It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The Small Business Innovation Research (SBIR) Program is an important mechanism by which the National Institutes of Health (NIH) and other Federal agencies help bring innovative solutions to public health challenges. A major objective of the Federal SBIR Program is to facilitate the commercialization of technologies developed by small business concerns (SBCs). Yet, the development of medical biotechnology products is often impeded by a significant funding gap, known as the "Valley of Death," between the end of the SBIR or STTR Phase II award and the commercialization stage. This Funding Opportunity Announcement (FOA) solicits SBIR grant applications from SBCs to support later stage research and development (referred to as Phase IIB) for projects that were previously funded under SBIR or STTR Phase II awards from any Federal agency. The goal of this FOA and Phase IIB awards is to assist applicants in pursuing the next appropriate milestone(s) necessary to advance a promising product or service along a commercialization pathway.

To be responsive to this FOA, proposed projects MUST pertain to the development of cancer-relevant products and/or technologies with strong commercial potential. The major NCI SBIR/STTR portfolio areas are listed below as a guide to general technology areas funded through the program. Applications proposing the development of technologies outside of these areas that fall within the broader mission of the NCI are also encouraged under this solicitation:

(1) Cancer Therapeutics and Preventative Agents

(2) Cancer Imaging Technologies, Interventional Devices, and In Vivo Diagnostics

(3) In Vitro and Ex Vivo Cancer Diagnostics and Prognostics

(4) Technologies for Cancer Prevention and Control, Supportive Care, and Survivorship

(5) Tools and Model Systems for Cancer Research

These Bridge Awards are designed to facilitate the continuation of promising SBIR or STTR Phase II projects in order to pursue the next appropriate milestone(s) toward ultimate commercialization. To achieve this goal, this FOA is designed to promote partnerships between Federally-funded SBIR or STTR Phase II awardees and third-party investors and/or strategic partners.

In particular, competitive preference and funding priority will be given to applications deemed likely to result in a commercial product or service as indicated by the applicant's ability to secure substantial independent third-party investor funds (i.e., third-party funds that equal or exceed the requested NCI funds). NCI support is thus intended to benefit cancer patients by accelerating the development of novel cancer-relevant products and services toward commercialization.

A major focus of this FOA is to provide additional support for products and services that require ultimate approval by a Federal regulatory agency. Accordingly, proposed projects may address preclinical and/or clinical stages of development (including clinical trials) that are essential steps for such approvals.

Since its inception in 1982, the SBIR program at the NIH (and other Federal agencies) has provided the small business community with critical seed funding to support the development of a broad array of commercial products and services for the detection, diagnosis, treatment, and prevention of disease. The SBIR Program is structured in three phases. The main objective in Phase I is to establish the technical merit and feasibility of the proposed research and development (R&D) efforts, whereas in Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. The objective in Phase III is for the small business to fully commercialize their product or service using non-SBIR funds. However, many of the early-stage projects initiated with SBIR or STTR funding require considerable financing beyond the SBIR or STTR Phase II award to achieve commercialization.

Large pharmaceutical and biotechnology companies, as well as venture capital firms, have traditionally provided the resources needed to fully develop and commercialize biomedical products and services initiated with Federal SBIR or STTR funding. More recently, however, many investors in life science technologies have shown a bias toward financing the continued development of relatively mature technologies at established companies, rather than the higher-risk, emerging technologies under development at many small businesses. Consequently, a number of SBIR and STTR awardees are successfully completing their Phase II activities, yet they are still unable to attract sufficient investment (by the end of the Phase II award) to continue the development of their product or service, thus exhausting their financial resources at a critical stage. The purpose of this FOA is to address this funding gap between the end of the SBIR or STTR Phase II award and the point at which non-Federal financing can be secured for the subsequent stages of product development a phase often referred to as the "Valley of Death". As such, a major goal of this FOA is to provide a platform to incentivize partnerships between Federally-funded SBIR or STTR awardees and a broad range of potential third-party investors.

