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 the 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

Purpose

The Small Business Innovation Research (SBIR) Program is an important funding mechanism that the National Institutes of Health (NIH) uses to develop innovative solutions that address public health challenges. A major objective of the SBIR Program is to facilitate the commercialization of technologies developed by small business concerns (SBCs). Yet, the development of biomedical products is often impeded by a significant funding gap between the end of the SBIR Phase II award and the commercialization stage. This Funding Opportunity Announcement (FOA) invites SBIR grant applications from SBCs to support later stage research and development (referred to as Phase IIB) for promising projects that were previously funded by SBIR or STTR Phase II awards and will require eventual Federal regulatory approval/clearance. The goal of this FOA and the resulting Phase IIB awards is to assist applicants in pursuing the milestone(s) necessary to advance a product to regulatory approval and commercialization by promoting partnerships between SBIR Phase II awardees and third-party investors and/or strategic partners.

• Projects proposed under this FOA MUST be relevant to the NHLBI mission (see B. Scientific/Technical Scope).
• This FOA is specifically intended to benefit clinical practice by accelerating the commercialization of novel products that require ultimate approval/clearance by a Federal regulatory agency.
• This FOA will give competitive preference and funding priority to applications deemed likely to result in a clinically-relevant commercial product as indicated by the applicant’s ability to secure independent third-party investor funds that equal or exceed the requested NHLBI funds (total costs).

Background

Since its inception in 1982, the NIH SBIR program has provided the small business community with seed funding to support the development of a broad array of commercial products to detect, diagnose, treat, and prevent disease. It provides an important funding mechanism for bringing new interventions to patients and clinicians. The SBIR program is structured in three phases. The objective in Phase I is to establish the technical merit and feasibility of a proposed research and development (R&D) effort, while in Phase II it is to continue the R&D effort for successful Phase I projects. The expectation is that in Phase III a SBC will be able to launch a product commercially with non-SBIR funds.

However, many projects initiated with SBIR funding require considerable financing beyond the SBIR Phase II award to complete the validation studies required to obtain regulatory approval and launch a product. In particular, the development of therapeutics, medical devices, and combined technologies often requires a number of years and substantial capital investments because of the costs associated with conducting clinical trials and/or other steps mandated by the Federal regulatory approval process. Thus, despite the extensive R&D performed on such products during Phase II projects, the results are often insufficient to attract the substantial private investment needed for the eventual commercialization of the product. Many small businesses therefore become cash-starved before reaching the next critical milestone along the path toward commercialization. Hence, this FOA is designed to address this funding gap between the end of the SBIR or STTR Phase II award and the point at which non-SBIR financing can be secured for the subsequent stages of product development.

A number of public and private organizations have begun to recognize the challenges associated with this funding gap and are taking steps to provide additional resources to advance a greater number of promising early-stage technologies toward commercialization. Importantly, many of these organizations are not only providing financial support but are also establishing programs to provide commercialization guidance. For example, in the area of drug development, a number of major pharmaceutical firms have developed corporate venture funds focused on supporting projects in the preclinical stages of development, and some of these firms have established technology incubators to provide development support, including regulatory guidance. In addition, a growing number of universities are creating venture funds to support innovative technologies developed by their resident investigators, and numerous state-sponsored technology funds have also been created across the U.S. to support start-up companies. Such programs can provide additional financing and commercialization support for SBIR awardees that have received initial seed funding and a rigorous technical evaluation through the NIH peer review process. As such, a major goal of this FOA is to provide a platform to incentivize partnerships between NIH-funded SBIR awardees and a broad range of potential third-party investors. It is anticipated that funding by third-party investors will be predicated on significant due diligence, thus encouraging awardees to formulate credible business plans for product commercialization. In addition, it is expected that third-party investors will maintain an active role in supporting the awardee during the product development phase and during pursuit of follow-on funding for commercialization.

