Advancing Sustained/Extended Release for HIV Prevention (A-SER)

Advancing Sustained/Extended Release for HIV Prevention (A-SER) is sponsored by NIH/NIAID. This Funding Opportunity Announcement (FOA) aims to stimulate the development of new and innovative sustained/extended release (SER) drug delivery systems (DDS) that can achieve extended durations (months to years) and provide systemic protection from all routes of HIV infection…

Expired RFA-AI-19-063: Advancing Sustained/Extended Release for HIV Prevention (A-SER) (R01 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 ) of Participating Organizations National Institute of Allergy and Infectious Diseases ( NIAID ) National Institute of Mental Health ( NIMH ) Funding Opportunity Title Advancing Sustained/Extended Release for HIV Prevention (A-SER) (R01 Clinical Trial Not R01 Research Project Grant Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to stimulate the development of new and innovative sustained/extended release (SER) drug delivery systems (DDS) that can achieve extended durations (months to years) and provide systemic protection from all routes of HIV infection/transmission in at-risk individuals.

This FOA focuses on the following scientific priority DDS: low-volume depots compatible with self-injection technologies, erosible/biodegradable implants including in situ forming implants, intrauterine delivery systems and transdermal delivery systems. Applications will require an industry partner.

Applications incorporating drugs that are already under development or approved for HIV prevention and/or treatment by their intellectual property/patent/license holder must involve these persons/entities in a meaningful and significant manner in the application through letters of support and/or other evidence of a substantial commitment.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date Only accepting applications for the AIDS Application Due AIDS Application Due Date(s) December 4, 2019, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on the listed date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) 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 the Announcement I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description The objective of this FOA is to support the development of specific SER DDS with rheological and biophysical properties that address scientific gaps in DDS development for SER HIV prevention.

This FOA is limited to support of the development of the following DDS: low-volume depots compatible with self-injection technologies, erosible/biodegradable implants including in situ forming implants, intrauterine delivery systems (IDS) and transdermal drug delivery systems.

The ultimate SER product should provide months to years of HIV prevention coverage, be reversible through removal of the DDS, while offering set it and forget it protection from HIV infection.

The SER DDS targeted by this FOA represent emerging approaches for delivery of SER HIV prevention strategies and are needed to enable users to more easily adhere to HIV prevention dosing regimens by reducing dosing frequency, enabling longer more effective durations of drug coverage.

For the purposes of this FOA, the target populations are ages 14 years and older males and females, including transgender and gender non-conforming populations desiring SER products to prevent HIV acquisition/transmission.

For DDS that are dependent on individual user decisions to use or not to use, multiple behavioral and social factors (individual, cultural, stigma-derived, DDS-related, etc.) have been identified that can contribute to low prevention product adherence.

The results of numerous non-vaccine biomedical HIV prevention (nBP) phase III clinical trials have demonstrated conclusively that both adolescents and adults, when required to use daily dosing or coital-associated (pre and/or post) dosing with gel or an intravaginal ring (IVR), encounter problems in maintaining adherence over longer timeframes.

Multiple user behavioral and social factors (individual, cultural, stigma-derived, DDS-related, etc.) have been identified that can contribute to low adherence for prevention products. Biological and pharmacological barriers may also play a role in the effectiveness of prevention strategies where individual use decisions control adherence and the pattern of drug use.

In vitro modeling and direct observed therapy pharmacokinetic (PK) studies of daily oral emtricitabine/ tenofovir disoproxil fumarate (TDF/FTC) pre-exposure prophylaxis (PrEP) have shown that with a daily pill-taking regimen approximately 28% adherence by men and 85% adherence by women are required to achieve active metabolite levels in the blood and mucosal tissues associated with efficacy.

To improve adherence and potentially reduce its impact on prevention strategies, the nBP field has begun to evaluate anti-HIV drugs with longer durations of action in an effort to reduce the impact of inconsistent drug use due to inconsistent adherence.

The most advanced of these efforts are Phase III clinical trials of a q8 weeks injection of a nanocrystal formulation of the integrase inhibitor cabotegravir for HIV prevention in men (HPTN 083) and women (HPTN 084). Although injectable SER prevention strategies could potentially have a significant impact on the HIV pandemic by removing the need for frequent dosing, there is still room for improvement.

