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Grant Details

https://www.grants.gov/search-results-detail/357817

Grant Analysis

Purpose & Target

The core objective of this grant is to accelerate the development of gene-based or transcript-directed therapeutic candidates for ultra-rare neurological and neuromuscular disorders. It specifically supports Investigational New Drug (IND)-enabling studies and planning activities for First-in-Human (FIH) clinical testing.
  • Target Recipient Type: A wide range of organizations including higher education institutions, nonprofits, for-profit organizations (small and large businesses), various government entities, and other specified organizations.
  • Target Recipient Size: Not explicitly limited by employee count or revenue, open to various organizational sizes with the capacity to conduct complex research.
  • Designation: SECTOR-SPECIFIC (biomedical research, neuroscience, gene therapy).
  • Geographic Scope: United States-based organizations. Foreign entities are not eligible to apply, but foreign components within U.S. organizations are allowed.
  • Key Filtering Criteria:
  • Focus on ultra-rare neurological and neuromuscular disorders (affecting <= 6,000 people in the U.S.).
  • Proposed intervention must be a gene-based or transcript-directed therapeutic.
  • Projects must be ready to undertake IND-enabling studies and clinical trial planning.
  • Applicants must demonstrate robust proof of concept (POC) data for their therapeutic candidate.
  • Must have scheduled or held pre-IND discussions with the FDA.
  • Grant Frequency and Program Context: This is a reissue (PAR-25-327) of a previous funding opportunity (PAR-22-030), indicating a recurring nature. It is part of the National Institute of Neurological Disorders and Stroke (NINDS) Ultra-Rare Gene-based Therapy (URGenT) network.

Financial Structure

  • Budget Range: Application budgets are not limited but must reflect the actual needs of the proposed project.
  • Matching Fund Requirements: This funding opportunity does not require cost sharing.
  • Project Period: The project period must not exceed 3 years**.
  • Pre-award Costs: Allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.
  • Financial Reporting: Recipients will be required to submit financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting.

Eligibility Requirements

Organization Types
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
  • Local Governments (State, County, City or Township, Special District, Indian/Native American Tribal (Federally Recognized & Other))
  • Federal Government (Eligible Agencies of the Federal Government, U.S. Territory or Possession)
  • Other: Independent School Districts, Public Housing Authorities/Indian Housing Authorities, Native American Tribal Organizations, Faith-based or Community-based Organizations, Regional Organizations.
Geographic Requirements
  • Non-domestic (non-U.S.) Entities are not eligible to apply.
  • Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
  • Foreign components, as defined in the NIH Grants Policy Statement, are allowed within eligible U.S. organizations.
Technical & Project Requirements
  • Must have identified and characterized a clinical therapeutic candidate for an ultra-rare neurological or neuromuscular disorder.
  • Must have robust proof of concept (POC) data obtained through scientifically rigorous experimentation supporting the therapeutic candidate.
  • Must have a sufficient understanding of the pathogenic variant and its consequences that forms the basis of the proposed therapeutic approach.
  • The Program Director/Principal Investigator (PD/PI) must have scheduled or held formal pre-Investigational New Drug (IND) discussions with the relevant FDA division regarding a future regulatory path.
  • The PD/PI must be able to provide an outline of the future clinical trial, detailing proposed study design, duration, population, outcomes, safety measures, and data analysis methods.
  • Projects focused entirely on biomarkers and/or clinical endpoint development are not responsive.
  • Clinical trials seeking to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device interventions are not supported under this NOFO. Only mechanistic trials are supported.
Registration Requirements
  • Applicant organizations must complete and maintain active registrations with:
  • System for Award Management (SAM), requiring annual renewal.
  • NATO Commercial and Government Entity (NCAGE) Code (if applicable for foreign organizations).
  • Unique Entity Identifier (UEI) (must be the same for all registrations).
  • eRA Commons (requires at least one Signing Official (SO) and one Program Director/Principal Investigator (PD/PI) account).
  • Grants.gov (requires active SAM registration).
  • Program Directors/Principal Investigators (PD(s)/PI(s)) must have an eRA Commons account affiliated with the applicant organization.
Cost Sharing
  • Cost sharing as defined in the NIH Grants Policy Statement is not required.
Number of Applications
  • Applicant organizations may submit more than one application, provided each application is scientifically distinct.
  • Duplicate or highly overlapping applications are not accepted.

