Required Application Instructions

It is critical that applicants follow the 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

The Small Business Innovation Research (SBIR) Program is an important National Institutes of Health (NIH) funding mechanism used 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 technology products is often impeded by a significant funding gap between the end of the SBIR Phase II award and the commercialization stage. This gap is increased by the barriers associated with technologies under development for small commercial markets, such as those focused on rare diseases or young pediatric populations. This Funding Opportunity Announcement (FOA) invites small businesses to submit SBIR grant applications to support later stage research and development (referred to as Phase IIB) for promising projects that were previously funded by SBIR or STTR (Small Business Technology Transfer) Phase II awards that address rare diseases or young pediatric populations (aged 0-12 years and defined in Section IV, part 7), 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 next appropriate milestone(s) necessary to advance a product/technology along a promising commercialization pathway by promoting partnerships between small business awardees and third-party investors and/or strategic partners, including patient advocacy organizations.

• This FOA will give competitive preference and funding priority to applications deemed likely to result in a commercial product as indicated by the applicant’s ability to secure independent third-party investor funds that equal or exceed one-third of the requested NHLBI funds (total costs).
• This FOA is specifically intended to benefit clinical practice by accelerating the commercialization of novel products and technologies that address a rare disease or young pediatric populations (aged 0-12 years and defined in Section IV, part 7). The primary indication of the product under development would:
• Address a rare disease as defined in the Orphan Drug Act Amendment of 1984 as any disease or condition that affects less than 200,000 persons in the United States
• OR qualify as a Humanitarian Use Device, defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 persons in the United States per year
• OR be targeted at a young pediatric population, defined as including neonates (0-28 days), infants (<2 years), and/or children (2-12 years of age), as indicated in the FDA Premarket Assessment of Pediatric Medical Devices.
• Proposed projects must be relevant to the NHLBI mission (see B. Scientific/Technical Scope) and require ultimate approval/clearance by a Federal regulatory agency. NCATS intends to co-fund applications that meet the NCATS mission to develop innovations that reduce, remove or bypass costly and time-consuming bottlenecks in the translational science process, to speed the development and delivery of new drugs, diagnostics, medical devices and behavioral interventions to patients. For a description of the NCATS SBIR/STTR research priorities, please refer to http://ncats.nih.gov/smallbusiness/priorities.

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 the objective in Phase II is to continue the R&D effort for successful Phase I projects. The expectation is that in Phase III, an SBC will be able to complete commercialization with non-SBIR funds. However, many projects initiated with SBIR funding require considerable financing beyond the SBIR Phase II award to complete the necessary validation studies required to arrive at Phase III. 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. Companies developing products that have small potential revenue streams or target small patient populations face additional barriers to market entry that make them less attractive at pre-clinical or early clinical stages of development to investors and strategic partners. In addition, many of these technologies require complex clinical trial designs because of small and geographically diverse patient populations. Thus, despite the extensive R&D efforts during Phase II projects in these areas, the results are often insufficient to attract the private investments needed for the eventual commercialization of a product and many small businesses 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 for technologies primarily focused on rare diseases or young pediatric populations.

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 pre-clinical 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. In the rare disease area, patient advocacy groups and foundations have organized to accelerate progress in the development of treatments for their disease. 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.

The NHLBI has published a separate FOA, the Phase IIB Bridge Award (RFA-HL-16-009), to address a similar critical gap for projects that do not meet the responsiveness criteria of the Small Market Award.

A. Independent Third-Party Investor Funds

This FOA specifically encourages business relationships between applicant SBCs and third-party investors/strategic partners who can provide substantial financing to help accelerate the commercialization of promising new products and technologies that were initiated with SBIR or STTR funding. In particular, applicants are expected to leverage their previous SBIR/STTR 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 one-third of the total amount of the NHLBI funds being requested over the entire Phase IIB Small Market 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 Small Market 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 addressing rare diseases or young pediatric populations, as well as engaging with the patient advocacy groups and foundations that focus on the indication of the developing technology. Applicants are encouraged to explore existing resources and groups to engage with the relevant communities, such as the NCATS Genetic and Rare Diseases Information Center (GARD), the National Organization for Rare Disorders (NORD), FasterCures, and the Patient-Centered Outcomes Research Institute (PCORI).

