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Grant Details

https://www.grants.gov/search-results-detail/357815

Grant Analysis

Purpose & Target

This opportunity, the Ultra-Rare Gene-based Therapy (URGenT) Network Resource Access (X01, Clinical Trial Not Allowed), aims to provide investigators with direct, in-kind access to contract research/medical organizations (CROs/CMOs) and subject matter experts (SMEs) within the NINDS URGenT Network. The core objective is to support planning, manufacturing, and limited nonclinical therapeutic development efforts, as well as other IND-enabling activities, to rapidly advance precision therapeutics for ultra-rare neurological and/or neuromuscular diseases towards clinical trials. This grant is SECTOR-SPECIFIC, focusing intensely on HEALTHCARE and TECHNOLOGY within the specialized domain of ultra-rare genetic diseases and gene-based therapies. It targets investigators and organizations in the US that are developing gene-based or transcript-directed clinical therapeutic candidates. Key filtering criteria include having established proof-of-concept (POC) data and a clear need for pre-IND or IND-enabling support, with the explicit exclusion of clinical trials. This is a recurring funding opportunity with multiple application cycles available through January 2028, forming a continuous mechanism within the broader NINDS URGenT Network to address unmet medical needs for ultra-rare neurological disorders.

Financial Structure

This funding opportunity provides resource access rather than direct financial awards.
  • Funding Type: This is an 'X01 Resource Access Award', meaning no direct funds are awarded to the applicant. It is explicitly stated that funds are not awarded via the X01 mechanism.
  • Budget Entry: Applicants are instructed to enter '$0' for 'Total Federal Funds Requested', 'Total Federal & Non-Federal Funds', and 'Estimated Program Income' on the application forms.
  • Cost Sharing: Cost sharing is NOT required for this NOFO.
  • Nature of Support: Successful applicants receive in-kind access to critical resources provided by the NINDS URGenT Network, including:
  • Contract Research/Medical Organizations (CROs/CMOs): For services like manufacturing, GLP toxicology studies, PK/PD studies, biodistribution/ADME studies, and bioassay development. This access is provided at no cost to the investigators.
  • Subject Matter Experts (SMEs): For strategic therapeutic development plans, regulatory advice, preparation for pre-IND meetings, and assistance with IND package preparation in disciplines such as Biologics CMC, Nonclinical/Preclinical, Bioassay Development, Regulatory Affairs, Medical Writing, Biostatistics, and Quality Assurance.
  • NINDS Dedicated Project Management.
  • NIH Intramural Research Program: If NIH intramural scientists are involved, their requests are limited to incremental costs (e.g., salary for temporary staff, consultants, equipment, supplies, travel), excluding salary and fringe benefits for permanent federal employees or administrative/facilities support.
  • Intellectual Property (IP):
  • The recipient institution retains its assignment of IP rights and gains assignment of IP rights from the URGenT contractors for candidate therapeutics developed within this network.
  • The recipient institution is expected to be responsible for patent filings, maintenance, and licensing efforts towards eventual commercialization.
  • Award recipients are encouraged to identify and foster relationships with potential licensing and commercialization partners early.
  • All SMEs within the URGenT Network will treat information shared as confidential.

