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

The National Institutes of Health (NIH), under the Department of Health and Human Services, intends to issue a Notice of Funding Opportunity (NOFO) under the Helping to End Addiction Long-term (HEAL) Initiative. This program will support the discovery and development of non-addictive analgesic therapeutics—specifically small molecules and biologics—for the treatment of pain. The opportunity will be structured as a milestone-driven, phased cooperative agreement utilizing the UG3/UH3 activity code and is forecasted for publication later in 2025. The primary aim is to accelerate the development of early-stage therapeutic candidates and prepare them for Phase II clinical trials, thereby addressing the ongoing national opioid crisis through innovative, non-addictive treatments. This opportunity is being initiated by twelve NIH Institutes including NINDS, NEI, NHLBI, NIA, NIAAA, NIAMS, NICHD, NIDCR, NIDDK, NIDA, NCCIH, and NCI. It is designed to facilitate both independent research efforts and collaborative projects involving NIH-funded consultants and contract research organizations (CROs). Eligible researchers are encouraged to pursue drug discovery and development efforts within their own laboratories while also leveraging external expertise and resources provided by the NIH to enhance their project's success. The scope of the initiative includes activities from early drug optimization to Phase I development, with an expectation that supported projects will progress to first-in-human studies by the end of the grant period. Basic research, development of therapeutic devices, and clinical studies beyond Phase I are not within the program’s scope. By making this forecast announcement, NIH aims to provide researchers adequate time to build necessary collaborations and formulate responsive proposals in advance of the official NOFO release. Eligible applicants for this opportunity include a wide range of entities such as state and county governments, Native American tribal entities, higher education institutions (both public and private), for-profit organizations including small businesses, non-profits with 501(c)(3) status, independent school districts, and public housing authorities. The absence of a cost-sharing or matching requirement may make this opportunity more accessible to a broader pool of applicants. The forecasted post date for this NOFO is November 24, 2025, with applications expected to be due by January 26, 2026. Awards are estimated to be announced on September 24, 2026, and the project start date is anticipated to be November 26, 2026. While specific funding levels and the total number of awards have not yet been disclosed, interested applicants are encouraged to monitor Grants.gov for the release of the official NOFO. For more information, potential applicants may contact Dr. Mohamed Hachicha at the National Institute of Neurological Disorders and Stroke by phone at 301-496-1779 or via email at mohamed.hachicha@nih.gov. This opportunity remains in the forecast stage, and applications are not yet being accepted, but preparation and collaboration efforts are highly encouraged in advance of the NOFO's publication.