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Easy, fast, and powerful tool for parameter estimation in non-linear mixed effect models, model diagnosis and assessment, and advanced graphical representation.
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Quantitative Systems Toxicology (QST) software designed to be used during drug development to provide deeper insight into the mechanisms responsible for observed drug-induced liver injury (DILI) responses.
A mechanistic simulation engine for the in vitro dissolution experiment that predicts in vitro disintegration and dissolution of pharmaceutical dosage forms.
Quantitative Systems Pharmacology (QSP) software for mechanistic mathematical modeling of nonalcoholic fatty liver disease (NAFLD.)
A detailed modeling & simulation program for in vitro metabolism & transport studies.
Graphical and interactive software for non-compartmental and compartmental analysis.
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Quantitative Systems Pharmacology (QSP) software for mechanistic mathematical modeling of interstitial lung disease (ILD) associated with system sclerosis (SSc.)
Quantitative Systems Toxicology (QST) software for predicting and understanding drug-induced kidney injury.
FREE chemical sketching software tool which combines innovative molecule drawing features.
QSP software for predicting efficacy & guiding design.
The NAFLDsym modeling software is a mechanistic, mathematical model of nonalcoholic fatty liver disease (NAFLD), which can be used to predict efficacy for treatment modalities developed for NAFLD and nonalcoholic steatohepatitis (NASH). NAFLDsym has been utilized to evaluate a number of compounds from several large pharmaceutical companies, supporting clinical trial design optimization and clinical development decision making.
DILIsym Services, Inc. applies the NAFLDsym modeling software in proprietary services projects by performing simulations of compounds to evaluate and model their efficacy and other effects on key characteristics related to NAFLD. NAFLDsym is also available for in-house use through corporate software licensing.
Examples of NAFLDsym use within collaborative projects that have been presented publicly include:
NAFLD is a prevalent, worldwide disease with few available treatment options. Accumulating lipids within the liver cause steatosis and impose lipotoxicity upon hepatocytes that can lead to declining liver function and ultimately liver transplant. Bringing effective treatments rapidly to market is paramount to improve patient health. QSP modeling has been demonstrated to accelerate clinical development, and we anticipate NAFLDsym will contribute to accelerating the clinical development of effective treatments for NAFLD patients. NAFLDsym employs the QSP modeling practices of combining predictions of compound exposure with the pharmacodynamic characteristics of a compound and how they can produce efficacy across a range of patients with pathophysiologic variability.
DILIsym Services has significant quantitative systems toxicology (QST) expertise in the area of drug-induced liver injury (DILI), and has employed this expertise to develop and apply DILIsym to evaluate the safety risk of numerous drug candidates. DILIsym Services also has noteworthy experience in the area of metabolic diseases and has leveraged this expertise to develop the quantitative systems pharmacology (QSP) modeling software, NAFLDsym v2B. We apply this QSP platform to assist with clinical development in collaborative partnerships and offer access to the software via corporate software licenses.
NAFLDsym v2B includes the mechanistic underpinnings associated with steatosis and lipotoxicity, chronic inflammation, and fibrosis within the liver. It is useful for evaluating the efficacy of potential new drug candidates to treat NAFLD/NASH in each of these areas, including the powerful capability to evaluate combination treatment approaches. It is a powerful tool for understanding and predicting disease progression and the complications associated with clinical trial design for NASH/NAFLD studies, including predictions for weight-stable, weight-loss, and weight-gaining patients. Weight loss and gain are dynamically represented with a state-of-the-art body weight model (Hall 2010). 4 large pharmaceutical companies have sponsored the development of version 2A.
A number of key biomarkers or endpoints are incorporated into NAFLDsym v2B, such as
The heterogeneity of NAFLD/NASH is a major challenge in the quest for new treatments. To this end, NAFLDsym v2B includes well over 1,000 simulated patients with varying stages of NAFLD and NASH. The simulated patients, or SimPops®, can be used to optimize clinical trial protocols by determining favorable measurement frequencies and dosing levels, evaluating targets using key internal laboratory or mechanistic clinical data, testing combination treatment approaches across varying patient backgrounds, and comparing efficacy in different patient groups (e.g. stratification by NAS, etc.). The SimPops has been validated against a large backdrop of key data sets, such as those shown below for liver fat and ALT, Plasma TGF-beta and ALT, activation of stellate cells by liver zone, and mean liver stiffness versus fibrosis stage.
Validation of the various relationships within NAFLDsym v2B working in harmony comes from predicted efficacy when body weight is applied as a treatment. The results below were predicted from the first principle mechanisms included (emergent behavior from the model) during 5% weight loss over the course of a year. Several other validations have been completed and/or are on-going in the context of confidential consulting projects.
NAFLDsym v2B is available for in-house use through corporate software licenses. Contact us today for more information on license terms and pricing.
NAFLDsym v2B is a computational model of nonalcoholic fatty liver disease (NAFLD) and can be used to predict efficacy for treatment modalities developed for treating NAFLD and NASH. NAFLDsym v2B includes many of the primary components of NAFLD and NASH pathophysiology such as:
NAFLDsym® is computer software, namely, downloadable computer software for conducting simulations of compounds such as drugs or chemicals to evaluate and model their effects on liver disease, namely, non-alcoholic steatohepatitis or non-alcoholic fatty liver disease.
To request a license for or evaluation of NAFLDsym®: https://www.simulations-plus.com/software-evaluation-request-form/
These mechanistic components have been combined to generate >1000 simulated NAFLD/NASH patients in NAFLDsym v2B. Reflecting the variability in clinical patient populations, these populations of simulated patients (SimPops®) have a range of liver fat levels (steatosis), mediator levels (inflammation), collagen production levels (fibrosis), body weight, and many also have liver injury (e.g., elevated ALT). The SimPops responds diversely to simulated treatments such as weight loss.
NAFLDsym applications have been conducted to address important questions for Pfizer and Gilead and also several other pharmaceutical companies.
Key features of NAFLDsym v2B Beta within Julia include:
