The Preclinical Screening Platform for Pain (PSPP) uses a tiered approach to evaluate assets in a number of preclinical models.
Tier 1 focuses on ruling out opioid activity and assessing potential abuse liability using in vitro screens. Assets without opioid receptor activity will then continue into pharmacokinetic studies to determine the best dose and timepoint for testing.
Within Tier 2, assets will be evaluated in a side effect profile, to determine neurological side effects, that then enable setting a dose range for the evaluation in pain models, an acute to sub-chronic model, and a chronic / persistent model.
Given efficacy in Tier 2, Tier 3 will evaluate abuse liability in vivo and will further assess efficacy in disease specific models.
Importantly, additional models and endpoints will be evaluated continuously for possible incorporation into the PSPP program. PSPP decided on the initial use of certain models based on feedback from ECB members and based on consensus guidance from the Critical Evaluation of Animal Pain Models for Therapeutics Development Workshop in January 2019.