Science Pool

Watch the webinar to learn more about exciting new developments in predictive toxicology!

About the Webinar

In this webinar, John Barker, SVP Global Head of Protein Sciences discusses bacterial infections and global health within anti-infectives. John gave this talk at the Oxford Global Discovery UK event in October 2021.

About the Speaker

John Barker, PhD FRSB Senior Vice President, Global Head of Protein Sciences | Evotec Currently responsible for more than 150 scientists across four sites, Princeton NJ, Abingdon UK, Toulouse and Hamburg. Team delivering Protein Production, Structural Biology and Cellular Sciences both internally and to Evotec’s partnerships. Over the past 18 years built from the ground up the current Evotec structural biology unit, now with more than 30 PhD scientists, one of the largest units in industry. Supporter of UK industry as the Industrial Life Science representative on the Diamond Scientific Advisory Board. John has worked on more than 40 collaborations across a range of drug discovery projects including multiple structure and fragment guided programmes in all therapeutic areas.

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Watch our webinar and learn about exciting new developments in toxicology prediction and how transcriptomics is transforming DILI prediction.

Drug-induced toxicity remains a major source of attrition in preclinical and clinical. In particular, drug-induced liver injury (DILI) can be difficult to predict as it often has poor translation from animals to humans and so issues are only picked up during clinical development or post-market approval. In fact, 18% of drug withdrawals from the market are caused by DILI. These statistics have led to a push within the industry to bring testing earlier using more human relevant cell-based models. However, challenges still exist and more accurate techniques are required to improve the predictive capabilities.

About the Webinar

The webinar covers our ground-breaking work in the field of transcriptomics. Cyprotex and Evotec have jointly created a fully integrated in vitro prediction platform using 2D and 3D cell-based models combined with high throughput RNA-seq and sophisticated machine learning and artificial intelligence techniques. The company is building the largest transcriptomic database in the world. This will be used to predict the likelihood of DILI risk, mechanistic information and similarity profiles to existing compounds. Our initial data shows an impressive accuracy of DILI prediction of 82% compared with 70% for a seven read-out HCS-based DILI platform.

About the Speaker

Paul Walker PhD VP, Head of Tox and Innovation Efficiency | Cyprotex Dr Paul Walker is the Head of Toxicology at Cyprotex where he is responsible for the development of strategy, innovation and management of client work performed within the Toxicology Group. Paul obtained his Ph.D. from King’s College London in Molecular Toxicology being awarded the Tadion-Rideal prize for molecular sciences (2004). Paul further developed his understanding of molecular biology and toxicology during his post-doctoral years at the University of Manchester with a keen interest in the application of high content imaging and 3D models within this field. Paul joined Cyprotex in 2010 with his research interests focused on the role of drug metabolism in drug toxicity and in vitro assays to predict toxicity in early drug discovery.

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Watch the webinar to learn more about exciting new developments in predictive toxicology!

About the Webinar

In this webinar, Dr Alicia Rosell-Hidalgo will present how high content screening (HCS) and high throughput RNA-seq techniques in conjunction with 3D liver models can be used to improve toxicology prediction and gain an in-depth mechanistic understanding of drug-induced toxicity. The presentation will focus predominantly on drug induced liver injury (DILI) with relevant case studies to demonstrate utility in safety profiling.

About the Speaker

Alicia Rosell-Hidalgo PhD Associate Principal Scientist | Cyprotex Dr Alicia Rosell-Hidalgo is an Associate Principal Scientist in Toxicology at Cyprotex Discovery Ltd, a subsidiary of Evotec SE. She leads the in vitro research and development carried out in the UK site for the “Panomics” project, aimed at improving predictive toxicology through 2D and 3D cell-based models combined with high throughput RNA-seq and machine learning/artificial intelligence techniques. Alicia has a bachelor’s of science in Biology and master’s degree in Biochemistry at the University Complutense of Madrid. During her undergraduate years, she gained laboratory experience through collaborations with the Spanish National Research Council (CSIC) and the University of Brighton. In 2020, she was awarded a Ph.D. by the University of Sussex, where she researched drug-induced mitochondrial dysfunction.

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Learn about exciting new developments in pharmacokinetic prediction, and how to transform your use of ADME data.

About the Webinar

Whilst early in vitro screening for absorption, distribution metabolism and elimination (ADME) properties has significantly transformed early drug screening in many companies, the corresponding ability to quickly, and reliably, predict pharmacokinetics (PK) from these data has lagged behind. In vivo human prediction still largely relies on scaling from animal in vivo PK data, precluding its use for mass PK screening in early discovery.

