Publications

QSP versus the rest: let the competition commence!

Dr Hitesh Mistry

A Decision Support System for the treatment of esophageal cancer

Hitesh Mistry, Fernando Ortega, Frances Brightman, Jim Millen, John M Findlay, Mark R Middleton, Christophe Chassagnole.

Modelling the Emergence of Resistance to Chemotherapeutics with Virtual Tumour

Frances Brightman, Eric Fernandez, David Orrell, Christophe Chassagnole

Modelling and translating head and neck radiation therapy on all three levels: in vitro, in vivo and clinical

Éric Fernandez, Frances Brightman, David Orrell, Christophe Chassagnole

Modeling the Emergence of Resistance to Chemotherapeutics with Virtual Tumour

Dr Eric Fernandez, Project Leader

Virtual Tumour Pre-clinical Technology Webinar

Duration: 25 minutes

Virtual Tumour is an in silico PK/PD platform used to determine optimal doses, schedules and combinations for oncology candidates in preclinical development. Optimising drug administration can also be a key component of the regulatory aspects that affect every stage of the preclinical development process. Dr Eric Fernandez, Senior Simulation Scientist, will present a brief overview of how the technology works. He will show how the technology saves time and money by reducing animal experimentation and also how the potency of combinations can be improved. Several case studies will be presented, including usage of chemotherapy, biologics and irradiation.

DrugCARD

Duration: 18 minutes

DrugCARD collates curated publicly available pre-clinical and clinical drug regimen data into one easily searchable tool. It also contains further clinical data and analysis which is only available through the collaboration with Pharmacometrics. DrugCARD® currently contains clinical data for over 160 drugs used in over 700 regimens. Standards of care, novel targeted small molecule agents and biologics are all represented. Using DrugCARD®, researchers, who will access the database on a subscription basis, will be able to rapidly compare regimen data and outcomes across a number of studies, saving them time and effort when literature-hunting. The Pharmacometrics data also adds pre-clinical and clinical modelling information not available elsewhere.

Cardiotoxicity modelling

Duration: 46 minutes

The in silico cardiac toxicity model is used to determine the effects of drugs on:
  1. the dog action potential duration;
  2. the rabbit left ventricular QT interval;
  3. the torsadegenic potential in humans.
The model takes as input routinely measured high-throughput screening data such as those produced by PatchXpress and IonWorks.
Dr Hitesh Mistry, will present a brief overview of the current models in the literature before presenting the Physiomics model. He will show the performance of the Physiomics model against current existing models in the literature.
Finally there will be a brief overview on how the model will be extended.

Immunotherapy modelling

Duration: 16 minutes

Immunotherapy has recently developed into a highly active area of anticancer drug development. While early results for monotherapies are promising, the real potential of immunotherapy agents could be in combining them together or with other anticancer treatments. However, there is currently no rational basis on which to select optimal dosing regimens or combination schedules, and a clear unmet need for predictive tools to aid this process.
In this webinar we will describe our recent development and application of the VT technology for modelling preclinical efficacy of immune-checkpoint blockers, with a focus on agents targeting the PD-1/PD-L1 axis. The VT platform has been extended by the addition of an immunotherapy module, which captures the mechanisms by which the immunotherapy activates the antitumor immune response and synergizes with conventional anticancer therapies. Through a preclinical case study derived from the literature, we will demonstrate that the extended VT can be applied to model the efficacy of an anti-PD-L1 antibody/irradiation combination in syngeneic mouse xenografts.
This enhanced VT capability represents the first step towards a ground-breaking tool for optimizing dosing and scheduling of immunotherapy, both alone and in combination with conventional anticancer therapies.

Virtual Tumour Clinical: Applications within Translational Science

Duration: 37 minutes

This webinar will review the clinical Virtual Tumour model used to predict optimal doses and schedules of combination therapy. The translational capabilities of the Physiomics' Virtual Tumour Clinical will be demonstrated in the following case study: prediction of the changes in tumour size in both arms of a metastatic melanoma phase 2 study using only preclinical xenografts data and clinical PK.

Modeling Synergistic Anti-PD-1/PD-L1 Immunotherapy Combinations with the Virtual Tumour

Frances Brightman, Eric Fernandez, David Orrell, Christophe Chassagnole

EasyAP cardiotoxicity web platform demo

Duration: 13 minutes

EasyAP is an online simulation platform, which has been developed to help cardiac safety assessment of pharmaceutical drug candidates. EasyAP currently uses the activity against up to 3 ion channels to simulate action potential profiles and calculate action potential duration values, based on literature models. Importing compound data, as well as exporting simulations and results, is easy and secure. Further, EasyAP provides researchers a convenient way to freely organise their compounds in multiple project directories.
Dr Eric Fernandez will do a live demo of EasyAP, using as an example several drugs associated with varied risks of Torsade de Pointes.

