Innovation Grants to Nurture Initial Translational Efforts (IGNITE Program)

Innovation Grants to Nurture Initial Translational Efforts (IGNITE Program) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Supports early-stage therapy development in neurological disorders, serving as a feeder to later-stage programs.

PAR-25-225: Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Neurotherapeutic Agent Characterization and In vivo Efficacy Studies (R61/R33 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Funding Opportunity Title Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Neurotherapeutic Agent Characterization and In vivo Efficacy Studies (R61/R33 Clinical Trial Not Allowed) R61 / R33 Exploratory/Developmental Phased Award March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) provides funding to conduct pharmacodynamic, pharmacokinetic, and in vivo efficacy studies to demonstrate that proposed therapeutic agent(s) have sufficient biological activity to warrant further development to treat neurological disorders that fall under the NINDS mission.

Therapeutic agents include small molecules or biologics. This NOFO is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE). Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions 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.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description This notice of funding opportunity (NOFO) is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE) to encourage the translation of research discoveries into new treatments for disorders that fall under the NINDS mission.

Supported therapeutic agents include small molecules and biologics (modalities such as peptides, proteins, oligonucleotides, gene therapies, cell therapies, and novel emerging modalities). This NOFO uses the R61/R33 Phased Innovation Award mechanism in which the R61 phase is generally utilized to support preparatory or prerequisite activities that establish feasibility for execution of the R33 phase.

The R61 and R33 phases cannot overlap in time. By design, this R61/R33 supports dependent aims; the R33 depends on the R61. The risk of dependent aims is mitigated by milestones between the R61 and R33 (discussed in detail below).

Only if the milestones are met does the project progress from the R61 to the R33. This NOFO provides support to conduct therapeutic agent characterization and pharmacokinetic studies in the R61, and pharmacodynamic and in vivo efficacy studies in the R33 to demonstrate that proposed therapeutic agent(s) have sufficient biological activity to warrant further development to treat neurological or neuromuscular disorders.

This NOFO does not support optimization of potential therapeutic agents. For this NOFO, optimization is defined as the rational, iterative design of new agents based on data obtained in the prior iteration. Testing of a few pre-defined potential therapeutics to determine the best option is supported.

(For example, testing 2 different pre-defined promotors in a gene therapy could be supported.) In preclinical efficacy studies, a combination of in vivo efficacy, pharmacodynamic (PD) and pharmacokinetic (PK) measures are warranted to determine the feasibility of candidate therapeutic agent(s) to serve as a starting point for further therapy development.

Combined measures of PK and PD greatly increase the understanding of the in vivo efficacy of the therapeutic agent(s) by exploring the relationship between the concentration of the agent(s) at the site of action and the resulting efficacy measures. PK measurements reflect the body’s effect on the absorption, metabolism, distribution and excretion of the therapeutic agent.

For some biologic modalities, traditional PK might not apply; such applicants should still aim to measure the kinetics and distribution as needed for therapeutic development. For the purposes of this NOFO, in vivo efficacy measures reflect the effects of the therapeutic agent on endpoints that are closely tied to the desired clinical endpoints, but do not necessarily reflect target engagement.

While PD measures may also reflect the effects of the therapeutic agent on endpoints closely tied to the desired clinical endpoint, they must also reflect target engagement. Pharmacodynamic studies may include but are not limited to determination of 1) target occupancy (e.g., binding) and 2) proximal target activation (i.e., signal transduction, neurotransmission, protein synthesis, and gene regulation and transcription).

Examples of target occupancy studies may include but are not limited to Positron Emission Tomography (PET) and Single-Proton Emission Computed Tomography (SPECT).

In addition to the examples of proximal target activation listed above, more remote measures of target activation may also be considered, for example (but not limited to): ex vivo studies of ion channel function, EEG modulation, or changes in cerebral blood flow or metabolism as measured by fMRI.

Further development of potential therapeutic agents identified in IGNITE-supported efforts can be supported in later-stage programs such as the NIH Blueprint Neurotherapeutics Program (BPN) for Small Molecules , NIH BPN-Biologics , NIH SBIR/STTR , or other private or public sources. This NOFO uses the R61/R33 Phased Innovation Award mechanism.