B. Scientific/Technical Scope

The technical and commercial objectives described in the SBIR Phase IIB Small Market 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 Phase II project and also that the proposed product/technology has significant commercial potential. Applicants should also be able to demonstrate that the proposed product/technology has or would have a clear advantage over existing and/or competing products/technologies and should clearly define an appropriate path toward ultimate product commercialization.

This FOA is specifically designed to provide additional support for products/technologies that require ultimate approval/clearance by a Federal regulatory agency, such as the Food and Drug Administration (FDA).

Although projects previously funded by another NIH Institute/Center or another Federal agency are eligible to apply under this FOA, proposed projects must be relevant to the NHLBI and/or NCATS mission. Applicants are strongly encouraged to contact the NHLBI Scientific/Research Contact (listed in Section VII) to discuss whether their proposed project meets this criterion.

The NHLBI supports development of technologies to detect, prevent, or treat cardiovascular, lung, and blood diseases 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 programs foster basic, applied, and clinical research on all product and service development related to the mission of the NHLBI. This FOA invites applications for all topics within the NHLBI mission, not limited to those listed. NCATS intends to co-fund applications that meet the NCATS mission to develop innovations that reduce, remove or bypass costly and time-consuming bottlenecks in the translational science process, to speed the development and delivery of new drugs, diagnostics, medical devices and behavioral interventions to patients. For a description of the NCATS SBIR/STTR research priorities, please refer to http://ncats.nih.gov/smallbusiness/priorities.

The NHLBI program priority areas for technology development research include:

Blood Diseases and Resources areas:

In vitro diagnostic devices and therapeutic biologics, devices, and drugs for rare diseases, and diseases affecting young children and neonates, including, but not limited to: coagulation and other laboratory based assays; transfusion/infusion and non-transfusion/non-infusion treatments for bleeding complications in acquired and inherited bleeding disorders; point of care diagnostics for Sickle Cell Disease and other hemoglobinopathies to facilitate testing in low resource settings to provide earlier diagnosis and access to medical interventions; devices that facilitate transfusion of small volumes of blood components; and long-term, indwelling catheters for transfusion, blood sample collection or medication administration that provide very low thrombosis/infection risk. Other blood disease and resource areas may be proposed, as areas of interest are not limited to those listed.

Cardiovascular Diseases areas:

Diagnostics, therapeutics (including cell and gene therapies), or instruments for treating congenital or acquired heart disease in young pediatric populations, including heart pumps and valves, atrial septal defect closure devices, surgical tools, and devices for cardiac catheterization; diagnostics and therapies for rare arrhythmias (such as LQTS-1, -2, and -3, Brugada's, and Timothy's syndromes) and lipid disorders (such as lecithin-cholesterol acyltransferase or lipoprotein deficiencies or genetic diseases such as Pompe disease); technologies, instruments, and therapeutics for heart (and lung) transplantation, including devices for perfusion of donor organs and technologies for less invasive tissue biopsies and detection of organ rejection. Other cardiovascular disease areas may be proposed, as areas of interest are not limited to those listed.

Lung Diseases areas:

Diagnostics and therapeutics for rare lung diseases and those affecting young pediatric populations, including, but not limited to: respiratory distress syndrome, cystic fibrosis, adult and pediatric pulmonary arterial hypertension, adult and childhood interstitial lung diseases, lymphangioleiomyomatosis, and sarcoidosis. Examples include, but are not limited to, non-invasive monitoring of cardiopulmonary function for neonates and young children, portable imaging systems compatible with Intensive Care Unit environments, therapies to prevent bronchopulmonary dysplasia, improved aerosol delivery devices for young children, portable home diagnostic and treatment devices for sleep disordered breathing in young pediatric populations. Other lung disease areas may be proposed, as areas of interest are not limited to those listed.

