HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R41/R42 - Clinical Trial Optional)

The National Center for Advancing Translational Sciences (NCATS) will not accept primary assignment to applications proposing clinical trial(s) under this funding announcement. Please direct any questions to the NCATS scientific contact.

Purpose

More than 2 million individuals in the United States have an opioid use disorder (OUD), most starting with opioid analgesics prescribed to them or procured from diverted medications, but once addicted, patients often shift to illicit heroin or synthetic opioids (https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR1-2016/NSDUH-FFR1-2016.pdf). Millions more misuse opioids, taking opioid medications longer or in higher doses than prescribed. The scope of this crisis is staggering, but there is a hope that scientific advances and the product development based on those scientific advances can offer strategies to help the nation overcome the crisis.

The FY 2018 Consolidated Appropriations Act provided the resources needed to jumpstart an ambitious and targeted research strategy focused on tackling unmet needs of those with opioid addiction.  With the support of the President and the U.S. Department of Health and Human Services (HHS), the National Institutes of Health (NIH) launched HEAL, Helping to End Addiction Long-term, to provide science- and research-based solutions to the national opioid crisis and offer new hope for individuals, families, and communities affected by this devastating crisis. The NIH HEAL Initiative will bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at:  https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative. 

The National Institute on Drug Abuse (NIDA) remains committed to addressing the national crisis on all fronts, with a special focus of its small business programs on encouraging biomedical product innovation to prevent new cases of opioid abuse and addiction and to treat those addicted. This funding opportunity is being offered as part of the NIH’s HEAL initiative to accelerate scientific solutions to the national opioid public health crisis. This FOA invites eligible United States small business concerns (SBCs) to submit Small Business Innovation Research (SBIR) grant applications. Biomedical technologies that lead to the prevention and treatment of opioid use disorder are highly desired and their developers are strongly encouraged to apply. The small business companies that developed currently marketed technologies or are developing technologies for different indications and who are interested in demonstrating that their product (device, therapeutics, diagnostics, etc.) has a potential application in the OUD space, are also encouraged to apply.

Specific Research Objectives for SBIR “America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis” Applications

A. Scientific/Technical Scope

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

The following descriptions provide additional details for each of these areas, as well as guidance on potential research and development activities that may be proposed under this FOA. The topic areas and potential activities listed below are not intended to be exhaustive. Projects outside of these areas that fall within the broader mission of NIH HEAL Initiative (https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative) are within the scope of this funding opportunity.

Area 1: OUD Therapeutics (to treat OUD, and to prevent and reverse overdose)

Projects proposed under Area 1 may include (but are not necessarily limited to) the development of the following categories of therapeutics for opioid addiction, overdose prevention and reversal:

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

The activities and steps in the R&D process which can be funded under this FOA:

For projects pertaining to Area 1, applicants are expected to propose and conduct activities that will eventually 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:

Other R&D activities needed to meet the requirements and expectations of the relevant regulatory agencies may also be proposed, as necessary and required for commercialization. The proposed product must have a clear advantage over existing and/or competing products and a clearly defined path toward ultimate commercialization. Applicants are encouraged to establish the Target Product Profile (TPP) for the proposed products.

Area 2: OUD Devices, including Interventional, and Diagnostics

Projects proposed under Area 2 may include (but are not necessarily limited to) the development of the following categories of biomedical products:

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

The activities and steps in the product development process which can be funded under this FOA:

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:

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: Technologies for OUD Prevention, Control and Supportive Care

Projects proposed under Area 3 may include (but are not necessarily limited to) the development of the following categories of technologies for OUD prevention and control, supportive care for neonatal opioid withdrawal syndrome (NOWS), also referred to as neonatal abstinence syndrome (NAS), and overdose sensing and prevention:

The activities and steps in the development process which can be funded under this FOA:

For projects pertaining to Area 3, 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) benchmarking studies against relevant market-leading technologies and completion of clinical validation and other activities that would be required for FDA approval, as necessary.

Area 4: Tools and Model Systems for OUD Research

Projects proposed under Area 4 may include (but are not necessarily limited to) the development of the following categories of tools and model systems for OUD research:

The activities and steps in the product development process which can be funded under this FOA:

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 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.