In this webinar our expert, Simon Thomas, outlines Cyprotex's most recent work in the prediction of human PK from early ADME data. Combining ADME data with physicochemical and structural information within a novel physiologically based pharmacokinetic (PBPK) model, we have developed a service that returns a comprehensive array of reliable PK data and metrics: summary PK parameters and plasma concentrations are predicted for oral, intravenous bolus and intravenous infusion administration, whether single- or repeat-dose regimes. Generation of these predictions greatly enhances the value of the ADME data, and facilitates multiple options for directing compound progression: use of the predicted PK parameters enables compounds with desirable properties to be identified, whilst reliable plasma concentration prediction enables the implementation of pharmacokinetic/pharmacodynamic (PK/PD) modelling for early assessment of in vivo potential. High throughput and rapid turnaround maximally facilitate the make-test-analyse process.

About the Speaker

Simon Thomas PhD Head of Modelling and Simulation | Cyprotex Dr Simon Thomas is the Head of Modelling and Simulation at Cyprotex where he is responsible for the development of mathematical models for predicting ADME properties, pharmacokinetics, toxicity and clinical efficacy. Simon studied chemistry at the University of Oxford, as a final year student writing his first computer models, on the emission of electrons via the photoelectric effect. He obtained his Ph.D. and carried out post-doctoral work in the nascent field of systems biology at Oxford Brookes University, modelling the regulation of biochemical pathways in plants and animals, particularly with respect to pathways of energy metabolism. He joined Cyprotex in 1999, initially leading the company’s modelling efforts in PK prediction, over time extending the company’s capabilities into prediction of toxicity and pharmacological activity.

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Seizure Prediction using MEA: Importance of Receptor Expression, Cell Type, and Maturity

The fourth webinar in this series on New Approaches in Toxicology was presented by Christopher Strock PhD from Cyprotex.

About the Webinar

For the prediction of seizurogenic and neurotoxic compounds, microelectrode array (MEA) technology has proven to be a very powerful tool. Early human induced potent stem cell (hiPSC) derived neuronal models lacked complex burst organization, making electrophysiological neurotoxic prediction challenging when utilizing an MEA platform. However, advancements in hiPSC neuronal models have addressed these challenges. In this presentation, we learn more about how maturation of the hiPSC model is critical for neuronal characteristics such as bursting and synchrony, we demonstrate how time dependent receptor expression plays a role in this maturation process, and we understand the impact of different cell types and co-culture models on the sensitivity and robustness of the neuronal and seizurogenic activity.

About the Speaker

Christopher Strock PhD Director of Scientific Operations | Cyprotex Chris Strock received his BS in Chemistry from Gannon University in Erie, PA. He worked as an organic chemist for DuPont Ag for a few years before getting his PhD in Biochemistry and Molecular Biology from the University of Maryland, Baltimore where he determined the calcium binding sites on the SR Calcium. Following his PhD, Chris was a Postdoctoral Fellow and Research Associate in the Oncology Department at Johns Hopkins University School of Medicine under Barry Nelkin, PhD where he identified CDK5, a protein important in migration of cells in neural development, as an essential molecule for metastasis in numerous cancer models. He then joined Cellumen where he developed his expertise in High Content Screening technology. While there, he specialized in assay development and was responsible for the design and development of High Content HTS Protein: Protein Interaction biosensor assays. He also worked in the HCS toxicology group, developing and optimizing assays for the in vitro toxicology assay, CellCiphr®. After Cyprotex acquired Cellumen, Chris joined Cyprotex US in Watertown, MA where he has brought his expertise for the last 10 years in the area of HCS assay development, electrophysiology and toxicology. He is the co- chairman of the HesI NeuTox Group for prediction of Seizures using Microelectrode Array. He currently is the Watertown Site Head and the Head of the in vitro Toxicology group and has more than 30 peer reviewed publications.

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Development of an In Vitro T-cell Assay to Assess the Intrinsic Immunogenicity of Drugs and Chemicals

The third webinar in this series on New Approaches in Toxicology was presented by Monday Ogese PhD from University of Liverpool.

About the Webinar

The prediction of drug hypersensitivity is difficult due to the lack of appropriate models and an incomplete understanding of risk factors/mechanisms of immune tolerance. Our research at the MRC centre of Drug Safety Science, University of Liverpool combine aspects of genetics, cell biology and chemistry in order to study the fundamental principles of immunological drug reactions. We have recently developed an in vitro naïve T-cell priming assay with the potential to screen immunogenic drug candidates during preclinical drug development and the application of the assay will be discussed during my presentation.