Specific Objectives for SBIR Phase IIB Bridge Award Applications

A. Independent Third-Party Investor Funds

This FOA specifically encourages business relationships between applicant SBCs and third-party investors/strategic partners who can provide financing to help accelerate the commercialization of promising new products whose development was initiated with SBIR funding. Applicants are expected to leverage their previous SBIR support, as well as the opportunity to compete for additional NHLBI funding under this FOA, to attract and negotiate third-party financing needed to advance a product or technology toward commercialization. The applicant’s ability to secure independent third-party investor funds that equal or exceed the total amount of the NHLBI funds being requested over the entire Phase IIB Bridge Award project period will help to validate the commercial potential that is essential for the SBIR projects solicited under this FOA. This potential will be strongly considered in review (refer to Section V. Application Review Information) and making funding decisions.

If a Phase IIB Bridge Award application is selected for funding, the applicant’s plan for securing independent third-party investor funds (i.e., the Finance Plan submitted as part of the application) will become a term of award as described in Section VI.1 Award Notices

It is anticipated that many of the partnerships between applicant SBCs and third-party investors will involve a considerable level of project due diligence by the private sector, thereby increasing the likelihood of commercial success for the funded projects. In light of these goals, the NHLBI strongly encourages applicants to establish business relationships with investors and/or strategic partners that have appropriate prior experience in commercializing emerging biomedical technologies.

B. Scientific/Technical Scope

The technical and commercial objectives described in the SBIR Phase IIB Bridge Award application MUST represent an extension of the development efforts that were pursued in a previously funded SBIR or STTR Phase II award. It is essential that significant progress was accomplished during the current/preceding SBIR or STTR Phase II project and that the proposed product has significant commercial potential. Applicants are expected to demonstrate that the proposed product has a clear advantage over existing and/or competing products and to define an appropriate path toward ultimate product commercialization.

This FOA is specifically designed to provide additional support for products that require ultimate approval/clearance by a Federal regulatory agency.

Although projects previously funded by another NIH Institute/Center or another Federal agency are eligible for funding under this FOA, proposed projects MUST be relevant to the NHLBI mission. Applicants are strongly encouraged to contact the NHLBI to discuss whether their proposed project meets this criterion. The NHLBI supports development of technologies to detect, prevent, or treat cardiovascular, lung, blood and sleep disorders. It also supports research on the clinical use of blood and all aspects of the management and safety of blood resources. The NHLBI SBIR/STTR program fosters basic, applied, and clinical research on products related to the mission of the NHLBI. The NHLBI program priority areas for technology development research include:

Cardiovascular Diseases areas: heart failure, atherothrombosis, heart attack, high blood pressure, atrial fibrillation along with other atrial and ventricular arrhythmias, sudden cardiac death, adult and pediatric congenital heart disease, cardiovascular complications of diabetes and obesity, acquired valve disease, cardiomyopathies, and peripheral vascular diseases.

Lung Diseases areas: asthma, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, cystic fibrosis, respiratory neurobiology, sleep-disordered breathing, critical care and acute lung injury, developmental biology and pediatric pulmonary diseases, immunologic and fibrotic pulmonary disease, rare lung disorders, pulmonary vascular disease, and pulmonary complications of AIDS and tuberculosis.

Blood Diseases and Resources areas: sickle cell disease (SCD), the thalassemias, Fanconi anemia, Diamond-Blackfan anemia and other bone marrow failure syndromes, iron chelation, fetal hemoglobin production, white blood cell disorders, myeloproliferative and myelodysplastic syndromes, hematopoietic stem cell transplantation and novel cell-based therapies, transfusion medicine (red blood cells, platelets, and plasma) and blood banking including technologies to store, process, and screen blood, thrombosis and hemostatic disorders including but not limited to idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemophilia, and coagulation factor deficiencies and disorders.

Please note that the companion NHLBI SBIR Phase IIB Small Market Awards funding opportunity, RFA-HL-19-018, supports the development of products addressing rare and pediatric diseases.

Examples of appropriate development activities to be proposed under this FOA include, but are not limited to the following areas:

• For projects pertaining to the development of therapeutics - Applicants are expected to propose activities that will lead to the successful filing of an Investigational New Drug (IND) application or clinical studies to support the filing of a New Drug Application (NDA) and/or Biological License Application (BLA).
• For projects pertaining to imaging technologies, interventional devices, and in vivo diagnostics - Applicants are expected to propose activities that will lead to the successful filing of a 510(k) application, Premarket Approval (PMA) application, or an Investigational Device Exemption (IDE) application.
• For projects pertaining to ex vivo or in vitro diagnostics, prognostics, and screening tests - Applicants are expected to propose activities that will lead to the successful filing of a 510(k) application, Premarket Approval (PMA) application, an Investigational New Drug (IND) application, and/or Investigational Device Exemption (IDE) application, as needed for the specific technology/system/assay.

