IND-enabling Studies for Platform Clinical Trials of Genome Editing in Multiple Diseases (U01 Clinical Trial Not Allowed) | RFA RM 24 001

FAQs: NIH RFA-RM-24-001 (IND-enabling studies for an in vivo genome editing platform)

What is this funding opportunity trying to support?

This NIH funding opportunity (RFA-RM-24-001) supports IND-enabling preclinical studies for a new in vivo genome editing therapeutic platform. The goal is to advance a platform toward multiple disease indications in a coordinated, reusable way, rather than treating each indication as a standalone program.

What does NIH mean by a "platform" in this RFA?

A platform is defined as a single, consistent combination of (1) the genome editor and (2) the delivery system. Applicants are expected to keep key elements constant across indications, including the same editor, the same delivery vehicle, and the same route of administration, while applying the platform to at least two distinct disease targets.

How many disease indications must be included?

The project must apply the same platform to at least two distinct disease targets (two or more indications). The intent is to test what data and documentation can be shared across programs when the core platform and administration approach are held constant.

What must stay the same across the different indications?

NIH expects the following to remain constant across the selected indications: the genome editor, the delivery vehicle, and the route of administration. This consistency is central to the platform approach and to evaluating potential regulatory efficiencies.

Why is NIH emphasizing the platform approach?

NIH is testing whether a platform model can reduce duplicated effort across indications, clarify what evidence can be reused from one program to the next, and streamline the regulatory path when transitioning the same platform between different disease targets.

Is this a clinical trial opportunity?

No. The notice specifies "Clinical Trial Not Allowed." The work is expected to remain in the preclinical and IND-enabling phase and should not involve enrolling human participants.

What type of award mechanism is being used?

The award mechanism is a U01 cooperative agreement. Compared with a standard research grant, this typically means NIH staff will have substantial scientific or programmatic involvement, and the project is expected to operate with coordinated milestones, deliverables, and active NIH engagement.

Who is the sponsor, and what is the activity area?

The sponsor is the National Institutes of Health (NIH). The activity area is health, listed under CFDA 93.310.

What kinds of studies are typically included in IND-enabling work for an in vivo genome editing platform?

While specific study plans depend on the proposed platform and indications, the notice describes preclinical/IND-enabling activities commonly associated with this type of program, such as:

• Establishing or optimizing the genome editing construct and delivery formulation
• Demonstrating proof-of-concept editing in relevant models
• Conducting biodistribution and persistence studies
• Characterizing on-target and off-target effects
• Evaluating immunogenicity risks where relevant
• Developing assays and release methods
• Conducting toxicology and other safety studies aligned with regulatory expectations for an IND submission

What does NIH mean by "IND-enabling" in the context of this RFA?

IND-enabling refers to generating the package of preclinical data, assays, and supporting documentation typically needed to support an Investigational New Drug (IND) application. The emphasis here is on reaching a level of readiness that is close to first-in-human development, without conducting clinical trials under this award.

How should applicants handle shared versus indication-specific evidence?

Because this opportunity is built around a platform approach, strong applications are expected to clearly explain what data can be shared across the two (or more) indications versus what must be generated separately for each indication. NIH is specifically interested in learning where efficiencies are possible when the platform components and administration route are kept constant.

How should disease indications be selected for a platform-based application?

The notice indicates that a strong application would typically justify why the platform is broadly applicable, explain how the two (or more) indications are chosen, and define how the program will execute a coordinated path across multiple disease targets using the same editor, delivery system, and route of administration.

What is the role of regulatory documentation and "regulatory lessons" in this opportunity?

A major emphasis is not only generating IND-enabling data, but also capturing and sharing the regulatory lessons and supporting documentation so others can learn what worked and what regulators required. The opportunity explicitly values dissemination of regulatory information and documentation that could be reused or adapted by other platform developers.

What types of regulatory and quality-related elements does NIH expect teams to consider?

NIH signals that applicants should think beyond scientific experiments and consider the documentation and systems that make IND packages credible. Examples mentioned include:

• How manufacturing and controls information (CMC) will be generated
• What standardized assays and release methods will be used
• What comparability approaches will support the platform as it moves between indications
• How study designs map to FDA expectations for an IND submission
• How decisions and rationales will be recorded so they can be disseminated to the broader community

Is dissemination to the broader community actually required or just encouraged?

The opportunity explicitly mentions dissemination of regulatory information and supporting documentation, signaling that the program places value on producing shareable materials (for example, reusable templates, rationales, and evidence packages) that other researchers can adapt when pursuing additional indications.

Are foreign organizations eligible to apply?

No. Foreign organizations are not eligible to apply.

Can a U.S. organization include work performed outside the United States?

Non-U.S. components of U.S. organizations are not eligible to apply. However, foreign components (as defined in the NIH Grants Policy Statement) are allowed, which typically means discrete parts of the project may be carried out abroad if they meet NIH policy requirements and are well-justified.

What types of U.S.-based organizations are eligible?

Eligibility is broad and includes many types of U.S.-based organizations, including:

• State, county, and city governments
• Special districts
• Independent school districts
• Public and private institutions of higher education
• Federally recognized tribal governments
• Tribal organizations that are not federally recognized
• Public housing authorities/Indian housing authorities
• Nonprofits (with or without 501(c)(3) status)
• For-profit organizations (other than small businesses)
• Small businesses

Are there specific institution categories highlighted by NIH?

Yes. The notice highlights categories commonly called out in NIH eligibility language, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, eligible federal agencies, faith-based or community-based organizations, regional organizations, and U.S. territories or possessions.

What is the application due date listed in the notice?

The key administrative details provided include an original application due date of 2024-02-22.

What is the maximum award amount (ceiling)?

The notice provides an award ceiling of $2,000,000.

What is the overall end goal NIH is pushing toward?

The opportunity is designed for teams aiming to bring an in vivo genome editing platform to the brink of first-in-human readiness across multiple diseases, while also generating clear, shareable regulatory roadmaps that can help make genome editing development more efficient and repeatable across indications.

How does a U01 cooperative agreement affect project management and expectations?

Because this is a cooperative agreement, NIH expects an active partnership in shaping milestones, deliverables, and overall program direction. Applicants should anticipate more NIH involvement than with a standard research grant and plan accordingly for coordinated progress tracking and defined outputs.

What makes this opportunity different from funding a single-indication genome editing program?

This opportunity is structured to evaluate whether a single in vivo genome editing platform can support multiple disease targets using the same core elements (editor, delivery system, and route of administration). It also places unusual emphasis on documenting and sharing regulatory learnings and supporting materials so that future programs can build on what was learned rather than repeating the same groundwork.