Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) is sponsored by National Institute on Aging (NIA). Supports pre-clinical and early-stage clinical development of novel drug candidates aimed at preventing or treating Alzheimer's disease.

PAR-25-297: Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) 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 Funding Opportunity Title Alzheimer's Drug-Development Program (U01 Clinical Trial Optional) U01 Research Project – Cooperative Agreements Notices of Special Interest associated with this funding opportunity 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 See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) invites applications proposing pre-clinical and early stage clinical (Phase I) development of novel small-molecule and biologic drug candidates that aim to prevent Alzheimer's disease (AD), slow its progression, or treat its cognitive and behavioral symptoms.

Grant recipients will receive funding for therapy development activities, such as the following: Absorption, Distribution, Metabolism, Excretion, Toxicology (ADMET) Efficacy in animal models Development of biomarkers for target engagement Formulation development chemical synthesis under Good Manufacturing Practices (GMP) Investigational New Drug (IND) enabling studies Initial Phase I clinical testing Funding Opportunity Goal(s) To encourage biomedical, social, and behavioral research and research training directed toward greater understanding of the aging process and the diseases, special problems, and needs of people as they age.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. 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 AD is the most common cause of dementia in older persons and is among the greatest healthcare challenges of the 21st century.

The disease currently affects an estimated 6. 7 million in the United States; by 2050, this number could rise as high as 14 million. To avert this public health crisis, effective therapies that prevent AD, slow its progression, or treat its cognitive and behavioral symptoms are urgently needed.

To catalyze drug development for AD, NIA is reissuing, with this NOFO, the Alzheimer's Drug Development Program (ADDP).

The ADDP offers researchers funding for drug development activities that can be conducted in their own laboratories, in collaboration with contract research organizations (CROs) that specialize in various drug development activities including the following: Efficacy in animal models Development of biomarkers for target engagement Chemical synthesis under GMP IND enabling safety-toxicology Initial Phase I clinical testing The overarching goal of the ADDP is the development of a broad range of novel drug candidates for AD, including small molecules, natural products, and biologics which will be eligible for Food and Drug Administration (FDA) approval.

Projects can enter the ADDP at one of the following stages: Early Stage - To optimize the agent's potency, drug-like properties, specificity, pharmacological properties, and/or ADMET properties and undergo dose-range finding toxicology and initial IND-enabling safety toxicology, or Late Stage - To advance development of candidates through all required IND-enabling toxicology studies, IND document preparation, and initial single dose, single ascending dose, or multiple ascending dose Phase I clinical testing Applicants are encouraged to contact the NIA Scientific/Research contact listed in Section VII.

Agency Contacts of this NOFO regarding the suitability of their projects for the ADDP and to clarify which entry stage is most appropriate for their project.

Stage Specific Entry Criteria Early Stage Entry Criteria for Small Molecule Projects Small molecule projects must meet the following requirements prior to entering the Early Stage: Rigorous data supporting the hypothesis that modulating the putative drug target/affected pathway will produce a desirable outcome for the intended AD indication (i.e., pre-clinical, prodromal/Mild Cognitive Impairment (MCI), early, mid and late stage).

A bioactive compound, in hand, that will serve as a starting point for optimization with proof of identity and purity (typically greater than 95%, as determined by, e.g., Nuclear Magnetic Resonance (NMR), melting point, or Liquid Chromatography/Mass Spectrometry (LC/MS), with no single impurity greater than 0. 5%).

In vitro biological activity (typically less than 1 micromolar (μM) in biochemical assays and less than 10 μM in cell-based assays relevant to the drug target), confirmed by repeat dose-response testing, with more than one batch of compound. Selectivity for the intended target over closely related targets, if desired (and when the target is known).

Availability of primary and secondary in vitro bioactivity assays that can be used or optimized for driving Structure-Activity Relationship (SAR) studies. Availability of preclinical animal model(s) that can be used to assess in vivo efficacy or target engagement (i.e., measurement of target binding or proximal downstream effects).

Studies using animal models presented to justify the choice of therapeutic target, drug candidate or, to determine efficacy, must be in compliance with NIH guidance on rigor and reproducibility . In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated.

Availability of selectivity and counter-screening assays to address potential activity at related targets and other undesirable activities or artifacts. Demonstration that the proposed secondary bioactivity assays and counter-screening and selectivity assays have sufficient reliability and throughput for their proposed use in the project.

Demonstration of a clear correlation between activity in the primary assay and activity in confirmatory assays and models, sufficient to justify advancement criteria in a testing funnel. No obvious legal (e.g., intellectual property) constraints to pursuing the proposed chemical scaffold(s) and using the proposed assays and models for research purposes and/or commercial development.