NHLBI expects that activities to be pursued under this FOA will address any relevant requirements for clinical validation and regulatory approval, as necessary and required for commercialization of the technology. Specific activities to be proposed will vary among applications.

C. Plan for Full Commercialization (all applications)

The goal of the SBIR Phase IIB Bridge Award is to advance SBIR Phase II projects toward ultimate commercialization. All applicants are expected to describe a realistic plan (extending beyond the SBIR Phase IIB Bridge Award project period) that outlines how and when full commercialization can be accomplished. The long-term commercialization strategy should be presented as part of the 12-page Commercialization Plan. The full commercialization plan for the product should extend beyond the period of SBIR funding.

Criteria for Complete, Compliant, and Responsive Applications

Applications deemed to be non-responsive will not proceed to review. The following are considered non-responsive to this FOA:

• Applications that do not propose a budget amount and project period that conform to the limits described under Section II ("Award Budget" and "Award Project Period")
• Applications that do not propose R&D that represents the continuation of work conducted under a previously-funded SBIR or STTR Phase II award (grant or contract)
• Applications that do not propose R&D that falls within the technical scope of this FOA as described under Section I (Specific Objectives for SBIR Phase IIB Bridge Award Applications)
• Applications that do not contain a Commercialization Plan that includes all sections (a-l) and the required elements for each section, as described under Section IV ("SBIR/STTR Information: Commercialization Plan")
• Does the application include letters of support from third-party investors in the Letters of Support section ("PHS 398 Research Plan"), and/or documentation of support from third-party investors in the Other Project Information section ("Other Attachments")

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

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;

3.

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), 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; 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.

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.

Definitions:

• 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.

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.

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. This Transition Rate requirement applies to 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. For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to apply for a new Phase I award. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that do not meet or exceed the benchmark rate 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. 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 benchmark minimum Transition Rate is 0.25.

SBA calculates individual company Phase I to Phase II Transition Rates daily using SBIR and STTR award information across all federal agencies. For those companies that have received more than 20 Phase I awards over the past 5 years, SBA posts the company transition rates on the Company Registry at SBIR.gov. Information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Applicants to this FOA that may have received more than 20 Phase I awards across all federal SBIR/STTR agencies over the past five (5) years should, prior to application preparation, verify that their company’s Transition Rate on the Company Registry at SBIR.gov meets or exceeds the minimum benchmark rate of 0.25.

Phase II to Phase III Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Phase III Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537).

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. 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. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10 year period, excluding the two most recently-completed Fiscal Years.

Information on the Phase II to Phase III Commercialization Benchmark is available at SBIR.gov.

Applicants to this FOA that may have received more than 15 Phase II awards across all federal SBIR/STTR agencies over the past ten (10) years should, prior to application preparation, verify that their company’s Commercialization Benchmark on the Company Registry at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this benchmark will be notified by SBA annually and 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.

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

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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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.

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.

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 SF424 (R&R) SBIR/STTR 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 SF424 (R&R) SBIR/STTR Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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. 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 NOT-OD-11-101).

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.

Eligibility Requirements for Phase IIB Bridge Award

The SBIR Phase IIB Bridge Award application must represent a continuation of the R&D efforts performed under a previously funded SBIR or STTR Phase II award. Applications must be predicated on a previously funded SBIR or STTR Phase II grant or contract award. Qualifying "parent" SBIR or STTR Phase II projects may be renewed only once. Following the Phase IIB Bridge Award period (i.e., up to 3 years), recipient SBCs are expected to pursue the full commercialization of these SBIR-funded projects using non-SBIR funds.