Transition from the R61 to the R33 phase is contingent upon the successful completion of proposed milestones. Milestones are success criteria that are quantifiable and can be used for go/no-go decision-making at the R61/R33 transition point and must have timelines and quantitative criteria associated with them. The R61 and R33 must be distinct phases that do not overlap in time.

NINDS emphasizes the importance of the robustness and reproducibility of experimental results in evaluating progress (see https://www. ninds. nih.

gov/funding/preparing-your-application/preparing-research-plan/rigorous-study-design-and-transparent-reporting). Specific Aims or a list of activities are not considered milestones because they do not provide decision-making criteria for success. Section IV includes additional information regarding project milestones.

For frequently asked questions and milestone examples, please see https://www. ninds. nih.

gov/Current-Research/Research-Funded-NINDS/Translational-Research/Funding-Programs-Researchers/IGNITE . Rigor of Experimental Data NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency and provides additional guidance to the scientific community .

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. Rigor is particularly important for translational work, which forms a foundation for further development of potential therapeutic agents.

Rigorous efficacy studies are studies done with multiple doses that are supported by the pharmacokinetics data and done with clinically relevant routes of administration. Rigorous studies are also done using timings of treatments that reflect what is planned for in the patient population in models that reflect the relevant aspects of human disease as much as possible.

Novelty: This NOFO seeks to apply new knowledge around targets, mechanisms, pathways or therapeutic indications. Projects should aim to develop or “re-purpose” therapeutics that are significant improvements over existing therapeutics for neurological or neuromuscular disorders.

Biological rationale and preliminary data: Projects funded through this opportunity must have a strong biological rationale for the intended approach, along with preliminary data or literature-based evidence supporting the feasibility and importance of the approach. Preliminary data should be rigorous from well-designed experiments and can include outcomes analysis or validation studies.

Examples of the most critical elements for a well-designed study are summarized on the NINDS website (https://www. ninds. nih.

gov/funding/preparing-your-application/preparing-research-plan/rigorous-study-design-and-transparent-reporting). Relevance for therapy development: Projects should utilize early-stage therapeutic agents that have potential to be further developed for a neurological or neuromuscular disorder.

Applications should illustrate how the early-stage therapeutic(s) will be advanced toward later stages of discovery/development once the R33 phase is complete. Applicants should describe which patients would ultimately benefit from a successful therapeutic and how/when an eventual successful therapy would be delivered.

Examples of activities for the R61 phase include, but are not limited to: Preparation (such as synthesis of a pre-defined small molecule or small-scale manufacture of a biologic) of the therapeutic agent to support proposed activities.

This is not intended to support manufacture of material for IND-enabling or clinical studies For use and development of iPSC line therapeutics, please see NOT-NS-24-019 Confirm the identity and characterization of therapeutic agent(s).

This could include for example, confirmation of purity, stability, biophysical properties, in vitro absorption, distribution, metabolism, and excretion, in vitro potency and selectivity, degradation products, and process impurities Studies to develop dosage form(s) to support the proposed studies Pharmacokinetics studies to determine direct or indirect therapeutic agent levels.

For gene and cell therapy, these include characterization of gene copy numbers or tropism in tissues Studies to confirm that therapeutic agent reaches and engages the target site/tissue (directly or indirectly) at a concentration that exceeds in vitro pharmacological potency over the desired time period Studies to confirm selectivity of the therapeutic agent Limited studies to identify potential pharmacodynamic biomarkers specific for the purposes of developing the therapeutic agent(s) to be tested in the application Studies to inform design and refinement of the PD measure and/or in vivo efficacy models and testing procedures, including examination of model variability to estimate sample size, calibration of the model according to positive and negative controls, along with the age, time course and window of disease that are relevant for therapeutic testing.

For complete model validation, see PAR-25-060.

At the end of the R61 phase, investigators must exhibit successful completion of 1) all necessary preparation and characterization of proposed therapeutic agent(s), 2) pharmacokinetic studies (for gene and cell therapy, this can be the level of tropism by copy numbers and engraftment in various tissue or cells), 3) design, refinement, and validation of pharmacodynamic and/or in vivo efficacy animal studies using the appropriate positive and negative controls and demonstrating feasibility of conducting therapeutic agent testing and 4) a further refined in vivo study design (e.g., in an animal model) that meets the NIH guidance for rigor and transparency in grant applications and the NINDS NIH and NINDS Rigorous Study Design and Transparent Reporting guidelines and will allow for correlation of dose, therapeutic agent exposure in the target tissue, and pharmacological effect (i.e., demonstration of dose response and exposure response), thereby addressing subsequent feasibility.

