Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) (R61/R33 Clinical Trial Not Allowed)

Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) (R61/R33 Clinical Trial Not Allowed) is sponsored by NIH/NIAID. The purpose of this NOFO is to accelerate the development of safe and effective long-acting drug delivery systems for improved, simplified treatment of HIV-1 in children.

Expired RFA-AI-23-061: Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) (R61/R33 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. 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 Allergy and Infectious Diseases ( NIAID ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Mental Health ( NIMH ) Funding Opportunity Title Long-Acting Drug Delivery Systems for ART Optimization in Children Living with HIV-1 II (LADDS II) (R61/R33 Clinical Trial Not Allowed) R61 / R33 Exploratory/Developmental Phased Award 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 .

Notice of Funding Opportunity (NOFO) Number Companion Funding Opportunity See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to accelerate the development of safe and effective long-acting drug delivery systems for improved, simplified treatment of HIV-1 in children.

This NOFO invites applicants engaged in the development of existing long-acting platforms at early stages of development stages to perform specific preclinical activities that enable product optimization and accelerated translation to HIV-infected children. Collaborative research partnerships with industry are required.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due 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.

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 While some advances are being made in antiretroviral therapy (ART) coverage for pediatric populations, significant gaps remain. Currently available ART regimens for children have limitations and result in suboptimal viral suppression. Infants and young children achieve even lower rates of viral suppression and are more likely to experience subsequent viral rebound.

Key factors underlying these suboptimal viral suppression outcomes include suboptimal regimen potency, poor adherence in all pediatric populations, often the result of poor regimen tolerability, lack of appropriate formulations, and poor palatability of many of the existing formulations.

Additional factors contributing to limitations in treatment efficacy include high rates of pre-treatment drug resistance, hypervariable antiretroviral (ARV) drug exposures in early life due to ontogeny of drug metabolizing enzymes and transporters, significant and pervasive stigma, and non-disclosure of HIV status affecting mothers living with HIV, all of which can perpetuate poor virologic suppression rates and associated morbidity and mortality.

While the roll out of a promising daily pediatric friendly oral dolutegravir formulation is underway in many low- and middle-income settings and presents the prospect of improving dismal viral suppression rates in this population, its impact is still limited by factors common to daily oral ART including stigmatization concerns and persistent adherence challenges.

Long acting ARVs represent a major therapeutic advance for people living with HIV across the age spectrum. They offer the prospect of enhanced treatment convenience and improved treatment adherence and stigma reduction, potentially removing a key barrier to maintenance of viral suppression.

A combination of two long-acting injectable drugs has received regulatory approval for 2-monthly administrations for the treatment of HIV-1 in adults and adolescents and is being investigated in younger children. Another long-acting drug was also recently approved for 6-monthly administration in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current ART regimen.

Despite such remarkable progress, further advances are needed to fully realize the promise of long-acting treatment for HIV treatment and sustained effort is necessary to accelerate their introduction in pediatric populations.

Long-Acting Drug Delivery Systems (LADDS) that can overcome limitations of daily oral ART are needed to significantly simplify dosing requirements and optimize ART outcomes in infants and children through achievement and maintenance of consistent and effective drug levels and suppression of HIV replication.

Stimulating critical optimization and preclinical activities at an earlier stage in the product development lifecycle could significantly facilitate and accelerate introduction of promising LADDS platforms to young pediatric populations, often the last ones to benefit from treatment innovations. The goal of this Notice of Funding Opportunity (NOFO) is to support development of LADDS for optimized treatment of HIV-1 in children.

This initiative will stimulate the optimization and evaluation of LADDS formulations in suitable preclinical animal models, at an earlier stage of adult drug development. Supporting optimization and evaluation of LADDS formulations in suitable preclinical animal models could accelerate clinical translation in pediatric populations and improve HIV-1 treatment outcomes in children.

Research Objectives and Scope Successful applications will need to propose: A long-acting drug delivery platform which must include the following attributes: Platform is already in development, ideally for ART use in adult populations, however, innovative platforms in development for non-pediatric or non-ART use are also acceptable. This should serve to increase future market prospects of any product developed as part of this program.

A single platform that can deliver a complete ART regimen (consisting of 2 or more ARVs) for HIV treatment. However, inclusion of a single ARV is allowable, if needed to meet the minimum required dosing interval, even if separate administrations of the ARVs are required, provided that a complete ART regimen is proposed as part of the application.

