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

The funding opportunity titled HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain is offered by the National Institutes of Health under the U.S. Department of Health and Human Services, with leadership from the National Institute of Neurological Disorders and Stroke and multiple participating NIH institutes. This program is part of the broader Helping to End Addiction Long-term Initiative, which seeks to address the national opioid crisis by advancing safer, non-addictive approaches to pain management. The initiative reflects a federal priority to reduce reliance on opioids and accelerate translational science that can lead to new therapeutic options for millions of individuals suffering from chronic pain. The purpose of this funding opportunity is to support the preclinical optimization and development of promising small molecule and biologic therapeutics for pain treatment. Projects must demonstrate a strong biological rationale, possess a viable lead candidate, and include established assays to guide optimization. The program is designed to advance early-stage therapeutic candidates through critical development steps, including lead optimization, pharmacokinetic and pharmacodynamic studies, IND-enabling activities, and ultimately Phase I clinical testing. It excludes basic research, diagnostic development, and late-stage clinical trials beyond Phase I, ensuring that all supported work is focused on translational advancement toward clinical readiness. Funding is delivered through a cooperative agreement mechanism using a phased UG3/UH3 structure. The UG3 phase, lasting up to two years, supports preparatory and optimization work, while the UH3 phase, up to four additional years, funds execution activities including IND submission and early clinical testing. The total project period cannot exceed five years. NIH program staff play an active role in project planning and monitoring, and funded projects operate under milestone-driven frameworks with go/no-go decision points. Although specific award amounts per project are not fixed, the program anticipates allocating approximately eleven million dollars to fund around three awards in a given fiscal year, contingent on appropriations and application quality. Eligibility for this opportunity is broad and includes higher education institutions, nonprofit organizations, for-profit entities including small businesses, and various government bodies at the state, local, and tribal levels. However, foreign organizations and non-U.S. components are not eligible to apply. Applicants must ensure proper institutional registrations, including SAM, Grants.gov, and eRA Commons, and all principal investigators must have ORCID identifiers. The program encourages interdisciplinary teams and collaboration with NIH-provided contractors and subject-matter experts, particularly for specialized development activities such as manufacturing, toxicology, and clinical trial support. Applications must be submitted electronically through Grants.gov or NIH ASSIST systems and must adhere strictly to NIH application guidelines. Required components include detailed research strategies covering both UG3 and UH3 phases, milestone plans, an intellectual property strategy, and a data management and sharing plan. Evaluation criteria emphasize scientific merit, innovation, feasibility, team expertise, and the potential to produce meaningful clinical impact. Reviewers assess the strength of preliminary data, the appropriateness of proposed assays, and the likelihood of achieving a safe and effective non-addictive therapeutic. The application timeline includes multiple submission cycles each year, with the earliest submission date beginning August 21, 2026, and recurring deadlines approximately every four months. For example, one of the first deadlines is October 21, 2026, followed by February, June, and October cycles in subsequent years through 2029. Awards are typically reviewed within several months, with earliest start dates occurring roughly nine months after submission. Applicants are encouraged to engage NIH program staff early in the process to ensure alignment with program goals and optimal use of NIH resources. Overall, this funding opportunity represents a significant federal investment in translational neuroscience and drug development. It aims to foster collaboration across academia, industry, and government to deliver innovative, non-addictive pain treatments. By supporting projects through critical development milestones and providing access to extensive NIH infrastructure, the program seeks to accelerate the path from discovery to clinical application while addressing a major public health challenge.

Align project milestones with NIH go/no-go criteria and ensure strong preliminary data supporting therapeutic candidate; engage NIH staff early to optimize use of contract resources