HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)

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This FOA invites applications for pre-clinical research to stimulate the development of novel, mechanism-based pharmacotherapies to selectively reverse breathing suppression produced by opioids. Two critical phases of pre-clinical investigation are supported. Phase I: the identification and rigorous validation of candidate targets; Phase II: development of therapeutic candidates, such as small molecules, biologics, and natural products that modulate validated targets identified in Phase I, using relevant animal models or human cells/tissue. Specific Phase I and II milestones, which will be formalized pre-award and serve as a schedule of performance expectations to maximize the output from each phase of the study. Milestone performance will be a major factor in determining which applications will be selected to transition from Phase I to Phase II. Phase II extends up to addressing preclinical functional outcomes, toxicology, and pharmacokinetics needed to support an Investigational New Drug (IND) application. Multi-disciplinary, multiple PI teams combining expertise in respiratory neurobiology, opioid pharmacology and pre-clinical drug development are strongly encouraged. This FOA is intended for pharmacotherapeutic development. Projects proposing device and model development or validation, the elucidation of biological mechanisms, population-based epidemiology, or human subjects research would not be responsive. Reversal of the respiratory depression, without inducing generalized opioid withdrawal, or interfering with analgesic effects addresses the ultimate goal of developing better medical strategies for management of deleterious consequences of synthetic illicit, as well as prescription opioids.

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