About the Speaker

Monday Ogese PhD Postdoctoral Scientist at the MRC Centre for Drug Safety Science | University of Liverpool Monday O. Ogese is a postdoctoral scientist at the MRC Centre for Drug Safety Science, University of Liverpool. He was awarded his PhD (Pharmacology) in 2014 at the University of Liverpool. His first postdoctoral fellowship with AstraZeneca R&D, UK focused on drug-specific signalling between primary human hepatocytes and immune cells, and the role of hepatocyte-derived exosomes in drug-induced liver injury. His current research interest focuses on the development of screening assay systems to predict intrinsic immunogenicity of candidate drugs and chemicals. Monday has published 23 peer reviewed articles on various aspects of drug hypersensitivity reactions. In 2021, Monday joined Cyprotex as a Principal Scientist in the UK Toxicology team.

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Understanding the Applicability and Limitations of In Silico and In Vitro Safety Models Towards the Design and Selection of the Safest Drug Candidates

The second webinar in this series on New Approaches in Toxicology was presented by Takafumi Takai PhD from Takeda.

About the Webinar

A variety of in silico and in vitro safety assays are widely used in lead optimization in order to capture the safety-related liability as early as possible. Understanding the applicability and limitation of each assay based on the chemical space/chemotype is important for the effective usage. Several case studies of the applicability analysis including in silico phototoxicity prediction and low-dose in vivo toxicity prediction by cytotoxicity assay will be presented.

About the Speaker

Takafumi Takai PhD Senior Scientist | Takeda Takafumi has more than 15 years of industry experience in drug discovery. He currently manages safety assessments mainly during compound optimization at Takeda California by using his expertise in medicinal and computational chemistry. Prior to joining the drug safety department, he led drug discovery projects as a medicinal chemist at Takeda in Japan. He holds a Ph.D. from Okayama University, Japan as well as a Master’s Degree from Tohoku University, Japan.

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Drug Discovery and Development:  Challenges and Opportunities in Toxicology

The first webinar in this series on new approaches in toxicology was presented by Professor Ruth Roberts from ApconiX.

About the Webinar

Ruth will present lessons learned from >20 years’ experience in the pharmaceutical industry focusing on attrition, prediction and the challenges posed by non-clinical to clinical concordance. Several case studies that focus on science-driven design will be shared for discussion. Chemical liabilities should be eliminated early in discovery while there are still options in chemistry. Equally important is a thorough understanding of potential target-related risks and their likelihood of occurrence. The triple challenge of attrition, concordance and the 3Rs should drive us to take a longer term, strategic approach to drug discovery and safety testing. New technologies such as micro physiological systems (MPS), artificial intelligence and big data all offer opportunities to do things differently. But are we ready for change?  These issues and potential solutions will be presented for discussion.

About the Speaker

Professor Ruth Roberts PhD, ATS, FBTS, ERT, FRSB, FR CPath Director and Co-founder | ApconiX Ruth is chair of drug discovery at Birmingham University, UK and Co-founder of ApconiX, an integrated toxicology and ion channel company that brings together a team of world-renowned nonclinical safety experts with over 300 years of drug discovery and development experience.  Before that Ruth was Global Head of Regulatory Safety at AstraZeneca and Director of Toxicology for Aventis in Paris, France. With >150 publications in peer reviewed journals, she is interested in developing and implementing new models to increase success rates in drug discovery and development. Ruth is former president of EUROTOX, former past president of the Academy of Toxicological Sciences and was recently elected to vice-chair of the Board of Trustees of the Health and Environmental Sciences Institute (HESI), based in Washington, DC. She was the recipient of the SOT Achievement award in 2002, the EUROTOX Bo Holmstedt Award in 2009 and the SOT 2018 Founders award, given in recognition of outstanding leadership in fostering the role of toxicological sciences in safety decision making.

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Investigating Protein-Facilitated Uptake of OATP Substrates: From In Vitro Data to PBPK Modeling

The fourth and final webinar in this series on drug transporters was presented by Christine Bowman from Genentech.

About the Webinar

Christine will discuss the concept of protein-facilitated uptake and the recently proposed hypothesis of a transporter-induced protein binding shift In vitro data generated with hepatocytes and HEK293 cells will be described as well as the results of using the HEK293 data for input in PBPK models. The results suggest that high affinity binding to transporters may change the equilibrium of nonspecific binding between drugs and plasma proteins, leading to greater cellular uptake and clearance than currently predicted.

About the Speaker

Christine Bowman PhD Associate Scientist, DMPK | Genentech Christine Bowman is an Associate Scientist in the Drug Metabolism and Pharmacokinetics Department at Genentech, Inc. Her research interests include improving in vitro to in vivo extrapolation with new in vitro methods and PBPK modeling. Prior to Genentech, Christine received her PhD from the University of California, San Francisco in the laboratory of Dr. Leslie Benet during which time she was the recipient of a National Science Foundation Graduate Research Fellowship and PhRMA Foundation Pre-Doctoral Fellowship in Pharmaceutics. Christine is an author and coauthor of 16 peer-reviewed scientific publications.

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