LADDS are able to support a minimum dosing interval of 8 weeks delivering ARV exposures that are expected to match adult exposure associated with efficacy or that remain above four times the protein-adjusted IC90 (paIC90) for each ARV at the end of the dosing interval.

ARVs and ART regimen chosen should be clinically relevant and ideally supported by existing treatment guidelines or if in pre-approval stages, recognized as high priority ARVs with early data supporting their high potential for future development.

Platform development that targets pediatric populations aged less than 12 years of age and preferably children less than 6 years of age and are well suited to accommodate unique growth and development characteristics of the target pediatric population.

Innovative PB-PK modelling and other in silico approaches to inform optimization of LADDS formulations for pediatric use and ARV dose selection to be applied in future pediatric clinical studies. Appropriate use of preclinical animal models including: Pre-clinical in vitro studies to characterize potential platforms and select ARV candidates during the R61 phase of the award.

An animal antiviral efficacy study of the LADDS candidate in age/maturation-matched non-human primates (NHP)s during the R33 phase of the award. Socio-behavioral studies initiated during the R61 phase to assess end-user preferences and inform final production design. Where possible, preferences from all stakeholders (e.g., caregivers, children, providers) should be considered.

The methods should be appropriate to the stage of product development, and could involve qualitative methods, discrete choice surveys, or other novel product acceptability methods. Where possible, the research should be iterative; that is, behavioral research should occur throughout development to provide feedback on the product at each step and inform future iterations.

A behavioral scientist with appropriate expertise in the proposed behavioral methods should be included. An industry/drug development partner which could be an established company, startup biotech company or non-profit organization with knowledge and resources to support early product development and regulatory interactions to enable a possible future path to market.

Planning for a Pre- Investigational New Drug (pre-IND) meeting with the FDA before the end of the R33 Phase.

In addition, inclusion of a pediatric-focused Quality Target Product Profile (pQTPP) is recommended at the R61 stage to summarize long-acting drug product critical properties and targets for development, with attention to those properties of key relevance to pediatric populations living with HIV in Low- and Middle-Income settings.

The pQTPP might describe the essential product attributes (product release profile and duration of action, target age, optimal dosing regimen, dose flexibility, acceptable duration of PK lag periods and tails, maximum and minimum PK targets, PD targets, stability and storage requirements, desirable acceptability/desirability-derived attributes, and cold chain/storage requirements, regulatory pathway) by identifying optimal and minimally acceptable attributes for the drug and its platform.

Applications proposing the following types of studies or approaches will be considered non-responsive and will not be reviewed: de novo LADDS engineering. New molecular entity discovery work. Applications proposing human clinical trials.

LADDS not meeting the minimum duration of action defined in the NOFO. Use of any live biotherapeutic or vector system. Development of broadly neutralizing antibodies.

LADDS and ARV combinations previously developed for pediatric populations. Applications without an industry partner as defined above. Applications without end-user preferences studies.

Due to the high-risk, high-impact nature of the research, this funding opportunity will use the R61/R33 phased innovation grant award mechanism. Support will be provided for up to two years (R61 phase) for pre-clinical research to optimize the long-acting platform and ARV payload, characterize duration of action, setting up and initiating the end user preferences studies and other related activities.

Up to three years of support may follow (R33 phase) for additional activities as appropriate, such as completion of end user preferences studies, evaluation of optimized delivery system in suitable NHP models, preparation of the pre-IND package and pre-IND meeting with the FDA. Proposed milestones will be reviewed and negotiated prior to award with NIH program staff.

Before the end of the R61 phase, awardees will submit the R33 transition package, which includes a detailed progress report describing advancement toward the initial milestones and a description of how the completed work justifies continuation with the originally proposed R33 studies.

These materials will be evaluated by NIH Program staff; grants selected for continued funding will be transitioned to an R33 award without the need to submit a new application. Transition to the R33 phase is neither automatic nor guaranteed; R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, Program priorities, and availability of funds.

It is expected that approximately one-half of the projects supported during the R61 Phase will continue into the R33 Phase. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support 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 SF424 (R&R) 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 Issuing IC and partner components intend to commit an estimated total of $2,800,000 to fund 3-4 awards. Applications budgets are not expected to exceed $850,000 in direct costs per year during the R61 Phase and $1,250,000 in direct costs per year during the R33 Phase. All F&A costs are excluded from this limit.