A. Independent Third-Party Investor Funds

This FOA is specifically intended to encourage 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 services initiated with Federal SBIR or STTR funding. In particular, applicants are expected to leverage their previous SBIR or STTR support, as well as the opportunity to compete for additional funding under this FOA, to negotiate and attract third-party financing needed to advance a product or service toward commercialization. The applicant's ability to secure independent third-party investor funds that equal or exceed the total amount of the NCI funds being requested over the entire Bridge Award project period will provide a measure of the commercial potential that is essential for the SBIR projects solicited under this FOA. This potential will be strongly considered in respective funding decisions. 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, applicants are strongly encouraged to establish business relationships with investors and/or strategic partners that have appropriate prior experience in the commercialization of emerging biomedical technologies.

B. Scientific/Technical Scope

The technical and commercial objectives described in the SBIR Phase IIB Bridge Award application MUST represent an extension of the development efforts that were pursued under a previous Federally-funded SBIR or STTR Phase II award. It is essential that significant progress has been accomplished during the current/preceding SBIR or STTR Phase II project and also that the proposed product or service has significant commercial potential. The proposed product/service must also have a clear advantage over existing and/or competing products/services and a clearly defined path toward ultimate commercialization.

Applications received under this FOA may fall within, but are not limited to, these technical/scientific areas: (1) Cancer Therapeutics and Preventative Agents; (2) Cancer Imaging Technologies, Interventional Devices, and In Vivo Diagnostics; (3) In Vitro and Ex Vivo Cancer Diagnostics and Prognostics; (4) Technologies for Cancer Prevention and Control, Supportive Care, and Survivorship; (5) Tools and Model Systems for Cancer Research.

The following descriptions provide additional details on each of these areas, as well as guidance on potential development activities that may be proposed under this FOA. The topical areas and potential activities listed below are not intended to be exhaustive. Projects in other topical areas that fall within the broader mission of the NCI may also be appropriate for this FOA..

Area 1: Cancer Therapeutics

Projects proposed under Area 1 may include (but are not necessarily limited to) the development of the following categories of cancer therapeutics:

• Small molecule anticancer agents;
• Anticancer biologics, including antibodies and therapeutic vaccines;
• Multifunctional cancer therapeutics based on nanotechnology; and/or
• Anticancer drug delivery systems.

Therapeutic modalities other than those listed above may also be considered.

Applicants proposing projects under Area 1 are generally expected to have completed most of the following steps in the development process (as appropriate for the specific project):

• Target validation;
• Screening of candidates and identification of active entities (small molecules, biologics, etc.);
• Confirmation of hits based on repeat assay/concentration response curve (CRC);
• Identification of lead compound(s) or biologic(s) suitable for further development;
• Process development to support clinical manufacturing (e.g., scale-up feasibility);
• In vivo pharmacokinetics and toxicity studies;
• In vivo preclinical efficacy studies; and/or
• Other activities leading to the selection of a development candidate.

For projects pertaining to Area 1, applicants are expected to propose activities that will lead to the successful filing of an Investigational New Drug (IND) application, as well as clinical studies to support the filing of a New Drug Application (NDA) and/or Biological License Application (BLA).

Specific activities to be proposed will vary among applications. Appropriate activities that may be proposed for Area 1 include (but are not necessarily limited to) the following examples:

• Demonstration of acceptable pharmacokinetics and pharmacodynamics;
• Completion of in vivo preclinical efficacy studies (properly powered);
• Demonstration of acceptable safety (toxicity in rodents and large animals);
• Manufacturing of acceptable clinical dosage form [i.e., meeting Good Manufacturing Practices (GMP) quality];
• Other R&D activities that might be needed to complete an IND application; and

Clinical Proof of Concept (Phase I and/or Phase II clinical trials).

Other R&D activities needed to meet the requirements and expectations of relevant regulatory agencies may also be proposed, as necessary and required for commercialization.

