Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The NIH Somatic Cell Genome Editing (SCGE) program is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold and innovative approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for transformation of research processes.

The simplicity and broad applicability of targeted and programmable genome editing approaches, including, but not limited to those based on CRISPR-Cas9, raise the possibility of a fundamentally new way to treat a variety of genetic diseases. However, many challenges need to be overcome before such techniques could be widely used in the clinic. To maximize the potential of genome editing technology, the SGCE program was developed to accelerate the translation of genome editing technology into clinical applications.

Based on input received from stakeholders from academia, industry, and regulatory agencies, as well as the substantial progress in the field of genome editing since the launch of the first five-year phase of the SCGE program, the second five-year phase of SCGE will focus on translating and accelerating safe and effective genome editing therapeutics into the clinic. Specifically, SCGE Phase 2 will support the following initiatives: 1) Technologies and Assays for Therapeutic Genome Editing INDs; 2) IND-enabling Studies of Somatic Genome Editing Therapeutic Leads; 3) IND-enabling Studies and Platform Clinical Trials of Somatic Genome Editing for Multiple Diseases and 4) Somatic Cell Genome Editing Translational Coordination and Dissemination Center (TCDC).

The SCGE program will involve collaborative research by a consortium of award recipients with differing expertise to develop, optimize and demonstrate improved candidate genome editing therapeutic as treatments for human disease. Recipients from all four SCGE program components will form a consortium, governed by a steering committee of investigators and NIH staff that will develop consensus policies and procedures for Consortium-wide activities such as data and resource sharing. Collectively, these initiatives are intended to substantially expand the number of genetic diseases treated by in vivo genome editing, ultimately allowing this technology to achieve its potential as a therapeutic platform to treat genetic disease.

The traditional path to drug development is to develop a single drug to treat a single disease.

In contrast, technologies such as genome editing are fundamentally different, in that they are therapeutic platforms that are in principle applicable to a large number of diseases. Therefore, clinical trial design and the associated regulatory pathway should reflect the therapeutic platform capacity of genome editing. The purpose of this Notice of Funding Opportunity (NOFO) is to provide support for applications that propose Investigational New Drug (IND)-enabling studies for the development of a novel in vivo genome editing therapeutic platform (genome editor plus delivery system) for two or more disease indications. Furthermore, it is expected that projects supported under this NOFO will explore strategies to increase efficiencies in the regulatory path for a therapeutic platform leading to genome editing clinical trial(s) for two or more disease indications.

We anticipate that dissemination of the data and knowledge gained by projects supported by this NOFO will allow genome editing technology to achieve its promise as a therapeutic platform for the treatment of genetic diseases.

Program Formation and Governance

The awards funded under this NOFO will be cooperative agreements (see Section VI.2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the recipients and NIH will be required to maintain this complex program. The whole SCGE program governance will rest with the SCGE Program Steering Committee in collaboration with NIH program officials, with input and feedback from Program Consultants (PCs) providing critical scientific and managerial insights, and subject to oversight by the NIH SCGE Working Group. The NIH SCGE Working Group consists of NIH programmatic staff from multiple Institutes and Centers of the NIH as well as the Office of the Director. This group will be primarily responsible for the stewardship of the SCGE program. The SCGE Working Group is co-chaired by the Director of the National Center for Advancing Translational Sciences (NCATS) and the Director of the National Institute for Neurological Disorders and Stroke (NINDS). It reports to the Directors of the Office of Strategic Coordination/Common Fund and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.

Research Scope and Objectives

The primary objectives of this NOFO are to: 1) explore the extent to which the use of a therapeutic platform consisting of a single genome editor and delivery system, can streamline the regulatory path to in vivo genome editing clinical trial(s) for two or more disease indications, and 2) to disseminate this regulatory information (and supporting documentation) to the scientific community. Examples of streamlining in this context include, but are not limited to, reducing the number of biodistribution; toxicology and chemistry, manufacturing, and controls (CMC) studies necessary to support the regulatory approval process for clinical trial(s) two or more disease indications. The extent of streamlining should be considered in comparison to the traditional regulatory path for two entirely independent submissions, one for each disease indication, in which every step of the regulatory path is required for each disease indication, without consideration of the therapeutic platform. Importantly, it is up to the FDA to decide how much, if any, streamlining is acceptable. Therefore, applications submitted in response to this NOFO will be evaluated based on the extent to which the approach proposed in the application is technically feasible and could streamline the regulatory approval process if it were to be accepted by the FDA.

