NCATS Preclinical Proof of Concept Studies for Rare Diseases

NCATS Preclinical Proof of Concept Studies for Rare Diseases

Funds U.S. researchers and companies conducting preclinical efficacy studies to advance therapeutic candidates for rare diseases toward IND applications.

NCATS Preclinical Proof of Concept Studies for Rare Diseases is an R21 exploratory grant administered by the National Center for Advancing Translational Sciences (NCATS) under the NIH. The program operates under FOA RFA-TR-25-002 (reissue of RFA-TR-24-023). Awards cover up to $275,000 in direct costs over a two-year project period, with no more than $200,000 in any single year. NCATS intends to commit up to $1,200,000 in FY26, anticipating 3 to 5 awards.

The program funds efficacy studies in established rare disease preclinical models — both in vivo and advanced in vitro models such as tissue chips or microphysiological systems — to demonstrate that a proposed therapeutic agent warrants further development toward a full Investigational New Drug (IND) application or clinical trial. Therapeutic agents include small molecules, biologics, and biotechnology-derived products. In addition to efficacy, accompanying pharmacodynamic (PD) and pharmacokinetic (PK) studies are supported when the budget allows.

Eligible applicants include For-Profit Organizations (both small businesses and other for-profit companies), universities, nonprofits, and government entities. Foreign organizations are not eligible. The principal investigator can be any individual with the skills and resources to carry out the proposed research. A required element is a Readiness of Agent attachment (1 page) demonstrating the therapeutic candidate's readiness for efficacy testing, and a Partnership Plan (1 page) for a rare disease steering/oversight committee.

Applications are submitted via Grants.gov, eRA Commons, or NIH ASSIST. There are two annual deadlines: June 2, 2026 and June 2, 2027 (per NOT-TR-26-009 extension). Scientific merit review occurs approximately October of the application year; Advisory Council review follows in January; earliest start dates are April the following year. Applications are peer-reviewed against scientific merit, approach, innovation, and investigator/environment criteria.

Key exclusions: the program does not support rare cancer research (apply to NCI), model development (a validated model must already exist), applications without the Readiness of Agent and Partnership Plan attachments, or foreign subawards/subcontracts. The program also does not name committee members or partner organizations in the application — this is a hard requirement.