The following guidelines provide examples of appropriate development activities to be proposed under this FOA. Responsive applications are not limited to the following areas:

For projects pertaining to the development of therapeutics or imaging agents, applicants are expected to propose activities that will lead to the successful filing of an Investigational New Drug (IND) or exploratory Investigational New Drug (eIND) 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 Pre-Market Notification, 510(k) application, Premarket Approval (PMA) application, Humanitarian Use Device (HUD) application, a Humanitarian Device Exemption (HDE) 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, Humanitarian Use Device (HUD) application, a Humanitarian Device Exemption (HDE) application, an Investigational New Drug (IND) or exploratory Investigational New Drug (eIND) application, and/or Investigational Device Exemption (IDE) application, as needed for the specific technology/system/assay.

Activities to be pursued under this FOA should 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 Small Market Award is to advance SBIR/STTR Phase II projects toward ultimate commercialization. All applicants are expected to develop a realistic plan (extending beyond the SBIR Phase IIB Small Market Award project period) that outlines how and when full commercialization can be accomplished, beyond the period of SBIR funding.

Applicants are encouraged to leverage other available Federal resources where appropriate, including existing FDA incentives to increase and accelerate small market product development, such as Orphan Drug designation, Humanitarian Device Exemption, the Pediatric Exclusivity Provision, and the Orphan Products Grants program to assist with expenses related to clinical trials. Additional information about relevant FDA programs and resources may be found on the Developing Products for Rare Diseases & Conditions industry page.

Applicants are also encouraged to explore eligibility to participate in other NIH resources for translation, including:

• Science Moving towArds Research Translation and Therapy (SMARTT)
• Gene Therapy Resource Program (GTRP)
• Production Assistance for Cellular Therapies (PACT)
• Therapeutics for Rare and Neglected Diseases (TRND)
• Bridging Interventional Development Gaps (BrIDGs)
• Collaboration with NIH Intramural Investigators at the Clinical Center

To participate in these programs, the applicant needs to apply through a separate peer-reviewed open solicitation. Projects selected for these programs will be provided in-kind resources such as manufacturing, pharmacology & toxicology services, or regulatory affairs assistance to support drug development projects.

Applicants developing products that may benefit from access to clinical specimens are encouraged to explore the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

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 in response to 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.

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 be eligible to receive 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 apply for a Phase I award and do not meet or exceed the benchmark rate will not be eligible for a Phase I 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 receive New Phase I, Fast-track or Direct Phase II 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, 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.

The SBIR Phase IIB Small Market 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 Small Market 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 Small Market Award application that is predicated on an STTR 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 Small Market 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 Small Market 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 Small Market awards are non-renewable.

The NHLBI and NCATS will only accept 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 applies.

In all cases, the Phase II project period must end before a Phase IIB Small Market 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.

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) SBIR/STTR Application Guide, including Supplemental Grant Application Instructions 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
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express mail zip: 20817)
Telephone: 301-435-0270
Email: [email protected]

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. SBA Company registry

All applicants to the SBIR and STTR programs are required to register at the SBA Company Registry prior to application submission and attach proof of registration. Completed registrations will receive a unique SBC Control ID and .pdf file. If applicants have previously registered, you are still required to attach proof of registration. The SBA Company Registry recommends verification with SAM, but a SAM account is not required to complete the registration. In order to be verified with SAM, your email address must match one of the contacts in SAM. If you are unsure what is listed in SAM for your company, you may verify the information on the SAM site. Confirmation of your company's DUNS is necessary to verify your email address in SAM. Follow these steps listed below to register and attach proof of registration to your application.

a. Navigate to the SBA Company Registry.

b. If you are a previous SBIR/STTR awardee from any agency, search for your small business by Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in the search fields provided. Identify your company and click Proceed to Registration .

c. If you are a first time applicant, click the "New to the SBIR Program?" link on lower right of registry screen.

d. Fill out the required information on the Basic Information and Eligibility Statement screens.

e. Press Complete Registration on the lower right of the Eligibility Statement screen and follow all instructions.

f. Download and save your SBA registry PDF locally. The name will be in the format of SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

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

For questions and for technical assistance concerning the SBA Company Registry, please contact the SBA at http://sbir.gov/feedback?type=reg.

