NAFLDsym

NAFLDsym® is a mechanistic, mathematical computational model developed by Simulations Plus for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). The platform is designed to predict treatment efficacy for therapeutic modalities targeting MASLD and metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH). NAFLDsym has been utilized by several large pharmaceutical companies to evaluate compounds, supporting clinical trial design optimization and clinical development decision making.

The current version, NAFLDsym v2B, addresses the significant challenge posed by the heterogeneity of MASLD and MASH — a prevalent, worldwide disease with limited available treatment options. The software is available for in-house use through corporate software licenses, and can also be accessed through consulting arrangements with Simulations Plus experts, including through their DILIsym Services team.

Disease Pathophysiology Components Modelled

• Steatosis and regulation of liver triglycerides and fatty acids
• Lipotoxicity and liver injury and proliferation
• Fibrosis and inflammation
• Hepatocellular bioenergetics
• Dynamic body weight and its effects on lipids
• Clinically relevant biomarkers including ALT, AST, cytokeratin cleaved K18, NAS, MRI, MRE, and fibrosis score

Key Capabilities and Applications

• Prediction of efficacy for treatment modalities developed for MASLD and MASH
• Evaluation of compounds such as drugs or chemicals and modelling their effects on liver disease
• Support for clinical trial design optimization and clinical development decision making
• Leveraging quantitative systems pharmacology (QSP) and quantitative systems toxicology (QST) expertise
• Application within collaborative projects with large pharmaceutical companies

Recent Scientific Applications

• Accurate prediction of liver fat reductions across a range of weight-related outcomes (2024)
• Modelling of pemvidutide, a glucagon-like peptide 1/glucagon dual receptor agonist, and its effects on metabolic parameters (2024)
• Advancing the understanding of multi-targeted mechanisms of action of mitochondrial activators (2023)

NAFLDsym v2B is available under corporate software licenses for in-house deployment, or through expert consulting engagements. The platform is supported by a team of QSP specialists, including the Chief Science Officer and Vice President of QSP at Simulations Plus, and is backed by an active publication record of scientific posters and presentations at major industry conferences.