Eligibility Requirements

  • Eligible Organizations:
  • All organizations administering an eligible parent award may apply.
  • This includes a wide range of entity types:
    • UNIVERSITY: Public/State Controlled Institutions of Higher Education, Private Institutions of Higher Education
    • NGO: Nonprofits with or without 501(c)(3) IRS Status
    • ENTERPRISE: For-Profit Organizations (including SME: Small Businesses)
    • PUBLIC: Local Governments (State, County, City or Township, Special District, Federally Recognized Indian/Native American Tribal Governments, Other Indian/Native American Tribal Governments)
    • OTHER: Eligible Agencies of the Federal Government, U.S. Territory or Possession, Independent School Districts, Public Housing Authorities/Indian Housing Authorities, Native American Tribal Organizations (other than Federally recognized tribal governments), Faith-based or Community-based Organizations, Regional Organizations.
  • Geographic Restrictions:
  • US Organizations only. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are explicitly not eligible to apply.
  • Foreign components (research performed abroad by an eligible U.S. organization) are allowed.
  • Principal Investigator (PD/PI) Requirements:
  • Any individual with the skills, knowledge, and resources to carry out the proposed research.
  • For multiple PDs/PIs, their expertise should be complementary and integrated.
  • Project Specific Requirements (DEVELOPMENT stage):
  • Proposals must have rational proof of concept (POC) data (scientifically rigorous, in vivo and/or in vitro) for a viable gene-based or transcript-directed therapeutic clinical candidate for a specified ultra-rare disease patient population.
  • The identified patient or patient population must have an ultra-rare neurological or neuromuscular syndrome due to a defined pathogenic variant.
  • A sufficient understanding of the pathogenic variant must exist, forming the basis of the proposed therapeutic approach.
  • The PD/PI intends to conduct a formal pre-IND meeting with the FDA or submit an IND package, requiring planning and/or limited additional data.
  • The proposed activities must be completable within 2 years.
  • Exclusion Criteria (Applications Not Responsive):
  • Studies for ultra-rare diseases or disorders outside the mission of NINDS.
  • Development of in vitro screening assays and/or animal models.
  • Basic research of disease mechanisms or therapeutic mechanism of action studies.
  • Lead optimization studies before selecting a clinical therapeutic candidate.
  • Early stage discovery research (e.g., target identification and validation).
  • Clinical research and clinical trials involving human subjects are not allowed.
  • Required Registrations (Prior to Application Submission):
  • Applicant organizations must be registered and maintain active status in:
    • System for Award Management (SAM) - requires annual renewal.
    • NATO Commercial and Government Entity (NCAGE) Code (for foreign organizations registering in SAM, though foreign organizations are ineligible to apply for this NOFO).
    • Unique Entity Identifier (UEI) - issued as part of SAM.gov registration.
    • eRA Commons - organization must identify at least one Signing Official (SO) and one Program Director/Principal Investigator (PD/PI) account.
    • Grants.gov.
  • All PD(s)/PI(s) must have an eRA Commons account affiliated with the applicant organization.

Application Process

Application Process & Deadlines
  • Open Date (Earliest Submission Date): January 9, 2025.
  • Letter of Intent (LOI) Due Date: While not required or binding, applicants are encouraged to submit an LOI 30 days prior to their intended application submission date to assist NIH staff with planning.
  • Application Due Dates (Rolling): Applications are accepted on a rolling basis with multiple submission windows through January 2028. The latest submission period is October 1, 2027 - January 31, 2028.
  • All applications are due by 5:00 PM local time of the applicant organization.
  • Expiration Date: February 1, 2028.
  • Project Period: The maximum project period is two years.
  • Submission Methods:
  • NIH ASSIST system (online preparation, submission, tracking).
  • Institutional system-to-system (S2S) solution.
  • Grants.gov Workspace.
Required Documentation & Materials Applicants must follow the instructions in the 'Research (R) Instructions in the How to Apply - Application Guide' and any program-specific instructions outlined in this NOFO. Key components include: - SF424(R&R) Cover: Applicants must enter '$0' for all requested and total funds, as well as estimated program income. - SF424(R&R) Project/Performance Site Locations. - SF424(R&R) Other Project Information. - SF424(R&R) Senior/Key Person Profile. - R&R Budget & Subaward Budget: Marked as 'Not Applicable' since no direct funds are awarded. - PHS 398 Cover Page Supplement. - PHS 398 Research Plan: This is a critical section with specific content requirements: - Research Strategy: Limited to 12 pages. Must include: - Background, clinical significance, importance, and innovation of the project. - How the requested service will lead to IND submission and future clinical trials. - Current knowledge of disease etiology, characteristics, severity, prevalence, and benefits/limitations of current treatments. - Expected risk/benefit ratio of the therapeutic candidate. - Identified patient/patient population, existing advocacy groups/registries. - Novelty of the proposed approach to treating the disease indication. - Brief plan for conducting clinical trials (even though not part of this award), patient monitoring, and follow-up. - Natural history of the condition and clinical trial readiness (outcome measures, biomarkers, validation state). - Clear description of all available preliminary data supporting the request, detailing scientific rigor (blinding, randomization, sample sizes, statistical analysis, sex as biological variable, reagent authentication). - Dose determination strategy, preliminary toxicity/safety studies, immunology concerns, risk analysis, and detailed outline of additional nonclinical studies. - Approach: Describe all requested activities, services, and defined deliverables with justifications and expected impacts. For limited nonclinical studies, provide an abbreviated research plan and timeline with well-defined milestones for success. - Letters of Support: Required for established collaborations. For academic institutions, a letter from the technology transfer official managing IP and agreeing to share licensing details with NIH is needed. For multi-institutional projects, a letter clarifying IP sharing across institutions is required. - Resource Sharing Plan: Must comply with NIH instructions. - Data Management and Sharing Plan: Not applicable for this NOFO. - Appendix: Only limited materials allowed, specifically summarized FDA meeting outcomes (e.g., pre-IND, INTERACT meetings). - PHS Human Subjects and Clinical Trials Information: If human subjects research is involved (not clinical trials), specific forms must be completed. Review & Award Process
  • Applications undergo a two-step review process: initial assessment for program fit and feasibility, followed by peer review of scientific/technical merit.
  • Scientific Merit Review dates: Rolling, typically 1.5-3 months after submission period closes (e.g., for Jan 2028 applications, review in March 2028).
  • Advisory Council Review dates: Typically 2 months after Scientific Review (e.g., May 2028 for March 2028 review).
  • Earliest Start Date: Roughly 7-8 months after the end of the submission period (e.g., July 2028 for Jan 2028 submissions).
  • A written critique will be provided to all applicants.
  • Funding decisions consider scientific/technical merit, availability of funds (referring to capacity of the URGenT Network, not financial budget), and relevance to program priorities.

