UH3DA054825

A novel and highly selective orexin 1 receptor antagonist for the treatment of patients with opioid use disorder. - Project Summary

Opioid use disorder (OUD) is a public health crisis. Current treatments show limited efficacy and fail to prevent relapse to drug use during attempted abstinence and drug-overdose are all too frequent.

In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a potent and selective OX1 receptor antagonist (AZD4041/BPN-19302) with favorable drug-like physiochemical properties.

Selective OX1 receptor antagonism by AZD4041 reduces the addiction-relevant behaviors in rodents and primates relevant to those commonly found in opioid use disorder patients. Specifically, AZD4041 reduced the motivation to consume opioids (or nicotine) and attenuated relapse-like drug seeking behaviors in laboratory animals while avoiding OX2 receptor-associated effects that could limit its potential as a novel treatment for OUD (e.g., sleep-promoting effects).

AZD4041 did not have any non-specific behavioral effects in rodents or primates. AZD4041 shows favorable drug-like safety and pharmacokinetic (PK) profiles in rats and dogs.

Based on these findings, we initiated a phase 1 single ascending dose safety study in healthy volunteers (HV) (IND144437). To date in this trial, AZD4041 has shown a favorable PK and safety profile in human volunteers at exposures that encompass those predicted to have efficacy in OUD patients.

In this proposal, during the UG3 phase, we will conduct the multiple ascending dose and respiratory safety assessments required to test the compound in OUD patients. Contingent upon the successful completion of the UG3 milestones, which include favorable safety, PK and respiratory depression profiles, we will advance to the UH3 phase, during which a proof of concept efficacy study will be conducted in patients suffering from OUD.

Successful completion of the UH3 phase will deliver a selective OX1 receptor antagonist that is ready to advance to large-scale phase 2 and 3 pivotal efficacy studies, based upon which AstraZeneca will make this promising and highly beneficial therapeutic widely available to OUD patients.

Astrazeneca Pharmaceuticals Lp

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Delaware United States

State-Wide

Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional) (PAR-20-092)

Amendment Since initial award the End Date has been shortened from 01/31/27 to 02/28/25 and the total obligations have increased from $3,024,162 to $3,027,897.