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

> **NIH NIH UG3** · ASTRAZENECA PHARMACEUTICALS, LP · 2021 · $3,032,676

## Abstract

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.

## Key facts

- **NIH application ID:** 10322644
- **Project number:** 1UG3DA054825-01
- **Recipient organization:** ASTRAZENECA PHARMACEUTICALS, LP
- **Principal Investigator:** Thor Ostenfeld
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,032,676
- **Award type:** 1
- **Project period:** 2021-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322644

## Citation

> US National Institutes of Health, RePORTER application 10322644, A novel and highly selective orexin 1 receptor antagonist for the treatment of patients with opioid use disorder. (1UG3DA054825-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322644. Licensed CC0.

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