RESEARCH TRIANGLE PARK, N.C. – April 6, 2016 –Daiichi Sankyo Co., Ltd. has agreed to become the newest member of The DILI-sim Initiative. Daiichi Sankyo, headquartered in Tokyo, Japan, is a global pharmaceutical company dedicated to providing innovative products and services around the world, including the development of new and generic medicines and new methods of drug discovery and delivery. The organization is committed to addressing unmet medical needs in the areas of oncology, cardiovascular-metabolics, pain management, hypertension, and thrombotic disorders. Daiichi Sankyo now joins the DILI-sim consortium, comprised of current members AbbVie, Astellas, Bristol-Myers Squibb, Eli Lilly and Company, Gilead, GlaxoSmithKline, Janssen Research & Development, Merck, Mitsubishi Tanabe Pharma, Otsuka, Pfizer, and Takeda.

ABOUT THE DILI-SIM INITATIVE
The DILI-sim Initiative is a pre-competitive partnership between DILIsym Services, Inc. and a diverse set of stakeholders to develop a computational model that will predict whether new drug candidates will cause drug-induced liver injury (DILI) in patients. The goals of the Initiative are to improve patient safety, reduce the need for animal testing, and reduce the costs and time necessary to develop new drugs. The Initiative is led by Dr. Paul B. Watkins, Director of the University of North Carolina Institute for Drug Safety Sciences, located in the heart of Research Triangle Park, North Carolina. The vision for the DILI-sim Initiative over the next three years is for DILIsym® software to build upon its foundation as a key resource in the pharmaceutical industry’s preclinical toolbox by further optimizing and enhancing DILIsym® for the prediction of less frequent human DILI that may only become evident in late stage clinical development or post-marketing.

Non-profit research institute announces the release of the latest version of its flagship DILI platform

RESEARCH TRIANGLE PARK, NC – DILIsym Services Inc. (www.dilisymservices.com) announces the release of DILIsym® v4B. DILIsym® software is developed and released as part of the DILI-sim Initiative (www.dilisym.com), an effort to develop a mathematical, mechanistic model of drug-induced liver injury chaired by Dr. Paul B. Watkins. DILIsym® v4B was made available to all DILI-sim Initiative industry members as of September 3, 2015.

DILIsym® v4B introduces an entirely new and improved graphical user interface (GUI).  With the new GUI, model simulations are more easily reproduced, changes to parameter sets are more readily tracked, inputs and outputs can be organized better into panels, and results are more easily exported to Excel.  The GUI also features the ability to use PK simulation results from other software platforms to drive liver toxicity predictions, and contains built-in ‘eDISH’ plot capability.

Additional capabilities and improvements include:

·         New ASBT (gut transporter) inhibition module for bile acids

·         Updated cytokeratin 18 parameter values based on new data

·         Updated secondary necrosis function to be more biologically realistic, based on new data

·         Additional SimPops™, capturing impact of variability in key pathways


ABOUT THE DILI-SIM INITIATIVE

The DILI-sim Initiative is a pre-competitive partnership between DILIsym Services Inc. and a diverse set of stakeholders to develop a computational model that will predict whether new drug candidates will cause drug-induced liver injury (DILI) in patients. The goals of the Initiative are to improve patient safety, reduce the need for animal testing, and reduce the costs and time necessary to develop new drugs. It is the intent of the DILI-sim Initiative to make the model, in the form of DILIsym® software, broadly available so that it may be used by the pharmaceutical industry and other entities in academia, government, and industry. The Initiative is led by Dr. Paul B. Watkins, Director of the University of North Carolina Institute for Drug Safety Sciences, located in the heart of Research Triangle Park, North Carolina. For more information, please visit www.dilisym.com.

