APHIOS CORPORATION — Department of Health and Human Services SBIR Phase I: NIDA

Description

PROJECT SUMMARY Few therapeutics are available for individuals trying to recover from opioid use disorder. Buprenorphine and methadone, opioid receptor agonists, are approved by the FDA to treat Opioid Use Disorder (OUD) but long- term efficacy and treatment adherence are sub-optimal. Extended-release naltrexone (Vivitrol®, Alkermes), a full µ-opioid receptor antagonist, was approved by the FDA in 2010 for the prevention of relapse to opioid dependence but initiation and adherence to treatment are low. There is an urgent need for improved treatments for chronic relapsing opioid use disorder that has serious public health consequences. For the treatment of chronic relapsing OUD, we propose to develop an extended-release combination of low- dose naltrexone and cannabidiol (CBD) by nanoencapsulating them in biodegradable polymer nanospheres using an environmental-friendly proprietary SuperFluids™ technology. CBD has been shown to inhibit cue- induced heroin seeking in animals, and subsequent human clinical trial studies have revealed its potential utility and safety. Animal studies have shown that low-dose naltrexone, when combined with CBD, is better than either of the two in isolation to improve motivation and alcohol consumption in mice. This combination is promising, considering that naltrexone primarily targets the μ opioid receptor, and CBD binds the μ and δ opioid receptors. Lowering the dose of naltrexone will be impactful since it will reduce the side effects of Vivitrol®, and improve safety and compliance. This novel formulation will significantly enhance the bioavailability and pharmacodynamics of the two therapeutics, reduce dose frequency, and improve addiction treatment adherence. In Phase I, we will develop nanoformulations of CBD and low-dose naltrexone/CBD in biodegradable polymer nanospheres, and assess the intramuscular administration of the nanoparticles to reduce OUD relapse compared to Vivitrol® in an animal model of OUD relapse. In Phase II, we will conduct a more extensive RandD program that includes scale-up of cGMP manufacturing, GLP in vitro and in vivo product characterization, and establish the regulatory pathway for clinical development. In Phase III, with strategic corporate partners and/or investors, we will conduct clinical trials of CBD/naltrexone PLGA nanoparticles in patients suffering from chronic relapsing opioid use disorder.