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

Frequently Asked Questions (FAQs)

What is the NIH CounterACT: Optimization of Therapeutic Lead Compounds (U01 Clinical Trial Optional) opportunity (PAR-19-040)?

This funding opportunity supports late-stage preclinical and translational research intended to move a promising medical countermeasure closer to human use. It focuses on optimizing and maturing an already-identified therapeutic lead compound for treating or preventing harm caused by high-priority chemical threats.

What is the overall purpose of this program?

The program aims to strengthen national readiness by developing new or improved therapeutics that could be used in real chemical exposure scenarios. The emphasis is on practical, translational work that makes a candidate more viable for eventual deployment and human use.

What types of chemical threats does this opportunity target?

The scope includes high-priority chemical threats such as classic chemical warfare agents, toxic industrial chemicals (released accidentally or intentionally), pharmaceutical-based agents, and pesticides.

What funding mechanism is used, and what does it mean for applicants?

The award uses a cooperative agreement mechanism (U01). In practice, this typically means NIH staff will have an active partnership role during the project, including involvement in planning, monitoring progress, and helping guide key decisions over the course of the work.

Is a previously identified therapeutic lead compound required to apply?

Yes. A central eligibility requirement is that applicants must already have a previously identified therapeutic lead compound. This opportunity is not intended for early discovery or broad screening to find new hits.

How does the opportunity define a "therapeutic lead"?

A lead is described as a biologically active compound or hit for which affinity, potency, target selectivity, and preliminary safety have already been established. The expectation is that there is enough evidence to justify translational investment to reduce risk and mature the candidate toward human use.

Is this opportunity meant for early-stage discovery research?

No. The description specifically indicates it is not meant for early discovery or "fishing" for new hits. The focus is on optimization and translational maturation of an existing, promising compound.

What stage of development (Technical Readiness Level) is this program aiming for?

Projects are situated at Technical Readiness Levels (TRLs) 4 to 5. This generally corresponds to validation in a laboratory environment and then validation in a relevant environment, with increasing emphasis on integrated performance and translational evidence beyond proof-of-concept.

What kinds of research and development activities are supported?

Supported work emphasizes optimization and development activities that make a lead compound more viable as a therapeutic product. Examples mentioned include: developing or refining human-relevant animal models aligned to intended clinical use; generating in vivo efficacy data aligned with realistic deployment; bioanalytical assay development and validation; laboratory-scale and scalable manufacturing approaches; and non-GLP toxicity and pharmacology studies.

Does the program support development or refinement of animal models?

Yes. The scope can include building or refining human-relevant animal models that match the intended clinical use, such as aligning exposure route, timing of treatment, and clinically meaningful endpoints.

Why is there an emphasis on treatment windows and dosing practicality?

Many chemical threats involve acute, time-sensitive emergencies. The opportunity emphasizes demonstrating that the countermeasure works under practical treatment windows and dosing approaches that could realistically be used in an emergency or mass casualty context.

Are bioanalytical assays within scope?

Yes. The opportunity explicitly supports bioanalytical assay development and validation, including assays for measuring drug levels, biomarkers, or exposure/toxicity markers.

Does the program support manufacturing or scale-up activities?

Yes. The scope includes laboratory-scale and scalable manufacturing approaches to help ensure the product can be made reproducibly and positioned for potential scale-up.

Are toxicity and pharmacology studies supported, and do they need to be GLP?

Non-GLP toxicity and pharmacology studies are explicitly included. The inclusion of non-GLP work indicates the focus at this stage is on de-risking and generating decision-quality data, rather than producing fully regulated GLP packages, while still expecting rigor and relevance to eventual human use.

What is the significance of the milestone requirement?

A defining feature is the requirement for annual milestones that create clear go/no-go decision points. Applicants are expected to propose a progressive translational plan with discrete, measurable milestones each year, tying continued investment to objective progress and keeping the project focused on outcomes that move the therapeutic forward.

Who is eligible to apply?

Eligibility is broad and includes many organization types, such as: 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 (including small businesses and other-than-small businesses); and other eligible entities.

Are certain institution categories specifically highlighted as eligible?

Yes. The description highlights categories including 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.

Can foreign institutions apply?

No. Foreign institutions (non-US entities) are not eligible to apply, and non-US components of US organizations are not eligible to apply.

Are foreign components allowed at all?

Yes. While foreign institutions cannot apply as applicants, foreign components (as defined by the NIH Grants Policy Statement) are allowed, enabling certain international collaborations when justified.

Is this funding opportunity considered discretionary funding?

Yes. It is listed as discretionary funding under NIH.

What CFDA numbers are associated with this opportunity?

The opportunity is associated with CFDA numbers 93.113, 93.279, 93.846, 93.853, and 93.867.

When was this opportunity originally posted, and what closing date is shown?

The provided data lists an original posting date of 2018-10-26 and an original closing date shown as 2021-09-14.

What does "Clinical Trial Optional" mean in this FOA?

"Clinical Trial Optional" generally means a clinical trial is not required and many projects will be preclinical. However, applicants may propose clinical trial-related elements if allowed under the announcement and appropriate to the stage and goals of the work.

What types of project teams is this opportunity best suited for?

It is best suited for teams that already have a credible therapeutic lead compound for a chemical threat indication and are ready to conduct translational work such as optimizing the candidate, demonstrating efficacy in relevant in vivo models, establishing assay capabilities, developing manufacturing approaches, and generating non-GLP safety and pharmacology data under a milestone-driven development plan.

What is the main thing this program is trying to avoid funding?

Based on the description, it is trying to avoid funding early discovery efforts that lack a credible lead compound, as well as projects focused primarily on basic mechanism exploration without a clear translational optimization and development pathway.