ABOUT DILISYM SERVICES INCORPORATED

DILIsym Services, Inc. was incorporated in 2015 and is operated in Research Triangle Park, North Carolia. DILIsym Services, Inc. is a startup company committed to providing the pharmaceutical industry with the tools, resources, and information to efficiently develop safer drug therapies that increase the availability of vital therapeutics for the patients who need them. DILIsym Services, Inc.applies the DILIsym® software to improve the safety profiles of therapeutics reaching the market. 

For more information, please visit www.dilisymservices.com

The new company will focus on proprietary simulation projects for pharma

RESEARCH TRIANGLE PARK, N.C. – DILIsym Services, Inc., (www.dilisymservices.com), is a newly launched services-focused business that aims to use mechanistic modeling to solve liver toxicity problems for the pharmaceutical industry. Day-to-day operations of the company will be led by Dr. Brett Howell as Chief Executive Officer, and Dr. Scott Siler as President.   

DILIsym Services, Inc. evaluates the risk of Drug Induced Liver Injury (DILI) for new drug candidates throughout the clinical development pipeline, and provides clients access to simulation results to better inform internal decision making via its team of experts. To accomplish this, the company utilizes DILIsym^® software, a mechanistic, mathematical model of drug-induced liver injury that has been developed as a part of the DILI-sim Initiative since 2011. Predictions on liver safety are made by entering into the model results of laboratory testing that does not involve animals.  In addition to making predictions of liver toxicity for new drug candidates, DILIsym^® has also been applied to provide an enhanced understanding of traditional and novel blood tests used to evaluate liver safety in clinical trials.  Simulation analyses with DILIsym^® have been included in multiple communications with regulatory agencies. DILIsym^® is a registered trademark licensed to DILIsym Services, Inc. 

The DILIsym^® software was developed under the DILI-sim Initiative, a major public-private partnership including scientists from 13 major pharmaceutical companies and the FDA, which have provided financial and in-kind support. The DILI-sim Initiative, now in its fourth year, is led by Dr. Paul B. Watkins, Director of the University of North Carolina Institute for Drug Safety Sciences, who also will serve as a scientific advisor to DILIsym Services, Inc.  Drs. Brett Howell and Scott Siler have led the development of the DILIsym^® software since its inception, and will continue in their roles as Associate Directors of the DILI-sim Initiative going forward.

QUOTES:

Dr. Paul Watkins, director of the University of North Carolina Institute for Drug Safety Sciences and chair of the board of directors of DILIsym Services, Inc.:

“The DILI-sim Initiative has been a tremendous success as a public-private partnership.   When liver safety concerns surface in a clinical trial, the question is increasingly asked “What does the DILIsym^®modeling show?”  The creation of DILIsym Services, Inc. will provide a means to rapidly answer this question without diluting the continued development of the software through the public-private partnership (the DILI-sim Initiative). DILIsym Services, Inc. will greatly improve the efficiency of drug development while reducing the need for animal testing.”

Dr. Brett Howell, Chief Executive Officer of DILIsym Services, Inc.,:

"DILIsym Services will provide us the opportunity to increasingly apply the DILIsym^® software to liver safety scenarios within drug development to impact decision-making.  I am excited to continue working for Dr. Watkins and alongside Dr. Siler and our development team to support both the development of the software through the DILI-sim Initiative as well as its application through this new venture."

MEDIA CONTENT:

- DILIsym Services, Inc. website
http://www.dilisymservices.com

ABOUT DR. BRETT HOWELL:

Brett Howell, Ph.D., is the Chief Executive Officer of DILIsym Services, Inc. and has served as Associate Director of the DILI-sim Initiative since 2011. In addition to being involved in operations, training oversight, software architecture, personnel management, and budget oversight, Dr. Howell has and continues to contribute technically in the areas of PBPK modeling, immune response, and biomarkers.  Dr. Howell has published numerous scientific papers in the areas of PBPK/PD modeling, in vitro toxicity testing, and novel drug delivery systems.  He holds Bachelors of Science degrees in chemical engineering and textile engineering from North Carolina State University and a Ph.D. in chemical engineering from the University of Florida.

