New Chemistries for Un-drugged Targets through A Specialized Platform for Innovative Research Exploration (ASPIRE) Collaborative Research Program (UG3/UH3 Clinical Trials Not Allowed) | RFA TR 21 001

Opportunity Information: Apply for RFA TR 21 001

The New Chemistries for Un-drugged Targets through A Specialized Platform for Innovative Research Exploration (ASPIRE) Collaborative Research Program is a National Institutes of Health (NIH) funding opportunity from the National Center for Advancing Translational Sciences (NCATS) designed to speed up early drug discovery for biological targets that currently have no known drugs capable of modulating their function. The central idea is to bring together NCATS intramural scientists (researchers working inside the NIH) with outside (extramural) investigators to create and apply new chemistry capabilities that can open up previously inaccessible parts of drug discovery. The program focuses on building practical, scalable ways to generate and test novel chemical matter against these hard-to-drug or never-before-drugged targets across a wide range of human diseases and conditions, with the expectation that successful projects will yield credible starting points for downstream drug development.

A defining feature of this opportunity is its reliance on the NCATS ASPIRE platform, an integrated set of physical and virtual modules that combine automated synthetic chemistry with modern computational and experimental tools. On the computational side, the platform leverages artificial intelligence and machine learning to help guide molecule design and decision-making. On the experimental side, it integrates engineering, informatics, and biological testing to support iterative cycles of designing, making, and evaluating compounds. Rather than funding stand-alone projects that operate independently, the program emphasizes true collaboration where extramural teams work closely with NCATS staff and infrastructure, using the platform as a shared engine for translation from concept to validated chemical starting points.

The funding announcement specifically aims to support collaborations that develop additional physical modules to expand what the ASPIRE platform can do. In practice, this means applicants are expected to propose tangible, buildable enhancements that strengthen the platform's end-to-end capabilities, such as new automated synthesis approaches, novel hardware or workflows that improve throughput or reliability, improved integration between chemistry and biological testing, or other modular additions that make the platform more powerful and generalizable for many targets. The overall direction is platform-driven innovation: not just discovering one interesting molecule, but also improving the underlying machinery and processes that will make many future discoveries easier, faster, and more reproducible.

The anticipated outcomes are framed in terms of concrete deliverables that matter for early drug discovery. These include the identification, design, synthesis, and validation of new chemical entities that can serve as credible starting points (often referred to as "hits" or "leads") for drug development against novel targets. Another emphasized outcome is expanding chemical space available for screening, meaning generating structurally diverse molecules and new chemotypes that increase the odds of finding active compounds for targets where traditional libraries and conventional medicinal chemistry strategies have come up empty. While the program is translational in intent, it is not meant to support clinical trials; the funding mechanism explicitly states "Clinical Trials Not Allowed," indicating the work should remain in the preclinical-to-translational space where methods, prototypes, and validated chemical matter are developed.

Mechanistically, this opportunity uses a cooperative agreement funding instrument, reflecting that NIH (through NCATS intramural scientists) expects substantial involvement in the conduct of the project rather than acting only as a funder. The activity category is health, and the Assistance Listing (CFDA) number provided is 93.350. The specific FOA is identified as RFA-TR-21-001. The original application closing date listed is July 8, 2021, and the opportunity was created on December 10, 2020. (Award ceiling and expected awards were not specified in the provided source data.)

Eligibility is broad and includes many types of organizations, which aligns with the program's collaborative, platform-expanding goals. Eligible applicants include state, county, city, township, and 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; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and additional categories. The announcement also highlights a wide range of other eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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, and even non-U.S. entities (foreign organizations). Taken together, this signals an intent to attract diverse technical expertise and institutional perspectives to build new modules and methods that can be broadly used to tackle undrugged targets.

In plain terms, ASPIRE is trying to solve a persistent bottleneck in biomedical research: many disease-relevant proteins and pathways remain "undrugged" because existing chemistry approaches, screening libraries, and development workflows are not well-suited to them. By funding cooperative, module-building collaborations that plug into an established NCATS platform combining automation, AI/ML, and biological testing, the program aims to produce both near-term chemical starting points for novel targets and longer-term infrastructure improvements that expand what drug discovery can reach.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "New Chemistries for Un-drugged Targets through A Specialized Platform for Innovative Research Exploration (ASPIRE) Collaborative Research Program (UG3/UH3 Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.350.
• This funding opportunity was created on 2020-12-10.
• Applicants must submit their applications by 2021-07-08. (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.

Apply for RFA TR 21 001

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