Ultra-Rare Gene-based Therapy (URGenT) Network Resource Access (X01, Clinical Trial Not Allowed)

The Ultra-Rare Gene-based Therapy (URGenT) Network Resource Access funding opportunity, offered by the National Institute of Neurological Disorders and Stroke (NINDS), provides investigators with access to contract research/medical organizations (CROs/CMOs) and subject matter experts (SMEs) within the URGenT Network. This resource access supports planning, manufacturing, and limited nonclinical therapeutic development efforts for ultra-rare neurological and neuromuscular diseases, culminating in pre-IND meetings or IND package submissions to the FDA. The program is aimed at addressing the unmet medical needs of individuals with debilitating, ultra-rare disorders caused by single-gene pathogenic variants. The URGenT Network facilitates a streamlined approach to therapeutic development, leveraging data and experience across projects to improve efficiency and outcomes. Investigators can request support for gene-based or transcript-directed therapies, such as antisense oligonucleotides, small interfering RNAs, viral vector-based therapeutics like AAVs, gene-modified cell therapy approaches, genome editing tools like CRISPR, and other innovative therapeutic strategies. Eligible activities include strategic planning, bioassay development, confirmatory pharmacology studies, GLP toxicology studies, small-scale manufacturing, and other IND-enabling tasks. The program is designed to generate critical data for pre-IND regulatory feedback and future clinical trials. To be eligible, applicants must demonstrate sufficient preliminary proof-of-concept data supporting the viability of a proposed clinical therapeutic candidate. Investigators must provide evidence of an identified ultra-rare disease caused by a defined pathogenic variant and describe the potential intervention strategy. Successful applicants will form a multi-disciplinary project team with URGenT SMEs and NINDS staff to define and execute a development strategy tailored to their proposed therapeutic. Eligible applicants include public and private institutions of higher education, nonprofit organizations, small businesses, for-profit organizations, state and local governments, and other eligible entities. Non-domestic organizations are not eligible, though foreign components of U.S. organizations are allowed. Applications must be scientifically distinct, and organizations may submit more than one application. Applications will be reviewed on a rolling basis, with standard submission windows closing in May, September, and January each year through January 2028. The application requires a detailed research strategy that includes background data, clinical significance, current knowledge of the disease, patient population, risk/benefit ratio, and a clear description of the requested services. Applicants must include well-defined milestones, timelines, and a plan for leveraging URGenT resources to advance their therapeutic candidate. Letters of support from technology transfer offices, collaborators, and patient advocacy groups are encouraged. Applications will undergo a two-step peer review process that includes evaluation of feasibility, scientific merit, and alignment with the URGenT program’s goals. Review criteria will focus on the significance of the proposed research, the strength of the preliminary data, the scientific rationale, the feasibility of the approach, and the potential for advancing the therapeutic candidate to IND submission and clinical evaluation. Successful applicants will gain access to URGenT network resources but will not receive direct funding through this mechanism. This funding opportunity represents an effort to overcome challenges in therapeutic development for ultra-rare diseases, offering critical support to investigators and expediting the advancement of novel interventions for underserved patient populations. Applications will be accepted through January 2028.