HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)

The Department of Health and Human Services, through the National Institutes of Health (NIH), has announced a funding opportunity under the HEAL Initiative for the development of non-addictive analgesic therapeutics. Multiple NIH Institutes and Centers are participating, including the National Institute of Neurological Disorders and Stroke (NINDS), the National Eye Institute (NEI), the National Heart, Lung, and Blood Institute (NHLBI), and others. This funding opportunity is a reissue of RFA-NS-21-010 and seeks to support both small molecules and biologics for the treatment of pain. The program is part of the broader NIH HEAL Initiative aimed at addressing the opioid crisis by promoting safer, non-addictive pain treatments. This grant opportunity supports the development of preclinical therapeutic candidates with the end goal of filing an Investigational New Drug (IND) application and initiating Phase I clinical studies. Applicants must enter at the UG3 phase, focused on optimization and early development, and may progress to the UH3 phase upon successful achievement of specified milestones. The full project period can span up to five years. Projects must be milestone-driven and will involve close collaboration with NIH program staff, including participation in a Lead Development Team (LDT) that guides project strategy and progress. NIH will provide contract-based resources for specific research and development tasks, but applicants must lead studies involving disease- or target-specific assays and biomarkers. Eligible applicants include a wide range of U.S.-based entities such as higher education institutions, nonprofit and for-profit organizations, and government entities at all levels. Non-U.S. entities are not eligible to apply, although foreign components of U.S. organizations are allowed. Required registrations include SAM, eRA Commons, and Grants.gov. Applications must be submitted electronically using one of the NIH-approved submission platforms. Each application must include comprehensive project details, a Target Product Profile (TPP), go/no-go milestones, and a well-defined intellectual property strategy. Applications are due by NIH’s standard due dates through September 2026, with the earliest start date for awards in December 2024. A letter of intent is encouraged and must be submitted 30 days prior to the selected application due date. The application process includes multiple components, such as detailed research strategy sections on clinical impact, biological rationale, and testing strategy, alongside budget justifications and team management plans. NIH encourages meaningful engagement with people who have lived experience with pain or opioid use, and collaborative involvement with relevant stakeholders. Award budgets are to be determined based on the needs of the proposed research, and the NIH HEAL Initiative anticipates committing $11 million to fund approximately four awards in FY 2024. Matching funds are not required, and both new and resubmission applications are accepted. The funding mechanism is a cooperative agreement, emphasizing NIH’s substantial involvement in guiding and monitoring funded projects. NIH contractors may support additional drug development activities outside the grant budget. Applicants are encouraged to leverage additional NIH-supported resources such as the Preclinical Screening Platform for Pain (PSPP) and NCATS capabilities. Each funded project will be expected to meet rigorous standards for scientific rigor and transparency, especially in preclinical validation, and to maintain progress toward IND submission and clinical translation.