NeuroNEXT Small Business Innovation in Clinical Trials (U44)

NeuroNEXT Small Business Innovation in Clinical Trials (U44) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS), NIH. This program supports small businesses in conducting clinical trials related to neurological disorders through the NeuroNEXT network. It is designed to encourage innovation in clinical trial design and execution for neurotechnologies.

Expired PAR-21-224: NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional) 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 Neurological Disorders and Funding Opportunity Title NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional) U44 Small Business Innovation Research (SBIR) Cooperative Agreements - Fast track, Phase II Reissue of PAR-18-628 -NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional) November 12, 2024 - This PAR has been reissued as PAR-25-133 .

November 30, 2023 - Notice of Change: Extension of PAR-21-224 "NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional)". See Notice NOT-NS-24-037 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 . ( See updates incorporated into NOFO content in Sections IV, V, VI, and VIII applicable for applications submitted for due dates on or after September 5, 2023.

) February 23, 2023 - Notice of Change to Minimum Performance Standards for SBIR and STTR Applicants. See Notice NOT-OD-23-092 .

NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

See Notice NOT-OD-21-169 . August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel.

See Notice NOT-OD-21-109 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-21-223 - NeuroNEXT Clinical Trials (U01 Clinical Trial Optional) See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number Funding Opportunity Purpose Successful applicants will be given access to the NeuroNEXT infrastructure. Following peer review, NINDS will prioritize and order trials that are given access to the NeuroNEXT infrastructure. The NeuroNEXT Clinical Coordinating Center (CCC) will work with the successful applicant to efficiently implement the proposed study.

The NeuroNEXT Data Coordinating Center (DCC) will provide statistical and data management support. The NeuroNEXT clinical sites will provide recruitment/retention support as well as on-site implementation of the clinical protocol. Applicants do not need to be part of the existing NeuroNEXT infrastructure.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) *** Note new SBIR/STTR Standard Due Dates. All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

AIDS Application Due Date(s) New Date September 06, 2024 (Original Date: April 06, 2024) per issuance of NOT-NS-24-037 Required Application Instructions It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR 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 Announcement Section I. 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. Funding Opportunity Description To facilitate the cooperation and partnering of public and private funding organizations, universities, academic medical centers, research institutes, contract research organizations, biotechnology companies, and pharmaceutical companies, NINDS has formed the Neurology Network of Excellence in Clinical Trials (NeuroNEXT, www. NeuroNEXT.

org). NeuroNEXT has a Clinical Coordinating Center (CCC), a Data Coordinating Center (DCC) and a group of 25 geographically distributed clinical sites. This clinical research network develops and conducts multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, whether from academic, foundation or industry discoveries.

Examples include Phase 2 clinical trials and clinical research studies aimed at validating biomarkers and clinical outcomes in preparation for clinical trials. A separate clinical trials network has been established and funded by NINDS to conduct clinical trials and biomarker studies for stroke treatment, prevention and recovery; thus NeuroNEXT has been established for the conduct of studies in neurological disorders other than stroke.

NeuroNEXT provides a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. While the network is not specific to one disease, it has the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities.

The network is designed to increase the efficiency of clinical trials, to facilitate patient recruitment and retention, to increase the quality of neuroscience clinical trials, and to enable public-private partnerships. This FOA uses the U44 cooperative agreement mechanism and is open to eligible applicants, as defined in Section III.

Academic researchers may wish to consider applying through PAR-21-223 "NeuroNEXT Clinical Trials (U01)". "NeuroNEXT Infrastructure Resource Access (X01)" or any reissue if they wish to gain access to the network infrastructure but do not require funds for trial costs.

Since conducting the clinical trials needed for commercialization may be capital-intensive, this FOA encourages business relationships between NIH's SBIR/STTR awardees and third-party investors and/or strategic partners.

In particular, this FOA will give competitive preferences and funding priority to applications deemed likely to result in a commercial product as indicated by an applicant's ability to secure independent third-party funds. An objective of the SBIR and STTR programs is to foster and encourage participation in innovation and entrepreneurship by socially and economically disadvantaged persons and women-owned small businesses.

This PAR encourages applications from diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www. nsf. gov/statistics/showpub.

cfm? TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

For this funding opportunity announcement, Phase I and II clinical studies or trials refer to the common phases of a clinical trial. SBIR Phase I and II refer to the project phases of the SBIR program. Phase 1 clinical trials should be directed to the exploratory clinical trial FOA ( PAR-18-420 and PAR-18-617 ) .