Area 2: Cancer Imaging Technologies, Interventional Devices and In Vivo Diagnostics

Projects proposed under Area 2 may include (but are not necessarily limited to) the development of the following categories of cancer imaging technologies, interventional devices, and in vivo diagnostics:

• Medical devices for in vivo cancer imaging and/or image-guided interventions (e.g., systems for image-guided surgery);
• Radiation therapy devices and other ablative techniques;
• Cancer imaging agents, including imaging radiopharmaceuticals and nanotechnology-based contrast agents;
• Devices and technologies for in vivo cancer diagnostics; and/or
• Devices and technologies that directly enable the delivery of cancer therapies.

Cancer imaging modalities and interventional devices/technologies other than those listed above may also be considered.

Applicants proposing projects under Area 2 are generally expected to have completed the following steps in the development process (as appropriate for the specific project):

• Development of a prototype system with desired functionality;
• Measurements and/or phantom studies to characterize system parameters;
• Initiated efficacy studies in an animal model; and
• Initiated transfer of the technology/device to manufacturing.

For projects pertaining to Area 2, applicants are expected to propose activities that will lead to the successful filing of a 510(k) application, Premarket Approval (PMA) application, Investigational Device Exemption (IDE) application, and/or the successful approval of a study protocol by the Radioactive Drug Research Committee (RDRC).

Specific activities to be proposed will vary among applications. Appropriate activities that may be proposed for Area 2 include (but are not necessarily limited to) the following examples:

• Efficacy studies in an animal model;
• Process development for manufacturing;
• GMP/QS manufacturing;
• Non-clinical safety studies (e.g., toxicology, biocompatibility); and/or
• Clinical trials.

Other R&D activities needed to meet the requirements and expectations of relevant regulatory agencies may also be proposed, as necessary and required for commercialization of the technology.

Area 3: In Vitro and Ex Vivo Cancer Diagnostics and Prognostics

Projects proposed under Area 3 may include (but are not necessarily limited to) the development of the following categories of in vitro and ex vivo cancer diagnostics and prognostics:

• Molecular diagnostics and prognostics, including in vitro diagnostic multivariate index assays (IVDMIA);
• Image analysis tools for diagnosis; and/or
• Spectroscopic techniques for in vitro and ex vivo tissue analysis.

In vitro and ex vivo cancer diagnostic and prognostic technologies other than those listed above may also be considered. Prognostic technologies may be focused on (predicting) disease progression, response to therapy, or both.

Applicants proposing projects under Area 3 are generally expected to have completed the following steps in the development process (as appropriate for the specific project):

• Identification and development of a selective biomarker(s) for the detection of cancer;
• Design and development of a prototype system/assay;
• Characterization of the system/assay in terms of reproducibility, variability, and accuracy;
• Development of a qualified assay for the biomarker that is applicable in the clinical setting; and
• Initiated validation studies in a relevant patient population(s).

For projects pertaining to scientific Area 3, applicants are expected to propose activities that will lead to the successful filing of a 510(k) application, Premarket Approval (PMA) application, and/or Investigational Device Exemption (IDE) application, as needed for the specific technology/system/assay. In general, for scientific Area 3, applicants are expected to propose activities that address any relevant requirements for clinical validation and regulatory approval, as necessary and required for commercialization of the technology.

Area 4: Technologies for Cancer Prevention and Control, Supportive Care, and Survivorship

Projects proposed under Area 4 may include (but are not necessarily limited to) the development of the following categories of technologies for cancer prevention and control, supportive care, and survivorship:

• Digital health technologies and mobile applications focused on behavioral health interventions to alleviate the burden of cancer through prevention and reduced risk, improvements to screening and diagnosis, efficacy of therapy, and end of treatment transitions;
• Software tools and bioinformatics technologies for data integration and cancer control;
• Tools for genetic, epidemiologic, behavioral, social and/or surveillance cancer research.

Applicants proposing projects under Area 4 are generally expected to have completed the following steps in the development process (as appropriate for the specific project):

• Completion of initial usability, user acceptance and/or validation studies;
• Design and development of a functional prototype system;
• Specification of the detailed functional, technical, and customization requirements;
• Initial integration of the technology into the targeted clinical system software environment;
• Data visualization, feedback, and reporting systems (for population or clinical monitoring applications);
• Activities that address scalability, security and privacy (e.g. enhance communication system architecture and capability for data reporting to intended recipients).