There are several questions that remain to be answered as well as capabilities that may need to be incorporated into SER HIV prevention strategies.

These include: the impact of excess drug exposure (drug burst) after dose initiation on safety and establishment of protection; the impact of periods of suboptimal drug exposure (PK tail, time during which drug drops below effective levels) on emergence of resistance; the safety implications of not being able to terminate dosing if adverse events occur when deviceless (e.g. injection) DDS strategies are used; creation of user-friendly dosing schemes (volume of injection, size/number of devices used/implanted, and placement); and methods for renewing the dose (site of drug application, surgical procedures and user friendly durations) that facilitate the decision to engage in the SER prevention strategy.

Therefore, this FOA focuses on developing the next generation of SER DDS optimized not only for delivery of HIV prevention (PK, PD, etc.), but also for their interaction with the user (look and feel) to increase the potential for initial uptake and continued use.

For the purposes of this FOA, sustained release is defined as continuous exposure to the anti-HIV drug from a DDS that is achieved using either a continuous release device or through creation of a tissue depot. Extended release is defined as providing protection from HIV infection/transmission for a longer duration resulting in more consistent exposure to the prevention drug.

Combining these 2 concepts into an optimal DDS supports development of only the following DDS for the indicated Low-volume self-injectables (depot and non-depot forming) optimized for delivery in a self-injector for 3 months or more. Low volume is defined as a total injection volume (single site or multiple sites of less than Erosible implants or in situ forming biodegradable implants/depots for 6 months or more.

A non-contraceptive intrauterine delivery system (IDS) that will deliver an antiviral for 3 years or more and that will provide systemic protection Transdermal patches (continuous use or short exposure depot-forming) for 1 month or more The following areas of preclinical drug development and behavioral research may be proposed for any of the above DDS: Development of single and combination drug SER strategies with the ability to protect against HIV infection/transmission/acquisition from all routes of HIV mucosal exposure: female reproductive tract (FRT), male genitourinary system (MGS), and/or gastrointestinal (GI) tract.

Understanding the PK of SER products by mapping the characteristics of drug(s) release including: drug burst (initial and during biodegradation of the DDS), lag period (time to establish effective concentrations), PK tails (duration of drug exposure beyond the effective concentration), and forgiveness intervals (dosing intervals during which the drug/DDS must be renewed to maintain continuous efficacy).

Understanding the processes of DDS erosion and degradation, specifically its impact on drug PK during terminal erosion/degradation (terminal drug burst), the time to full DDS dissolution after drug exhaustion, and the impact of redosing in the presence of residual DDS on the user.

Understanding the potential for and identifying/characterizing drug-drug interactions (DDI) and drug/device interactions that could compromise the effectiveness of a SER DDS or maintenance/prevention medicines.

Understanding the impact of continuous antiviral drug delivery or DDS degradation products on tissue sites, such as activation of drug transporters, foreign body reactions (wound healing, acute and chronic inflammation, foreign body responses, etc.) and/or local and systemic distribution of drug to HIV target tissues.

Understanding Preferred User Characteristics (PUC), which will govern decisions made by individuals to use the SER strategy (look and feel), and whether to adopt and maintain use of longer duration strategies. For this FOA, PUCs are defined as the rheological/biophysical properties of the SER DDS that invoke user judgments/decisions resulting in first-use, subsequent-use or no-use and/or early termination.

Areas of Research Interest Examples of the types of research responsive to this FOA include, but are not limited to: SER DDS that provide systemic prevention of HIV replication and infection in both male and female animal models of HIV/SIV/SHIV infection. Combination SER which deliver all drugs simultaneously from a single DDS.

DDS which compartmentalize the drugs to address drug-drug interactions (DDI) and/or create different release rates are responsive. Use of animal model PK, PD and toxicokinetic (TK) studies to support the proposed duration of use and safety of the SER DDS.

Of significant interest are PK studies that establish efficacy and safety relationships between plasma and GI, MGS, and FRT (upper and lower) tissues/secretions, lymphoid tissues, and dosing/implantation site drug concentrations.