NOTE: Applicants who intend to submit a Phase IIB Bridge Award application that is predicated on an SBIR Phase II contract or a Phase II award from a non-NIH Federal agency MUST contact the NHLBI prior to submission (see Section VII. Agency Contacts) so that the NHLBI can properly arrange for such applications to be accepted. See NIH FAQs for more information about submitting a Phase IIB application based on a Phase II contract or Phase II award from a non-NIH Federal agency:

https://sbir.nih.gov/faqs#app-prep-sub26

To qualify for renewal under the Phase IIB Bridge Award, the prior Phase II award could have been funded in response to any Federal SBIR or STTR solicitation and could have been funded by the NHLBI, by another NIH Institute/Center, or by another Federal agency. However, the proposed objectives for the Phase IIB application must fall within the technical scope required for this FOA as defined in Section I (under Specific Objectives for SBIR Phase IIB Bridge Award Applications ). In addition, the development activities completed under the previous Phase II award must provide the appropriate technical foundation to justify continued development of the technology for an NHLBI mission-related indication/use. Platform technologies that were initially developed for a non-NHLBI mission-related indication/use (i.e., certain Phase II projects funded by another NIH Institute/Center or another Federal agency) may be eligible for continued support under this FOA only if the earlier data demonstrate technical proof-of-concept that is scientifically relevant to the NHLBI mission-related indication/use. For all projects supported under this FOA, the aims of the project should focus on an NHLBI mission-relevant indication/use as the primary product or service. SBIR Phase IIB Bridge awards are non-renewable.

The NHLBI will accept only one new Phase IIB Competing Renewal application and one Phase IIB Resubmission application for a particular project. For Resubmissions, the NIH policy described in NOT-OD-14-082 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-082.html) applies.

In all cases, the Phase II project period must end before a Phase IIB Bridge Award can be issued.

In Phase II, normally, a minimum of one-half or 50% of the research or analytical effort must be 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 generally may not exceed 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of SF424 (R&R) application forms.

Additional details are contained in the SF424 (R&R) SBIR/STTR Application Guide.

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR 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 review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 [Express mail zip: 20817
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF 424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed, with the following additional instructions:

Other Attachments:

1. SBIR Application Certification for small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms:

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g., majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive. Follow the instructions below.

Applicant small business concerns who are 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), or any combination of these (i.e., NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it to their application package.

a. Download the VCOC Certification.pdf at the NIH SBIR Forms webpage.

b. Answer the 3 questions and check the certification boxes.

c. The authorized business official must sign the certification.

d. Save the certification using the original file name. The file must be named SBIR Application VCOC Certification.pdf . DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

e. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the Research and Related Other Project Information form.

2. Include copies of letters, emails or minutes documenting interactions with the FDA or other regulatory agencies.

3. Include documentation of support from third-party investors (other than letters of support) such as term sheets or redacted bank statements.

At the time of application, applicants must provide detailed, verifiable documentation (e.g., redacted bank statement or other documentation) of any independent third-party investor support that has been secured up to one year prior to the application receipt date.

Applicants should also provide detailed, verifiable documentation of any independent third-party investor support that will be provided to the SBC during the proposed Phase IIB Bridge Award project period. Documentation of support from third-party investors should corroborate the Finance Plan.

Adequate documentation of planned (i.e., future/expected) third-party funding may include, but is not limited to, a term sheet from the third party (or parties) stipulating the terms of the proposed investment. At the time of application, evidence of a firm third-party commitment is ideal, but not required. Appropriate documentation of third-party investor support may include a conditional commitment stating that the third-party funding is contingent upon NIH selecting the application for an award. Partners should indicate any actual or planned/conditional financial commitment (as a specific dollar figure or range).

Applicants seeking further information regarding preferred sources and/or types of support that would

demonstrate a third-party investor commitment are strongly encouraged to communicate with the Scientific/Research Contact(s) listed under Section VII.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed, with the following additional instructions:

Letters of Support:

At the time of application, applicants must provide letters of support that detail any independent third-party investor support that has been secured up to one year prior to the application due date. Applicants should also provide letters of support of any independent third-party investor support that will be provided to the SBC during the proposed Phase IIB Bridge Award project period. These letters of support from third-party investors should corroborate the Finance Plan.

Adequate documentation of planned (i.e., future/expected) third-party funding may include, but is not limited to, a letter of commitment from the third party (or parties) stipulating the terms of the proposed investment. At the time of application, evidence of a firm third-party commitment is ideal, but not required. Appropriate documentation of third-party investor support may include a conditional letter of commitment stating that the third-party funding is contingent upon NIH selecting the application for an award. Partners should indicate any actual or planned/conditional financial commitment (as a specific dollar figure or range).