Application Process

Application Types
  • New
  • Resubmission
  • Revision
Submission Methods
  • Applications must be submitted electronically via:
  • NIH ASSIST system
  • Institutional system-to-system (S2S) solution
  • Grants.gov Workspace
Key Dates and Deadlines
  • Posted Date: December 18, 2024
  • Open Date (Earliest Submission Date): January 09, 2025
  • Letter of Intent Due Date(s): 30 days prior to each application due date (optional, not binding).
  • Application Due Dates (by 5:00 PM local time of applicant organization):
  • February 10, 2025
  • June 09, 2025
  • October 09, 2025
  • February 09, 2026
  • June 09, 2026
  • October 09, 2026
  • February 09, 2027
  • June 09, 2027
  • October 08, 2027 (Latest deadline)
  • Expiration Date for this funding opportunity: October 09, 2027.
Required Documentation & Materials
  • Follow all instructions in the 'How to Apply - Application Guide' and any program-specific instructions in this NOFO.
  • Standard application forms (SF424(R&R) series, PHS 398 series).
  • Other Attachments (Mandatory):
  • Pre-IND Meeting Minutes: Include any available minutes from pre-IND meetings with the FDA. If unavailable, explain the FDA feedback received and provide minutes as soon as possible.
  • Intellectual Property Documentation: Details of existing patents/IP filings, plans for IP management (patent filings, maintenance, licensing), and an outline of the commercialization strategy.
  • Research Strategy section: Limited to 30 pages.
  • Resource Sharing Plan: Required.
  • Data Management and Sharing Plan: Required for all applications regardless of direct costs requested.
  • Appendix: Only limited materials allowed (e.g., blank questionnaires/surveys); no publications or other materials.
Pre-Application Requirements
  • Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/Research Contact at least 6 weeks before submitting the application.
  • Consultation with NINDS Scientific/Research staff is strongly encouraged at least 6 weeks prior to the application receipt date.
Review & Selection Process
  • Applications are evaluated for scientific and technical merit through the NIH peer review system.
  • An overall impact score will be provided.
  • Applications may undergo a selection process where generally the top half are discussed.
  • Funding decisions consider: scientific and technical merit, availability of funds, and relevance to program priorities.
  • If an application is under consideration for funding, NIH may request 'just-in-time' information.
Post-Submission Materials
  • Regulatory meeting minutes, transcripts, patents, and late-breaking data will be accepted.
Post-Award Reporting Obligations
  • Research Performance Progress Report (RPPR) annually.
  • Financial statements as required.
  • Final RPPR, invention statement, and expenditure data for closeout.
Project Implementation Timeline
  • The project period must not exceed 3 years**.
  • Nonclinical and clinical trial planning milestones combined are generally expected to be completed within 3 years.
  • Projects are milestone-driven cooperative agreements with clear Go/No-Go criteria established by a Multi-disciplinary Project Team (MPT).

