency. Investigators should follow the NIH guidance for rigor and transparency in grant applications (see guidelines). This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully.

The UG3 phase should include hit to lead activities that enable down-selection from candidate therapeutics to a single lead compound. Applicants are encouraged to also have a back-up candidate. At the end of the UG3 phase, the applicant should have completed SAR activities to optimize compound structure and have demonstrated preliminary proof-of-concept efficacy, safety, and PK/PD properties.

The UH3 phase should include optimization activities that enable characterization of the lead candidate for further development. Applicants are expected to develop a preliminary Target Product Profile during the UH3 phase that is consistent with the intended end use of the candidate therapeutic. At the conclusion of the UH3 phase, the project should deliver a single, well-characterized candidate therapeutic that is an improvement over the standard of care, if applicable. A well-characterized therapeutic will have demonstrated affinity, potency, target selectivity and engagement, in vivo efficacy, ADME/Tox in an animal model that is predictive of the human condition during or shortly after a mass casualty event, including timing and route of administration.

Specific Aims: Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

Milestones: The application must include well-defined annual milestones and timelines (e.g., a Gannt Chart) for assessing progress in both the UG3 and UH3 phases, including specific milestones for transitioning from the UG3 phase to the UH3 phase. The proposed series of translational research milestones should demonstrate a clear path towards the selection and characterization of a lead therapeutic by the end of the proposed project period. Milestones and timelines for each UG3 and UH3 stage must be provided in a separate heading at the end of the Approach section.

Milestones are a quantitative description of what constitutes successful research progress and development and not just a restatement of the specific aims or list of experiments to be conducted. These should be measures that would be recognizable as appropriate go or no-go decision points in the specific scientific area, such as a required limit of detection and coefficient of variation, or sensitivity and specificity (examples of acceptable milestones are available on the CounterACT website). Applicants are expected to refer to these milestones in annual progress reports.

Proposed milestones will be periodically revisited and may be revised when necessary as challenges are encountered or new information becomes available based on the trajectory of the research and the field at large. Given the high-risk and progressive nature of MCM discovery and development, results at any stage of a project might indicate a dead end, for example a toxicology study may reveal that a molecule is unsuitable for human use. Unmet milestones and an incomplete data package that prevents an adequate interpretation of the results will have a negative impact on the approval of these annual non-competing applications. Partial budget reductions/restrictions and/or project termination may occur if aspects of the research are deemed futile.

Environment: The application must include a description of adequate protection and safeguards when working with highly toxic chemicals.

Letters of Support:

  • Many of the chemical threat agents of interest to this announcement are extremely hazardous to humans. Applicants must include a letter from the appropriate institutional biosafety committee or institutional review entity indicating that studies are deemed safe for research personnel and the environment.
  • A formal letter of support (and estimated budget, if applicable) must also be provided for all proposed collaborative, consultative, and contract arrangements.
  • If applying from an academic institution, include a letter of support from the technology transfer official who will be managing existing and future intellectual property associated with this project.
  • If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions as appropriate and consistent with achieving the goals of the program.
  • If collaborating with a private entity (e.g., regulatory support), include a letter of collaboration that addresses any agreement to provide service(s), any limits on the services that can be performed, any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place, if applicable. This letter should come from an official within the private entity who has the appropriate authority.

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof 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 FOA 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 SF424 (R&R) 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.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific to this FOA:

Will the proposed therapeutic reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents, i.e., clinical impact?

Will the therapeutic represent an improvement over the current standard of care, if applicable?

How strong are the preliminary data supporting the choice of the proposed injury mechanism and/or therapeutic(s) for the indication, i.e., biological relevance?

What is the likelihood that completion of all proposed research objectives will lead to development of a characterized therapeutic candidate for the intended indication and proposed concept of use?

If provided, based on the available information presented for compound structure, what is the potential to develop a characterized therapeutic candidate?

Investigator(s)

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

Specific to this FOA:

Do the researchers have sufficient preclinical and therapeutic discovery and early-stage development expertise, including design and implementation of the preclinical studies?

Do the researchers have appropriate expertise working with chemical threat agents?

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:

Does the project pursue novel targets, mechanisms, pathways, or treatment approaches?

