HEAL Initiative: Studies to Enable Analgesic Discovery (R61/R33 - Clinical Trial Not Allowed)

The NIH’s “HEAL Initiative: Studies to Enable Analgesic Discovery” funding opportunity (R61/R33) invites applications to support early translational research focused on developing new non-opioid, non-addictive treatments for pain. Administered by multiple NIH Institutes, this funding opportunity provides resources to develop and validate assays, conduct screening, and characterize potential therapeutic agents—including small molecules, biologics, and natural products. Projects that meet the completion criteria will become eligible for further funding under the Pain Therapeutics Development Program (PTDP), which supports advanced preclinical and clinical trials. The program is open to U.S. and international applicants, excluding foreign entities as lead organizations. This NOFO aligns with the NIH HEAL Initiative, which addresses pain management innovation as part of the national effort to reduce opioid misuse. Applications may focus on a broad spectrum of pain conditions, including acute, chronic, and neuropathic pain, and are encouraged to include underrepresented populations and incorporate insights from individuals with lived pain experience. In particular, the program supports assay development and validation for high-throughput screening, the synthesis and initial in vitro characterization of candidate agents, and the development of bioanalytical methods to evaluate therapeutic impact. For promising therapeutic agents, applicants may propose in vivo studies, provided that sufficient data is presented to support initial proof-of-concept pharmacokinetic (PK), pharmacodynamic (PD), and efficacy studies. However, target identification projects, clinical trials, and optimization activities such as SAR or GMP manufacturing are outside the scope of this NOFO. The R61/R33 phased award structure includes separate project goals and milestones for each phase, with a clear transition based on go/no-go criteria set in the R61 phase. The R61 phase focuses on establishing feasibility through assay development and initial screening, while the R33 phase builds upon this by advancing hits into more detailed characterization and preclinical testing. Application budgets are capped at $350,000 annually, with a maximum project period of three years (up to two years for each phase). The program anticipates funding 4-5 awards, with an estimated total budget of $2.5 million in FY 2025. Eligible applicants include U.S. higher education institutions, nonprofits, for-profit organizations, and some government entities. Applications must include a detailed IP strategy, addressing potential constraints or ownership issues for therapeutic agents. Additionally, applicants are advised to consult NIH scientific staff early in the proposal preparation to ensure project alignment with HEAL Initiative goals and NOFO objectives. Collaboration with technology transfer officials and industry experts is encouraged to support IP and commercialization pathways. Key deadlines for this funding cycle begin with a Letter of Intent due 30 days before the application deadline. Full applications are due on various dates, starting June 18, 2024, with NIH review scheduled to ensure an earliest start date in April 2025. Specific instructions on formatting and submission, including the required inclusion of a Data Management and Sharing Plan, are provided in the NIH How to Apply Application Guide. This NOFO mandates adherence to NIH rigor and transparency standards to enhance the reliability and reproducibility of the research outcomes. Applications must demonstrate strong rationale, robust preliminary data, and a clear pathway to developing clinically relevant pain management therapies.