MEB-1170: A New Chemical Entity for the Treatment of Opioid Use Disorder

Project Summary / Abstract Mebias Discovery, Inc. is developing a new chemical entity, MEB-1170, to treat Opioid Use Disorder (OUD) as a maintenance medication. Currently, all of the FDA-approved medications for treating OUD (MOUD) – buprenorphine, methadone, and naltrexone – come with liabilities (abuse potential, medication diversion, need for detoxification prior to administration, risk of respiratory depression, etc.) and ~50% of patients discontinue treatment after 6 months.1,2 MEB-1170 is a full mu opioid receptor agonist and partial kappa opioid receptor agonist that has a unique pharmacological profile. Specifically, it produces a robust analgesic response that is mediated through mu opioid receptors but has no abuse liability as measured in multiple preclinical assays (conditioned place preference, intravenous drug self-administration, drug discrimination) and no typical opioid-related adverse effects such as respiratory depression, constipation, and sedation. A Phase 1 Single Ascending Dose study supported its safety and tolerability in healthy adult volunteers. In the UG3 phase of the proposed research, we will complete preclinical studies in rodents and non-human primates to evaluate the efficacy of MEB-1170 as an MOUD. We will assess the ability of MEB-1170 to reduce fentanyl self- administration, as well as its propensity to produce respiratory depression and precipitate opioid withdrawal in opioid- dependent animals. In the UH3 phase, we will conduct a Phase 1 Multiple Ascending Dose clinical trial to further evaluate the safety, tolerability, and pharmacokinetics of multiple doses of MEB-1170 in healthy adult volunteers over a 10-day regimen. In addition, we will conduct a Phase 1b clinical study to assess the ability of MEB-1170 to reduce fentanyl-induced ratings of drug liking and precipitate opioid withdrawal in opioid-dependent individuals with OUD who are not currently not seeking treatment for OUD. Our overarching goal is to develop MEB-1170 as a safe and effective MOUD to prevent relapse and facilitate long-term recovery. 1 Montoya, I. D. & Volkow, N. D. IUPHAR Review: New strategies for medications to treat substance use disorders. Pharmacol Res 200, 107078, doi:10.1016/j.phrs.2024.107078 (2024). 2 Marsden, J. et al. Measurement-based care using DSM-5 for opioid use disorder: can we make opioid medication treatment more effective? Addiction 114, 1346-1353, doi:10.1111/add.14546 (2019).