Harnessing Artificial Intelligence and Polypharmacology to Discover Pharmacotherapeutics for Substance Use Disorders (R43/R44 Clinical Trials Not Allowed)

Harnessing Artificial Intelligence and Polypharmacology to Discover Pharmacotherapeutics for Substance Use Disorders (R43/R44 Clinical Trials Not Allowed) is sponsored by National Institute on Drug Abuse (NIDA) - NIH. This SBIR program aims to leverage AI/ML tools to identify pharmacotherapeutic development candidates with lower toxicity and higher efficacy to prevent or treat Substance Use Disorders (SUDs).

Expired RFA-DA-25-054: Harnessing Artificial Intelligence and Polypharmacology to Discover Pharmacotherapeutics for Substance Use Disorders (R43/R44 Clinical Trials 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 on Drug Abuse ( NIDA ) Funding Opportunity Title Harnessing Artificial Intelligence and Polypharmacology to Discover Pharmacotherapeutics for Substance Use Disorders (R43/R44 Clinical Trials Not Allowed) R43 / R44 Small Business Innovation Research (SBIR) Grant - Phase I, Fast-Track and Direct to Phase II November 14, 2023 - Clarification of Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements.

See Notice NOT-OD-24-029 . June 12, 2023 - Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements­­. See NOT-OD-23-139 .

February 23, 2023 - Notice of Change to Minimum Performance Standards for SBIR and STTR Applicants­­. See NOT-OD-23-092 . 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 Small Business Technology Transfer (STTR) Grants - Phase I/ * Small Business Technology Transfer (STTR) Grants - Phase II See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number Notice of Funding Opportunity Purpose This notice of funding opportunity (NOFO) encourages Small Business Innovation Research (SBIR) grant applications from small business concerns (SBCs) proposing research projects directed towards commercialization to harness artificial intelligence (AI), including machine learning (ML), tools, and polypharmacology to identify pharmacotherapeutics with lower toxicity and higher efficacy to prevent or treat substance use disorders (SUDs).

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 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 SBIR/STTR (B) Instructions in the How to Apply – Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from the 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 Drug discovery and development is a high-cost, high-risk, and time-consuming endeavor where the failure rate of therapeutic candidates that enter clinical trials is 90%. Because of this, in recent years, artificial intelligence (AI), including machine learning ( ML) technologies, has been embraced to reduce clinical failure rates and to speed up drug discovery.

AI/ML technologies are used to identify novel targets, design new molecules, conduct virtual preclinical studies, and analyze preclinical and clinical data. Multiple AI/ML-discovered compounds have advanced into Phase II clinical trials. While AI/ML is transforming drug discovery and promises to deliver new classes of medications, AI/ML-driven drug discovery for substance use disorders (SUDs) has lagged.

A contributing reason is that the traditional drug discovery paradigm involves identifying highly potent and selective molecules that act on specific targets (i.e., enzymes and receptors) in a "one disease, one target, one molecule" model.

Although single-target-based drug discovery has been successful in developing new medications for some indications, SUDs can be caused by complex mechanisms and, therefore, can be outside the traditional single-target-drug paradigm. Another complicating factor for SUDs is that polysubstance use is increasingly more common.

Polysubstance use involves the intentional or unintentional co-use of two or more drugs, such as alcohol, tobacco, benzodiazepine, cannabis, cocaine, fentanyl, xylazine, or nitazene. Due to polysubstance use, individuals face a greater risk of toxicity from the drug combinations, leading to increased morbidity and mortality. For instance, drug poisoning deaths involving fentanyl and stimulants climbed from 0.

6% in 2010 to 32. 3% in 2021. Polypharmacology is emerging as a new paradigm that can advance drug development for multifactorial diseases such as SUDs.

Polypharmacology is the study of how drug molecules interact with multiple targets. In the context of this notice of funding opportunity (NOFO), polypharmacology is defined as a single drug acting on multiple targets of a unique disease pathway or multiple targets of multiple disease pathways. These molecules are multi-target directed ligands (MTDL).

The concepts for polypharmacology and MTDL design are supported by several approved drugs that elicit their therapeutic effect through complex polypharmacology. Some key challenges in polypharmacology are identifying the target combination, predictions of the off-target toxicities, and the rational design of MTDLs , especially when the targets of interest are not phylogenetically or structurally related.

Implementing a polypharmacology strategy in drug discovery relies on advances in computational approaches such as data mining, ligand-based analysis and virtual screening. Since drug discovery is a multidimensional search and optimization process, artificial intelligence and machine learning (AI/ML) technologies trained in polypharmacology could significantly improve SUD discovery and development efforts.

By unlocking insights from the network of drug-drug, protein-drug, and protein-protein interactions that drive substance use, AI/ML tools can efficiently evaluate and predict the effects of binding to multiple biological targets, thereby enhancing potential clinical efficacy ("beneficial polypharmacology").

AI/ML can also identify pathways and mechanisms leading to side effects caused by drug binding to unintended off-targets ("adverse polypharmacology"), thereby reducing unmanageable toxicity. Such AI/ML tools can identify the best targets, design effective MTDLs, and inform the in vitro and in vivo assays to characterize the effects of these ligands on targets and functions.

The goal is to leverage AI/ML tools to identify pharmacotherapeutic development candidates with lower toxicity and higher efficacy to prevent or treat SUDs. Molecules may include new chemical entities, investigational compounds, and repurposed marketed medications.

AI/ML tools can pinpoint the most promising targets, design effective ligands based on predicted drug-likeness, and guide in vitro and in vivo assays to assess the effects of these ligands on biological targets and functions. Applicants should propose and conduct activities that use AI/ML tools to streamline, enhance decision-making, and accelerate the identification of SUD pharmacotherapeutics.

Applications may aim to conduct the following process: Identify and validate disease targets. Screen potential compounds to develop preliminary hits. Develop assays to test the activities of candidate compounds in vitro.

Synthesize novel series of compounds; test efficacy and toxicities in vitro. Test pharmacokinetics and toxicity of selected compounds in relevant in vivo models on a non-GLP level. Conduct non-GLP in vivo toxicity and efficacy of lead compound; pharmacokinetic studies.

Application Not Responsive to this NOFO The following types of projects are not responsive to this NOFO and will not be reviewed : Applications that pursue a single target. Applications solely focused on alcohol use disorders. Applications pursuing pain as a sole focus without addressing substance dependence and SUD.

Applications that do not propose using computer-based approaches to augment drug discovery efforts. The Small Business Innovation Research (SBIR) program is a phased program. An overall objective of the SBIR program is to increase private sector commercialization of innovations derived from federally supported research and development.

The main objective in SBIR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts. In contrast, the SBIR Phase II objective is to continue the R&D efforts to advance the technology toward ultimate commercialization.

Beyond the scope of this NOFO, it is anticipated and encouraged that the outcomes of successful SBIR projects will help attract strategic partners or investors to support the ultimate commercialization of the technology as a publicly available product or service. The following types of applications are accepted in response to this NOFO: Phase I.

The objective of Phase I is to establish the technical merit, feasibility, and commercial potential of the proposed R/R&D efforts and determine the quality of performance of the small business recipient organization before proceeding to Phase II. Fast Track. The NIH Fast Track process allows Phase 1 and Phase II grant applications to be submitted and reviewed together.

It expedites award decisions and funding of SBIR and STTR Phase II applications for scientifically meritorious projects that have high potential for commercialization. Importantly, before Fast Track Phase II can start, the National Institute on Drug Abuse (NIDA) conducts an administrative review and evaluates the achievement of the stated milestones.

In addition to Approach and Investigator(s), Fast-Track milestones are assessed as Additional Review Criteria: Does the Phase I application specify milestones that should be achieved prior to initiating Phase II? Applicant’s failure to provide milestones and specific, measurable, achievable, relevant, and time-bound milestone deliverables may be sufficient reason for the peer review to exclude the application from the Fast Track review.

Fast Track applicants must propose two separate sets of milestones and associated with the specific, measurable, achievable, relevant, and time-bound milestone deliverables, one set for Phase I and another set for Phase II. It is important to clearly state the go/no-go milestone decisions that will determine transition to Phase II. Failure to adequately address these criteria may negatively affect the application’s impact score.

Based on peer review recommendations, NIDA Program Officer may negotiate the Phase I milestones with the Fast Track potential awardees before they are included in the terms of the award. Direct to Phase II. NIH can issue a Direct to Phase II award for a small business that has already demonstrated scientific and technical merit and feasibility but has not received a Phase I award for that project.

The NIH SBIR Direct to Phase II is appropriate for Phase II submissions regardless of the funding source for the proof of principle work on which the proposed Phase II research is based.

Small businesses eligible to submit Phase II applications for projects supported with a Phase I SBIR award are expected to submit the regular Phase II application as a "Renewal" application based on the awarded Phase I SBIR or Small Business Technology Transfer (STTR) project. Only one Phase II application may be awarded for a specific project supported by a Phase I award. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed New (Phase I, Fast-Track, Direct Phase II) 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 the 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 NIDA intends to commit $3M in FY 2025 to fund 4-7 awards depending on the mix of the different application types (e.g., Phase I, Fast-Track, or SBIR Direct Phase II) for both RFA-DA-25-054 and companion NOFO RFA-DA-25-053. Budgets up to $400,000 total costs for Phase I and up to $3,000,000 total costs for Phase II may be requested.

Award periods may not exceed 1 year for Phase I and 3 years for Phase II. Applicants are encouraged to propose a project duration period that is reasonable and appropriate for completion of the research project. 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 Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria: 1.

Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor; 2.

Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture; i. SBIR and STTR.

Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR ii.

SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these.

No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund , or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR iii. SBIR and STTR.

Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with § 121. 705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees. SBIR and STTR.

Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR SBIR-only.

Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these.

No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund , or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR SBIR and STTR.

Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with § 121. 705(b) concerning registration and proposal requirements.

If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner. If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner. Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C.

1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State. Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.

Private equity firm has the meaning given the term “private equity fund” in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

Venture capital operating company means an entity described in § 121. 103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

ANC means Alaska Native Corporation. NHO means Native Hawaiian Organization. SBCs must also meet the other regulatory requirements found in 13 C.

F. R. Part 121.

Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq. , are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both.

Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the NIH STTR program.

Performance Benchmark Requirements Phase I to Phase II Transition Rate Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022.

The benchmark establishes a minimum number of Phase II awards the company must have received relative to a given number of Phase I awards received during the 5-fiscal year time period.

The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently completed year.

The Transition Rate requirement, agreed upon and established by all 11 SBIR agencies, was published for public comment in a Federal Register Notice on October 16, 2012 (77 FR 63410) and amended on May 23, 2013 (78 FR 30951).

For SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years (excluding the most recently-completed fiscal year): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0. 25 will not be eligible to apply for a Phase I, Fast-Track, or Direct Phase II (if available) award for a period of one year from the date of the application submission.

This requirement does not apply to companies that have received 20 or fewer Phase I awards over the prior 5-fiscal year period. For application deadlines that fall on or after April 5, 2023: For SBIR and STTR Phase I applicants that have received more than 50 Phase I awards over the past 5 fiscal years (excluding the most recently-completed fiscal year): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0.

5 will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase I awards over the 5-fiscalyear period. On June 1 of each year, SBA will identify the companies that fail to meet minimum performance requirements.

SBA calculates individual company Phase I to Phase II Transition Rates using SBIR and STTR award information across all federal agencies. SBA will notify companies and the relevant officials at the participating agencies. More information on the Phase I to Phase II Transition Rate requirement is available at SBIR.

gov. Phase II to Commercialization Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Programs are implementing the Phase II to Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022.

The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 ( 78 FR 48537 ), with a reopening of the comment period published on September 26, 2013 (78 FR 59410).

For companies that have received more than 15 Phase II awards from all agencies over the past 10 fiscal years (excluding the two most recently completed fiscal year): Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0. 15 (15%) patents per Phase II award resulting from these awards during the past 10- fiscal year period.

Applicants that fail this benchmark will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

For application deadlines that fall on or after April 5, 2023: For companies that have received more than 50 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $250,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period.

Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

For application deadlines that fall on or after April 5, 2023: For companies that have received more than 100 Phase II awards from all agencies over the past 10-fiscalyears (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $450,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period.

Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 100 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , may be 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.

Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement 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. 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. SBA Company Registry – See How to Apply – Application Guide for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a UEI to complete this registration.

SBA Company registration is NOT required before SAM, Grants. gov or eRA Commons registration. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.

gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov – Applicants must have an active SAM registration in order to complete the Grants. gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her 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. Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project.

For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur. The How to Apply – Application Guide should be referenced for specific details on eligibility requirements.

For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section 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. NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization.

This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. NIH Grants Policy Statement 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 ).

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure.

To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively. Contractual/Consortium Arrangements In Phase I, normally, two-thirds or 67% of the research or analytical effort is carried out by the small business concern.

The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 33% of the total amount requested (direct, F&A/indirect, and fee). In Phase II, normally, one-half or 50% of the research or analytical effort is carried out by the small business concern.

The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 50% of the total