Investigational New Drug (IND)-enabling Study for a New Therapeutic for Alcohol Use Disorder (AUD)

Summary. While the stress response is essential for survival, it can become dysregulated. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis plays a mechanistic role in the pathophysiology of alcohol use disorder (AUD). This SBIR Phase I proposal in response to PAR-22-102 is aimed at initiating Investigational New Drug (IND)-enabling studies for an innovative first-in-class therapeutic aimed at the chronic management of pathologic HPA axis hyperactivity for the treatment of AUD. Evidence indicates that preventing excessive HPA activation in the setting of AUD will restore HPA negative feedback and reset the system at more physiological levels, reducing motivation for drinking and relapse. Therapeutics to modulate the HPA axis have been under research for decades. Several medications for HPA axis hyperactivity have been studied extensively but have generally been unsatisfactory due to limited efficacy on the HPA and side effects. Thus, there is a considerable unmet medical need for identification of novel therapeutics to normalize HPA hyperactivity that are effective and tolerable for long-term use. This Phase I SBIR will manufacture and validate the test article for Investigational New Drug (IND)-enabling studies and initiate IND-enabling studies including the development and validation of a UV-VIS method for the determination of test material concentration in dose formulations; development and validation of an enzyme-linked immunosorbent assay (ELISA) method for the quantification of test material in serum; and will carry out single-dose intravenous bolus injection pharmacokinetic and tolerability studies in two species. These activities will lay the foundations for the completion of IND-enabling studies and IND submission in the eventual Phase II of this SBIR.