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

1. • Small molecule agents;
   • Biologics, including antibodies and therapeutic vaccines;
   • Natural products;
   • Longer-acting formulations of existing addiction medications;
   • Longer-acting formulations of opioid antagonists, including longer-lasting naloxone formulations and new medications;
   • Advanced drug delivery systems.
   • Target validation;
   • Confirmation of hits;
   • Identification of lead compound(s) or biologic(s) suitable for further development;
   • In vivo pharmacokinetics and toxicology studies;
   • In vivo preclinical efficacy studies;
   • Formulation development studies;
   • Process development to support clinical manufacturing (e.g., scale-up feasibility);
   • Other activities leading to the selection of a development candidate.
   • Demonstration of acceptable pharmacokinetics and pharmacodynamics;
   • In vitro pharmacological assays that cover a broad range of targets including receptors, ion channels, transporters, enzymes and second messengers to identify lead compounds, to define mechanism of action, and to identify off-target activities, especially, for repurposed compounds;
   • Completion of in vivo preclinical efficacy studies;
   • Demonstration of acceptable safety (e.g. toxicity in rodents and/or 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;
   • Clinical Proof of Concept (Phase I and/or Phase II clinical trials).
   • Imaging technologies for investigating brain function and enhancing disease diagnosis and treatment of OUD;
   • Devices and technologies that directly detect and/or reduce craving;
   • Innovative methods and tools to identify and treat newborns exposed to opioids, along with other drugs, to improve both short- and long-term developmental outcomes; novel approaches to managing neonatal opioid withdrawal syndrome (NOWS), also referred to as neonatal abstinence syndrome (NAS);
   • Diagnostic or therapeutic medical devices, including diagnostic tests (e.g. diagnostic devices that identify patients at increased risk for addiction, opioid-sparing approaches for pain, and devices that monitor the use and prevent diversion of prescription opioids);
   • Digital health technologies and therapeutics (mobile medical applications) to help combat the opioid crisis and achieve the goal of preventing and treating OUD;
   • Interventions against respiratory depression.
   • Development of a prototype system/MVP with desired functionality;
   • Initiated efficacy studies in an animal model; and
   • Initiated transfer of the technology/device to manufacturing.
   • Studies to Support 510k Clearance for Digital Therapeutics (e.g. development and testing of mobile medical app/device platforms, diagnostic tests, sensors, and other digital technologies) for treatment of OUD, opioid withdrawal, overdose, and to improve medication adherence);
   • Testing the platform technologies that were initially developed for a non-OUD indication/use (e.g. lead application extension);
   • Efficacy studies in an animal model;
   • Process development for manufacturing;
   • GMP manufacturing;
   • Non-clinical safety studies (e.g., toxicology, biocompatibility); and/or
   • Clinical trials (e.g. studies designed to test neuromodulatory devices (E.G., TMS, TDCS) in combination with behavioral treatments or medications).
   • Digital health technologies and mobile applications focused on behavioral health interventions to alleviate the burden of OUD through prevention and reduced risk;
   • Technologies for remote detection of vital signs (breathing, heart rate, etc.): wearable sensors, health monitoring/emergency notification systems — tailored to patients with OUD, designed to alert their providers and family members of any important changes in vital signs;
   • Software tools and bioinformatics technologies for data integration and OUD control;
   • Tools for OUD genetic, epidemiologic, behavioral, social and/or surveillance research;
   • Services and implementation research to develop new models of care for OUD within the health care and criminal justice settings that can expand access to medications and improve treatment retention;
   • Technologies to facilitate delivery of evidence-based interventions, engagement in care, and continuity of care across secure (i.e., jails and prisons) and community-based settings for justice-involved populations;
   • Tools for simultaneous preventive efforts in multiple domains including education, mental health, stigma, and socioeconomics;
   • Tools for parents and family support of patients with OUD.
   • Completion of initial usability, user acceptance, beta-testing and/or validation studies;
   • Design and development of a functional prototype system/MVP;
   • Testing the platform technologies that were initially developed for a non-OUD indication/use (e.g. lead application extension);
   • 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);
   • Field studies that reflect the breadth of settings in which OUD care is delivered; complete integration of the proposed technology with existing EHR, mobile technology platforms, and existing community and clinical resources;
   • Activities that address scalability, security and privacy (e.g. enhance communication system architecture and capability for data reporting to intended recipients).
   • Drug discovery and development-enabling technologies (e.g. drug screening and preclinical profiling technologies, epitope discovery technologies, and biospecimen acquisition and analysis technologies, etc.);
   • Research reagents and assays (e.g. high throughput screens for testing agents useful in treating respiratory depression and development of high throughput screens to detect addiction potential);
   • Biomarkers (e.g. discovery of metabolic, algorithmic biosignature biomarkers for OUD and respiratory depression; assay validation of potential biomarkers, which could also include development of a companion device; clinical validation of potential biomarkers for OUD/respiratory depression);
   • 3D cell culture and animal model systems for phenotypic drug development;
   • Software and bioinformatics tools for OUD research;
   • Tools to collect and analyze big data related to OUD and opioid-induced respiratory depression.
   • Testing the platform technologies that were initially developed for a non-OUD indication/use;
   • 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;
   • Implementation of quality assurance controls and assays.