Resource Sharing Plans: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) SBIR/STTR Application Guide,

Appendix:

Note that Phase I SBIR/STTR Appendix materials are not permitted. Limited items are allowed in the Appendix of other small business applications. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide Instructions.

Commercialization Plan: All applications are expected to describe a realistic plan that outlines how and when full commercialization can be accomplished. The long-term commercialization strategy should be presented as part of the 12-page Commercialization Plan. The full commercialization plan for the product should extend beyond the period of SBIR funding.

The following subsections must be included within the page limit of the Commercialization Plan, in addition to the requirements listed in the SF424 Application Guide:

a) Value of the SBIR/STTR Project, Expected Outcomes, and Impact: Follow the instructions provided in the SF424 Application Guide.

b) Company: Follow the instructions provided in the SF424 Application Guide. Highlight how the proposed project relates to the company's core competencies.

c) Market, Customer, and Competition: Follow the instructions provided in the SF424 Application Guide.

d) Intellectual Property (IP) Protection: Follow the instructions provided in the SF424 Application Guide.

e) Finance Plan [this section replaces section e) Finance Plan described in the SF424 Application Guide].

Consistent with achieving the goals of this program, applications must provide a Finance Plan. This plan must include the following information:

• A detailed and specific plan for securing substantial, independent third-party investor funds. Any third-party investment support received up to ONE year prior to the application receipt date may be counted toward the total.
• The type(s) of independent third-party investor funds (i.e., cash, convertible debt, etc.) that will be secured during the project period.
• The source(s) of independent third-party investor funds (e.g., venture capital, state funds) that will be secured during the project period.
• The total amount of independent third-party investor funds that will be secured during the project period.
• The anticipated schedule for receiving independent third-party investor funds, including any relevant terms and conditions.
• A table summarizing the above information, with rows corresponding to each year of the project and the year prior to the receipt date and columns including the name of source, the type of funds, the amount, a concise description of terms and conditions, and the type of evidence provided and its location in the application (e.g., Letter of Support or bank statement in Other Project Information, Other Attachments)

The NHLBI considers the raising of independent third-party investor funds to be an important means to facilitate and accelerate the capital-intensive steps that are required to commercialize new products emerging from SBIR/STTR Phase II projects. As such, it is expected that applicants for the Phase IIB Bridge Award will secure substantial independent third-party investor funds. In all cases, it is expected that the level of this independent third-party funding will equal or exceed the NHLBI funds (total costs) being requested for the entire project period of the Phase IIB Bridge Award. If the project period spans multiple years, the portion of the total third-party investment received in any given year must represent a substantial portion of the total investment, generally at least $250,000 in any given year.

Examples of third-party investors include, but are not necessarily limited to, another company, a venture capital firm, an individual angel investor, a foundation, a university, a research institution, a state or local government, or any combination of the above. Third-party investors generally should not include owners of the applicant SBC, their family members, and/or affiliates of the applicant SBC, or other Federal sources of funding. Preferred independent third-party investor funds under this FOA include cash, liquid assets, and/or convertible debt. Independent third-party investor funds generally should not include intangible assets, self-funding, and/or other debt. Applicants must clearly indicate within their third-party Finance Plan the total amount of funding that will be secured from the preferred sources listed above.

SBIR-eligible public companies may include as part of their fundraising plan the issuance of stock. In such a case, the preferred documentation is a letter of commitment, signed by the Chairman of the Board of Directors, which stipulates the following: (1) the amount of capital raised from the issuance of stock; (2) the amount of capital that will be dedicated to the proposed project under this FOA; (3) sufficient information regarding the use of the dedicated capital to demonstrate a substantial, value- added contribution toward the development and commercialization of the product to be developed under this FOA (see instructions below, Use of Third-Party Investment Funds ).

It is likely that several months will have elapsed between the time an application is submitted and the time it is peer reviewed and subsequently considered for possible funding. Accordingly, applicants must present a detailed summary of all past and/or planned (i.e., future/expected) third-party investor funds that clearly shows, relative to the estimated award date, when these funds have been and/or will be secured. For example, if the fundraising efforts of the SBC are in progress, and/or if the third-party investment is contingent upon NIH selecting the application for funding, then such plans must be clearly described in the Finance Plan.