Early Stage Entry Criteria for Biologics Projects Biologics projects should meet the following qualifications prior to entering the Early Stage: Applicants should have one or more drug lead(s) from which a candidate can be derived. The drug lead(s) should be sufficiently characterized so that the parameters to be optimized can be quantitatively specified.

Established preliminary in-vivo efficacy and target engagement data using agent(s) in relevant animal model(s).

The agent(s) should show in-vivo efficacy using clinically relevant outcome measures (e.g., biochemical, neuropathological, behavioral, and/or functional, when possible) and in-vivo target engagement (e.g., measurement of target binding or proximal downstream effects) at the clinically intended site of action using sufficient experimental and statistical rigor in a relevant animal in-vivo proof-of-concept model.

Applicants should have pre-existing data demonstrating that the key in vitro and in vivo assays proposed to optimize the leads are suitable for the proposed purpose and available in either the applicant's or collaborator's laboratories. Availability of animal and/or cell-based model(s) that can be used to assess in vivo efficacy or target engagement (i.e., measurement of target binding or proximal downstream effects).

Studies using animal models presented to justify the choice of therapeutic target, drug candidate or to determine efficacy must be in compliance with NIH guidance on rigor and reproducibility . In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated.

No obvious legal (e.g., intellectual property) constraints to pursuing the proposed biologic agent(s) using the proposed assays and models for research purposes and/or commercial development.

Late Stage Entry Criteria for Small Molecule Projects Small molecule projects should meet the following qualifications prior to entering the Late Stage: A strong data package linking the putative drug target/affected pathway to the proposed disease indication and supporting the hypothesis that altering the target activity as proposed will produce desirable outcomes for the disease.

Proposed compounds should have in vitro and in vivo biological activity and ADMET properties appropriate for the intended clinical use (i.e., the disease indication, patient population, delivery mode, treatment duration, and treatment regimen) and outcomes. In vivo study results that include assessments of PK, bioavailability at the relevant site of action, and the pharmacokinetics-pharmacodynamics (PK/PD) relationship.

Rigorous evidence that the agent is a blood-brain-barrier penetrant (unless the agent is proposed to be delivered directly to the Central Nervous System (CNS)). A data package showing a clear and convincing demonstration of preclinical efficacy. The data package can include in vivo efficacy in an established AD animal model and/or in vivo target engagement.

Studies using animal models presented to justify the choice of therapeutic target, drug candidate or, efficacy must be in compliance with NIH guidance on rigor and reproducibility . In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated.

A data package that includes Ames mutagenicity, hERG activity, microsome stability, cytochrome P450 (CYP) inhibition, plasma protein binding, and aqueous solubility. A data package that includes counter-screening aimed at determining selectivity across a broad panel of closely related and unrelated pharmacological targets (e.g., G protein-coupled receptors, kinases, etc.).

No obvious legal (e.g., intellectual property) constraints to pursuing the proposed small molecule(s) using the proposed assays and models for research purposes and/or commercial development.

Late Stage Entry Criteria for Biologics Projects Biologics projects should meet the following qualifications prior to entering the Late Stage: A data package demonstrating completed optimization and final characterization of the candidate, such as structure/identity, selectivity, bioavailability stability, formulation, manufacturability, sufficient purity, clinically intended route of administration, minimal effective dose, optimal effective dose, time and duration of treatment as determined in relevant in vivo assays using clinically relevant functional and/or pathological outcome measures, and/or in vivo target engagement assays.

Proposed compounds should have in vitro and in vivo biological activity and ADMET properties appropriate for the intended clinical use (i.e., the disease indication, patient population, delivery mode, treatment duration, and treatment regimen) and outcomes. In vivo study results that include assessments of PK, bioavailability at the relevant site of action, and the PK/PD relationship.

Details concerning special formulations, if proposed (i.e., slow release, liposomes, nanoparticles, etc.). Rigorous evidence that the agent is a blood-brain-barrier penetrant (unless the agent is proposed to be delivered directly to the CNS). A data package showing a clear and convincing demonstration of efficacy.

The data package can include in vivo efficacy in an established AD animal model and/or in vivo target engagement at the clinically intended site of action. Studies using animal models presented to justify the choice of therapeutic target, drug candidate or, efficacy must be in compliance with NIH guidance on rigor and reproducibility .

In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated.

A data package that includes Ames mutagenicity, hERG activity, microsome stability, CYP inhibition, plasma protein binding, and aqueous solubility. No obvious legal (e.g., intellectual property) constraints to pursuing the proposed biologic agent(s) using the proposed assays and models for research purposes and/or commercial development.

Drug Development Activities Supported Through this NOFO Supported Early Stage Activities for Small Molecule Projects Examples of Early Stage activities for small molecule projects include, but are not limited to, the following: Testing of analogs in bioactivity assays and animal models Testing of analogs in selectivity and counter-screening assays Assessment of efficacy and/or target engagement.

