Tier II: Long-term DILI prediction (14 days)
Ensure highest sensitivity for DILI drugs with long-term exposure
In our experience working with long-lived 3D human liver microtissue models, exposure to clinically known DILI compounds is best predicted using a 14-day long-term DILI Prediction dosing regimen. Using a 110-compound validation set, we observed up to 2-fold higher sensitivity for the detection of clinically known DILI drugs than with conventional 2D hepatocyte culture.
- Double sensitivity in DILI prediction without sacrificing specificity using an organotypic, metabolically robust, long-lived spheroid model validated with a set of 110 clinically defined DILI compounds
- Reduce late-stage market withdrawal liability by leveraging a high positive predictive value (sensitivity) that correctly predicted 18 known DILI drugs (black box or discontinued) missed by 2D primary human hepatocyte (PHH) cultures of the same hepatocyte donor
- Retain more blockbusters in your pipeline with a high negative predictive value (>92% specificity) that ensures valuable drugs aren’t prematurely discarded as with low specificity (60-90%) models
3D InSight™ Liver Microtissues capture DILI responses to compound exposure that other in vitro models miss through InSphero's long-term DILI prediction
Compounds with clinically defined DILI severity (1 = severe, 2 = high concern, 3 = low concern) predicted [+] or missed [-] by 3D InSight™ Human Liver Microtissues and 2D PHH from the same donor lots.
These data are from Proctor et al. (Arch Toxicol, 2017), a collaborative study conducted by AstraZeneca, Genentech, and InSphero using 3D InSight™ Human Liver Microtissues.