Phase 1b/2a trials requiring multi-center implementation can be considered under this FOA. Applications in rare diseases are encouraged while recognizing that available patient pools may not be adequate to meet the sample size requirements normally required to establish the efficacy of an intervention. NINDS acknowledges that innovative, non-traditional trial designs including adaptive designs may be appropriate in rare disease studies.

While NeuroNEXT is primarily intended for exploratory trials, the network will consider Phase II/III trials in diseases with a US prevalence of under 5,000 persons. Examples of appropriate studies under this FOA include, but are not limited to, those designed to: Evaluate and optimize the dose, formulation, safety, tolerability or pharmacokinetics of an intervention in the target population.

Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, pharmacodynamic response, target engagement, dose-response trends) in a human "proof of concept" trial.

Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., futility trials). Evaluate biological activity relative to clinical endpoints.

Applications seeking to obtain data needed for pharmacometric modeling are encouraged, with the ultimate aim of enabling the optimal design of a future efficacy trial of an intervention.

For medical devices, in addition to providing initial clinical safety data, appropriate studies are those that inform the next phase of development, usually by finalizing the device design, establishing operator technique, and/or finalizing the choice of study endpoints for the design of a pivotal clinical trial. Fast Track Studies should implement clear go-no go criteria for continuing to the next Phase II SBIR.

When possible, all studies should also include go-no go criteria for proceeding to the next trial phase after the Phase II award. These should be biomarker-informed wherever possible. https://www.

fda. gov/regulatory-information/search-fda-guidance-documents/qualification-process-drug-development-tools-guidance-industry-and-fda-staff This FOA is not intended to support the conduct of a clinical trial where the primary aim is to confirm efficacy of a proposed intervention. Applicants should make note of the following: (1) Applicants to this FOA will be required to incorporate the NeuroNEXT infrastructure ( www.

neuronext. org ) into their proposed study. Additional (ad-hoc) sites may be proposed to fulfill specific study requirements.

All applicants will be required to use the master clinical trial agreements and central IRB that have been established for NeuroNEXT. (2) Rationale: Exploratory trials primarily test hypotheses in relatively small programs so that the acceptable risk and uncertainty are higher than in later stage programs.

Exploratory clinical trials must anchor their rationale in (1) an unmet medical need; (2) a plausible biological mechanism; (3) non-clinical (in vitro and/or in vivo) data; and/or (4) early clinical data. Their individual weight should be carefully assessed in the specific context of the application at hand. ; there is no requirement to provide support from all four areas.

However, supporting data should be robust enough to justify the proposed phase of study. Applicants should consider the limitations of those studies with regards to the scientific rigor guidelines published by NINDS (see https://grants. nih.

gov/grants/guide/notice-files/NOT-NS-11-023. html ). Preclinical data (such as from animal studies) that do not sufficiently meet the rigor guidelines or are not sufficiently associated with the human condition may be inadequate to support the rationale for the study.

Issues of study feasibility and refinement of study procedures may be addressed as secondary aims in an exploratory clinical trial, but not as the primary aim.

Examples of such secondary aims include, but are not limited to, the following: Determining the optimal measure (endpoint), its variability, and/or the optimal timing of outcome evaluations in the context of the intervention, Collecting information on the utility of questionnaires, rating scales, or biomarkers, For Early Feasibility or Traditional Feasibility studies of medical devices, issues of study feasibility and refinement of study procedures are expected to be addressed as primary aims in addition to providing initial clinical safety data at this stage.

These may include: Identifying appropriate modifications to the procedure or device to enable a subsequent Pivotal study on a finalized system; Refining the intended use population; Developing and refining data collection procedures; Refining the non-clinical test plans or methodologies; and Developing subsequent clinical study protocols.

(4) The NIH recognizes that devices can vary greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. Consequently, the appropriate pathway to market may require a traditional Feasibility and Pivotal study in support of an eventual Pre-Market Approval submission, or may require a more limited study to address specific issues in support of an FDA 510(k) or 510(k) De Novo submission.

Clinical studies involving devices may utilize the entire NeuroNEXT Network, or a more limited subset of centers selected based on appropriate expertise for the given device. Investigators are encouraged to contact NINDS Scientific/Research Staff as early as possible to discuss how the NeuroNEXT network may best be utilized in support of their specific device project.