Studies using animal models to measure target engagement and/or efficacy must be in compliance with NIH guidance on rigor and reproducibility . In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated Identification of biomarkers for target engagement Testing of analogs in ADMET assays (e.g., microsome stability, CYP induction and inhibition, solubility, permeability in Madin-Darby Canine Kidney (MDCK) or Caco-2 cells, plasma protein binding, brain/plasma ratio, PK in multiple species) Compound stability studies Multiple dose rodent PK testing with PD correlations, if possible Dose-range finding toxicology studies Initial IND-enabling toxicology Supported Early Stage Activities for Biologics Projects Examples of Early Stage activities for biologics projects include, but are not limited to, the following: Optimization of leads for improvement in potency, specificity, bioavailability, and suitability for human testing Selection of the best promoter or viral serotype for a gene therapy product Humanization of a mouse monoclonal antibody Characterization of identity and properties (e.g., cell phenotype, aggregation, epitope mapping, post-translational modifications, sequences, viscosity, stability) Assessment of in vitro activities (e.g., affinity, specificity, activity in cells, cellular uptake) Assessment of efficacy and/or target engagement.

Studies using animal models to measure target engagement and/or efficacy must be in compliance with NIH guidance on rigor and reproducibility . In particular, investigators proposing animal model studies are expected to follow the general ARRIVE guidelines for rigorous animal research and the best practices guidelines for AD preclinical efficacy studies .

These studies should include a power analysis and associated assumptions for the determination of sample size, statistical handling of the data (such as criteria for data inclusion or exclusion), procedures used for blinding and randomization, and whether studies were balanced for sex and were replicated Identification of biomarkers for target engagement Assessment of in vivo pharmacology such as determination of dose range, dosing regimen, duration of treatment Assessment of PK/PD properties Minimizing a predicted or previously encountered toxicity Optimization of delivery systems and special formulations (i.e., slow release, liposomes, etc.) Optimization to have better suitability for the route of administration Developing a production plan Dose-range finding toxicology studies Initial IND-enabling toxicology Supported Late Stage Activities for Small Molecule Projects Examples of Late Stage activities for small molecule projects include, but are not limited to, the following: Chemistry, Manufacturing, and Control (CMC) activities (e.g., purification development, CMC analytical development, formulation development, salt and polymorph screening, scale-up manufacturing, compound stability studies, and GMP manufacturing) for IND-enabling pharmacology/toxicology testing Multiple dose rodent PK testing with PD correlations, if possible Dose-range finding toxicology studies Metabolite identification IND-enabling toxicology, with toxicokinetics, if applicable IND document preparation (the PD/PI will be responsible for the submission of the IND application and scheduling meetings with the Food and Drug Administration (FDA)) GMP manufacturing of material for Phase I clinical testing First-in-human Phase I clinical trial (i.e., single dose, single ascending, or multiple ascending study.

Clinical trial outcomes may include safety, tolerability, PK and PD, target engagement, and target modulation endpoints) Supported Late Stage Activities for Biologics Projects Examples of Late Stage activities for biologics projects include but are not limited to the following: CMC activities (e.g., master and working cell banks development, purification development, CMC analytical development, formulation development, scale-up manufacturing, compound stability studies, and cGMP manufacturing) for IND-enabling pharmacology/toxicology testing PK evaluations in species relevant for toxicology or human dose-prediction Preliminary safety such as safety pharmacology and/or dose-range finding toxicology IND-enabling toxicology, with toxicokinetics, if applicable Tumorigenicity evaluations particularly for gene therapies and cell therapies Immunogenicity evaluations GMP manufacturing of material for Phase I clinical testing First in-human Phase I clinical trial (i.e., single dose, single ascending or multiple ascending dose study.

Clinical trial outcomes may include safety, tolerability, PK and PD, target engagement, and target modulation endpoints) Non-Responsiveness Criteria: The following types of applications will be considered non-responsive to this NOFO and will be administratively withdrawn prior to scientific peer review: Basic research and studies of disease mechanism Studies aimed at mechanisms of drug action Animal model development studies Stand-alone preclinical efficacy studies in animal models Screening studies to identify hit compounds Projects aimed at anti-amyloid therapies (e.g., beta- and gamma-secretase inhibitors, amyloid aggregation inhibitors, and anti-amyloid immunotherapies) Projects aimed at developing anti-tau immunotherapies Projects that propose to develop generic or off-patent compounds for AD Projects that propose to repurpose or develop new formulations or drug delivery systems for compounds that have previously been approved for another indication by FDA or any other worldwide regulatory agency Projects that propose to develop and/or test combination therapies Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers projects Development of diagnostics and diagnostic devices projects Stand-alone clinical trials Studies directed beyond Phase I clinical testing Milestone-driven research is used to ensure research is focused on a well-defined goal and achieving that goal with the greatest efficiency.

