Quotient’s use of its Translational Pharmaceutics platform reflects the fact that the dose and release rate that will deliver the required exposure profile in humans, in both normal and overdose situations, is not known.
Traditionally, the developer would need to live with that uncertainty, selecting fixed dose and release rate formulations and doses to take into clinical development and then essentially starting again if they failed to meet the target product profile. Translational Pharmaceutics opens up another approach to the uncertainty by enabling real-time manufacture of formulations during a clinical study.
“Using our unique Translational Pharmaceutics model allows refinement of the formulation (dose and release rate) during the clinical study, based on emerging human clinical data. This model allows optimization of the formulation within a single clinical study, offering time-saving advantages, and does not rely on preclinical data which can often be non-predictive to man,” said Dr Vanessa Zann, Sr. Drug Development Consultant at Quotient Science.
Quotient will apply its capabilities to PF614-MPAR, an extended-release oxycodone prodrug that features trypsin-activated abuse protection (TAAP) and overdose protection through multi-pill abuse resistance (MPAR) technology.
Using TAAP chemical modification, Ensysce inactivates the active ingredient in PF614 to provide abuse deterrence. The combination with the trypsin inhibitor, nafamostat, in MPAR is designed to provide an additional layer of overdose protection.
Last year, Ensysce secured a grant from the National Institute on Drug Abuse to take the candidate into a Phase I clinical trial. However, the nature of early-phase drug development means there remain gaps in the knowledge about how the candidate will perform in humans, creating a need for the flexibility of the Quotient platform.
“When we develop a modified release formulation in the lab it’s based on data from a dissolution bath. At this point we don’t know if it will perform the same in the body or how the formulation will behave when dosed in man, therefore we need the flexibility to alter the dose and release rate to give the required exposure profile,” said Dr Zann.