Evaluation Criteria

Applications will be evaluated for scientific and technical merit through a modified, two-step review process: 1. Assessment of Program Fit and Feasibility: Conducted by NIH staff and individual external experts, focusing on whether the project aligns with the program and can effectively utilize the resources. 2. Peer Review of Scientific and Technical Merit: Comprehensive evaluation by expert reviewers. Reviewers provide an Overall Impact Score based on the likelihood of the project exerting a sustained, powerful influence on the research field. Scored Review Criteria:
  • Significance: Addresses an important problem, rigorous prior research, how scientific knowledge/capability/clinical practice will improve, potential to change the field. Note: Market size for the candidate therapeutic is explicitly NOT considered in assessing significance.
  • Investigator(s): Suitability of the PD(s)/PI(s), collaborators, and other researchers. Experience, training, record of accomplishments. For collaborative projects, complementary and integrated expertise, appropriate leadership/governance.
  • Innovation: Whether the application challenges and shifts current paradigms through novel concepts, approaches, methodologies, instrumentation, or interventions. Refinement, improvement, or new application of existing concepts.
  • Approach: Reasonableness and appropriateness of overall strategy, methodology, and analyses. Plans to address rigor weaknesses, ensure unbiased approach, manage risks. Adequacy of plans for biological variables (e.g., sex), human subjects protection, and inclusion (if applicable).
  • Environment: Contribution of the scientific environment to success, adequacy of institutional support, equipment, and resources. Benefit from unique features or collaborative arrangements.
Additional Review Criteria (Considered, but not separately scored):
  • Resource Utility: Evaluate if the requested resource (URGenT Network access) is likely to lead to significant advances toward IND submission and future clinical evaluation.
  • Strategic Planning: Assessment of the designed strategy including Milestones, Timeline, Objectives, and a clear plan for future clinical studies.
  • Network Engagement: Whether the NINDS URGenT resources are appropriate for the project and how well the project leverages and collaborates with the URGenT Network.
  • Clinical Justification: Sufficiency of scientific rationale and justification of the clinical need for the requested resources.
  • Proof of Concept (POC) Data: Evaluation of sufficient and convincing evidence (from published literature and/or PI/PD-generated preliminary data) supporting proposed activities. Rigor of experiments that produced the POC data (e.g., blinding, randomization, sample sizes, statistical analysis, sex as biological variable, reagent authentication).
  • Patient Advancement Plan: Whether the proposed plan includes a discussion of the accessible patient population (target candidates, number of eligible patients, genetic variant) and other feasibility considerations (recruitment potential, follow-up requirements, data quality).
  • Human Subjects/Animal Welfare: Evaluation of protections for human subjects (even though clinical trials are not allowed, research may involve human biological materials), inclusion of women, minorities, and individuals across the lifespan, and involvement of vertebrate animals, including justification for choices made.
  • Biosafety: Assessment of potential hazards and proposed protections for research personnel and the environment.
  • Resource Sharing & Authentication: Reasonableness of resource sharing plans and plans for validating key biological/chemical resources.
  • Budget Justification: Reasonableness of the requested period of support in relation to the proposed research (note: no direct funds are awarded).

