NHLBI SBIR Phase IIB Small Market Awards to Accelerate the Commercialization of Technologies for Heart, Lung, Blood, and Sleep Disorders and Diseases (R44 Clinical Trial Optional)

Purpose

The Small Business Innovation Research (SBIR) Program is an important National Institutes of Health (NIH) funding mechanism used to develop innovative solutions that address public health challenges. A major objective of the SBIR Program is to facilitate the commercialization of technologies developed by small business concerns (SBCs). Yet, the development of biomedical products is often impeded by a significant funding gap between the end of the SBIR Phase II award and the commercialization stage. This gap is increased by the barriers associated with technologies under development for small commercial markets, such as those focused on rare diseases or young pediatric populations. This Funding Opportunity Announcement (FOA) invites small businesses to submit SBIR grant applications to support later stage research and development (referred to as Phase IIB) for promising projects that were previously funded by SBIR or STTR (Small Business Technology Transfer) Phase II awards that address rare diseases or young pediatric populations (aged 0-12 years and defined in Section IV, part 7), and will require eventual Federal regulatory approval/clearance. The goal of this FOA and the resulting Phase IIB awards is to assist applicants in pursuing the next appropriate milestone(s) necessary to advance a product to regulatory approval and commercialization by promoting partnerships between small business awardees and third-party investors and/or strategic partners, including patient advocacy organizations.

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

Background

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

However, many projects initiated with SBIR funding require considerable financing beyond the SBIR Phase II award to complete the validation studies required to obtain regulatory approval and launch a product. In particular, the development of therapeutics, medical devices, and combined technologies often requires a number of years and substantial capital investments because of the costs associated with conducting clinical trials and/or other steps mandated by the Federal regulatory approval process.

Companies developing products that have small potential revenue streams or target small patient populations face additional barriers to market entry that make them less attractive at preclinical or early clinical stages of development to investors and strategic partners. In addition, many of these technologies require complex clinical trial designs because of small and geographically diverse patient populations.

Thus, despite the extensive R&D performed on such products during Phase II projects, the results are often insufficient to attract the substantial private investment needed for the eventual commercialization of the product. Many small businesses therefore become cash-starved before reaching the next critical milestone along the path toward commercialization.  Hence, this FOA is designed to address this funding gap between the end of the SBIR or STTR Phase II award and the point at which non-SBIR financing can be secured for the subsequent stages of product development.

A number of public and private organizations have begun to recognize the challenges associated with this funding gap and are taking steps to provide additional resources to advance a greater number of promising early-stage technologies toward commercialization. Importantly, many of these organizations are not only providing financial support but are also establishing programs to provide commercialization guidance. For example, in the area of drug development, a number of major pharmaceutical firms have developed corporate venture funds focused on supporting projects in the preclinical stages of development, and some of these firms have established technology incubators to provide development support, including regulatory guidance. In addition, a growing number of universities are creating venture funds to support innovative technologies developed by their resident investigators, and numerous state-sponsored technology funds have also been created across the U.S. to support start-up companies. In the rare disease area, patient advocacy groups and foundations have organized to accelerate progress in the development of treatments for their disease.

Such programs can provide additional financing and commercialization support for SBIR awardees that have received initial seed funding and a rigorous technical evaluation through the NIH peer review process. As such, a major goal of this FOA is to provide a platform to incentivize partnerships between NIH-funded SBIR awardees and a broad range of potential third-party investors. It is anticipated that funding by third-party investors will be predicated on significant due diligence, thus encouraging awardees to formulate credible business plans for product commercialization. In addition, it is expected that third-party investors will maintain an active role in supporting the awardee during the product development phase and during pursuit of follow-on funding for commercialization.

Specific Objectives for SBIR Phase IIB Small Market Award Applications

A. Independent Third-Party Investor Funds

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

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

It is anticipated that many of the partnerships between applicant SBCs and third-party investors will involve a considerable level of project due diligence by the private sector, thereby increasing the likelihood of commercial success for the funded projects. In light of these goals, the NHLBI strongly encourages applicants to establish business relationships with investors and/or strategic partners that have appropriate prior experience in commercializing emerging biomedical technologies addressing rare diseases or young pediatric populations, as well as engaging with the patient advocacy groups and foundations that focus on the indication of the developing technology. Applicants are encouraged to explore existing resources and groups to engage with the relevant communities, such as the NCATS Genetic and Rare Diseases Information Center (GARD), the NCATS Therapeutics for Rare and Neglected Diseases (TRND) program, the National Organization for Rare Disorders (NORD), FasterCures, and the Patient-Centered Outcomes Research Institute

(PCORI).

B. Scientific/Technical Scope

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

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

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

The NHLBI supports development of technologies to detect, prevent, or treat cardiovascular, lung, blood and sleep disorders. It also supports research on the clinical use of blood and all aspects of the management and safety of blood resources. The NHLBI SBIR/STTR program fosters basic, applied, and clinical research on products related to the mission of the NHLBI. The NHLBI program priority areas for technology development research are listed below.

NCATS intends to co-fund applications that meet the NCATS mission to develop innovations that reduce, remove or bypass costly and time-consuming bottlenecks in the translational science process, to speed the development and delivery of new drugs, diagnostics, medical devices and behavioral interventions to patients. For a description of the NCATS SBIR/STTR research priorities, please refer to http://ncats.nih.gov/smallbusiness/priorities.

The NHLBI program priority areas for technology development research include:

Blood Diseases and Resources areas:

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

Cardiovascular Diseases areas:

Diagnostics, therapeutics (including cell and gene therapies), or instruments for treating congenital or acquired heart disease in young pediatric populations, including heart pumps and valves, atrial septal defect closure devices, surgical tools, and devices for cardiac catheterization; diagnostics and therapies for rare arrhythmias (such as LQTS-1, -2, and -3, Brugada's, and Timothy's syndromes) and

lipid disorders (such as lecithin-cholesterol acyltransferase or lipoprotein deficiencies or genetic diseases such as Pompe disease) ; technologies, instruments, and therapeutics for heart (and lung) transplantation, including devices for perfusion of donor organs and technologies for less invasive tissue biopsies and detection of organ rejection. Other cardiovascular disease areas may be proposed, as areas of interest are not limited to those listed.

Lung Diseases areas:

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

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

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

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

C. Plan for Full Commercialization (all applications)

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

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

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

Criteria for Complete, Compliant, and Responsive Applications

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

• Applications that do not propose a budget amount and project period that conform to the limits described under Section II ("Award Budget" and "Award Project Period")
• Applications that do not propose R&D that represents the continuation of work conducted under a previously-funded SBIR or STTR Phase II award (grant or contract)
• Applications that do not propose a product under development with a primary indication that:
• ·         Addresses a rare disease as defined in the Orphan Drug Act Amendment of 1984 as any disease or condition that affects fewer than 200,000 persons in the United States;
• OR qualifies as a Humanitarian Use Device, defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 persons in the United States per year;
• OR targets a young pediatric population, defined as including neonates (0-28 days), infants (<2 years), and/or children (2-12 years of age), as indicated in the FDA Premarket Assessment of Pediatric Medical Devices
• Applications that do not propose R&D that falls within the technical scope of this FOA as described under Section I (Specific Objectives for SBIR Phase IIB Small Market Award Applications)
• Applications that do not contain a Commercialization Plan that includes all sections (a-l) and the required elements for each section, as described under Section IV ("SBIR/STTR Information: Commercialization Plan")
• Applications that do not include letters of support from third-party investors in the Letters of Support section ("PHS 398 Research Plan") and/or documentation of support from third-party investors in the Other Project Information section ("Other Attachments")