Phase I Amount
$1,011,134
Oral mu-opioid receptor (MOR) agonists with high receptor level activity remain the primary treatment for pain (about 702 million oral opioid pain prescriptions are dispensed per year in the US). However, these compounds are addictive and have dangerous levels of respiratory depression. MOR agonists that are classified as "weaker" like buprenorphine and tramadol reduce these serious adverse events (SAE), but they retain many liabilities that keep them from displacing more addictive and dangerous compounds like oxycodone. Up to 25% of patients receiving opioid prescriptions are at risk of addiction or an SAE that requires medical care. Stemming this tide requires a better partial MOR agonist. Using a novel MOR-ligand scaffold, Epiodyne has developed a promising series of potent orally bioavailable drug-like small molecules. From this series, our development candidate EPD2520 was selected; EPD2520 is a MOR partial agonist, that exhibits analgesic efficacy comparable to non-lethal doses of oxycodone, with little to no respiratory depression, and with apparently less abuse liability in rats than buprenorphine. In addition to a promising behavioral profile, EPD2520 also appears to be suitable for chronic administration. Safety issues were not detected in in-vitro screens including receptor selectivity, carcinogenicity, QT prolongation, metabolism ID and CYP inhibition assays. In this project we will 1) advance EPD2520 to IND enabling studies and file an IND. And 2) investigate novel ligand-receptor-physiology interactions to design 2nd generation compounds that build on the efficacy, drug like properties and reduced liabilities of EPD2520. We anticipate that EPD2520 will be a highly efficacious analgesic with reduced respiratory and addiction liabilities.
Public Health Relevance Statement: Public Health relevance Approximately 70 million oral opioid pain prescriptions are dispensed per year in the USA. These commonly prescribed oral analgesics are high intrinsic activity mu opioid receptor agonists and, accordingly, their benefits are offset by dose limiting respiratory and addiction liabilities that can lead to overdose and death. The goal of this project is to develop an oral analgesic that is highly effective analgesic with reduced respiratory and addiction liabilities.
Project Terms: Pain management; Pain Control; Pain Therapy; pain treatment; Analgesics; Analgesic Agents; Analgesic Drugs; Analgesic Preparation; Anodynes; Antinociceptive Agents; Antinociceptive Drugs; pain killer; pain medication; pain reliever; painkiller; Biological Assay; Assay; Bioassay; Biologic Assays; Brain; Brain Nervous System; Encephalon; Buprenorphine; Clinical Trials; Dangerousness; Canis familiaris; Canine Species; Dogs; Dogs Mammals; canine; domestic dog; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Evolution; Exhibits; Goals; Government; Grant; Human; Modern Man; In Vitro; Lead; Pb element; heavy metal Pb; heavy metal lead; Libraries; Ligands; Metabolism; Intermediary Metabolism; Metabolic Processes; Persons; Dihydrohydroxycodeinone; Oxycodeinon; Oxycodone SR; Oxycontin; Roxicodone; Oxycodone; Painful; Pain; Patients; Physiology; Common Rat Strains; Rat; Rats Mammals; Rattus; Opiate Receptors; Opioid Receptor; Research; Risk; Rodentia; Rodents Mammals; Rodent; Safety; Testing; Toxicology; Tramadol; Work; mu opioid receptors; μ opioid receptors; μ-OR; μOR; Generations; Caring; base; Chronic; Clinical; Phase; Medical; Series; Chemicals; Evaluation; insight; Respiratory Depression; depressed breathing; depression of breathing; Ventilatory Depression; Opiates; Opioid; Agonist; Therapeutic; scaffolding; scaffold; Oral; respiratory; meetings; Receptor Protein; receptor; novel; carcinogenicity; Property; drug development; single molecule; small molecule; Dose; Data; Dose-Limiting; Serious Adverse Event; Severe Adverse Event; serious adverse experience; serious adverse reaction; Molecular; Development; developmental; Behavioral; pre-clinical; preclinical; design; designing; Treatment Efficacy; intervention efficacy; therapeutic efficacy; therapy efficacy; stem; addiction; addictive disorder; public health relevance; comparative efficacy; compare efficacy; overdose death; overdose fatalities; risk mitigation; prescription opioid; licit opioid; opiate medication; opioid medication; prescribed opiate; prescribed opioid; prescription opiate; Opioid agonist; Opiate agonist; Opiate receptor agonist; Opioid receptor agonist; therapeutic opioid; abuse liability; abuse potential; addiction liability; addiction potential