Performance of PK/PD studies which characterize and optimize the lag, duration, PK tail, forgiveness interval and characterize and minimize the interval between drug exhaustion and full degradation of erosible/biodegradable Use of novel polymers, nanotechnology, 3-D printing and other novel/emerging technologies to solve specific problems related to the responsive DDS, such as: DDI, duration of action, tissue/systemic distribution, Hypothesis-driven research focused on the impact of the SER drug on the FRT/MGS/GI tract, specifically on mucosal barrier and immune function as it relates to the safety/efficacy of the proposed SER drug product and DDS.

This may include impact on drug transporters, inducible and non-inducible cellular drug-degradation and metabolism pathways, as well as the impact of the DDS/drug on epithelial cell function, mucosal wound repair, immune cell trafficking, and the impact of prolonged exposure of the drug on innate, adaptive and cellular immunity. Histology of implant/depot sites that encompass the proposed duration of the DDS.

PUC research focusing on identifying factors which may influence an individual’s choice to use, using behavioral and social science tools that measure user perceptions of the DDS, such as ethnographic studies, perceptibility assessments, mental modeling, user journeys, discrete choice and conjoint analysis.

Research involving potentially prescribing physicians/health givers in the U.S. focusing on identifying attributes of the SER DDS, such as implant size, location and placement, that could negatively impact their willingness to provide the product.

Pilot manufacturing of the SER DDS to determine if the proposed SER DDS can be manufactured using Good Manufacturing Practices (GMP) quality Responsive applications will demonstrate substantial collaboration and participation in the proposed research of at least one industrial partner.

An industrial partner/collaborator is broadly defined as an individual, group, or unit from a for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical company with an established expertise in product development.

Substantive collaboration is defined as a significant commitment of one or more resources to the project including, but not limited to: personnel, provision of drug substance/product, product development support/guidance, provision of animal resources or laboratory models for testing, data management resources and/or regulatory support.

Inclusion of a Contract Research Organization (CRO) to provide fee-for-service deliverables without significant participation/scientific collaboration in the research agenda does not meet the definition of an industry partner.

Industry applicants are not required to involve collaborators from academic and/or non-profit research organizations, but are encouraged to do so, where Drug and DDS Intellectual Property/Patent/License Holder For SER DDS incorporating antiviral drugs or DDS that are already under clinical development or approved for HIV prevention and/or treatment by their intellectual property/patent/license holder, the applicant must involve these persons/entities in a meaningful way that results in a significant involvement in the proposed research.

Meaningful and significant involvement will be demonstrated by provision of documentation that identifies the role of the intellectual property/patent/license holder in the proposed research.

Evidence of commitment/involvement can be established through confidentiality, data sharing and material transfer agreements or similar approaches which outline the applicant’s access to the resource, data sharing process and communication plan that demonstrates participation and awareness of the intellectual property/patent/license holder in the proposed research and its projected outcomes.

A letter of support that does not address these criteria will not be considered adequate to demonstrate meaningful and significant involvement.

If the proposed DDS is protected by intellectual property/patent(s) covering a unique DDS architecture and/or component whose use is limited by such intellectual property/patent(s), then agreements with and participation by the intellectual property/patent/license holder of the DDS architecture/component will need to be demonstrated.

Intellectual property/patent/license holder involvement and industrial partner requirements may be met by the same entity, but only if the requirements for both are met individually. Models for Efficacy and PK Determinations Animal models to assess efficacy of the SER strategy should propose research in both males and females using well-characterized product to assess PK, efficacy and safety in both the FRT and GI tract.

Since MGS efficacy models are not as well developed, inclusion of MGS infection models is This FOA will only support clinical research for assessing PUCs at a U.S. site.

To meet the objectives of the FOA it is critical that proposed PUC study outcomes are linked and integrated into the proposed research and lead to and inform on the selection of SER DDS rheological/biophysical (look and feel) properties, and only research in which a DDS is handled to support look and feel assessments by participants are allowed, e.g. A mano studies.

A mano research with prototype, over the counter (OTC) or licensed DDS may be proposed. Care should be taken when selecting SER DDS surrogates that the rheological/biophysical properties either span a range of potential user perceptions or match the biophysical/rheological properties of the proposed SER All products used for A mano testing must be managed to minimize all potential safety risks for the participants.