Examples of activities for R33 phase include, but are not limited to: Pharmacodynamic and/or in vivo efficacy studies with chemically and biologically characterized therapeutic agent(s) including positive and negative controls, as appropriate Dose (exposure)-response activity with a route of administration relevant to future clinical use Studies correlating pharmacokinetic and pharmacodynamics measures (PK/PD) Preliminary studies to assess early safety or off-target effects (not including IND-enabling toxicity) Validation and replication studies to confirm observed results Developing therapeutics requires a multidisciplinary approach.

Investigators should form collaborations with those familiar with successful drug/biologic development (such as those from industry) as well as those familiar with what the desired end-product should look like (such as biostatisticians, technical experts and clinicians).

Applicants should consider how they will identify and foster relationships with potential licensing and commercialization partners early in the therapy development process once an award is made.

PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed at an appropriate time and that commercialization plans are developed and updated over the course of the project.

Additional Considerations: Applicants are strongly encouraged to contact NINDS Scientific/Research Staff to discuss potential research projects prior to submitting an application. This is to ensure this is the right NOFO and institute for your project and to help make sure critical elements (such as milestones and phases) are included. 2.

Small Business applicants who are eligible for the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs are strongly encouraged to submit through either the SBIR or STTR Omnibus Solicitations or other appropriate SBIR or STTR funding opportunity to take advantage of the congressionally mandated set-aside specifically for small businesses. Please see https://www. ninds.

nih. gov/Funding/Small-Business-Grants for more information about the programs. 3.

Prior to funding an application, NINDS Program staff may contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or Program staff. A final set of approved milestones will be specified in the Notice of Award.

Applications Not Responsive to this NOFO: Non-responsive studies include those that involve any of the following activities: Applications containing the following later-stage activities: Medicinal chemistry optimization or Structure-Activity-Relationship (SAR) studies for small molecules (for support for this work, please consider PAR-24-043 ) Optimization for biologics (for support for this work, please consider PAR-24-293 ) Investigational New Drug (IND)-enabling studies Manufacture of therapeutic agents for IND-enabling studies or clinical use Applications containing the following basic science activities: Studies designed to establish proof of concept for a biological target or use of therapeutic agents to identify targets relevant to a disease Studies of disease mechanism Development of assays or probes to support basic understanding of disease or other basic research Applications containing the following activities covered in companion IGNITE NOFOs: Extensive development and validation of animal or ex vivo models (for support for this work, please consider PAR-25-060 ) Screening/identification of novel therapeutic agents (for support for this work, please consider PAR-25-059 ) Applications with a significant focus (e.g. an entire aim) on developing pharmacodynamic biomarkers Discovery and development of diagnostic, monitoring, predictive or prognostic biomarkers (for support for this wok, please consider the NINDS Biomarker Program ).

Development of devices (for support for this work, please consider the NINDS Translational Devices Program ) device/drug combinations, surgical procedures, diagnostics, and rehabilitation strategies Projects that are entirely in silico Applications that are missing any of the following will be deemed to be incomplete and will be withdrawn and not reviewed: Activities for both the R61 and R33 phases with a clear demarcation of which activities are in the R61 phase and which are in the R33 phase, as described in Section IV.

2. The R61 and R33 phases cannot overlap in time; they are separate, sequential phases. Quantitative go/no-go milestones as an attachment, as described in Section IV.

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

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Direct costs cannot exceed $499,000 in any one year. Cumulative direct costs for the entire three-year project period may not exceed $750,000.

The total project period for a combined R61/R33 application submitted in response to this NOFO may not exceed three years, with no more than two years for the R61 phase and no more than two years for the R33 phase. (For example, a project could have a 1-year R61 and a 2-year R33 or could have a 2-year R61 and a 1-year R33.)

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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations). Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply-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 the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

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.

Eligible Individuals (Program Director/Principal Investigator) 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.

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 How to Apply- Application Guide. 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 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission 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 How to Apply- Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply-Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply-Application Guide must be followed.

Other Attachment #1: Milestones (required, 1-page limit) Transition from the R61 to the R33 phase is contingent upon the successful completion of one set of proposed milestones. These milestones will be evaluated as part of the scientific and technical merit of the R61/R33 application.

