QST Modeling Using BIOLOGXsym Informed by Liver Microphysiology Data Predicts Biologics Induced Liver Injury and Enhanced Susceptibility in MASLD

Authors: Beaudoin J, Clemens L, Vernetti L, Miedel MT, Castiglione M, Taylor DL, Huizar F, C Vallejo, Sandefur CI, Kelley M, Lakhani VV, Battista C, Siler SQ, Yang K, Shoda LKM
Conference: ASCPT
Keywords: BIOLOGXsym, drug induced liver injury (DILI), metabolic dysfunction-associated steatotic liver disease (MASLD), quantitative systems toxicology (QST) modeling
Software: BIOLOGXsym

Background

Drug development has grown to include biologic treatments that address a range of unmet medical needs. However, biologics may induce liver injury, particularly in contexts such as metabolic dysfunction-associated steatotic liver disease (MASLD), which has been associated with increased susceptibility to drug-induced liver injury (DILI)1,2. While quantitative systems toxicology (QST) modeling integrating mechanistic in vitro data has been successfully applied to mitigate small molecule DILI3-5, biologic-induced liver injury (BILI) presents distinct challenges due to extracellular target engagement and involvement of non-hepatocyte cell types. Microphysiological systems offer a means to capture these complexities. Here, mechanistic outputs from a microphysiological system are leveraged in a QST model to predict BILI risk in healthy and MASLD patients for a range of biologics.

By J.J. Beaudoin, L. Clemens1, L.A. Vernetti, M.T. Miedel, M.W. Castiglione, D.L. Taylor, F. Huizar, C. Vallejo, C.I. Sandefur, M. Kelley, V.V. Lakhani, C. Battista, S.Q. Siler, K. Yang, L.K.M. Shoda

ASCPT 2026 Annual Meeting, March 4-6 in Denver, CO