For projects pertaining to Area 4, applicants are expected to propose activities that will demonstrate and validate the commercial utility and value proposition of the proposed technology. Specific activities may include (but are not necessarily limited to) usability testing, beta-testing, and user-acceptance testing of the technology (as required); benchmarking studies against relevant market-leading technologies; field studies that reflect the breadth of settings in which cancer care is delivered; complete integration of the proposed technology with existing EMR, PHR, mobile technology platforms, and existing community and clinical resources; and completion of clinical validation and other activities that would be required for FDA approval, as necessary.

Area 5: Tools and Model Systems for Cancer Research

Projects proposed under Area 5 may include (but are not necessarily limited to) the development of the following categories of tools and model systems for cancer research:

• 3D cell culture and animal model systems;
• Software and bioinformatics tools for cancer research;
• Enabling technologies (i.e. drug screening and preclinical profiling technologies, epitope discovery technologies, and biospecimen acquisition and analysis technologies, etc.); and/or
• Research reagents and assays.

Applicants proposing projects under Area 5 are generally expected to have completed the following steps in the development process (as appropriate for the specific project):

• Completion of initial validation studies and demonstration of utility in basic or translational research (may include demonstration of reliability, sensitivity, and specificity, as appropriate);
• Specification of the detailed functional, technical, and customization requirements;
• Development and demonstration of the capability of bioinformatic methods or algorithms for research data integration and data harmonization;
• Design and development of a functional prototype system;
• Establishment and molecular characterization of an experimental model system;
• Demonstration that the established model system is phenotypically stable and clinically relevant;
• Scale up of the synthesis and/or manufacture of necessary agents, chemicals, devices, or products; and/or
• Implementation of quality assurance controls and assays.

For projects pertaining to Area 5, applicants are expected to propose activities that will demonstrate and validate the commercial utility and value proposition of the proposed technology. Specific activities may include (but are not necessarily limited to) usability and/or beta-testing; benchmarking studies against relevant market-leading technologies and/or experimental model systems; and completion of studies that would be required for FDA approval, if necessary.

Responsiveness

To be responsive to this FOA, applications must have the following characteristics:

• The development activities completed under the previous SBIR or STTR Phase II award MUST provide the appropriate technical foundation to justify continued development of the technology for a cancer-relevant indication/use.
• Platform technologies that were initially developed for a non-cancer indication/use (e.g., SBIR or STTR Phase II projects funded by an NIH Institute/Center other than the NCI, or SBIR or STTR Phase II projects funded by a Federal agency other than the NIH) may be responsive only if the earlier data demonstrate technical proof-of-concept that is scientifically relevant to the cancer indication/use.
• The aims of the project must focus on a cancer-relevant indication/use as the primary product or service.

Non-responsive applications will not be reviewed.

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

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

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

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

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

3.

i. SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these; OR

ii. SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern; OR

iii. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.

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

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

If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner.

If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner.

Definitions:

• Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
• Private equity firm has the meaning given the term private equity fund in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
• Venture capital operating company means an entity described in 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

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

Phase I to Phase II Transition Rate Benchmark

In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011. This Transition Rate requirement applies to SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years, excluding the most recently-completed fiscal year. For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to be eligible to apply for a new Phase I award. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5-year period.

Companies that do not meet or exceed the benchmark rate will not be eligible to apply for a Phase I Fast-Track, or Direct Phase II (if available) award for a period of one year from the date of the application submission. The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently-completed year. The benchmark minimum Transition Rate is 0.25.

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

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

Phase II to Phase III Commercialization Benchmark

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

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-year period, excluding the two most recently-completed Fiscal Years.

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

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

Applicants that fail this benchmark will be notified by SBA annually and will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year.

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

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.

