The goal of this project is to develop novel technology for predicting biologics-induced liver
injury such as caused by anti-inflammatory biologics such as anti-IL6 receptor antibody (e.g.,
tocilizumab), and by growth factors such as neuregulin-1β isoform, glial growth factor 2 (GGF2),
as well as by other biologics (e.g., checkpoint inhibitors). Biologics now account for more than
half of the drugs in development, and have the potential to address many acute diseases,
chronic diseases, and other unmet medical needs. Biologics-induced liver injury can manifest as
focal hepatocyte necrosis, steatosis, and fibrosis. In some cases, liver transplantation is
required for patients with biologics-induced liver injury. A significant problem is that while there
is increased development and use of biologics, there lacks tools available for the assessment of
biologics for the ability to cause biologics-induced liver injury. For example, because biologics
are typically designed specifically for human targets, standard preclinical models used for small
molecule drug development are inadequate for assessing the efficacy or safety of biologics. In
this project, we will develop novel technology that will serve as a prototype for use in testing
biologics (preclinical, clinical, or after-market) for potential to cause biologics-induced liver
injury. In developing this new technology, we will also further develop the state-of-the-art
human liver MPS (vLAMPS) to assess the liver effects of biologics from human liver cells in the
liver acinus with the aim of using vLAMPS as the eventual key source of input data for
BIOLOGXsym simulations. Additionally, we will perform validation of this new technology. Once
validated, this system will serve as a prototype that can then be expanded for commercialization
for use by our existing base of pharmaceutical company customers, regulatory agencies, and
academic institutions for teaching and academic research use.
