HHS SBIR RFA-CA-15-010

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 product or service along a promising commercialization pathway.

To be responsive to this FOA, proposed projects MUST be applicable to at least one of the following technical/scientific areas:

(1) Cancer Therapeutics;

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

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

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.

This FOA is specifically intended to provide additional support for products and services that require ultimate approval by a Federal regulatory agency; therefore, proposed projects may address preclinical and/or clinical stages of development (including clinical trials).

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. In particular, the development of therapeutics and medical devices often requires several years and substantial capital investments, due in large part to the costs associated with conducting clinical trials and/or other steps mandated by the Federal regulatory approval process.

Among the areas of R&D supported by the Federal SBIR program, cancer therapeutics, imaging technologies, interventional devices, diagnostics and prognostics typically require substantial levels of additional financing beyond the SBIR Phase I and Phase II funding. Moreover, a number of emerging products in these areas are becoming increasingly complex due to the technological advances in multi-disciplinary fields. For example, new products may involve measurements of both physical and molecular signatures, combine device(s) and molecular probe(s), or perform dual functions of diagnosis and therapy. These products are referred to as “combined technologies” by the Food and Drug Administration (FDA), and examples in oncology include those related to genomics, proteomics, certain approaches to imaging, image-guided diagnosis and therapy, and other therapeutics. Importantly, the developers of such technologies often face additional challenges during the regulatory approval process, requiring even more time and effort to commercialize such technologies.

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.”

A number of public and private organizations have begun to recognize the challenges associated with the “Valley of Death” and are taking steps to provide additional resources to advance a greater number of early-stage technologies toward commercialization. Importantly, many of these organizations are not only providing financial support but also establishing programs to provide commercialization guidance. For example, in the area of drug development, a number of major pharmaceutical firms have developed corporate venture funds focused on supporting projects in the pre-clinical stages of development, and some of these firms have established technology incubators to provide regulatory guidance. In addition, a growing number of universities are creating venture funds to support innovative technologies developed by their resident investigators, and numerous state-sponsored technology funds have also been created across the U.S. to support start-up companies. Taken together, these programs can provide additional financing and commercialization support for SBIR/STTR awardees that have received initial seed funding and a rigorous technical evaluation through the peer review process at the NIH and other Federal agencies. 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 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, the 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.

In particular, this FOA is specifically designed to provide additional support for products and services that require ultimate approval by a Federal regulatory agency.

Applications received under this FOA must fall within at least one of three technical/scientific areas: (1) Cancer Therapeutics; (2) Cancer Imaging Technologies, Interventional Devices, and In Vivo Diagnostics; or (3) In Vitro and Ex Vivo Cancer Diagnostics and Prognostics. The following descriptions provide additional details on each of these areas, as well as appropriate development activities to be proposed under 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);
• Structure-Activity Relationship (SAR) studies;
• 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;
• Human Proof of Concept (Phase I clinical trial); and/or
• Clinical Proof of Concept (Phase II clinical trial).

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 & 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;
• Verification of the classification;
• 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.

Responsiveness

To be responsive to this FOA, 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. To be responsive under this FOA, the aims of the project must focus on a cancer-relevant indication/use as the primary product or service.