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Jonathan Franca-Koh, PhD, MBA
SBIR Development Center
Telephone: 240-276-7622
Email: francakohjc@mail.nih.gov

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

Instructions for Application Submission

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

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

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

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

Project Summary/Abstract: Provide the name of awarding agency and identification/serial number of the Phase II award (grant or contract) upon which the application is predicated (for NIH awards, use the full standard format for grant number, such as "5R44CA123456-04").

Other Attachments

1. 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 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.

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:

Specific Aims: Outline Specific Aims of the project and key milestones that will serve as benchmarks for accomplishing these Aims.

Research Strategy: In addition to standard content of Research Strategy, the applicants must address the following items (under the headings indicated below).

Commercialization Readiness and Competitive Advantage. Applicants should demonstrate in their application that significant progress has been accomplished during the "parent" SBIR or STTR Phase II project, and also that the product or service has significant commercial potential. Applicants should also demonstrate that the proposed product/service has a clear advantage over existing and/or competing products/services and should clearly define an appropriate path toward ultimate commercialization.

Milestones. Applicants should describe appropriate milestones to be achieved during the proposed project period toward accomplishing the stated aims of the project. For multi-year awards, applicants should indicate specific milestones for each year of the award. Milestones proposed should be specific and quantitative, if possible. If applicable, proposed milestones should include meeting specific regulatory requirements [e.g., Investigational New Drug (IND) filing].

Letters of Support: Include letters of support documenting commitments from third-party investors. Letters of support from these institutional partners should indicate any actual or planned/conditional financial commitment as a specific dollar figure or range, and these letters should corroborate the information provided in the "Fundraising Plan" section of the Commercialization Plan. Appropriate documentation of third-party investor commitment(s) may include a conditional letter of support stating that the third-party funding is contingent upon NIH selecting the application for an award.

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 support, 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 or service to be developed under this FOA. The letter should corroborate the information provided in the Commercialization Plan.

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

Commercialization Plan: All applicants must propose a realistic plan (extending beyond the SBIR Phase IIB Bridge Award project period), which outlines how and when full commercialization can be accomplished and reflects appropriate third-party commitments. The full commercialization of the product or service should be carried out with non-SBIR funds.

The following subsections with the headings a-d should be included within the Commercialization Plan, in addition to the requirements listed in the SF424 Application Guide

a. Statement of Need

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

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

b. Fundraising Plan

Consistent with achieving the goals of this program, applicants are expected to provide a detailed and specific plan (i.e., "Fundraising Plan"), for securing substantial, independent third-party investor funds. Any third-party investment support received up to one (1) year prior to the application receipt date may be counted toward the total. The Fundraising Plan is expected to include the following information:

• 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.

The NCI 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 or services emerging from Federally-funded SBIR or STTR Phase II projects. It is expected that the level of this independent third-party funding will equal or exceed the NCI funds being requested throughout the Phase IIB Bridge Award project period.

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. 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 in-kind support, intangible assets, self-funding, and/or other debt. Applicants should clearly indicate within their third-party fundraising plan the total amount of funding that will be secured from the preferred sources listed above.

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 should present a detailed summary of all past and/or planned (i.e., future/expected) third-party investor funds which 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 should be clearly described in the Fundraising Plan.

Evidence of a firm third-party commitment at the time of application submission would be considered optimal and is strongly encouraged (if possible), but will not be required. For any third-party commitment (firm, conditional, or tentative), at the time of application submission, applicants must obtain detailed, verifiable documentation of any independent third-party investor support that will be provided to the SBC during the proposed Bridge Award project period. Applicants should also obtain 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, which may be counted toward the third-party funding that is expected under this FOA. Documentation of support from third-party investors should corroborate the Fundraising Plan.

Note: Applicants are expected to describe their matching funds (or plans for raising them) as concretely as possible. For example, plans to raise additional funds from venture capital companies and/or other pharmaceutical companies should name specific partners and investors. The description of any commitments in this section must be properly supported by specific documentation (following instructions under "Other Attachments" and "Letters of Support").