Requested budgets should reflect the actual needs of the proposed project. Applicants may request up to two years of support for the R61 phase, and up to three years of support for the R33 phase. The maximum project period for an application submitted in response to this NOFO cannot exceed five years total.

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 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 (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 Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 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. The NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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.

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. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement. 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. 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: All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) 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. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile 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. PHS 398 Cover Page Supplement 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: Briefly describe in clearly demarked sections the overall objective(s) and specific aims for both the R61 and R33 phases of the proposed research plan. Research Strategy: Describe how the proposed LADDS represents an advance beyond and is different from products currently being developed.

Describe how the proposed development pathway helps to establish the next generation of products for possible accelerated clinical testing in pediatric populations, and how achievement of the proposed R61 and R33 milestones enable product development. Clearly describe the justification for using the pediatric population/age range proposed for LADDS development.

Describe the LADDS pediatric development plans, including: The ARVs selected, selection process, rationale and how the ARVs will be incorporated into the drug delivery system (DDS) to achieve the required durations of action, at the targeted exposures.

The strategy to ensure that the appropriate exposure target(s) are selected and outline plans to optimize exposure matching with levels associated with efficacy in adult populations or, if not yet available, plans to achieve exposures exceeding paIC90.

The approach to enable incorporation of a full HIV regimen in a single LADDS, or alternatively if a single ARV is incorporated in the LADDS, the strategy to develop a complete ARV treatment with more than one LADDS, that can generate end-user acceptance. The rationale and approach to achieving the minimum duration of action (8 weeks) required for the LADDS.

Suitability of the proposed LADDS for the target age group(s) in relation to the development stage and trajectory. TPP (optional): applicants may include a TPP to summarize sustained/extended-release drug product critical properties and targets for development.

The TPP might describe the essential product attributes (product release profile and duration of action, optimal dosing regimen, acceptable duration of PK lag periods and tails, maximum and minimum PK targets, PD targets, stability and storage requirements, desirable acceptability/desirability-derived attributes, and cold chain/storage requirements) by identifying optimal and minimally acceptable criteria for the drug and its platform.

Describe how the animals proposed are appropriate (type, age, sex, and maturity) for the LADDS development in the target population; describe the study design features that allow for an assessment of potential safety and effectiveness of the LADDS strategy, including study design elements that support the integrity of the study endpoints.

End User Acceptance Acceptability: Describe how Social Behavioral Studies (SBS) assess end user acceptance, and how they will be performed iteratively throughout the product development stages and inform final product design. Describe how the appropriate behavioral scientific expertise will be reflected within the research team.

Regulatory Strategy and FDA Pre-IND Meeting: In a clearly labeled section provide the strategy to collect the necessary data and put together the required package for a pre-IND meeting with the FDA during the R33 Phase. Describe how the meeting will contribute to product development and enable clinical testing in pediatric populations. Applicants must submit a single application that includes both the R61 and R33 phases.

Relevant information or data to support the rationale/hypothesis should be provided as evidence that the proposed project is feasible and well-designed for the intended purpose. In a clearly labeled section, provide milestones for BOTH the R61 and R33 phases of the award. Proposed milestones should describe research outcomes by providing quantifiable measures for success within the R61 and R33 phases.

Milestones must be specific, scientifically rigorous, and not simply a restatement of the specific aims. Descriptions of the milestones must include Go/No-Go criteria to support critical parameters of the milestone that will determine whether the research should move forward or cease due to pediatric product development failures (transition milestones).

Milestones should address critical points required for sustained/extended-release products. The following milestones are examples that may be included: Demonstration of proposed duration of action. Definition of optimal dosing regimen including PK lag and tail.

Identification of active pharmaceutical ingredient (API), API-DDS (Drug Delivery System) and DDI (Drug-Drug Interaction). Characterization of anti-HIV efficacy of the sustained/extended-release prototype in an animal model. Socio-behavioral studies to assess end-user acceptability/desirability outcomes and integration into LADDS development for pediatric indications.

Letters of Support: Provide a letter of support indicating the availability of non-human primates for experiments in the R33 phase from a non-human primate facility that includes infant and juvenile animals and/or a breeding program. 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.

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. Appendix: 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.

PHS Human Subjects and Clinical Trials Information 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.

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. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. 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 4.

Submission Dates and Times 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 SF424 (R&R) 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 .

7. Other Submission Requirements and Information 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.

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 Institute of Allergy and Infectious Diseases, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy Section V. Application Review Information 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