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Rheumatoid Arthritis PhysioLab

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The Rheumatoid Arthritis PhysioLab from Entelos is a mechanistic model of the dynamic interplay of key cell types and mediators in an inflamed joint used to evaluate the efficacy and effects on rheumatoid arthritis.

Rheumatoid arthritis is a chronic debilitating autoimmune disease affecting over 1.3 million americans it is characterized by joint inflammation that results in progressive destruction of joint cartilage and bone the past 12 years has seen several new drugs approved for ra despite the increase in treatment options many patients do not respond or are intolerant of

Currently available treatments the ra physio lab platform is a mechanistic mathematical model of rheumatoid arthritis that models the dynamic interplay of key cell types and mediators in the inflamed joint the platform represents established are a disease in a prototypical joint and is characterized by chronic inflammation and progressive structural destruction

Predictive bio simulation research conducted in the ra platform is used to evaluate promising new therapeutic strategies within the competitive landscape the are a platform simulates inflammatory endpoints specifically the american college of rheumatology or acr score structural endpoints including joint space narrowing or jsn and bone erosion scores as well as

Serum markers such as c-reactive protein or crp consistent with the intellistation knees clinical endpoints emerged from the simulated mechanistic interplay between a therapeutic strategy and the underlying biology in the ra platform the under ba underlying biology includes a synovial tissue compartment corresponding to the purple area shown in the central graphic

This is populated with synovial macrophages fibroblast-like synoviocytes t cells and other inflammatory cells there’s a cartilage compartment corresponding to the blue gray region in the graphic populated by chondrocytes and this is the site where the cartilage extracellular matrix may be degraded by may trix metalloproteinase asst and agri kinases lastly there is

A bone compartment corresponding to the tan region in the graphic where the bone is maintained by the balance of osteoblasts and osteoclasts activities and bone erosion results from perturbation of this balance by inflammation in the adjacent synovial compartment the various inflammatory cell populations are recruited to the local environment activated proliferate

Produced mediators and undergo apoptosis according to what is known about the particular life cycle of each cell type and the joint levels of the various mediators that regulate these functions we know that ra is a heterogeneous disease with considerable inner patient variability in both the mechanistic underpinnings of disease and clinical responses to address

This variability and telus creates virtual patients characterized by a wide range in baseline measures and responses to approve therapies as listed here these include some of the more recently approved biologic drugs such as a dilemma mom and adam body specific for tnf alpha and toast ilysm an antibody specific for the il-6 receptor within the super set of virtual

Patient variability the ra platform further distinguishes virtual patients based on phenotypes commonly identified in our a clinical trials more specifically virtual patients are characterized as patients with moderate to severe disease who are naive to methotrexate a commonly prescribed disease-modifying anti-rheumatic drug or dmart alternatively virtual patients

Are characterized as patients whose disease is inadequately controlled on methotrexate or as patients who have failed anti tnf alpha therapy and telus conducts predicted by simulation research in these three virtual populations to facilitate the more rapid and focused advancement of drug discovery and development programs this includes predicting competitive

Efficacy of novel therapeutic strategies predicting structure structural endpoints to refine the clinical trial design before undertaking the lengthy trials required to assess these endpoints and identifying multi analyte biomarker panels which may be validated for patient selection or surrogate endpoints and telus evaluates platform predictions by testing against

Key clinical data sets defined as phase three clinical trials conducted in ra patients and measuring clinical endpoints for which the ra platform simulates a corresponding clinical output as mentioned in the previous slide virtual patients may be categorized by commonly identified clinical phenotypes and telus creates virtual populations that recapitulate baseline

And clinical response data for these clinical phenotypes the key critical data sets for patients with moderate to severe disease disease who have not been treated with methotrexate are shown here these phase 3 clinical trials have evaluate have evaluated methotrexate mono therapy varies anti tnf alpha mono therapies including at aluminum etanercept and infliximab

And anakinra the aisle 1 receptor just virtual population simulation results are consistent with the reported clinical endpoints in these trials including ac our scores for inflammation jsn and bone erosion scores for structural endpoints and crp for serum data as new trials are published for this clinical phenotype they are added to the validation tests the key

Data sets for patients with active disease despite concomitant treatment with methotrexate are shown in the lower table in these trials the new drug is added to a maintenance dose of methotrexate depicted here in square brackets data are available for anti tnf alpha therapies adalimumab and infliximab as well as the anti cd20 therapy rituximab and the anti alex

Receptor therapy tosyl is imam again validation tests are expanded on an ongoing basis to include newly published data this last table lists phase 3 clinical trials published on ra patients who have failed anti tnf alpha therapy in these trials patients are most commonly receiving maintenance treatment with methotrexate and the trials assess the clinical efficacy

Achieved when adding the novel drug data are available for both rituximab and hustlas imam thus the entire platform includes three virtual populations consistent with commonly identified clinical phenotypes and validated against the relevant clinical data sets these virtual populations provide the means to prospectively evaluate novel therapeutic strategies in

The clinical phenotypes most commonly included in our a drug development this summary has provided you with a brief overview of the ra platform its representation of the underlying biology and different patient subpopulations predictive bio simulation research conducted in the ra physio lab platform is being used prioritized compounds optimize clinical trials and

Identify biomarker panels for those interested in for they’re details i would encourage you to visit the case studies on the intelliwhite thank you and have a nice day

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Rheumatoid Arthritis PhysioLab By Entelossolutions