NINDS anticipates that the majority of device projects utilizing NeuroNEXT will be traditional Feasibility Studies in order to best leverage the advantages of the network. A Traditional Feasibility Study is a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan a Pivotal Study.

If an Early Feasibility Study is proposed, it should be designed in accordance with FDA's draft guidance, "Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies", to allow for early clinical evaluation of devices to provide proof of principle and initial clinical safety data while device design and operations are still in development.

Early Feasibility and Traditional Feasibility study designs may include single-arm case series, on-off interventions (patients as own controls), device-device comparisons, comparisons to historic controls, comparisons to performance controls, or adaptive/Bayesian designs.

(5) Rare Diseases: Applications in rare diseases are encouraged while recognizing that available patient pools may not be adequate to meet the sample size requirements normally required to establish the efficacy of an intervention. NINDS acknowledges that innovative, non-traditional trial designs including adaptive designs may be appropriate in rare disease studies.

Regardless of the design it is especially important to ensure that the study design and statistical analysis plans will meet the stated objectives , and allow for the most efficient evaluation of the limited subjects.

The application should clearly demonstrate recruitment feasibility at the participating sites and applicants are encouraged to fully engage patient advocacy groups or similar representatives of the affected disease community in study design, execution, and reporting. While NeuroNEXT is primarily intended for exploratory trials, the network will consider Phase 2/3 trials in diseases with a US prevalence of under 5,000 persons.

(6) The award and continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies. (7) NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including: (a) Clinical and Translational Science Award (CTSA) program ( https://ncats. nih.

gov/ctsa ); (b) NeuroQOL ( http://www. neuroqol. org ); (c) NIH Toolbox ( http://www.

nihtoolbox. org ); (d) PROMIS ( http://www. nihpromis.

org ); and (e) NINDS Common Data Elements ( http://www. commondataelements. ninds.

nih. gov ). (8) Mobile Technologies: Applicants are encouraged to consider utilizing (at least experimentally) mobile technologies to facilitate data collection and protocol adherence on the part of research participants and study site staff.

(9) For Biomarker Validation Studies, biomarkers are defined as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Categories of biomarkers include: Susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, and safety.

Biomarker studies should define their intended Context of Use (a statement that fully and clearly describes the way the biomarker will be used in future clinical trials). Working with NeuroNEXT is a cooperative venture between NINDS, the NeuroNEXT network and the applicant. NINDS will provide guidance to potential applicants with input from NINDS Program Staff and the NeuroNEXT Executive Committee.

Potential applicants are strongly encouraged to contact NINDS Scientific/Research Contacts (see Agency Contacts, Section VII) in order to discuss the feasibility of conducting the proposed trial through the NeuroNEXT infrastructure before submitting an application.

Pre-application consultation may include an introductory teleconference (at least 3 months prior to submission), followed by a conference call or in-person meeting with NINDS staff, as needed. Funding decisions will also be based on a study's fit for the network relative to other proposed and ongoing trials.

Prior to grant award, awardees who do not have an exemption from the FDA must provide any additional FDA correspondence regarding the status of the protocol to the NINDS, especially if the trial has been placed under full or partial hold. See Section VIII. Other Information for award authorities and regulations.

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

Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this FOA. Application Types Allowed New (SBIR Direct Phase II) Resubmission (all phases) 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 FOA.

Optional: Accepting applications that either propose or do not propose clinical trial(s) Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Applicants should rarely exceed $1,000,000 in total cost per year for a Phase I and $1,500,000 in total cost per year for a Phase II/Phase IIB . Applicants are strongly encouraged to contact NIH program officials prior to submitting any application in excess of the guidelines and early in the application planning process.

In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project. Durations up to 2 years for a Phase I and up to 3 years for Phase II may be requested. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

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: 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; 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; 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.

Has, including its affiliates, not more than 500 employees. 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-fiscal year 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-fiscalyear 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-fiscal years (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-fiscalyear period, excluding the two most recently-completed fiscal years.

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

The NIH 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 late submission. Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, 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. SBA Company Registry See Section IV. Application and Submission Information , SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package.

Applicants must have a DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants. gov or eRA Commons registration.

eRA Commons - Applicants must have an active DUNS number number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov