Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antibiotic-Resistant Gram-Negative Bacteria (R01 Clinical Trial Not Allowed) | RFA AI 24 021

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This grant opportunity, titled "Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antibiotic-Resistant Gram-Negative Bacteria (R01 Clinical Trial Not Allowed)," is a discretionary NIH research grant (Funding Opportunity Number RFA-AI-24-021) focused on speeding up antibiotic discovery for a short list of especially hard-to-treat Gram-negative pathogens. The central idea is to fund milestone-driven, tool-building projects that make it easier to find and optimize small-molecule therapeutics against carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa. Rather than funding broad exploratory biology, the NOFO is oriented toward practical, predictive methods that can reduce failure rates in antibiotic programs by better accounting for two core barriers in Gram-negative drug development: getting compounds into the bacterial cell (penetration) and keeping them there long enough to work (avoiding or overcoming efflux).

The work NIH is trying to enable under this NOFO centers on developing and then applying novel predictive models, assays, tools, and platforms tied specifically to small-molecule penetration and efflux. In Gram-negative bacteria, the outer membrane, porins, and active efflux pumps combine to block or expel many otherwise promising antibacterial compounds, so discovery programs often stall because in vitro potency does not translate into intracellular exposure. Projects responsive to this opportunity would therefore be expected to create or refine experimental or computational approaches that measure, predict, or systematically improve intracellular accumulation, permeability across Gram-negative envelopes, and susceptibility to efflux mechanisms, with the explicit purpose of facilitating therapeutic discovery. The emphasis on "milestone-driven" research signals that applicants should structure their aims around clear, measurable technical deliverables (for example, validated assays, benchmarked models, or platforms that can be adopted by drug discovery teams), with go/no-go decision points rather than open-ended investigation.

The award mechanism is an R01, and clinical trials are not allowed, meaning the scope should remain preclinical and tool-focused rather than testing interventions in humans. The activity category is health, and the CFDA listing provided is 93.855. The posting indicates an award ceiling of $750,000, which frames the upper bound of support under the opportunity, and the original application closing date is August 20, 2024. The opportunity was created on April 1, 2024, and the sponsoring agency is the National Institutes of Health.

Eligibility is broad and includes many organization types that commonly participate in biomedical R&D. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits both with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories as specified); for-profit organizations other than small businesses; and small businesses. The NOFO also explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); eligible federal agencies; faith-based or community-based organizations; regional organizations; U.S. territories or possessions; tribal governments other than federally recognized; and non-domestic (non-U.S.) entities, meaning foreign organizations may apply where allowed under NIH policy and the terms of the announcement.

In practical terms, this NOFO is aimed at strengthening the antibiotic discovery pipeline by funding partnerships and translationally oriented research capabilities that help researchers and developers quickly screen, rank, and optimize candidate molecules based on whether they can realistically reach effective concentrations inside these priority Gram-negative bacteria. The expected end products are not simply new scientific insights, but robust, validated discovery-enabling tools and platforms that can be used to guide medicinal chemistry and therapeutic development decisions for these high-priority resistant pathogens.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antibiotic-Resistant Gram-Negative Bacteria (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2024-04-01.
• Applicants must submit their applications by 2024-08-20. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $750,000.00 in funding.
• 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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