Translational modelling of vemurafenib, selumetinib and docetaxel in metastatic melanoma with Virtual Tumour Clinical

Dr Christophe Chassagnole, COO

EasyAP: a Web-Based Simulation and Analysis Tool for High-Throughput Ion-Channel Screening Data

Eric Fernandez, Hitesh Mistry, Frances Brightman, David Orrell, Jonathan Swinton and Christophe Chassagnole

Virtual Tumour Clinical development, part II: translational modelling of vemurafenib, selumetinib and docetaxel in metastatic melanoma

Hitesh Mistry, Eric Fernandez, Frances Brightman, David Orrell, Mark Middleton, Linda Collins, Avinash Gupta, Christophe Chassagnole

Virtual Tumour Clinical development, part I: translational modelling of docetaxel-thalidomide combination treatment in metastatic, castrate-resistant prostate cancer

Frances Brightman, Hitesh Mistry, Eric Fernandez, David Orrell, William L. Dahut, William D. Figg, Sr., Wilfried D. Stein, Christophe Chassagnole

Physiomics Showcase Presentation

Dr Marck Chadwick, CEO

Reducing animal experiments with the Virtual Tumour

Eric Fernandez, Frances Brightman, Hitesh Mistry, David Orrell and Christophe Chassagnole

drugCARD: a database of anti-cancer treatment regimens and drug combinations

Eric Fernandez, Jianxiong Pang, Chris Snell, Cheryl Turner, Cathy Derow, Frances Brightman, Christophe Chassagnole and Robert Jackson

Virtual Tumour Clinical: Literature Example

Hitesh Mistry, Frances Brightman, Eric Fernandez, David Orrell, Christophe Chassagnole

Predicting Torsades de Pointes (TdeP) risk from data generated via highthroughput screening

Hitesh Mistry, Frances Brightman, Eric Fernandez, David Orrell, Jonathan Swinton, Christophe Chassagnole

The application of three-dimensional cell cultures in combination with the Virtual Tumor™ for designing optimal drug dosing schedules

Frances Brightman, Eric Fernandez, David Orrell, David Fell, Christophe Chassagnole

Modeling the sequence-sensitive gemcitabine-docetaxel combination using the Virtual Tumor

Eric Fernandez, David Orrell, Caroline Mignard, Zina Koob, Damien France, Nicolas Hoffmann, Francis Bichat, David Fell, Christophe Chassagnole

Predicting the effect of combination schedules on xenograft tumor using the Virtual Tumor

David Orrell, Eric Fernandez, Damien Cronier, Lawrence M. Gelbert, David A. Fell, Dinesh De Alwis and Christophe Chassagnole

Cancer Modeling and Drug Schedule Optimization

Dr Christophe Chassagnole, COO

Using Predictive Mathematical Models to Optimise the Scheduling of Anti-Cancer Drugs

David Orrell and Eric Fernandez

Computer modelling of Nocodazole exposure on cell cultures in vitro

E Fernandez, G Johnson, D Orrell, C Snell, DA Fell, SH Doak and C Chassagnole

Making better Cancer Therapies with Modelling

Dr. Christophe Chassagnole, COO

Chronotherapy: Seliciclib dosing schedules determined using a detailed computational cancer model

AR Hardy, E Fernandez, C Snell, D Orrell, DA Fell and C Chassagnole

Systems Biology for Cancer Drug Development

Dr. Christophe Chassagnole, COO

Optimal cancer chronotherapeutics schedules using a Systems Biology approach – Chronotherapeutics of Seliciclib

Dr. Christophe Chassagnole, COO

Systems biology analysis of CYC116, a novel aurora kinase inhibitor

C Chassagnole, E Fernandez, F Scaërou, C Snell, D Zheleva, DM Glover, RC Jackson, DA Fell

Optimal cancer chronotherapeutic schedules of Seliciclib revealed by a systems biology approach

E Fernandez, A Hardy, D Orrell, L Ramsell, DA Fell and C Chassagnole

Modelling DNA Damage-Induced Apoptosis

A R Hardy, D Orrell, C M Snell, C Chassagnole, G Morris and D A Fell

Virtual Tumour Modelling The Effect of Aurora Kinase Inhibitors on the Cell Cycle

C Chassagnole, C M Snell, A R Hardy, A Finney, E Fernandez and D A Fell

Drug Discovery and the New Biology

Pr David A Fell, CSO