2. SBIR Application Certification for small business concerns 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.

Applicants 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 their application package.

a. Download the SBIR Application 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.

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

4. 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 Small Market 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 Small Market 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).

In situations where a large market indication is identified as part of the overall commercialization strategy in addition to the small market indication, letters of support from third-party investors should indicate a strong commitment to advance the development of the project for the small market indication (rare disease or young pediatric population).

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: Do not use the Appendix to circumvent page limits. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide.

Commercialization Plan: All applicants are expected to describe a realistic plan (extending beyond the SBIR Phase IIB Small Market 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/technology should extend beyond the period of SBIR funding.

The following subsections should 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, applicants 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).

In addition to plans for securing third party funds, 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. Applicants must provide a detailed analysis of the value of in-kind contributions (e.g., standard market rates for consultant work, value of equipment).

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/technologies emerging from SBIR/STTR Phase II projects. As such, it is expected that applicants for the Phase IIB Small Market 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 one-third of the NHLBI funds (total costs) being requested for the entire project period of the Phase IIB Small Market 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/technology 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 Small Market Award project period. Third-party funds (or plans for raising them) must be documented as concretely as possible including the names of specific partners and investors and any actual or planned/conditional financial commitment (as a specific dollar figure or range). 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 one-third of the NHLBI funds, the NHLBI encourages applicants to secure in-kind contributions that will add value to the company and the project in a way that accelerates the commercialization of the technology being developed. Applicants must explain how these in-kind contributions facilitate the research and commercialization plan. In-kind contributions will not be considered as part of the independent third-party funding expected to equal or exceed one-third of 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 should 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 company gone through any name changes within the past five years? If so, list all previous company names in the application.
• Is the company a subsidiary or a spin-off? If so, provide the name of the parent company.
• What percentage of the company’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 company 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 (Pre-clinical development, Clinical development, Commercially available, Discontinued).
4) FDA approval status of award 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 technology.
• 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 that includes evidence indicating that the project meets the responsiveness criteria for developing a product primarily designed to address a rare disease or young pediatric populations. In addition, the applicant must provide evidence that the eventual product faces specific commercialization barriers as a result of addressing a rare disease or young pediatric populations, such as the small size of the commercial market or the difficulty or expense of running clinical trials. Appropriate evidence could include an independent analysis of the net present value of the investment required to commercialize the technology for the indicated market.

In addition, this statement is expected to provide answers to the questions listed below:

• What is the perceived funding gap for the product/technology under development?
• Why is additional government funding critically needed to accelerate the development of the product or technology 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 or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

k) Use of Third-Party Investment Funds

The Federal funds provided by a Phase IIB Small Market 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/technology. In particular, 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?
• Have the investors indicated a commitment to the development of the technology for the rare or pediatric indication, even if a larger market exists and is part of the overall commercialization strategy?

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 company and the appropriate FDA Center personnel or meeting minutes concerning a presubmission meeting or regarding a 510(k), IDE, PMA, HDE, BLA, IND, or NDA application, or the Humanitarian Use Device (HUD) Designation letter. 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 conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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 NHLBI, NIH. Applications that are incomplete, non-compliant, and/or non-responsive will not be reviewed.

