Develop Therapeutics as Countermeasures Against Chemical Threats

NIAID and its partners under the Chemical Countermeasures Research Program (CCRP) invite applications for the early-stage development of therapeutics and medical countermeasures (MCMs) to mitigate the adverse health effects resulting from toxic chemical exposure, including validation of therapeutic targets and preclinical characterization of lead compounds.

Through the funding opportunity announcement (FOA) CCRP Initiative: Countermeasures Against Chemical Threats (CounterACT) Therapeutics Discovery and Early-Stage Development (UG3/UH3, Clinical Trial Not Allowed), our ultimate aim is to generate well-characterized therapeutic candidates that may one day advance the nation's medical and public health preparedness for, response to, and recovery from chemical-related disasters and public health emergencies.

The FOA supports research on specific chemicals of concern, arranged into toxidromes grouping, i.e., based on their primary modes of toxicity such that a single countermeasure with broad spectrum activity can treat multiple threats that have similar effects. We highly encourage proposals that contemplate expanding indications of already approved or authorized therapeutics.

The FOA also specifies that by the end of the project, efficacy of the lead MCM candidate(s) must be demonstrated in an appropriate model predictive of the human response in a mass casualty or emergency care setting, including an extended post-exposure treatment window and clinically relevant routes of administration. Before applying, you should already have rigorous data on the putative therapeutic target or affected pathway; initial lead compounds; assays to down-select to a single lead candidate; and lead compounds that can be advanced towards optimization and development with no obvious legal constraints, i.e., freedom to operate. Discuss your candidate therapeutic with NIAID’s scientific contact listed below if you’re unsure whether it meets all these requirements.

UG3/UH3 Phased Award

Applications must be structured around two phases: the UG3 (phase 1) and UH3 (phase 2).

The UG3 award supports hit-to-lead activities to enable down-selection from candidate therapeutics to a single lead compound. Example research activities include:

• Validating target/pathway engagement and optimizing 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
• Developing and utilizing 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
• Demonstrating preliminary safety and pharmacodynamic/pharmacokinetic (PD/PK) properties of the candidate therapeutic

The UH3 award funds optimization activities that enable characterization of the lead candidate for further development. Possible topics include:

• Studying specificity, affinity, potency, target selectivity/uptake/engagement, and post-exposure in vivo efficacy
• Demonstrating efficacy in animal model more predictive of the human condition and more easily scalable in terms of therapeutic dose, e.g., swine, nonhuman primates
• In vivo dose-ranging and efficacy studies against the chemical threat consistent with the product's intended therapeutic use regimen
• Determining the route and times of administration of the therapeutic consistent with the intended use in humans, including the likely environment where the candidate would be administered
• Developing assays, surrogate markers, correlates of protection, and endpoints to be used during nonclinical and clinical studies to further evaluate and characterize candidates
• Optimizing 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
• Optimizing pharmacokinetic and metabolic properties of lead candidates using a relevant formulation via the intended route of administration in animals using relevant post-exposure models
• Demonstrating 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.

NIH staff will determine whether applicants can transition to the UH3 award through evaluation of Go/No-Go Transition Milestones accomplishment. Read our article “Don't Be Fazed by Phased Awards” to learn more about the award mechanism.

Additional Requirements

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. Special safety certifications may be required to conduct research with some chemical threat agents.

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

Awardees funded under this FOA must participate in the annual network research symposium of CCRP-funded projects.

Applicants may request up to $350,000 annual direct costs for the UG3 phase and up to $450,000 annual direct costs for the UH3 phase. Both the UG3 and UH3 phases may extend as many as three years, but the total proposed project period cannot exceed five years.

Applications are due once annually on October 17, from 2022 through 2024.

Work supported through the NOSI may help you later prepare an application for other CCRP Funding Opportunities, including the FOA described above.