Although this FOA also supports and encourages repurposing drugs approved for other indications, is the therapeutic approach innovative for this new indication?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

Was the selection of the model(s), chemical injuries, research tool(s), potential therapeutic approach(es), etc. based on sound and rigorous scientific rationales, e.g., target/pathway activity?

Is the overall timeline reasonable for the work proposed?

Is the proposed post-exposure animal model appropriate to develop a therapeutic for civilian mass casualty/emergency settings, including timing and route of administration?

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:

Are special biosafety precautions for working with highly toxic chemicals adequate?

Have all proposed studies been deemed safe for research personnel and the environment by the appropriate institutional biosafety committee or institutional review entity?

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.

Milestones and Timelines:

Are milestones robust and associated with clear, quantitative criteria for success that allow go/no-go decisions annually and at the UG3/UH3 transition point?

Does the set of milestones allow the evaluation of progress in the UG3 phase and will successful completion of these milestones provide confidence that the research team will be able to successfully execute the UH3 phase?

Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without unnecessary steps?

Are there additional key experiments that need to have milestones designated?

Are the milestones and approach proposed scientifically justified, rigorous, and appropriate to address the goal of the FOA?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, 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.

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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, Recipients, and Activities, including of note, but not limited to:

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 and 2 CFR Part 200.206 “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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 2 CFR 200, 45 CFR Part 75 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • Defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
  • Initial development and proposal of annual milestones and timeline towards the development of the therapeutic(s) that will be achieved during the project period.
  • Timely acquisition of all appropriate proprietary rights in accordance with the NIH Grants Policy Statement, including securing intellectual property rights, and all materials needed for the applicant to perform the project. Recipients will retain primary intellectual rights and/or property to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the recipient any proprietary rights, including intellectual property rights, or any materials needed by the recipient to perform the project.
  • Preparation of all materials, e.g., Pre-PreIND, Pre-IND, Techwatch meeting packages, in support of interactions with regulatory agencies and advanced developers
  • Recipients agree to participate in the overall NIH research effort to develop medical countermeasures against chemical threats. This participation includes collaboration and consultation with fellow recipients under this and previous CCRP FOAs and attendance to the annual CounterACT Research Network Symposium. Collaboration may include sharing of information and research materials.

Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

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

The NIH Program Official will be responsible for all scientific and programmatic stewardship and final approvals of the award and will be named in the award notice.

NIH Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards as described below.

  • Providing input on experimental approaches, assisting in designing protocols, and consulting on updates to project milestones;
  • Providing advice to the recipients on specific scientific and analytical issues;
  • Assisting and advising recipients with regard to various regulatory and compliance issues;
  • Participating in regular teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
  • Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
  • Reviewing all major transitional changes that the recipients might propose (e.g. from the UG3 to the UH3 project) and advising on their appropriateness prior to implementation to ensure consistency with the goals of this FOA;
  • Stimulating interactions among other CCRP recipients;

NIH reserves the right to terminate or curtail any individual award, including the UH3 phase if there is insufficient progress towards meeting milestones.

Areas of Joint Responsibility include:

None; all responsibilities are divided between recipients and NIH staff as described above.

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Shardell Spriggs, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-443-8189


Email: shardell.spriggs@mail.nih.gov

Houmam H Araj
National Eye Institute (NEI)
Phone: (301) 435-8166
E-mail: ha50c@nih.gov

Kiran Vemuri, Ph.D
National Institute on Drug Abuse (NIDA)
Phone: 301-435-4446
E-mail: kiran.vemuri@nih.gov

Srikanth Nadadur, PhD
National Institute of Environmental Health Sciences (NIEHS)
Phone: 984-287-3296
E-mail: nadadurs@mail.nih.gov

Hung H Tseng, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-496-0810
E-mail: tsengh@mail.nih.gov

Dave Yeung, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (301) 761-7237
Email: dy70v@nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)

Email: FOAReviewContact@csr.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: kyr@nei.nih.gov

Pamela G Fleming
National Institute on Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: pfleming@mail.nih.gov

Jenny L Greer
National Institute of Environmental Health Sciences (NIEHS)
Phone: 984.287.3332
E-mail: jenny.greer@nih.gov

Sheila Simmons
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-594-9812
E-mail: simmonss@mail.nih.gov

Jason Lundgren
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 669-2973
Email: Jason.Lundgren@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.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.