Pre-IND Development of PPL-103: A Potent Opioid Analgesic that is Safe, Non-Addicting, and Free of Other Dangerous Opioid Side Effects
Abstract
Mu opioid receptor agonists are the gold standard for opioid pain relief, however, they exhibit graveside effects, including abuse and addiction liability, constipation, respiratory depression, and death from overdose. Kappa agonists are dysphoric and thus not clinically useful. Phoenix is developing PPL-103: a kappa and mu partial agonist with potent analgesic activity and little to no abuse liability, constipation or respiratory depression. PPL-103 is efficacious in several acute and chronic pain models, is not self-administered in rats but is clearly not dysphoric like other kappa agonists, as determined by a conditioned place preference assay. PPL-103 substitutes for morphine and blocks morphine withdrawal, suggesting that it could be given to morphine-naive or morphine dependent patients without inducing withdrawal. Objective: Through this project we propose to advance PPL-103 for safe, potent, non-addicting pain relief by validating the analgesic activity and non-addicting nature in non-human primates, producing of GLP material, completing the necessary package of pre-clinical testing and filing an IND with the FDA, to fully preparing for initiation of first-in-man clinical trials.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1097637
Entities
People
- Lawrence Toll