The milestones proposed in the application must be well-described, quantifiable, and scientifically justified to allow program staff to assess progress in the R61 phase. In addition, milestones should reflect the objectives of the application and be appropriate for the therapeutic approach, stage of development, and indication. Rationale should be provided for the choice of measures and values proposed for the milestones.

Specific aims or a list of activities are not considered milestones because they would not provide decision-making goals. A discussion of the milestones relative to the progress of the R61 phase and the implications of successful completion of the milestones for the R33 phase should be included. The clarity and completeness of the R61/R33 application with regard to specific goals and feasibility milestones are critical.

Milestones should provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application as part of the consideration of the awarded project for further funding of non-competing award years by the Program Director(s)/Principal Investigator(s), and Program Official(s).

For example, for a therapeutic where brain exposure is necessary, one milestone might be to show brain exposure of free drug or distribution of a biologic at a specified level for a specified time in an animal model. Applicants should propose milestones based on their particular project and should measure success of all essential R61 activities. More example milestones can be found at https://www.

ninds. nih. gov/Funding/Apply-Funding/Application-Support-Library/IGNITE-Milestone-Examples .

The existence of clear, quantitative, go/no-go milestones for transition from the R61 to the R33 phase is a requirement for this NOFO. Applications lacking an attached milestone document will be administratively withdrawn without review. Other Attachment #2 : Intellectual Property (required, 1-page limit) Applications must include an Intellectual property (IP) strategy.

Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials. Applicants should describe the IP landscape surrounding their therapy and assay.

Applicants should describe any known constraints that could impede their therapeutic discovery and development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, applicant's out-licensing agreements, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program.

If the applicant proposes using an agent(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should include a letter (see letter of support) from any entities owning the IP indicating there will not be any limitations imposed on the studies or the product which would impede achieving the goals of the funding program.

If patents pertinent to the therapy being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable. Applicants should also discuss future IP filing plans.

For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved, consistent with achieving the goals of the program.

For information on exceptions to the NIH data sharing policy due to intellectual property considerations, please see here: https://sharing. nih. gov/faqs#/data-management-and-sharing-policy.

htm? anchor=56972. Applicants are encouraged to contact Scientific/Research Staff if they have any questions or concerns.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Specific Aims: Within the Specific Aims section, include headers titled “R61 Phase Specific Aims” and “R33 Phase Specific Aims”.

Under each header, state the specific objectives of the efforts, including the technical questions you will try to answer to determine the feasibility of the proposed approach.

Since the goal of the R61 phase of this NOFO is the characterization of the therapeutic agent(s) (such as physio-chemical characteristics or pharmacokinetics of a small molecule, biological characteristics or distribution/tropism of a biologic agent(s)) along with the design and refinement of the pharmacodynamic and/or in vivo efficacy models or tests, hypothesis testing, per se, may not be the driving force in developing such an application, and therefore, may not be applicable in the R61 phase.

Research Strategy: Within the Research Strategy, applicants must describe both the R61 phase and the R33 phase, including the R61 transitional milestones and timeline. The R61 and R33 must be distinct phases that do not overlap in time.

The Research Strategy section should include a background section that clearly outlines the biological and therapeutic rationale for the application, including: 1) a description of the biological rationale linking the proposed therapeutic target and the disease of interest, 2) evidence for unmet medical need in the therapeutic disease area, 3) a brief description of any pertinent history for therapeutic development in the disease area, 4) evidence supporting the novelty of the therapeutic approach, and 5) a summary of the project status, including information regarding therapeutic agents to be tested in the current application.

The applicant should discuss the strengths and weaknesses of the prior research used to support the application and describe how the proposed research will address weaknesses or gaps identified by the applicant. This may include the applicant’s own preliminary data, data published by the applicant, or data published by others.

NINDS urges investigators to follow the NIH guidance for rigor and transparency in grant applications and additionally recommends the research practices described at Rigorous Study Design and Transparent Reporting . This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully.

These recommended research practices include, where applicable, expressing clear rationale for the chosen model(s) and primary/secondary endpoint(s), describing tools and parameters clearly, blinding, randomizing, ensuring adequate sample size, pre-specifying inclusion/exclusion criteria, appropriately handling missing data and outliers, implementing appropriate controls, preplanning