Applicants are expected to document any independent third-party investor support that has been secured up to one year prior to the application receipt date and any independent third-party investor support that will be provided to the SBC during the proposed Phase IIB Bridge Award project period. Specific evidence supporting the applicant's fundraising plan should be provided as described in PHS 398 Research Plan, "Letters of Support" and Other Project Information, "Other Attachments."

Applicants seeking further information regarding preferred sources and/or types of support that would demonstrate a third-party investor commitment are strongly encouraged to communicate with the Scientific/Research Contact(s) listed under Section VII.

In addition to the expected independent third-party funding equal to or exceeding the NHLBI funds, the NHLBI encourages applicants to secure in-kind contributions that will add value to the SBC and the project in a way that accelerates the commercialization of the technology being developed. Applicants must:

• explain how the in-kind contributions facilitate the research and commercialization plan;
• provide a detailed and specific plan for securing independent in-kind contributions and the anticipated schedule for receiving them, including any relevant terms and conditions; and,
• provide a detailed analysis of the value of in-kind contributions (e.g., standard market rates for consultant work, value of equipment).

In-kind contributions will not be considered as part of the independent third-party funding that is expected to equal or exceed the NHLBI funds.

f) Production and Marketing Plan: Follow the instructions provided in the SF424 Application Guide.

g) Revenue Stream: Follow the instructions provided in the SF424 Application Guide.

h) SBIR/STTR Commercialization History: Applicants MUST provide an SBIR/STTR Commercialization History that addresses the questions listed below. The following questions should be addressed for all SBIR/STTR awards received from ANY Federal agency:

• Has the SBC gone through any name changes within the past five years? If so, list all previous company names in the application.
• Is the SBC a subsidiary or a spinoff? If so, provide the name of the parent company.
• What percentage of the SBC's revenue was derived from SBIR/STTR funding during each of the past 5 years, including both Phase I and Phase II awards? Report a percentage value for each year individually.
• What is the total number of SBIR/STTR Phase II awards that the SBC has received from the Federal government? For each award, provide (as a table):

1) the award number, the award amount, project duration, and the name of the awarding agency.

2) the product name resulting from the award project.

3) the current status of the project (preclinical development; clinical development; commercially available; discontinued).

4) FDA approval status of the product resulting from the project (PMA, IND, NDA, etc.; not yet submitted; submitted; approved, not approved).

5) follow-on funding (amount and investor name), strategic partnership (name of partner), or out-licensing (name of licensee).

6) the total revenues generated to date as a result of commercialization of the award project.

• What are the total revenues that have been generated to date as a result of the commercialization of the SBIR/STTR projects funded in the past 5 years?

i) Project Management Plan

Applicants must provide a Project Management Plan detailing how the research and commercialization plans will be kept on track. The plan should include:

• Specific milestones for the research and development of the product.
• Specific milestones for the commercialization of the product.
• A description of how the third-party investor will contribute to milestone-driven project management processes for the technology development and commercialization. For example, will the third-party investor have a seat on the Board of Directors or the Scientific Advisory Board?

j) Statement of Need

Applicants must provide a concise Statement of Need. This statement is expected to provide answers to the questions listed below:

• What is the perceived funding gap for the product under development?
• Why is additional government funding critically needed to advance the development of the product toward commercialization? Specifically, what activities are being proposed under this FOA that would not otherwise be possible through independent third-party investments OR would be significantly delayed without additional NIH support?
• To what extent would a possible award under this FOA advance the product far enough to attract independent third-party financing and/or strategic partnerships to commercialize the product?

k) Use of Third-Party Investment Funds

The Federal funds provided by a Phase IIB Bridge Award can only be used for advancing the research- related elements of the project. The use of any third-party investor funds will be at the discretion of the SBC. Applicants must provide sufficient information regarding the use of any third-party

support to demonstrate a substantial, value added contribution toward the development and commercialization of the product. Applicants are expected to address the following questions regarding the use of third-party funds:

• What are the specific activities that the third-party investor funds will support?
• Have the investors attached any restrictions/triggers/milestones to future payments (i.e., tranches)? If so, what are they?