Evaluation Criteria

Overall Impact
  • Reviewers will assess the likelihood of the project to exert a sustained, powerful influence on the research field(s) involved.
Factor 1: Importance of the Research
  • Significance:
  • Evaluation of the proposed research's importance in advancing knowledge, solving critical problems, or creating conceptual/technical advances.
  • Assessment of the scientific background's rigor and justification for the study.
  • Specific to this NOFO:
    • Strength of the Proof of Concept (POC) data (in vitro and/or in vivo models) supporting the therapeutic modality and patient population for the identified genetic disease.
    • Adequacy of understanding of the pathogenic variant and its consequences.
    • Convincing address of target selection, its role in disease pathogenesis, and clinical relevance.
    • Discussion of limitations if nonclinical data do not meet rigor guidelines.
    • Likelihood that research objectives will lead to a therapy with a clear path into the clinic.
    • For clinical studies/planning: whether the intervention would lead to a change in clinical practice, community behaviors, or healthcare policy.
  • Innovation:
  • Extent to which novel concepts, methods, or technologies are applied, or existing ones are used in novel ways.
Factor 2: Rigor and Feasibility
  • Rigor:
  • Potential to produce unbiased, reproducible, robust data, including experimental design, controls, sample size justification, and plans for analysis/interpretation.
  • Adequate plans to address relevant biological variables (e.g., sex or age).
  • For human subjects/vertebrate animals: rigor of intervention, justification of outcome variables, generalizability/relevance, appropriateness/diversity of sample, adequacy of inclusion plans.
  • Feasibility:
  • Soundness and achievability of the proposed approach, including plans to address problems.
  • Balance of uncertainty with potential for major advances.
  • Adequacy and feasibility of the plan to recruit and retain a study population.
  • Likelihood of successfully achieving proposed enrollment.
  • Feasibility of the study timeline and milestones.
  • Specific to this NOFO:
    • Whether the eligible patient population can be identified based on pathogenic variant and other characteristics.
    • Availability and proposal of rigorous testing methodologies (e.g., biomarker assays).
    • Justification of administration route and initial dose; explanation of potential side effects.
    • Expectation that the therapeutic candidate will alter the target activity and produce desired outcomes in disease models.
    • Alignment of proposed studies with FDA pre-IND meeting guidance.
    • Feasibility of scaling synthesis/manufacture for IND-enabling studies and future clinical trials.
    • Inclusivity of appropriate studies and realistic timelines for obtaining an IND, with defined milestones and go/no-go criteria.
    • Incorporation of efficiencies and utilization of existing resources.
    • Expectation that the clinical therapeutic candidate will result in measurable clinical outcomes and be ready for clinical testing at project conclusion.
    • For clinical studies/planning: adequate plans for protocol standardization, quality assurance, monitoring; appropriate intervention methods and statistical approach; completion of data analysis within funding period.
Factor 3: Expertise and Resources
  • Investigator(s):
  • Demonstrated background, training, and expertise of the investigator(s).
  • Quality of the leadership plan for Multiple Principal Investigator (MPI) applications.
  • Specific to this NOFO:
    • For clinical studies/preparation: specific/demonstrated expertise in organizing/implementing clinical trials, study coordination, data management, and statistical design/analysis.
  • Environment:
  • Appropriateness of institutional resources.
  • Benefit from unique features of the scientific environment, subject populations, or collaborative arrangements.
  • Leveraging existing NIH tools and resources, including research networks.
Additional Review Criteria (No separate scores)
  • Protections for Human Subjects: Justification for involvement, proposed protections, potential benefits, knowledge to be gained, data and safety monitoring.
  • Vertebrate Animals: Description of procedures, justifications for use, minimization of discomfort, justification for euthanasia.
  • Biohazards: Evaluation of hazardous materials/procedures and proposed protection.
  • Authentication of Key Biological and/or Chemical Resources: Brief plans for identifying and ensuring validity.

Compliance & Special Requirements

Regulatory Compliance
  • Projects involving human subjects must comply with 45 CFR Part 46 (for both exempt and non-exempt research).
  • Clinical research projects using investigational interventions (therapeutics, vaccines, medical devices) must be performed under an FDA Investigational New Drug (IND) or Investigational Device Exemption (IDE).
  • ClinicalTrials.gov registration and results reporting are expected for all NIH-defined clinical trials.
  • Recipient institutions must ensure all protocols are reviewed by their Institutional Review Board (IRB) or Independent Ethics Committee (IEC).
  • Data and Safety Monitoring is required for all NIH-conducted or -supported human biomedical and behavioral intervention studies.
  • IND-enabling safety/toxicology studies must be conducted in compliance with Good Laboratory Practices (GLP).
  • If the award involves health IT, recipients must use health IT meeting standards and specifications adopted in 45 CFR part 170, Subpart B. If for eligible clinicians/hospitals, use ONC Health IT Certified Program IT.
Data & Intellectual Property (IP) Management
  • Compliance with the 2023 NIH Policy for Data Management and Sharing is required.
  • The recipient institution retains Intellectual Property (IP) rights and gains IP rights from URGenT contractors for candidate therapeutics developed within the network.
  • The recipient institution is expected to be responsible for patent filings, maintenance, and licensing efforts towards commercialization.
  • No IP will be held by NINDS or its contractors or consultants.
  • Applicants must submit comprehensive IP documentation, including details of existing IP, plans for IP management, and a commercialization strategy.
Ethical Standards
  • Studies must adhere to NIH guidance on rigor and reproducibility.
  • Ethical considerations for project continuation will be reviewed by the Multi-disciplinary Project Team (MPT).
Cooperative Agreement Terms (U01)
  • This is a 'Cooperative Agreement' (U01) mechanism, indicating substantial Federal scientific or programmatic involvement from NIH staff.
  • NIH staff will assist, guide, coordinate, or participate in project activities, but recipients retain primary responsibility and leadership for the project.
  • A customized Multi-disciplinary Project Team (MPT) will be assembled, including NINDS Program Staff, the PD/PI's team, and external subject matter experts (SMEs), to establish strategy, milestones, and monitor progress.
  • The MPT will have access to data, but recipients will retain primary custody and rights to data.
  • A formal Dispute Resolution procedure is in place for disagreements in scientific or programmatic matters.
Other Policies and Compliance
  • All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
  • Compliance with 2 CFR Part 200 (Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards) is required.
  • Recipients must comply with all applicable nondiscrimination laws and submit an Assurance of Compliance (HHS-690).
  • Recipients must comply with all federal statutes and regulations relevant to federal financial assistance.
  • Recipients dealing with HHS-owned information or personal identifiable information (PII)/personal health information (PHI) must develop cybersecurity plans modeled after the NIST Cybersecurity framework.
  • Mandatory disclosure of federal criminal law violations related to fraud, bribery, or gratuity affecting federal awards.
Special Considerations
  • The program addresses the urgent need for rapid therapeutic interventions for ultra-rare diseases.
  • Encourages a 'platform approach' to therapeutic development, leveraging nonclinical and manufacturing data across projects to enable continuous reassessment of best practices.
  • Aims to facilitate regulatory harmonization.
  • Award recipients are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the drug development process.

Grant Details

neurological disorders neuromuscular disorders ultra-rare diseases gene therapy transcript-directed therapy oligonucleotide-based therapy viral vector therapy cell therapy genome editing small molecule drugs precision medicine therapeutic development ind-enabling studies clinical trial planning first-in-human clinical trials proof of concept drug discovery biotechnology medical research translational research nih ninds urgent network cooperative agreement healthcare research and development orphan diseases genetic disorders ind gmp manufacturing toxicology studies pharmacodynamic studies pharmacokinetic studies biomarker development fda regulatory pathway ip management commercialization strategy us government funding
Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders (U01 - Clinical Trial Optional)
PAR-25-327
National Institutes of Health (NIH) - National Institute of Neurological Disorders and Stroke (NINDS) Ultra-Rare Gene-Based Therapy (URGenT) network
PUBLIC UNIVERSITY NGO SME ENTERPRISE OTHER
US
HEALTHCARE TECHNOLOGY
DEVELOPMENT
OTHER
SDG3
FUNDING RESEARCH_DEVELOPMENT CAPACITY_BUILDING MENTORSHIP
None
None
None
USD
None
Oct. 8, 2027, 5 p.m.
March 2028 - May 2028