As drug development research is inherently high risk, the use of milestones provides clear indicators of a project's continued success or emergent difficulties. The milestones must provide objective and quantitative success criteria which are recognizable as appropriate endpoints for a specific scientific goal and can be used to monitor the progress made by a research project.

The milestones will serve as a basis for go/no-go decision making between NIA program staff and the project research team. Therefore, the application must include a table or list of go/no-go milestones with quantitative success criteria for each year of funding.

Prior to funding of an application, NIA program staff will contact the applicant to discuss the proposed milestones and any modifications to the milestones recommended by the review committee or NIA Program staff. A final set of approved milestones will be specified in the Notice of Award. Progress towards achievement of the established milestones will be evaluated by a committee composed of NIA program staff.

If warranted, the milestones for future years may be revised based on data and research progress during the preceding year. Note : If a funded project does not make satisfactory progress toward the agreed upon milestones at any stage during the funding period, future year grant funding may be discontinued.

Quality and Compliance Requirements Since one of the goals of the ADDP is to generate drug candidates which will be eligible for FDA approval, adherence to compliance and quality criteria is required.

It is expected that all IND enabling nonclinical studies will be performed in a manner consistent with Good Laboratory Practices (GLP) and current FDA guidance All clinical trials must be performed following Good Clinical Practices (GCP) and in accord with the NIH Policy for Data and Safety Monitoring The creation and protection of intellectual property (IP) that will make drug candidates attractive to potential licensing and commercialization partners is an important activity to be undertaken by the PD/PI in consultation with their institutions' technology transfer officials.

This program is structured so that the awardee institution retains their assignment of IP and thereby controls the patent prosecution and licensing negotiations for drug candidates developed in this program. It is expected that the awardee institution will take responsibility for patent filings, maintenance, and licensing efforts toward eventual commercialization.

Evaluation of this Program In carrying out its stewardship of this NOFO, NIA may request information essential to an assessment of the effectiveness of this program from the participants. Participants may be contacted during and after the completion of this award for periodic updates on information helpful in evaluating the impact of the program.

In carrying out its stewardship of this NOFO, NIA may request information essential to an assessment of the effectiveness of this program from the participants. Participants may be contacted during and after the completion of this award for periodic updates on information helpful in evaluating the impact of the program. NIA will use this information to determine overall success of the program in developing drugs for AD.

OutreachPro. OutreachPro is an online recruitment materials generator that enables grantees to develop customizable and culturally appropriate materials in multiple languages to raise awareness of, and interest in, AD/ADRD clinical trials.

Grantees and research teams are encouraged but not required to use this free online resource to enhance their recruitment and retention plans and related activities for their NIA-funded clinical studies. Clinical Research Operations Management System NIA uses a central resource to NIA staff and extramural investigators to facilitate/support the conduct and management of clinical research.

NIA Clinical Research Operations & Management System (CROMS) is a comprehensive data management system to support the business functions, management, and oversight responsibilities of NIA grants that support the conduct of clinical research with human subjects.

NIA investigators of grants, contracts, and cooperative agreements that are active as of July 1, 2021, including clinical trials funded as pilots, exploratory studies, or other projects through this Consortium, and support human subjects research as defined by the DHS HHS OHRP regulations at 45 CFR 46 will be required to interact with and use existing and future components of CROMS as required by NIA throughout the lifecycle of the grant, as described in NOT-AG-23-017 .

Data to be submitted to NIA CROMS includes those elements reported in the standard NIH requirement annual progress report (GPS 4. 1. 15.

7). Details regarding the standard operating procedures for CROMS can be found on the NIA CROMS website . When applicable, all NIA grantees must ensure: 1.

The study’s Informed Consent Document (ICD) lists “The National Institutes of Health (NIH) and its authorized representatives” as one of the organizations that may look at or receive copies of information in participants’ study records. According to DHS HHS OHRP 45 CFR 46 §46. 116 , all ICDs must contain “A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained.

” If using the NIA informed consent template , please see Section 6: Statement of Confidentiality. 2. An assigned NIH ClinicalTrials.

gov identifier (NCT number) is reported in its respective CROMS study record within three months after assignment, and the reporting of final enrollment data to CROMS is consistent with final enrollment data reported in ClinicalTrials. gov. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

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. Optional: Accepting applications that either propose or do not propose clinical trial(s).

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.

Application budgets are limited to $1,500,000 in direct costs per year and need to reflect the actual needs of the proposed project For Early Stag e projects, the project period is limited to five years. For Late Stage projects, the project period is limited to four years. 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) are not 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 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 registrations; 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