To achieve the objectives, this NOFO is intended to support IND-enabling studies of a therapeutic platform (genome editor and delivery system) that will be used in a subsequent platform clinical trial of more than one disease indication. However, this NOFO will only support the IND-enabling studies necessary to prepare and submit a complete IND package, not the actual trial. IND-enabling studies proposed in the application may include, but are not limited to, in vitro studies, proof of concept (POC) studies in one or more animal models, toxicology, biodistribution, CMC studies, and preparation of an investigator’s brochure and clinical protocol. Given the time frame of the Award, we anticipate that applicants will at a minimum have in vivo POC data from at least one animal model of disease using the therapeutic platform prior to submission. The IND-enabling studies and resulting IND for the clinical trial(s) must utilize the same genome editor, route of administration, and in vivo delivery system for the target disease indications. The editor may be delivered in the form of DNA, mRNA, peptide nucleic acids, or protein, using either viral or non-viral based systems. Any genome editor, including but not limited to those that create a double-strand break, base editors, prime editors, RNA editors, or epigenome editors, can be chosen for use.

Examples of potential regulatory approaches include but are not limited to a single IND for two or more disease indications, or two or more related INDs in which each substantially cross-references the other(s) based upon the use of the same editor and same delivery vehicle for both disease indications. Formal and informal meetings with the FDA (i.e., INTERACT and pre-IND meetings) are essential components of projects supported by this NOFO, and will be required as project milestones. By the end of the project, award recipients must (1) successfully prepare and submit a complete IND regulatory package to initiate the FDA review process; and (2) provide documentation of this to NIH. Please note the documentation submitted to the NIH must also include but is not limited to the full IND package, all FDA-Sponsor interactive review and responses during the 30-day IND review, and FDA communication concerning meeting feedback and IND status. Additionally, award recipients must provide lessons learned and information to the TCDC about their approach to obtaining the IND(s) for more than one disease indication, as well as responses from regulatory authorities, so that this information can be disseminated within and outside the SCGE consortium.

Genome editing therapy development is a complex and time-consuming undertaking, and applicants should consider forming multidisciplinary teams that may consist of preclinical and clinical scientists, pharmacokinetic (PK) experts, CMC experts, regulatory experts, statisticians, project manager, and other academic/industry experts relevant to the therapeutic modality and disorder. Applicants are strongly encouraged to employ team and project management principles as appropriate. Collaborations with commercial entities that are developing genome editing therapeutics are encouraged. Applications containing risk mitigation strategies that proactively address potential delays or risks in meeting the milestones are strongly encouraged.

The following are examples of projects that would be considered non-responsive to this NOFO:

• IND-enabling studies for a genome editing for a single disease, even if targeting different causative genes
• Projects involving editing cells ex vivo, followed by in vivo injection of edited cells.
• Clinical trials of genome editing in humans

In preparing applications to this NOFO, investigators should be aware of requirements for gene editing clinical trials as identified in the relevant FDA Guidance documents (see https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances).

Rigor and Transparency

NCATS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NCATS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

Pre-application Consultation

As an U01 cooperative agreement, implementation will include substantial involvement of NCATS Program staff in the planning and execution of the therapy-directed projects. Applicants and their multidisciplinary team are strongly encouraged to consult with NCATS Scientific/Research staff when planning an application. Early contact provides an opportunity for NCATS Scientific/Research staff to provide further guidance on program scope, goals, developing appropriate milestones, and budget. Staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this NOFO.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

All organizations administering an eligible parent award may apply for a supplement under this NOFO.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than 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)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

• Eligible Agencies of the Federal Government-Including the NIH Intramural Program
• U.S. Territory or Possession

Other

• 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

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

P.J. Brooks, Ph.D.
Email: SCGEprogram@od.nih.gov

All page limitations described in the How to Apply Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply Application Guide and should be used for preparing an application to this NOFO.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

Also, applicants must provide a detailed budget and budget justification for each budget period of the U01. All applicants must budget for travel for personnel to attend two SCGE program PI meetings per year in the Washington, DC metropolitan area.