l) Regulatory Plan

Applicants must provide a regulatory plan describing the regulatory pathway that is being or will be pursued and a timeline for achieving regulatory approval with discrete milestones. Applicants are strongly encouraged to submit evidence that they have contacted the appropriate regulatory authority and that their research plan and objectives follow the relevant requirements or guidance of that authority. Examples that provide evidence of appropriate interactions are letters or emails between the SBC and the appropriate FDA Center personnel or meeting minutes concerning a pre-submission meeting or regarding a 510(k), IDE, PMA, HDE, BLA, IND, or NDA application. Copies of these letters, emails or minutes should be attached in the Other Project Information, "Other Attachments" section in the PHS398 Research Plan form.

Applicants may also provide details of their interaction with the regulatory authority in the description of their Regulatory Plan. This should include the regulatory authority contact and date of interaction. Applicants should describe any outside assistance they have obtained or plan to obtain for developing and achieving the proposed Regulatory Plan.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) SBIR/STTR Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), SBA Company Registry, eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and time. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) SBIR/STTR Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Instructions. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NHLBI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy -. Any instructions below are in addition to the instructions in the policy:

Updated documentation regarding third-party funding and regulatory agency communications are allowed as Post Submission materials to be submitted no later than 30 days prior to the scheduled review meeting and within the page limits defined in NOT-OD-17-066

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA
To what extent do the experience and qualifications of the project team members lend confidence that the team will be successful in developing and commercializing the proposed product? For example, if the PD(s)/PI(s) have had other Phase II awards, how successful have they been in commercializing those technologies and discoveries?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? For a Phase I application, are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA:

How promising are the outcomes of the previously funded SBIR/STTR Phase II project upon which the proposed Phase IIB Bridge Award is predicated? To what extent does the progress justify the continuation of the development efforts? How appropriate are the proposed milestones for the Phase IIB Bridge Award in determining whether the awardee has successfully reached the specified goals (e.g., IND filing)?

If the product proposed for development is based on a platform technology that was initially developed for a non-NHLBI mission-relevant indication/use, to what extent have the Phase II activities provided a solid foundation (i.e., relevant proof of concept) to support continued development of the technology for the proposed NHLBI mission relevant indication/use?

How sound is the proposed plan to meet Federal regulatory requirements?

How successful has the SBC been in commercializing prior SBIR/STTR projects supported by any Federal agency?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangement?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Commercialization Plan

Value Proposition. How compelling is the product's value proposition, and to what extent does the application demonstrate a substantial market-pull for the product under development? How well does the application describe the market niche(s) for the product and how urgent is the unmet medical need(s) being addressed? How well does the application identify the potential customers for the product and demonstrate a clear understanding of their needs?

Market, Customers, and Competitive Environment. How well has the application demonstrated an understanding of the competitive environment in which the product will be sold? To what extent has the application identified realistic, market-based milestones that can be achieved over the next five years? Does the SBC display an understanding of the hurdles that may delay or prevent acceptance of their product? How reasonable are the plans for generating a revenue stream, and how realistic are the revenue projections?

Company. To what extent do the prior experience and qualifications of the project team members lend confidence that the team will be successful in commercializing the proposed product or service? For example, how successful have the PD(s)/PI(s) been in commercializing other SBIR/STTR-supported technologies and discoveries in the past? To what extent does the applicant SBC have the ability to address regulatory issues, either through their own staff members or through appropriate arrangements with external regulatory consultants? To what extent is the applicant SBC concentrating on its core competencies in order to maximize its chances of success? How well can the applicant SBC sustain itself and grow as a business? To what extent will the applicant's business alliances and/or corporate partnerships help in facilitating commercialization? For example, will the third-party investors play an active role in facilitating the commercialization of the product or service, and if so to what extent?

Intellectual Property. How strong is the applicant SBC's intellectual property (IP) portfolio/position (pertinent to the proposed project), and to what extent does the SBC have a reasonable strategy to protect its IP going forward?