Criteria for Complete, Compliant, and Responsive Applications

Prior to the peer review process, program staff at the NHLBI will determine whether applications are responsive to this FOA. All applications will be administratively evaluated to determine whether:

• The proposed R&D represents the continuation of work conducted under a previously-funded SBIR or STTR Phase II award (grant or contract);
• The primary indication of the product under development would:
• Address a rare disease as defined in the Orphan Drug Act Amendment of 1984 as any disease or condition that affects less than 200,000 persons in the United States
• OR qualify as a Humanitarian Use Device, defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 persons in the United States per year
• OR be targeted at a young pediatric population, defined as including neonates (0-28 days), infants (<2 years), and/or children (2-12 years of age), as indicated in the FDA Premarket Assessment of Pediatric Medical Devices.
• The proposed R&D falls within the technical scope of this FOA as described under Section I (Specific Objectives for SBIR Phase IIB Small Market Award Applications);
• The budget amounts and project period conform to the limits stipulated under this FOA, as described under Section II ("Award Budget" and "Award Project Period");
• The application includes a Commercialization Plan addressing all sections (a-l) as described above under Section IV ("SF424 (R&R) SBIR/STTR Information: Commercialization Plan").
• The application includes 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").

Applicants are required to follow our Post Submission Application Materials policy. In addition, 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-13-030.

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.

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?)

Specific to this FOA:

How compelling is the value proposition, and to what extent does the application demonstrate a substantial market-pull for the technology under development? How well has the applicant described the market niche(s) for the product/technology, and how urgent is the unmet medical need(s) being addressed? To what extent has the applicant identified realistic, market-based milestones that can be achieved over the next five years?

What is the quality of the evidence provided that the product faces specific commercial barriers because of its focus on a rare disease or young pediatric population? How well has the applicant described the need for the award?

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 prior experience and qualifications of the project team members lend confidence that the team will be successful in commercializing the proposed product/technology? For example, if the PD(s)/PI(s) have had previous Phase II awards, how successful have they been in commercializing those technologies and discoveries?

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?

Specific to this FOA:

How well has the applicant demonstrated an understanding of the competitive environment in which they plan to sell their product?

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? 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 or STTR Phase II project upon which the proposed Phase IIB Small Market 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 Small Market Award in determining whether the awardee has successfully reached the specified goals (e.g., IND filing)?

If the technology proposed for development is a platform technology that was initially developed for a non-NHLBI mission-relevant indication/use, then 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?

To what extent has the applicant identified their customers and demonstrated a clear understanding of their needs? How well has the company addressed potential hurdles that may delay or prevent acceptance of their product? How reasonable are the applicant’s plans for generating a revenue stream, and how realistic are the revenue projections?

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

How well does the application support the ability of the SBC to secure substantial 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 to corroborate the Finance Plan? If the third-party investors have attached restrictions and/or triggers and/or milestones to future payments, then to what extent have these restrictions been clearly stipulated in the application?

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/technology, and if so to what extent?

If the SBC has received previous SBIR/STTR funding from ANY Federal agency, then how successful is the company s track record in commercializing prior SBIR/STTR projects?

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?

Specific to this FOA

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?

To what extent has the applicant demonstrated that the third-party investor support will provide a substantial, value-added contribution toward the development and commercialization of the product/technology? For example, has the applicant described the specific activities that the third-party investor funds will support?

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.

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 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 on the basis of established PHS referral guidelines 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 National Heart, Lung, and Blood 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.

SBIR Phase IIB Small Market Award Terms and Conditions

If a Phase IIB Small Market 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. 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 one-third of 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 fundraising 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

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 Progress Report (requirements have recently changed - please see the NOT-OD-12-152)
• 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.

For details about each specific required report, see Part III. Section 5, "SBIR/STTR Award Guidelines, Reporting Requirements, and Other Considerations, in the Supplement Grant Applications For All Competing Applications and Progress Reports.

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.

SBIR Phase IIB Small Market Award: Compliance with the Finance Plan (Reporting)

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 Small Market 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 non-compliance. 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
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (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: https://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

Jennifer C. Shieh, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-496-2149
Email: [email protected]

Lili M. Portilla, MPA
National Center for Advancing Translational Sciences
Telephone: 301-217-2589
Email: [email protected]

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

Shelia Ortiz
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: [email protected]

Artisha Y. Eatmon
National Center for Advancing Translational Sciences
Telephone: 301-435-0845
Email: [email protected]

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, and P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011). The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.