NIH will generally not provide F&A costs unless the recipient has established an F&A cost rate covering the applicable activities and period of time. Applicant organizations that do not have an established F&A cost rate should review the NIH Grants Policy Statement reimbursement of facilities and administrative (F&A) costs policies prior to application submission.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims:

This section should provide a concise description of the aims for the project, including a description of the proposed regulatory approach for studying a genome editing therapeutic platform for more than one disease.

Research Strategy:

Background

• Describe the genome editor, delivery system, route of administration, target tissue, and disease indication that will be studied in the future clinical trial. Provide biological rationale for each.
• Provide a description of any completed IND-enabling studies for the in vivo genome editing therapeutic platform (genome editor plus delivery system) as preliminary data. These data may be obtained from in vitro studies, as well as one or more in vivo animal models representative of the intended patient population. Given the aggressive timeline for the work to be carried out under this NOFO, investigators are expected to have substantial preclinical data on hand regarding the proposed editor and delivery system prior to submitting the application. At a minimum, this would include POC data in an animal model of at least one of the proposed disease indications, using the intended editor and delivery system.
• Provide a Target Product Profile (TPP) based on the FDA guidance [https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances] that summarizes the minimal/ideal profile of the final product and the ultimate goals of the proposed drug development effort, such as patient population, delivery mode, treatment duration, treatment regimen, and standards for clinical efficacy for each disease indication.
• Describe the disease indications to be studied, the clinical characteristics, and current and projected prevalence of the number of patients with each of the proposed disease indications that will be studied in the clinical trial.
• Explain how the project offers an approach to treating the patient population as proposed in the TPP.
• Describe collaborations with commercial entities that are developing genome editing technologies, if applicable.

IND-enabling Studies

• Describe all non-clinical testing necessary to support the filing of an IND, including the standards to which the testing will comply (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP))
• Describe the development of in vitro assays to identify and test guide RNAs to be used for the two disease indications in the clinical trial.

Regulatory Approach

• Describe plans for contact with and submissions to the FDA (e.g., pre-submission meetings, IND submissions, other interactions with FDA personnel.
• Include plans for how FDA feedback will be addressed (e.g., if additional IND-enabling studies are suggested).
• Address how the approach for clinical trial design of more than one disease indication results in increased efficiency compared to the standard approach of two or more independent clinical trials.

Other attachments:

Milestone Plan

Applications must include a Milestone Plan. The Milestone plan should include:

• A project timeline in the form of a Gantt chart, with all milestones included, to obtain regulatory approval to conduct the clinical trial. Required milestones include conducting and completing IND-enabling studies; INTERACT meeting; pre-IND meeting; compilation and submission of an IND package to the FDA; and providing documentation of the IND and FDA communications, submissions, and lessons learned to the NIH and the SCGE Translational Coordination and Dissemination Center (TCDC). Milestones should be well described (specific, quantitative) with clear indicators of a success.
• Provide any risk mitigation strategies that proactively address potential delays or risks in meeting the milestones.
• The filename "Milestone Plan-PI-NAME.pdf" should be used, must not exceed 50 characters, and will be reflected in the final image bookmarking for easy access by reviewers. The Milestone Plan is limited to 3 pages. Applications that do not include the Milestone Plan will be considered incomplete and will not be reviewed.

Team Management Plan

Provide a team management plan that describes how multidisciplinary expertise is incorporated in the overall project plan. Include if and how members have previous experience with the IND process. Describe how the team, including consultants, will work over the course of the project (e.g., recurring team meetings, review and report of data across disciplines, decision-making, participate in meetings with NIH, communication, etc.).

Letters of support: Statements of individual and institutional commitment, as appropriate to the Research Project, should be included in this section.

Letters of support should not be generic, but instead indicate what the collaborator has contributed so far and what they expect to provide during the project to allow an evaluation of team engagement. Indicate the willingness of the PD/PI(s) and key personnel to operate under the cooperative agreement terms and conditions outlined in section VI.2. Of the NOFO. Note: Multi-PI plans should not duplicate information from the multi-PI plan.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• Applicants should indicate their willingness to abide by software release, and public copyright license policies developed by the SCGE Program Steering Committee and approved by NIH staff. A primary goal of the SCGE program is to facilitate discoveries by the broad scientific community, thereby accelerating the translation of genome editing technologies into treatments for human disease. Restrictive licensing terms and sharing practices for SCGE-generated tools, and resources could substantially diminish their value and public benefit. Accordingly, recipients should manage resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would hinder, prevent or block access to or use of SCGE program tools and resources for research purposes will be considered to be hindering the goals of the SCGE program. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the recipients, through the SCGE Program Steering Committee, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on resource sharing.
• Applicants should indicate their willingness to make some applicant-generated animal and/or human samples from genome-editing therapeutic studies to other Consortium members. Recipients are encouraged to collaborate with other SCGE Consortium members to help evaluate the utility and performance of the assay(s) to further advance the field.
• Specific Plan for Protocol, Tool, and Reagent Sharing: As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols, tools, and reagents generated by the SCGE program be broadly available and distributed at no to minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible for research purposes by the larger scientific community, while encouraging rapid adoption and commercialization of the technologies for the development of genome editing therapies. For all applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including animal strains, protocols, biomaterials, and reagents. The SCGE TCDC will work with all SCGE program investigators to collect, curate, and disseminate information regarding tools and reagents being developed by the program and to disseminate this information through the SCGE Toolkit and other sources as appropriate and consistent with achieving the goals of the program.
• Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in applications that are developing software. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. A dissemination plan guided by the following principles is thought to promote the largest impact:
  • The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
  • The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
  • To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
  • The terms of software availability should include the ability of researchers outside the project and its collaborating projects to modify the source code and to share modifications with other colleagues. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.
  • Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.
  • Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.
• Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).

Prior to funding, NIH Program Staff may negotiate modifications to the Resource Sharing Plan with the applicant.

Intellectual Property:

Applicants should describe any constraints of which they are aware that could impede their use of compounds, assays, or models for research purposes and/or clinical development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present intellectual property (IP) filings and publications, compounds with similar structures that are under patent and/or on the market, etc.) and how these issues would be addressed. If the applicant has filed pertinent patents, the applicant should indicate filing dates, the type of patent, and application status. If multiple organizations are involved, explain how IP will be shared.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• Consistent with achieving the goals of this program, the NIH expects that information such as collected data and any metadata collected under this NOFO is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for data deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. Data should also be made available as appropriate via the SCGE Phase II Platform that will serve as the central access point for information regarding data, critical tools, protocols and reagents being developed by the SCGE program. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data management and sharing plan.
• Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, and data policies developed by the SCGE Program Steering Committee and approved by NIH staff. A primary goal of the SCGE program is to facilitate discoveries by the broad scientific community, thereby accelerating the translation of genome editing technologies into treatments for human disease. Restrictive sharing practices for SCGE-generated data could substantially diminish their value and public benefit. Sharing practices that would hinder, prevent or block access to or use of SCGE program data for research purposes will be considered to be hindering the goals of the SCGE program. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the recipients, through the SCGE Program Steering Committee, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data sharing.

Prior to funding, NIH Program Staff may negotiate modifications to the Data Management and Sharing Plan with the applicant.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Center for Advancing Translational Sciences (NCATS), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed and will not be eligible for award.

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above and, in the NIH, Intramural Source Book.

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This NOFO aims to explore the extent to which the use of a therapeutic platform consisting of a single genome editor and delivery system, can streamline the regulatory path to in vivo genome editing clinical trial(s) for two or more disease indications. Ultimately, it is up regulatory agencies to decide how much, if any, streamlining is acceptable. Therefore, applications submitted to this NOFO will not be evaluated based on anticipated FDA responses to the proposed streamlining, Applications will be evaluated based on the extent to which the approach proposed in the application is technically feasible and could potentially streamline the regulatory approval process if it were to be accepted by the FDA.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this NOFO:

Would the proposed platform approach substantially streamline the regulatory approval process for genome editing technologies for more than one disease indication, if it were to be accepted by the FDA?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this NOFO:

Has a multidisciplinary team been engaged, including expertise in preclinical; clinical; pharmacokinetics; chemistry, manufacturing, and controls (CMC); regulatory; statistics; and any other experts relevant to the therapeutic modality and disorder? Is there any expertise lacking? Based on the team management plan and letters of support, are critical team members committed and organized to successfully complete the activities needed to obtain an optimized therapeutic platform for more than one disease?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this NOFO:

Does the design/research plan include innovative elements, as appropriate, that streamline and increase the efficiency of obtaining an IND(s) through FDA interactions?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

Is the timeline feasible to complete all requirements for obtaining an IND(s), as described in the milestone plan? Is the platform approach proposed in the application technically feasible?

Are the proposed studies appropriate, feasible, and consistent with the proposed target product profile (TPP)?

Does the proposed Milestone Plan align with the objectives of this NOFO?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Specific to this NOFO:

Intellectual Property (IP) Strategy:

Are potential issues regarding the IP landscape for the therapeutic being developed and the freedom to operate addressed?

Are there any known constraints that could impede the development of the therapeutic?

Are IP filing plans described?

If multiple organizations are involved, is IP sharing adequate to complete the proposed aims and milestones?

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.

HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining research approaches, designing protocols, setting project milestones, and conducting research.
• Participation in regulatory meetings.
• Participating in group activities, including a Consortium-wide SCGE Program Steering Committee and subcommittees as needed.
• The SCGE Consortium will meet in person at least twice a year and the SCGE Program Steering Committee will recommend the frequency of other in-person and teleconference meetings.
• Providing reports and data in a timely fashion as agreed upon by the SCGE Program Steering Committee.
• Submitting all required data, SOPs, protocols, and resources as soon as they are scheduled for submission to the SCGE TCDC for quality control and compilation in the SCGE Phase II Platform.
• Preparing abstracts, presentations, and publications and collaborating Consortium-wide in making the public and professionals aware of the program.
• Assessing and disseminating data, protocols, and methods developed for or derived from the SCGE program within and outside the Consortium.
• Adhering to policies regarding data sharing and publication established by the NIH and the SCGE Program Steering Committee.
• Abiding by common definitions, protocols, and procedures, as chosen by a majority vote of the SCGE Program Steering Committee.
• Submitting periodic progress reports in a standard format, as agreed upon by the SCGE Program Steering Committee and NIH SCGE Working Group.
• In the event negotiated milestones are not accomplished, submitting a milestone report which will include a discussion of why the milestones were not met in the agreed-upon timeframe and propose a corrective action plan. The corrective recruitment action plan shall include amended milestones, plans to achieve the amended milestones, and any additional items required by NIH Working Group staff. The plan shall be provided to NIH Working Group staff no later than 2 months following the missed milestone.
• Attending and participating in SCGE Program Steering Committee meetings; accepting and implementing decisions by the NIH SCGE Working Group, as appropriate.
• Overseeing all aspects of the organization and execution of the studies outlined in the application and approved by NIH Working Group program staff after peer review. Putting all study materials and procedure manuals into the public domain. Recipients are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by NIH.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Additionally, prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and Project Scientist will negotiate with the applicant and agree on a final set of approved milestones which will be specified in the Notice of Award. The Program Official will be responsible for recommendations to the NIH to continue funding, or to withhold or restrict support for lack of progress or failure to adhere to NIH policies.

The NIH Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. The Project Scientist(s) will participate as members of the SCGE Program Steering Committee. The Project Scientist(s) will have the following substantial involvement:

• Participating with the other SCGE Program Steering Committee members in addressing issues that arise with SCGE planning, operation, assessment, and data analysis. The Project Scientist(s) will assist and facilitate the group process and not direct it.
• Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the recipients. The Project Scientist(s) will also help coordinate the efforts of the SCGE Consortium with other groups conducting similar efforts.
• Attending all SCGE Program Steering Committee meetings, assisting in developing standard operating procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the recipient as needed to manage the logistic aspects of the SCGE program.
• Reporting periodically on SCGE progress to the Common Fund SCGE Working Group and through it to the NIH Common Fund.
• Serving on subcommittees of the SCGE Program Steering Committee as appropriate.
• Assisting recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
• Providing advice on the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed during this program to the scientific community at large.
• Participating in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the program.
• Contributing to development of final milestones for the study and comparing actual results to the benchmarks and criteria identified in the application and negotiated prior to award. If negotiated milestones are not accomplished, reviewing the milestone report and corrective action plan submitted in collaboration with the NIH Working Group staff to determine the next course of action.
• Reviewing the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, volunteer logs, etc. Facilitate coordination among other U.S. Government agencies, promoting collaborations and facilitating information exchange.

NIH reserves the right to withhold funding or curtail an award in the event of:

• a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application,
• failure to meet procedures and/or negotiated milestones, and/or
• substantive changes in the management of award(s) that are not in keeping with the objectives of the NOFO.

Areas of Joint Responsibility include:

SCGE Program Steering Committee

The SCGE Program Steering Committee will serve as the main scientific body of the program. The SCGE Program Steering Committee will be responsible for coordinating the activities being conducted by the program and is the committee through which the NIH SCGE Working Group formally interacts with the SCGE investigators. The SCGE Program Steering Committee membership will include PD(s)/PI(s) of each SCGE award (limited to one person for a Project with multiple PIs), other staff as needed (ex-officio) and the NIH Project Scientist(s). The SCGE Program Steering Committee may add additional members, and other government staff may attend the SCGE Program Steering Committee meetings as desired. Each award recipient Steering Committee member will have one vote, and the NIH Project Scientist(s) together will have one vote.

The SCGE Program Steering Committee may establish subcommittees as needed to address particular issues which will include representatives from the program and the NIH, and possibly other experts. The SCGE Program Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.

Program Consultants (PCs):

Program Consultants provide critical scientific and managerial insight which will assist NIH staff, the SCGE Working Group (WG), and the awards for each program in determining whether the program is producing something of value to the biomedical research community. Program Consultants are volunteers who provide individual feedback and input on specific, timely issues arising for the program.The PCs will include 4-6 senior, non-federal scientific experts who are not directly involved in the activities of the SCGE program. NIH will appoint PCs and may adjust the roster of PCs in response to program needs. The SCGE POs, PSs, NIH SCGE Working Group, and other NIH staff may attend the PC meetings.

Program Consultants (PC) will:

• review and evaluate the progress of the entire SCGE program.
• as appropriate and at the request of the NIH SCGE Working Group, provide input to the NIH about the progress of the individual SCGE projects in meeting their individual and Consortium goals and milestones.
• meet at least once a year, in conjunction with a meeting of the SCGE Program Steering Committee in the DC Metro area.
• provide annual individual assessments to the NIH of the progress of the SCGE Consortium, and as necessary, present recommendations regarding any changes to the SCGE program. The individual assessments and recommendations will be provided to the Director of the Office of Strategic Coordination, NIH through the NIH SCGE Working Group.

Program Consultants (PC) will not:

• participate in peer review, funding decisions, grant specific meetings, reporting processes, and/or grant oversight.
• have access to PII sensitive data, internal guidance, and/or proprietary information. Exceptions may be made under rare circumstances.

The SCGE award recipient agrees to work collaboratively to:

• provide secure, accurate, and timely data, SOP, protocol, and resource submission.
• participate in presenting and publishing new processes and substantive findings.
• assess and disseminate the SCGE Phase II Platform.
• participate in the governance of the SCGE program as a member of the SCGE Program Steering Committee.
• make some recipient-generated animal and/or human samples from genome-editing therapeutic studies to other Consortium members. Recipients are encouraged to collaborate with other SCGE Consortium members to help evaluate the utility and performance of the assay(s) to further advance the field.
• interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.
• under the direction of NIH officials and through the SCGE Program Steering Committee, interact with program consultants, as appropriate.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

P.J. Brooks, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-443-0513
Email:pj.brooks@nih.gov

Center for Scientific Review
Email:?FOAReviewContact@csr.nih.gov

Jennifer Cho
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301 827-9171
Email: Jennifer.Cho@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.