Fundraising Plan. How well does the application support the ability of the SBC to secure independent third-party investor funds (i.e., third-party funds that equal or exceed the requested NHLBI funds), including the preferred types of liquid, third-party investor funds (i.e., cash, liquid assets, and/or convertible debt), as expected under this FOA? How detailed is the documentation (e.g., term sheet) that has been provided by the applicant SBC to corroborate the Finance Plan? If the third-party investors have attached restrictions and/or triggers and/or milestones to future payments, to what extent have these restrictions been clearly stipulated in the application? To what extent does the applicant SBC have access to resources needed to sustain itself and grow as a business? To what extent has the application demonstrated that the third-party investor support will provide a substantial, value added contribution toward the development and commercialization of the product? For example, has the application described the specific activities that the third-party investor funds will support?

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Not Applicable.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Phase IIB Applications, the committee will consider the progress made in the last funding period.

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan.

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by {the NHLBI}, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a committee process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

SBIR Phase IIB Bridge Award Terms and Conditions

If a Phase IIB Bridge Award application is selected for funding, the applicant’s plan for securing independent third-party investor funds (i.e., the Finance Plan submitted as part of application) will become a term of award. Prior to the issuance of an award, NIH will request Just-In-Time information from the applicant to verify compliance with the Finance Plan. Once the NHLBI grants management official has notified the SBC that their application is being considered for funding, the SBC is encouraged to submit all of the requested Just-In-Time information as soon as possible.

Just-In-Time information related to the Finance Plan may include, but is not limited to, the following:

• An updated, signed, fully executed, and binding agreement(s) between the SBC and all investors and all sources of third-party investor funds that have been committed over the entire project period;
• Substantial, detailed, verifiable proof (e.g., redacted bank statement or other documentation) of third-party investor funds that have been received by the SBC;
• Substantial, detailed, verifiable proof that the SBC will receive (or has already received) third-party investor funds that equal or exceed the NHLBI funds requested during the first year of the project period;
• Other information as necessary (in consultation with NHLBI SBIR program staff and the NHLBI Office of Grants Management), which adequately documents the third-party commitment as stipulated in the applicant s Commercialization Plan.

Prior to the issuance of an award, any substantive change to the applicant’s original Finance Plan (as reviewed by the Special Emphasis Panel) must be discussed with the assigned Program Director during the administrative review process. Substantive changes to the original Finance Plan may include, but are not necessarily limited to, the following: (1) one or more of the original investors has withdrawn or substantially reduced their committed level of support; (2) the financing mechanism or instrument, or other terms associated with the third-party investment, have been significantly altered relative to the originally proposed plan.

Prior to the issuance of award, if the applicant proposes to modify the Finance Plan, the assigned Program Director must verify that the updated type(s), source(s), total amount(s), and anticipated schedule(s) for receiving funds represent an equivalent or superior plan as compared to the originally evaluated Finance Plan.

All substantive changes to the original Finance Plan (i.e., the plan evaluated by the Special Emphasis Panel) will be evaluated on a case-by-case basis. All substantive changes to the applicant’s original Finance Plan must be appropriately addressed in a revised Finance Plan. If a revised Finance Plan is proposed, it must be approved by the Director of the Office of Translational Alliances and Coordination and the NHLBI Office of Grants Management prior to award. In such a case, the revised Finance Plan supersedes the original plan and becomes a term of award.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension. When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

• Final RPPR (requirements have recently changed - please see the NOT-OD-17-085)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR) replaced the Final Cash Transaction Report (PSC 272)
• Phase II Data Collection Requirement for Government Tech-Net Database

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

As described above, the applicant’s Finance Plan submitted at the time of application (or the revised Finance Plan approved by the NHLBI), becomes a term of award. Throughout the Phase IIB Bridge Award project period, grantees will be expected to provide detailed, verifiable documentation (e.g., redacted bank statement or other documentation) of independent third-party investor support that is planned/expected, according to the schedule that is stipulated in the Finance Plan.

A grantee’s failure to comply with the terms of award may cause NIH to take one or more enforcement actions, including suspension of the grant, withholding of support, or termination, depending on the severity and duration of the noncompliance. NIH will undertake any such action in accordance with applicable statutes, regulations, and policies.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)
Website to Email: http://sbir.gov/feedback?type=reg

Gary Robinson, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-496-2149
Email: NHLBI_SBIR@mail.nih.gov

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Shelia Ortiz
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: ortizs@nhlbi.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), and as reauthorized and extended under P.L. 114-328, Section 1834. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.