Notice of Intent to Publish a Funding Opportunity Announcement for CCRP Initiative: Countermeasures Against Chemical Threats (CounterACT) Therapeutics Discovery and Early-Stage Development (UG3/UH3 Clinical Trial Not Allowed)

Key Dates

• April 4, 2024 - Simplified Review Framework for NIH Research Project Grant Applications - Update and Implementation Plans. See Notice NOT-OD-24-085. 
• October 19, 2023 - Simplified Review Framework for NIH Research Project Grant Applications. See Notice NOT-OD-24-010. 

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

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

National Institute on Drug Abuse (NIDA)

The NIH Countermeasures Against Chemical Threats (CounterACT) program intends to publish a Notice of Funding Opportunity (NOFO) to solicit applications for the early-stage development of therapeutics to mitigate the adverse health effects resulting from toxic chemical exposure.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The NOFO is expected to be published in early 2025 with an expected application due date in October 2025. 

This NOFO will utilize the phased UG3/UH3 activity code. Preliminary details of the planned NOFO are provided below.

Background:

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 NOFO will be 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:

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 NOFO. Applicants are strongly encouraged to contact the NIH staff (listed below) to confirm that the proposed chemical threat(s) is of interest to the program.

UG3/UH3 Funding Mechanism:

This NOFO will use the UG3/UH3 Cooperative Agreement mechanism and has two phases, both of which are required in the application. This mechanism will utilize annual milestones as well as phase-transition milestones that govern transition from the UG3 to UH3 phases of the award. 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 should include hit to lead activities that enable down-selection from candidate therapeutics to a single lead compound. The UH3 phase should include optimization activities that enable characterization of the lead candidate for further development.

Applications Not Responsive to this NOFO:

The following applications will be considered non-responsive and will not be reviewed for this NOFO:

• 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 NOFO will only support 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.

Funding Information

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Shardell M. Spriggs, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
(301) 443-8189
[email protected]