Compliance & Special Requirements

Regulatory & Policy Compliance
  • All activities must comply with the NIH Grants Policy Statement and 2 CFR Part 200 (Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards).
  • Non-discrimination: Recipients must adhere to all applicable non-discrimination laws and submit an Assurance of Compliance (HHS-690) upon registration in SAM.gov.
  • Health IT: If the project involves health IT, it must meet standards in 45 CFR Part 170 Subpart B or be certified under the ONC Health IT Certification Program.
  • Cybersecurity: Organizations with ongoing access to HHS information or operational technology systems handling Personal Identifiable Information (PII) or Personal Health Information (PHI) must develop cybersecurity plans modeled after the NIST Cybersecurity framework.
  • Mandatory Disclosure: Recipients are required to disclose any violations of federal criminal law (fraud, bribery, gratuity) potentially affecting the federal award.
Project Specific Requirements & Limitations
  • Clinical Trial Status: This funding opportunity is explicitly designated as 'Clinical Trial Not Allowed'. Applications proposing clinical research or clinical trials will be considered non-responsive and will not be reviewed.
  • Scope Limitation: Access to the URGenT Network resources via this X01 mechanism is not intended to be a complete drug development program. It focuses on specific pre-IND and IND-enabling activities.
  • No Guarantees: Obtaining access to SMEs and/or CROs/CMOs through this program does not guarantee a successful therapy development plan nor does it imply success in securing funding from other NIH programs.
  • Data Management and Sharing Plan: A Data Management and Sharing Plan is not applicable for this specific NOFO.
Intellectual Property (IP) & Confidentiality
  • The recipient institution retains its IP rights for candidate therapeutics developed in the network and gains IP rights from the URGenT contractors.
  • Recipient institutions are expected to manage patent prosecution, licensing negotiations, filings, maintenance, and commercialization efforts.
  • All Subject Matter Experts (SMEs) within the URGenT Network are required to treat information as confidential and not disclose data or their assessments to third parties.
Application & System Requirements
  • Applications must be submitted electronically; paper applications are not accepted.
  • All required registrations (SAM, UEI, eRA Commons, Grants.gov) must be completed prior to the application being submitted.
  • PD(s)/PI(s) must include their eRA Commons ID in the application.
  • The application organization's UEI must match the one used in eRA Commons and SAM.
  • Pre-award costs are allowable only as described in NIH Grants Policy Statement Section 7.9.1.

Grant Details

ultra-rare disease gene therapy neurological disorders neuromuscular disorders precision medicine drug development ind-enabling activities nonclinical development manufacturing contract research organizations (cro contract manufacturing organizations subject matter experts (smes) resource access healthcare research biotechnology medical technology therapeutic development ninds urgent network fda regulatory pathway pre-ind meeting investigational new drug (ind) biologics chemistry manufacturing and controls pharmacokinetics (pk) pharmacodynamics (pd) toxicology bioassay development regulatory affairs medical writing biostatistics quality assurance oligonucleotide-based approaches viral vector-based approaches cell therapy-based approaches genome editing-based approaches nih us government
Ultra-Rare Gene-based Therapy (URGenT) Network Resource Access (X01, Clinical Trial Not Allowed)
PAR-25-326
National Institutes of Health (NIH)
UNIVERSITY NGO ENTERPRISE SME PUBLIC OTHER
US
HEALTHCARE TECHNOLOGY
DEVELOPMENT
SDG3
RESOURCES MENTORSHIP RESEARCH_DEVELOPMENT CAPACITY_BUILDING
None
None
None
None
USD
None
Jan. 31, 2028, 5 p.m.
March-May 2028