ABOUT DR. SCOTT SILER:

Scott Q Siler, Ph.D. is the President of DILIsym Services, Inc. Dr. Siler graduated with a Ph.D. in Nutrition from the University of California, Berkeley and worked for more than 12 years integrating physiology and mathematics with the company Entelos. While with Entelos, Dr. Siler oversaw the development of the Metabolism PhysioLab model and he led multiple projects evaluating potential treatments for type 2 diabetes. Dr. Siler began working with the Hamner Institutes in 2011 as an associate director of the DILI-sim Initiative.

 

Non-profit research institute announces the release of the latest versions of its flagship DILI platform and its accompanying sister platform focused on mitochondrial function

RESEARCH TRIANGLE PARK, NC – The Hamner Institutes for Health Sciences (www.thehamner.org) announces the release of DILIsym® v4A and MITOsym® v2B. DILIsym® and MITOsym® software are developed and released as part of the DILI-sim Initiative (www.dilisym.com), an effort to develop a mathematical, mechanistic model of drug-induced liver injury chaired by Dr. Paul B. Watkins. DILIsym® v4A and MITOsym® v2B were made available to all DILI-sim Initiative industry members as of March 31, 2015.

DILIsym® v4A includes several key upgrades, such as the addition of data from two new compounds, as well as new capabilities in steatosis, lipotoxicity, and mixed-type bile acid transporter inhibition, among other features. An expanded set of SimPops™, capturing impact of variability in key pathways, was added, and SimCohorts™ were introduced, which are subsets of existing SimPops™ selected randomly or based on sensitivity to DILI.

MITOsym® is a mathematical model similar to DILIsym®, executed in MATLAB with code and graphical interface versions provided. Unlike DILIsym®, MITOsym® is a model of mitochondrial function in the in vitro setting, designed to help with parameter identification and data interpretation from experiments conducted to infer mitochondrial function in hepatocytes using the Seahorse Bioscience XF Analyzer machines. Ideally, experiments are run on the XF Analyzer machine, data is interpreted and parameters identified with MITOsym®, and those parameters are then fed into DILIsym® for predictions of in vivo hepatotoxicity risk. MITOsym® v2B includes the ability to simulate inhibition of glycolysis, as well as reductions in ECAR in presence of compounds.

ABOUT THE DILI-SIM INITIATIVE

The DILI-sim Initiative is a pre-competitive partnership between The Hamner and a diverse set of stakeholders to develop a computational model that will predict whether new drug candidates will cause drug-induced liver injury (DILI) in patients. The goals of the Initiative are to improve patient safety, reduce the need for animal testing, and reduce the costs and time necessary to develop new drugs. It is the intent of the DILI-sim Initiative to make the model, in the form of DILIsym® software, broadly available so that it may be used by the pharmaceutical industry and other entities in academia, government, and industry. The Initiative is led by Dr. Paul B. Watkins, Director of the Hamner-University of North Carolina Institute for Drug Safety Sciences, located on the campus of The Hamner Institutes for Health Sciences in the heart of Research Triangle Park, North Carolina. For more information, please visit www.dilisym.com.

ABOUT THE HAMNER INSTITUTES FOR HEALTH SCIENCES

The Hamner Institutes for Health Sciences is a nonprofit translational biomedical research institute located on an open, multidisciplinary campus in North Carolina’s Research Triangle Park. Building upon 40 years of research excellence in toxicology, The Hamner works on drug and chemical safety in collaboration with academic, corporate and government partners. Novel technologies used at The Hamner include genomic and bioinformatic approaches for improving toxicity testing, in silico models for predictive toxicology, in vitro models that utilize human cells or cell lines to evaluate perturbations of cellular responses, and in vivo models to elucidate genes that play a role in susceptibility to drug-induced toxicities. For more information, please visit www.thehamner.org.