Discovery and Development of Novel Therapeutics for Select Fungal Pathogens (R21/R33 Clinical Trial Not Allowed) | RFA AI 24 065

Opportunity Information: Apply for RFA AI 24 065

The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Discovery and Development of Novel Therapeutics for Select Fungal Pathogens (R21/R33 Clinical Trial Not Allowed)" under Funding Opportunity Number RFA-AI-24-065 (CFDA 93.855). The program is designed to push promising antifungal ideas past the earliest research stage and into more practical, translational drug discovery and development work, with a strong emphasis on structured progress and clear deliverables. Applications are due by January 28, 2025, and the project scope sits within the broader health funding activity category.

The core goal of this NOFO is to support early-stage translational research aimed at discovering and developing new therapeutics against several high-priority fungal threats. The target pathogens called out are Candida species, with specific emphasis on Candida auris, along with Aspergillus fumigatus, Coccidioides, and members of the Mucorales order. In practical terms, the opportunity is looking for projects that can credibly move from initial discovery concepts toward tangible therapeutic candidates or development-ready approaches for these fungi, which are increasingly associated with serious disease, difficult-to-treat infections, and antifungal resistance concerns. While the announcement text does not list specific scientific approaches, the framing around "drug discovery and development" and "novel therapeutics" typically implies interest in work such as identifying and validating targets, discovering lead compounds or biologics, optimizing potency and selectivity, establishing mechanism of action, and generating key preclinical-enabling data that reduces risk for later-stage development.

A defining feature of this funding opportunity is its milestone-driven, biphasic award structure using the R21/R33 mechanism. The first phase (R21) supports the earlier, exploratory-but-translational portion of the project, where investigators are expected to hit specific, predefined milestones that demonstrate feasibility and meaningful technical progress. If those R21 milestones are met, the project can transition into the second phase (R33), which generally supports a more advanced level of development work building directly on the successful outcomes from the R21 phase. The transition is not automatic; it depends on successful completion of the agreed-upon milestones, which means applicants need to propose clear, measurable goals, realistic timelines, and decision points that show how the project will advance only if it is performing as expected.

The NOFO explicitly states "Clinical Trial Not Allowed," which signals that the funded activities must remain outside the conduct of clinical trials. In other words, the program is aimed at discovery and preclinical or translational development work rather than testing interventions in human subjects as clinical studies. Applicants should therefore shape their research plans around non-clinical development steps and avoid proposing clinical trial activities that would fall outside the eligibility rules for this announcement.

Eligibility for this opportunity is broad and spans many types of organizations. Eligible applicants include state, county, and city or township governments; special district governments; independent school districts; and public housing authorities/Indian housing authorities. Academic entities are included, such as public and state-controlled institutions of higher education and private institutions of higher education. The opportunity is also open to federally recognized Native American tribal governments, as well as tribal organizations and tribal governments that are not federally recognized. Nonprofit organizations may apply whether or not they have 501(c)(3) status (so long as they are not institutions of higher education, as specified in the eligibility list). For-profit organizations are eligible (other than small businesses), and small businesses are also eligible, alongside an "Other" category that NIH sometimes uses to capture additional applicant types permitted by the announcement.

In addition, the NOFO highlights a set of "other eligible applicants" to underscore that a wide range of mission-driven and community-connected institutions can participate. These include 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); faith-based or community-based organizations; eligible federal agencies; regional organizations; U.S. territories or possessions; and non-domestic (non-U.S.) entities, meaning foreign organizations may apply. Taken together, this makes the program accessible to a diverse applicant pool, including organizations that often bring specialized expertise, unique patient-population insights, regional fungal epidemiology experience, or translational partnerships needed to move an antifungal therapeutic concept forward.

Overall, this funding opportunity is best read as NIH support for practical, milestone-accountable translational antifungal development focused on a short list of urgent fungal pathogens. Successful applications will likely be those that pair a compelling therapeutic concept with a rigorous plan for hitting concrete R21 milestones, a credible path to deeper R33-stage development, and a project design that clearly stays within the non-clinical trial boundaries of the announcement.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Discovery and Development of Novel Therapeutics for Select Fungal Pathogens (R21/R33 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 2024-09-23.
• Applicants must submit their applications by 2025-01-28. (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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