01. Promo
03. ILDsym® WHAT & HOW
Novel Approaches

ILDsym version 1A includes key pathophysiologic mechanisms and clinical aspects of SSc-ILD, such as inflammation, endothelial and epithelial involvement, lung fibrosis and lung function tests (e.g., forced vital capacity–FVC). Key regions of the lungs, as commonly assessed by high resolution computed tomography (HRCT), are represented in regions including the normal alveolar parenchyma, ground glass opacity (GGO), reticular opacity (RO) and honeycombed (HC). ILDsym also includes the ability to simulate disease progression and inter-patient variability in pathophysiologic and clinical characteristics with SimPops®, including therapeutic responses to mycophenolate mofetil (MMF), nintedanib, and tocilizumab (TCZ) that align with reported clinical data.

As such, ILDsym in not only useful for evaluating the efficacy of potential new drug candidates to treat SSc-ILD as a monotherapy but can also evaluate new drug candidates in combination with or as add-on therapies to existing treatments!

ILDsym v1A Summary Diagram

A number of key biomarkers or endpoints are incorporated into ILDsym v1A, such as:

  • Forced vital capacity (FVC)
  • Diffusing capacity of the lungs for carbon monoxide (DLCO)
  • High resolution computed tomography (HRCT) of the lungs
    • Normal parenchymal volume
    • Ground glass opacity (GGO) volume
    • Reticular opacity (RO) volume
    • Honeycombing (HC) volume
  • Extracellular matrix (ECM) levels within the lungs, including collagen, elastin, and proteoglycans
  • ECM synthesis and degradation biomarkers
    • Pro-C3
    • Pro-C6
    • C3M
    • C6M
    • lysyl oxidase
  • Activated myofibroblasts
  • Inflammatory or injury related biomarkers
    • TNF-alpha
    • VEGF
    • PDGF
    • TGF-beta
    • TSP-1
    • MMP-1
    • MMP-7
    • TIMP-1
    • Neutrophil elastase
    • IL-1beta
    • IL-6
    • IL-10
    • CRP
    • CCL18
    • KL-6
  • Macrophage and neutrophil accumulation

The heterogeneity within SSc-ILD, including the large variability in rate of disease progression, is a major challenge in the quest for new treatments.  To this end, ILDsym v1A includes >700 simulated patients with varying disease levels and disease progression rates.  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).  The SimPops has been validated against a large backdrop of key data sets, including clinical data on lung function (e.g., FVC, DLCO) and various biomarkers (e.g., KL-6).

SimPops Validation with FVC Data

SimPops Validation with DLCO Data

SimPops Validation with KL-6 Data

Validation of the interactions within ILDsym v1A has also been done with standard treatments, including nintedanib, MMF, and TCZ. Simulation results from SimPops with these drugs compared to placebo effects are shown below. The ILDsym simulations successfully recapitulate drug efficacy in lung function relative to placebo.

ILDsym v1A is available for in-house use through corporate software licenses. The equations and parameter values are open for viewing and modification. MATLAB software is required for use and is available separately from MathWorks. Alternatively, let us partner with you on an ILDsym consulting project.

ILDsym is computer software, for conducting simulations of compounds such as drugs or chemicals to evaluate and model their effects on the respiratory system, including the lungs.

To request a license for or evaluation of ILDsym: https://www.simulations-plus.com/software-evaluation-request-form/

04. ILDsym® Experts
Meet the Experts
05. Events
Upcoming Events
06. ILDsym® Resources
Publications and Webinars