Prototypes manufactured specifically for use in a PUC study must be manufactured under Good Manufacturing Practices (GMP) with appropriate stability, sterility and skin/dermal irritation testing post-manufacture. For some prototypes there may be sufficient human safety data in humans to justify forgoing specific skin/dermal sensitization/irritation testing, e.g. drug-free silicone and ethylene-vinyl acetate (EVA) DDS.

Use of OTC or licensed products as surrogate products by study participants is allowed, if there are no documented handling safety risks and potential safety risks and allergic reactions are managed. Use of nonoxynol-9 (N-9) based or containing products will not be supported for PUC assessments.

If repackaging of an existing prototype is proposed for a PUC study, stability in, sterility and package compatibility assessments must be performed. Milestones are required for this FOA. Applications will include timelines and milestones as measures of research progress toward the development of a SER DDS.

Applications not including milestones and timelines will be considered incomplete and will not be reviewed. Applications proposing the following areas of research will be considered non-responsive and will NOT Inclusion of any phase clinical trial(s). Any form of human subject dosing or implantation.

Exposure of human subjects to a prototype or listened drug-containing DDS in PUC studies or conduct of PUC clinical research at a Applications proposing development of SER DDS with durations of action that do not meet the minimal duration defined in the FOA or proposal of a non-priority DDS, e.g. non-erosible implant or depot, IVR, etc. Development of SER DDS containing any antiviral or DDS (when applicable) for which the applicant has not demonstrated participation of the drug intellectual property/license/patent holder in the application.

Strategies or antiviral candidates without demonstrated antiviral activity to HIV. Incorporating antivirals selected specifically for creating a Multipurpose Prevention Technology SER DDS with activities against multiple sexually transmitted infections (STI).

Inclusion of drugs with activities against non-HIV sexually transmitted infection are not prohibited, but all proposed development and research must focus on the anti-HIV activity of the proposed SER DDS and not its anti-STI activity or properties. This includes experimental designs where analysis of anti-STI activity is proposed on samples from animal models.

Random, bulk or high-throughput screening of chemical or natural product libraries or collections to discover new anti-HIV candidates (discrete inhibitors or natural product mixtures) for incorporation into SER Medicinal chemistry efforts on new or previously described/licensed antivirals. Prodrug or chemical modifications of licensed antivirals for treatment or prevention to enable creation of or incorporation into a SER DDS.

This does not preclude using prodrugs if the intellectual property/patent/license holder provides the prodrug or the prodrug is developed in collaboration with the intellectual property/patent/license holder. Medicinal chemistry efforts in this latter case should be supported by the intellectual property/patent/license holder.

Development of an uncharacterized or a complex-mixture natural product as the antiviral component of a SER strategy.

Broad, generalized global assessments/hypothesis-generating research in animal models or humans to identify biomarkers of SER drug/DDS impact on the FRT, MGS, or GI tract using genomic, proteomic, scriptomic, metabolomic, and/or microbiome analysis/technologies that do not directly support the development and/or characterization of the safety and/or efficacy Intravenous infusion of any component of a SER strategy.

Cure or amelioration of bacterial vaginosis (BV) or vaginal dysbiosis by any chemical or biological means to reduce HIV susceptibility as part of a SER strategy. This restriction includes replacement of abnormal microbiomes with "normal" bacteria by supplementation or transplantation as a method to modulate genital or GI micro- or macro-environments as a SER anti-HIV strategy.

SER strategies employing a female or male condom, and/or diaphragm. Use of a Copper or hormone containing IUD or IDS as the SER DDS. Use of any live biotherapeutic or vector system (viral, bacterial, fungal, etc.) to produce/deliver the anti-HIV component of the proposed SER DDS.

Development or optimization of a Genetically Modified Organism (GMO) as a part of a SER DDS or incorporation of bacteria selected or engineered to be antiviral for HIV. Use of non-specific agents/products/drugs/candidates as the anti-HIV component(s).

For this FOA non-specific agents are defined as agents that display broad anti-microbial activity (nonspecific killing of viruses, parasites, yeast, and pathogenic and/or beneficial bacteria) and/or do not have a defined anti-HIV target. Non-specific anti-HIV inhibitors may be chemically characterized as detergents or sulfonated polymers that act as either viricidal agents or charge-based inhibitors of HIV entry.

Examples include, but are not limited to, N-9, BZK, C31G, and high molecular weight sulfonated polymers such as carrageenan, dextran sulfate, cellulose sulfate, Development of SER products incorporating any of the following SER composed solely of or combinations of tenofovir (TFV, PMPA, (R)-9-(2-phosphonoylmethoxypropyl) adenine), tenofovir disoproxil fumarate (TDF or Viread ) and/or tenofovir alafenamide fumarate (TAF).

The non-nucleoside reverse transcriptase inhibitor dapivirine as a single agent or in combination with TFV, TDF, TAF or Emtricitabine (FTC). Development of the following combination antiretrovirals as the anti-HIV component of a SER strategy: TFV, TDF or TAF combined with Incorporation of rilpivirine (TMC-278) or cabotegravir (GSK-744, GSK/S 1265744) singly or in combination as the anti-HIV component.

Development of combinations of these drugs with other active pharmaceutical ingredients (APIs) are responsive when requirements for involvement of the intellectual property /license /patent holder are met.

Any lectin or non-lectin active pharmaceutical ingredients that targets glycosylation on virus or non-virus targets as a means to prevent HIV replication, such as Cyanovirin-N, Griffithsin and other high glycosylation/mannose lectin-binding HIV inhibitors or their derivatives.

Vaccine development of any form (new mucosal vaccine, vector, insert, or delivery system) and/or use of a vaccine as the antiviral or efficacy-enhancing element of a SER prevention strategy. Basic behavioral research designed to develop and inform on broad issues of SER product use and uptake.

Surveys and research designed to provide information on specific groups/ community/ individual attitudes/acceptability using hypothetical, conceptual or theoretical products. Education programs focused on any potential stakeholder population to support introduction of a SER product. Structural and/or behavioral interventions to enhance projected product use or to prepare for product roll-out or implementation.

Research targeting individuals other than product users, such as policymakers, government officials or any non-user stakeholder to determine general enthusiasm/ openness to the product concept of a SER. Research or modeling designed to assess the theoretical impact of a SER strategy on HIV GMP manufacturing of drug substance or drug product to support a future, ongoing or proposed clinical trial.

Inclusion of Investigational New Drug (IND) or Investigational Device Exemption (IDE) preparation/application activities and/or performance of animal studies to specifically support an Applicants are encouraged to contact the Scientific/Research Contact(s) located at the end of this FOA to discuss planned strategies for developing an VIII. Other Information for award authorities and regulations.

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed Not Allowed: Only accepting applications that do not help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards NIAID intends to commit $3. 8 million in FY 2020 to fund Application budgets are limited to $600,000 in direct cost The scope of the proposed project should determine the project period. The maximum project period is 5 Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

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 Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions 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 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 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. 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. 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.

must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration, but 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. must have an active DUNS number and SAM registration in order to complete the 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 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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 This FOA 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.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 NOT-OD-11-101 ). Section IV. Application and Submission Information 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 FOA.

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 Research (R) Instructions (R&R) Application Guide , except where instructed in this funding opportunity announcement 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 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 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 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 All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Do not request funds for medicinal chemistry or chemistry to create/develop prodrugs or to chemically modify antivirals for the purpose of incorporating into a SER DDS.

Do not request funds for testing activity against STI(s) or experimental designs where analysis of anti-STI activity is performed. Travel funds may be requested for attendance at one scientific meeting per year by the PD(s)/PI(s).

All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Strategy: Applicants must discuss how the proposed SER DDS represents an advancement beyond the products currently being developed.

If the proposed SER DDS development approach/rationale relies on research in fields outside the current biology, pharmacology and pharmaceutical research and development of prevention products, the applicant should discuss their relevance to the proposed SER approach and how progress in these fields enables development plans, including: The rationale for selection of the specific drug (s) and DDS of the proposed SER, and how the proposed SER DDS addresses current scientific gaps in development of this DDS for SER use.

Discuss how the proposed SER DDS meets the requirement of providing systemic protection from