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.

c. Use of Third-Party Investment Funds

The Federal funds provided by a Phase IIB Bridge Award can only be used for advancing the research-related elements of the project. The use of any third-party investor funds will be at the discretion of the SBC. Applicants should 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 or service. In addition, 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?

d. 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, then all previous company names should be listed in the application.
• Is the company a subsidiary or a spin-off? If so, then the name of the parent company should be provided.
• 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? Applicants should 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, companies should provide the award number, the award amount, project duration, and the name of the awarding agency.
• What are the total revenues that have been generated to date as a result of the commercialization of the SBIR/STTR projects funded within the past 5 years?

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

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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: If the technology proposed for development is a platform technology that was initially developed for a non-cancer 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 cancer indication/use? Is there compelling justification for the continued development of the proposed product or service in terms of potential advances in clinical practice, public health, and/or patient quality of life?

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

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

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

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

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

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

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How appropriate are the proposed milestones for the Phase IIB Bridge Award in determining whether the awardee has successfully reached the specified goals? If the proposed project involves advancing the product or service through the Federal regulatory approval process, how sound is the proposed plan to meet these requirements?

In addition, for applications involving clinical trials: Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

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

In addition, for applications involving clinical trials: If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

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

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

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

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

Commercialization Plan

Commercialization Readiness. To what extent is the project ready for commercialization activities based on the outcomes of the previously-funded SBIR or STTR Phase II project upon which the proposed Phase IIB Bridge application is predicated?

Market, Customers, and Competition. To what extent is the project focused on a cancer-relevant indication/use as the primary product or service? 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 or service, and how urgent is the unmet need(s) being addressed? To what extent has the applicant identified realistic, market-based milestones that can be achieved during the project period and in the years beyond? How well has the applicant demonstrated an understanding of the competitive environment in which they plan to sell their product or service? 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 or service? How reasonable are the applicant's plans for generating a revenue stream, and how realistic are the revenue projections?

Intellectual Property (IP). 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?

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

Fundraising Plan. 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 NCI 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 Fundraising Plan? 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 or service? For example, has the applicant described the specific activities that the third-party investor funds will support? 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? In general, have the terms of the future investment rounds been sufficiently described, thus demonstrating a high level of confidence in the SBC's ability to execute the overall fundraising plan?

Study Timeline

Specific to applications involving clinical trials

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

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

Not Applicable

Not Applicable

For research that involves human subjects but does not involve one of the 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 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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

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

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

Not applicable.

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

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. 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.
• Commercial merit and viability of the proposed R&D efforts. Competitive preference and funding priority will be given to projects deemed likely to result in a commercial product or service as indicated by the applicant's ability to secure appropriate independent third-party investor funds that equal or exceed the total amount of the NCI funds being requested over the entire project period

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

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

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

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

If a Phase IIB Bridge Award application is selected for funding, the applicant's plan for securing independent third-party investor funds (i.e., the Fundraising Plan submitted as part of application) will become a term of award. Prior to the issuance of an award, NIH will request "Just-In-Time" information from the applicant to verify compliance with the Fundraising Plan. Once the NCI 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 Fundraising Plan may include, but is not limited to, the following:

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

All substantive changes to the original Fundraising 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 Fundraising Plan must be appropriately addressed in a revised fundraising plan. If a revised Fundraising Plan is proposed, it must be approved by the Director of the NCI SBIR Development Center and authorized person(s) in the NCI Office of Grants Administration prior to award. In such a case, the revised Fundraising Plan supersedes the original plan and becomes a term of award.

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

NIH requires that SBIR/STTR grantees submit the following reports within 120 days of the end of the grant budget period unless the grantee is under an extension. When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

• Final RPPR (requirements have recently changed - please see the NOT-OD-17-085)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR)
• SBIR.gov
• Quarterly reports are due to the Payment Mangement System 30 days following the end of each calendar quarter

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

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

Jonathan Franca-Koh, PhD, MBA
National Cancer Institute (NCI)
Telephone: 240-276-7622
Email: francakohjc@mail.nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

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

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

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, , and P.L. 115-232. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.