Countermeasures Against Chemical Threats (CounterACT): Optimization of Therapeutic Lead Compounds (U01 Clinical Trial Optional) | PAR 19 040

Opportunity Information: Apply for PAR 19 040

The NIH Countermeasures Against Chemical Threats (CounterACT): Optimization of Therapeutic Lead Compounds (U01 Clinical Trial Optional) opportunity (PAR-19-040) supports late-stage preclinical and translational work to move a promising medical countermeasure closer to human use. It is structured as a cooperative agreement (U01), which typically means NIH staff will have an active partnership role during the project, with ongoing involvement in planning, monitoring progress, and helping guide key decisions. The overall goal is to strengthen national readiness by developing new or improved therapeutics that can treat or prevent harm caused by high-priority chemical threats, including classic chemical warfare agents, toxic industrial chemicals released accidentally or intentionally, pharmaceutical-based agents, and pesticides.

A central eligibility requirement is that applicants must already have a previously identified therapeutic lead compound. This FOA is not meant for early discovery or fishing for new hits; it is meant for optimization and translational maturation of something that already shows real promise. Here, a "lead" is described as a biologically active compound or hit for which affinity, potency, target selectivity, and preliminary safety have already been established. In practical terms, NIH is looking for projects where there is enough evidence to justify investing in the kind of development work that reduces risk and positions the candidate for more formal development steps, rather than basic mechanism exploration alone.

The scientific scope emphasizes optimization and development activities that make a lead compound more viable as a therapeutic product for chemical exposure scenarios. Supported work can include building or refining human-relevant animal models that fit the intended clinical use (for example, matching the exposure route, timing of treatment, and clinically meaningful endpoints), and producing in vivo efficacy data aligned with how the therapy would realistically be deployed in humans. Because many chemical threats are acute and time-sensitive, studies often need to demonstrate not only that the agent works, but also that it works under practical treatment windows and dosing approaches that could be used in an emergency or mass casualty context.

Beyond efficacy, the FOA explicitly supports enabling capabilities that are often required before advancing toward regulated development. That includes bioanalytical assay development and validation (for measuring drug levels, biomarkers, or exposure/toxicity markers), laboratory-scale and scalable manufacturing approaches (so the product can be made reproducibly and potentially scaled), and non-GLP toxicity and pharmacology studies. The inclusion of non-GLP studies signals that the program is focused on de-risking and decision-quality data at this stage, rather than fully regulated GLP packages, while still expecting rigor and relevance to eventual human use.

The announcement situates projects at Technical Readiness Levels (TRLs) 4 to 5, which generally correspond to validating a technology in a lab environment and then in a relevant environment, with increasing emphasis on integrated performance and translational evidence. In other words, the work should be beyond proof-of-concept and moving into robust demonstration that the candidate performs as intended in realistic models and can be produced and measured reliably.

A defining feature of this FOA is the requirement for annual milestones that create clear go/no-go decision points. Applicants are expected to lay out a progressive translational plan with discrete, measurable milestones each year, so that continued investment is tied to objective progress. This milestone-driven structure is meant to keep projects focused on outcomes that move the therapeutic forward, identify problems early, and prioritize candidates that can credibly advance toward deployment.

Eligibility is broad across many organization types, reflecting the program's applied, translational focus and the need for multidisciplinary teams. Eligible applicants include state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other entities. The FOA also highlights categories such as HBCUs, Hispanic-serving institutions, AANAPISIs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, faith-based or community-based organizations, eligible federal agencies, regional organizations, and US territories or possessions. Foreign institutions (non-US entities) are not eligible to apply, and non-US components of US organizations are not eligible to apply; however, foreign components, as defined by the NIH Grants Policy Statement, are allowed, which can enable specific international collaborations when justified.

Administratively, the opportunity is listed as discretionary funding under NIH, using a cooperative agreement mechanism, and is associated with CFDA numbers 93.113, 93.279, 93.846, 93.853, and 93.867. The original posting date in the provided data is 2018-10-26, and the original closing date shown is 2021-09-14. The FOA title indicates "Clinical Trial Optional," which generally means clinical trials are not required and many projects will be preclinical, but applicants may propose clinical trial-related elements if allowed under the announcement and appropriate to the stage and goals of the work.

Overall, this grant opportunity is aimed at teams that already have a credible therapeutic lead for a chemical threat indication and are ready to do the hard translational work: optimizing the candidate, proving efficacy in relevant in vivo models, building the assays and manufacturing approach needed for development, and generating solid non-GLP safety and pharmacology data. The program is designed to move candidates through a disciplined, milestone-driven pipeline so that the most promising countermeasures can advance efficiently toward real-world readiness.

• The National Institutes of Health in the education, environment, health sector is offering a public funding opportunity titled "Countermeasures Against Chemical Threats (CounterACT): Optimization of Therapeutic Lead Compounds (U01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.113, 93.279, 93.846, 93.853, 93.867.
• This funding opportunity was created on 2018-10-26.
• Applicants must submit their applications by 2021-09-14. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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