NCATS Clinical Trial Readiness for Rare Diseases

NCATS Clinical Trial Readiness for Rare Diseases

Funds U.S. researchers and companies generating natural history data, biomarkers, and outcome measures needed to design clinical trials for rare diseases.

NCATS Clinical Trial Readiness for Rare Diseases is an R21 exploratory grant run by the National Center for Advancing Translational Sciences (NCATS) under the NIH. The program operates under PAR-25-450, a rolling program announcement with six deadlines spanning 2026 through 2028. Awards cover up to $275,000 in direct costs over a two-year project period, with no more than $200,000 allowable in any single year.

The program is specifically designed to close the gap between basic discovery and an actionable clinical trial protocol for a rare disease. Fundable activities include: natural history studies that generate longitudinal data on disease course; studies to identify, validate, and qualify biomarkers as endpoints or stratification tools; development and validation of patient-reported outcomes and other clinical outcome measures; and studies to establish preclinical models with direct relevance to a planned clinical trial design. The key requirement is that the proposed work must credibly advance clinical trial readiness — not simply produce interesting scientific data about the disease.

Eligible applicants include For-Profit Organizations (both small businesses and larger for-profit companies), universities, nonprofits, and government research organizations. Foreign organizations are not eligible. There are no limits on the number of applications a single institution may submit, and no partnership requirement — a small biotech company can apply on its own.

Applications are submitted through NIH ASSIST, Grants.gov Workspace, or institutional submission systems. There are six biannual deadlines: February 18, 2026; June 17, 2026; February 17, 2027; June 17, 2027; February 17, 2028; and June 20, 2028. The standard NIH peer review timeline applies: review approximately 4-5 months after submission, Advisory Council review ~3 months later, and earliest project start ~1 month after that.

Applications are scored using NIH's five core criteria: Significance, Innovation, Approach, Investigators, and Environment. For this program, reviewers pay close attention to whether the proposed work will meaningfully improve the ability to conduct a clinical trial — a weak connection to clinical trial readiness is a common weakness flagged in summary statements. There is no letter of intent required, and no pre-submission requirement. The R21 mechanism does not support preliminary data requirements, but applicants with some supporting data will generally score better.